Imaging

ABSTRACT

Femoroacetabular impingement (FAI) is an abnormality of the hip joint that is increasingly being recognized as a cause of athletic disability and early degenerative hip disease. Despite significant advances in the knowledge of FAI, it remains a frequently unrecognized cause of hip pain in adolescents and young adults among orthopedic providers. The purpose of this article is to present a simple 3-view radiographic approach to young adults with hip pain. The radiographs include a standing anteroposterior view of the pelvis, a cross-table lateral view, and a false profile view. Good quality radiographs showing the common sites of potential impingement combined with a basic understanding of certain radiographic parameters may allow faster diagnosis, eliminate unnecessary studies, and allow earlier referral and management.

Continue to: The prevalence of femoroacetabular impingement...

The prevalence of femoroacetabular impingement (FAI) in the general population is estimated at 23.1%.¹ While FAI is often bilateral,² patients usually present with unilateral symptoms.³ Young, highly active individuals are most commonly affected.³ Despite significant improvement in our understanding of FAI in recent years, it remains a poorly recognized cause of hip pain among orthopedic providers. Clohisy and colleagues³ found that the average time to diagnosis was 3.1 years (range, 3-15 years) and the average number of providers seen before correct diagnosis was 4.2 (range, 1-16) with nearly half those providers being orthopedic specialists. This is likely attributed to limited training and lack of appropriate imaging. Multiple comprehensive radiographic approaches have been described, including plain films, computed tomography, and magnetic resonance imaging.^2,4 The objective of this article is to present a simple 3-view plain film approach for young adults with hip pain. While history and physical examination remain key to FAI diagnosis, a basic knowledge of the common sites of impingement with appropriate radiographic views to visualize these sites may help eliminate unnecessary imaging and delayed diagnosis.

STANDING ANTEROPOSTERIOR VIEW OF THE PELVIS

An anteroposterior (AP) view of the pelvis, as opposed to an AP view of the hip, is an important first radiograph in the evaluation of young patients presenting with hip pain. Not only does it permit visualization of the contralateral hip for comparison, but it also allows more accurate measurements of several radiographic parameters (Table). An AP view of the hip often gives the false impression of global over coverage, such as coxa profunda² and protrusio acetabuli (Figures 1A, 1B), and may overestimate the amount of acetabular anteversion.²

Table. Summary of Common Radiographic Parameters When Assessing Young Adults with Hip Pain^2,4

^aNormal values are provided for reference only and should not be solely relied on for diagnosis.

Abbreviations: AP, anteroposterior; FAI, femoroacetabular impingement.

A good quality radiograph is important for accurate assessment. The X-ray beam should be perpendicular to the coronal plane of the pelvis. Neutral rotation of the pelvis is a prerequisite and can be confirmed by the presence of symmetric obturator foramina, iliac wings, and coccyx vertically in line with the pubic symphysis. Deviations from this configuration can significantly affect the ability to accurately assess the acetabular version. This is because the rotational profile of the acetabulum is sensitive to pelvic rotation.^5,6

While the AP view of the pelvis can be obtained in either supine or standing positions, the standing position is recommended. A supine view tends to increase the likelihood of finding a crossover sign that often disappears in the standing position (Figures 2A, 2B). This is attributed to the posterior tilt of the pelvis in the sagittal plane with standing, which functionally increases acetabular anteversion, eliminating the crossover sign.^5,6 In contrast, a crossover sign that persists in the standing position combined with other abnormal radiographic parameters, such as a negative Tonnis angle and/or increased lateral center edge angle, are concerning for pincer-type FAI (Figures 3A, 3B). An isolated crossover sign may be a normal variant in young asymptomatic patients⁷ and is not a reliable indicator of acetabular retroversion.⁵

In addition to assessing the acetabular coverage and version (Figures 1A, 1B, 3A, 3B, and 4A, 4B), the AP view of the pelvis can provide valuable information regarding the proximal femur. One should pay attention to the sphericity of the head (pistol grip cam lesions are most obvious on this view), congruency between the femoral head and the acetabulum, femoral offset, and neck-shaft angle. While we tend to traditionally classify FAI into cam and pincer osseous bumps, alterations in hip dynamics (i.e., coxa vara and coxa breva) can result in functional impingement even in the absence of the osseous bumps.

Continue to: CROSS-TABLE LATERAL...

CROSS-TABLE LATERAL

A cross-table lateral of the affected hip is another important radiographic adjunct in the evaluation of hip pain in young patients. This view provides AP axial visualization of the hip joint identifying potential pathologies such as anterior cam lesions that may not be apparent on frog-leg lateral radiographs (Figures 5A, 5B and 6A, 6B). The cross-table lateral view can also show posterior impingement and/or joint space narrowing from countercoup lesions associated with pincer-type FAI (Figures 3A, 3B). In addition, the rotational profile of the proximal femur is best assessed in this view (Figure 4B). The challenge with a cross-table lateral, however, is that it is operator-dependent. In circumstances where a good quality cross-table lateral cannot be obtained, we default to a frog-leg lateral to avoid excess radiation exposure.

FALSE PROFILE VIEW

A false profile view provides a good visualization of the anterosuperior aspect of the acetabulum. It can show anterior acetabular over or under coverage. It may also show sub-spine impingement (Figures 7A, 7B). Sub-spine impingement is characterized by a prominent anterior inferior iliac spine (AIIS) that extends to the level of the anterosuperior acetabular rim. The prominent AIIS can impinge on the femoral head-neck junction during hip flexion. A prominent AIIS has also been shown to give the false impression of a crossover sign.⁸

CONCLUSION

Even to the trained eye, radiographic findings of FAI can be quite subtle and easily missed. A systematic approach when interpreting plain radiographs is important. Radiographic assessment starts with good quality X-rays with the pelvis in neutral rotation. Because of the young age of most patients, radiation exposure should be minimized. An understanding of the potential sites of impingement and the specific radiographs to visualize these sites minimizes radiation exposure and other unnecessary imaging. In our experience, the 3-view radiographic approach presented combined with supportive history and physical examination findings are highly sensitive to identify cases of FAI. Advanced imaging is reserved for patients who have failed conservative management or considering surgical intervention.

ABSTRACT

Femoroacetabular impingement (FAI) is an abnormality of the hip joint that is increasingly being recognized as a cause of athletic disability and early degenerative hip disease. Despite significant advances in the knowledge of FAI, it remains a frequently unrecognized cause of hip pain in adolescents and young adults among orthopedic providers. The purpose of this article is to present a simple 3-view radiographic approach to young adults with hip pain. The radiographs include a standing anteroposterior view of the pelvis, a cross-table lateral view, and a false profile view. Good quality radiographs showing the common sites of potential impingement combined with a basic understanding of certain radiographic parameters may allow faster diagnosis, eliminate unnecessary studies, and allow earlier referral and management.

Continue to: The prevalence of femoroacetabular impingement...

The prevalence of femoroacetabular impingement (FAI) in the general population is estimated at 23.1%.¹ While FAI is often bilateral,² patients usually present with unilateral symptoms.³ Young, highly active individuals are most commonly affected.³ Despite significant improvement in our understanding of FAI in recent years, it remains a poorly recognized cause of hip pain among orthopedic providers. Clohisy and colleagues³ found that the average time to diagnosis was 3.1 years (range, 3-15 years) and the average number of providers seen before correct diagnosis was 4.2 (range, 1-16) with nearly half those providers being orthopedic specialists. This is likely attributed to limited training and lack of appropriate imaging. Multiple comprehensive radiographic approaches have been described, including plain films, computed tomography, and magnetic resonance imaging.^2,4 The objective of this article is to present a simple 3-view plain film approach for young adults with hip pain. While history and physical examination remain key to FAI diagnosis, a basic knowledge of the common sites of impingement with appropriate radiographic views to visualize these sites may help eliminate unnecessary imaging and delayed diagnosis.

STANDING ANTEROPOSTERIOR VIEW OF THE PELVIS

An anteroposterior (AP) view of the pelvis, as opposed to an AP view of the hip, is an important first radiograph in the evaluation of young patients presenting with hip pain. Not only does it permit visualization of the contralateral hip for comparison, but it also allows more accurate measurements of several radiographic parameters (Table). An AP view of the hip often gives the false impression of global over coverage, such as coxa profunda² and protrusio acetabuli (Figures 1A, 1B), and may overestimate the amount of acetabular anteversion.²

Table. Summary of Common Radiographic Parameters When Assessing Young Adults with Hip Pain^2,4

^aNormal values are provided for reference only and should not be solely relied on for diagnosis.

Abbreviations: AP, anteroposterior; FAI, femoroacetabular impingement.

A good quality radiograph is important for accurate assessment. The X-ray beam should be perpendicular to the coronal plane of the pelvis. Neutral rotation of the pelvis is a prerequisite and can be confirmed by the presence of symmetric obturator foramina, iliac wings, and coccyx vertically in line with the pubic symphysis. Deviations from this configuration can significantly affect the ability to accurately assess the acetabular version. This is because the rotational profile of the acetabulum is sensitive to pelvic rotation.^5,6

While the AP view of the pelvis can be obtained in either supine or standing positions, the standing position is recommended. A supine view tends to increase the likelihood of finding a crossover sign that often disappears in the standing position (Figures 2A, 2B). This is attributed to the posterior tilt of the pelvis in the sagittal plane with standing, which functionally increases acetabular anteversion, eliminating the crossover sign.^5,6 In contrast, a crossover sign that persists in the standing position combined with other abnormal radiographic parameters, such as a negative Tonnis angle and/or increased lateral center edge angle, are concerning for pincer-type FAI (Figures 3A, 3B). An isolated crossover sign may be a normal variant in young asymptomatic patients⁷ and is not a reliable indicator of acetabular retroversion.⁵

In addition to assessing the acetabular coverage and version (Figures 1A, 1B, 3A, 3B, and 4A, 4B), the AP view of the pelvis can provide valuable information regarding the proximal femur. One should pay attention to the sphericity of the head (pistol grip cam lesions are most obvious on this view), congruency between the femoral head and the acetabulum, femoral offset, and neck-shaft angle. While we tend to traditionally classify FAI into cam and pincer osseous bumps, alterations in hip dynamics (i.e., coxa vara and coxa breva) can result in functional impingement even in the absence of the osseous bumps.

Continue to: CROSS-TABLE LATERAL...

CROSS-TABLE LATERAL

A cross-table lateral of the affected hip is another important radiographic adjunct in the evaluation of hip pain in young patients. This view provides AP axial visualization of the hip joint identifying potential pathologies such as anterior cam lesions that may not be apparent on frog-leg lateral radiographs (Figures 5A, 5B and 6A, 6B). The cross-table lateral view can also show posterior impingement and/or joint space narrowing from countercoup lesions associated with pincer-type FAI (Figures 3A, 3B). In addition, the rotational profile of the proximal femur is best assessed in this view (Figure 4B). The challenge with a cross-table lateral, however, is that it is operator-dependent. In circumstances where a good quality cross-table lateral cannot be obtained, we default to a frog-leg lateral to avoid excess radiation exposure.

FALSE PROFILE VIEW

A false profile view provides a good visualization of the anterosuperior aspect of the acetabulum. It can show anterior acetabular over or under coverage. It may also show sub-spine impingement (Figures 7A, 7B). Sub-spine impingement is characterized by a prominent anterior inferior iliac spine (AIIS) that extends to the level of the anterosuperior acetabular rim. The prominent AIIS can impinge on the femoral head-neck junction during hip flexion. A prominent AIIS has also been shown to give the false impression of a crossover sign.⁸

CONCLUSION

Even to the trained eye, radiographic findings of FAI can be quite subtle and easily missed. A systematic approach when interpreting plain radiographs is important. Radiographic assessment starts with good quality X-rays with the pelvis in neutral rotation. Because of the young age of most patients, radiation exposure should be minimized. An understanding of the potential sites of impingement and the specific radiographs to visualize these sites minimizes radiation exposure and other unnecessary imaging. In our experience, the 3-view radiographic approach presented combined with supportive history and physical examination findings are highly sensitive to identify cases of FAI. Advanced imaging is reserved for patients who have failed conservative management or considering surgical intervention.

ABSTRACT

Femoroacetabular impingement (FAI) is an abnormality of the hip joint that is increasingly being recognized as a cause of athletic disability and early degenerative hip disease. Despite significant advances in the knowledge of FAI, it remains a frequently unrecognized cause of hip pain in adolescents and young adults among orthopedic providers. The purpose of this article is to present a simple 3-view radiographic approach to young adults with hip pain. The radiographs include a standing anteroposterior view of the pelvis, a cross-table lateral view, and a false profile view. Good quality radiographs showing the common sites of potential impingement combined with a basic understanding of certain radiographic parameters may allow faster diagnosis, eliminate unnecessary studies, and allow earlier referral and management.

Continue to: The prevalence of femoroacetabular impingement...

The prevalence of femoroacetabular impingement (FAI) in the general population is estimated at 23.1%.¹ While FAI is often bilateral,² patients usually present with unilateral symptoms.³ Young, highly active individuals are most commonly affected.³ Despite significant improvement in our understanding of FAI in recent years, it remains a poorly recognized cause of hip pain among orthopedic providers. Clohisy and colleagues³ found that the average time to diagnosis was 3.1 years (range, 3-15 years) and the average number of providers seen before correct diagnosis was 4.2 (range, 1-16) with nearly half those providers being orthopedic specialists. This is likely attributed to limited training and lack of appropriate imaging. Multiple comprehensive radiographic approaches have been described, including plain films, computed tomography, and magnetic resonance imaging.^2,4 The objective of this article is to present a simple 3-view plain film approach for young adults with hip pain. While history and physical examination remain key to FAI diagnosis, a basic knowledge of the common sites of impingement with appropriate radiographic views to visualize these sites may help eliminate unnecessary imaging and delayed diagnosis.

STANDING ANTEROPOSTERIOR VIEW OF THE PELVIS

An anteroposterior (AP) view of the pelvis, as opposed to an AP view of the hip, is an important first radiograph in the evaluation of young patients presenting with hip pain. Not only does it permit visualization of the contralateral hip for comparison, but it also allows more accurate measurements of several radiographic parameters (Table). An AP view of the hip often gives the false impression of global over coverage, such as coxa profunda² and protrusio acetabuli (Figures 1A, 1B), and may overestimate the amount of acetabular anteversion.²

Table. Summary of Common Radiographic Parameters When Assessing Young Adults with Hip Pain^2,4

^aNormal values are provided for reference only and should not be solely relied on for diagnosis.

Abbreviations: AP, anteroposterior; FAI, femoroacetabular impingement.

A good quality radiograph is important for accurate assessment. The X-ray beam should be perpendicular to the coronal plane of the pelvis. Neutral rotation of the pelvis is a prerequisite and can be confirmed by the presence of symmetric obturator foramina, iliac wings, and coccyx vertically in line with the pubic symphysis. Deviations from this configuration can significantly affect the ability to accurately assess the acetabular version. This is because the rotational profile of the acetabulum is sensitive to pelvic rotation.^5,6

While the AP view of the pelvis can be obtained in either supine or standing positions, the standing position is recommended. A supine view tends to increase the likelihood of finding a crossover sign that often disappears in the standing position (Figures 2A, 2B). This is attributed to the posterior tilt of the pelvis in the sagittal plane with standing, which functionally increases acetabular anteversion, eliminating the crossover sign.^5,6 In contrast, a crossover sign that persists in the standing position combined with other abnormal radiographic parameters, such as a negative Tonnis angle and/or increased lateral center edge angle, are concerning for pincer-type FAI (Figures 3A, 3B). An isolated crossover sign may be a normal variant in young asymptomatic patients⁷ and is not a reliable indicator of acetabular retroversion.⁵

In addition to assessing the acetabular coverage and version (Figures 1A, 1B, 3A, 3B, and 4A, 4B), the AP view of the pelvis can provide valuable information regarding the proximal femur. One should pay attention to the sphericity of the head (pistol grip cam lesions are most obvious on this view), congruency between the femoral head and the acetabulum, femoral offset, and neck-shaft angle. While we tend to traditionally classify FAI into cam and pincer osseous bumps, alterations in hip dynamics (i.e., coxa vara and coxa breva) can result in functional impingement even in the absence of the osseous bumps.

Continue to: CROSS-TABLE LATERAL...

CROSS-TABLE LATERAL

A cross-table lateral of the affected hip is another important radiographic adjunct in the evaluation of hip pain in young patients. This view provides AP axial visualization of the hip joint identifying potential pathologies such as anterior cam lesions that may not be apparent on frog-leg lateral radiographs (Figures 5A, 5B and 6A, 6B). The cross-table lateral view can also show posterior impingement and/or joint space narrowing from countercoup lesions associated with pincer-type FAI (Figures 3A, 3B). In addition, the rotational profile of the proximal femur is best assessed in this view (Figure 4B). The challenge with a cross-table lateral, however, is that it is operator-dependent. In circumstances where a good quality cross-table lateral cannot be obtained, we default to a frog-leg lateral to avoid excess radiation exposure.

FALSE PROFILE VIEW

A false profile view provides a good visualization of the anterosuperior aspect of the acetabulum. It can show anterior acetabular over or under coverage. It may also show sub-spine impingement (Figures 7A, 7B). Sub-spine impingement is characterized by a prominent anterior inferior iliac spine (AIIS) that extends to the level of the anterosuperior acetabular rim. The prominent AIIS can impinge on the femoral head-neck junction during hip flexion. A prominent AIIS has also been shown to give the false impression of a crossover sign.⁸

CONCLUSION

Even to the trained eye, radiographic findings of FAI can be quite subtle and easily missed. A systematic approach when interpreting plain radiographs is important. Radiographic assessment starts with good quality X-rays with the pelvis in neutral rotation. Because of the young age of most patients, radiation exposure should be minimized. An understanding of the potential sites of impingement and the specific radiographs to visualize these sites minimizes radiation exposure and other unnecessary imaging. In our experience, the 3-view radiographic approach presented combined with supportive history and physical examination findings are highly sensitive to identify cases of FAI. Advanced imaging is reserved for patients who have failed conservative management or considering surgical intervention.

MUNICH – The big news in the field of heart failure at the annual congress of the European Society of Cardiology concerned an obscure form of the disease traditionally considered rare: transthyretin amyloid cardiomyopathy (TAC).

Bruce Jancin/MDedge News

It turns out that TAC is far more common than previously recognized; it can now be diagnosed and staged noninvasively; and – most important of all – there is for the first time an effective disease-modifying treatment in the form of a novel oral drug called tafamidis, as demonstrated in the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT) presented at the meeting.

“This is the first phase 3 trial that can offer a chance for people with a terrible, severe disease. And within the last year, while the trial was being conducted, it became clear that this disease is much more underdiagnosed than rare,” said Claudio Rapezzi, MD, ATTR-ACT principal investigator and director of the school of cardiovascular diseases at the University of Bologna, Italy.

ATTR-ACT participants randomized to tafamidis showed significant reductions in all-cause mortality and cardiovascular hospitalizations, compared with placebo-treated controls at 30 months follow-up. They also experienced significantly lesser declines in both quality of life as reflected in Kansas City Cardiomyopathy Questionnaire scores and in physical function as captured in 6-minute walk distance.

Bruce Jancin/MDedge News

Designated discussant Jacob George, MD, was over the moon regarding the results.

“This is a pioneering, game-changing trial that is likely to transform the way we diagnose and treat patients with cardiac amyloidosis,” said Dr. George of Kaplan Medical Center in Rehovot, Israel.

“We’re now in an era that, to my opinion, any patient with nonischemic unexplained heart failure should be screened for the presence of amyloidosis because, first, we now know how to prognosticate these patients, and second, we can offer them a real disease-modifying agent,” he added.
 

An underdiagnosed disease

Transthyretin amyloid cardiomyopathy occurs when transthyretin, a transport protein, becomes destabilized and misfolds, promoting deposition of amyloid fibrils in the myocardium. This results in progressive ventricular wall thickening and stiffness, manifest as restrictive cardiomyopathy and progressive heart failure. The cause of transthyretin destabilization can be either autosomal dominant inheritance of any of more than 100 pathogenic mutations in the transthyretin gene identified to date or a spontaneous wild type protein.

Think of TAC as a sort of dementia of the heart. As Dr. George noted, the cardiac disease bears “remarkable similarities” to Alzheimer’s disease, with both conditions entailing extracellular deposition of amyloid.

In the heritable form of TAC, patients typically present with heart failure symptoms at about age 50-55, while the wild type form becomes symptomatic much later at a mean age of about 75. Average survival from time of diagnosis is only about 3 years.

Recent studies from multiple centers have reported that the prevalence of TAC was 16% in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis, 13% among patients with heart failure with preserved ejection fraction, and 5% in patients who had been presumed to have hypertrophic cardiomyopathy: So, not a rare condition.

“In our clinic, vast and surprising numbers of patients with unexplained nonischemic heart failure are scan positive [for TAC],” according to Dr. George.
 

Breakthroughs in diagnosis and staging

The echocardiographic red flag for TAC in a patient with heart failure symptoms is symmetric hypertrophy with a normal end-diastolic volume and thickened ventricles. The end-diastolic interventricular septal wall thickness is typically about 15 mm. The left ventricular ejection fraction is typically in the normal range, “but the clue is not the preservation of the ejection fraction, it’s the [normal] quality of the volume,” Dr. Rapezzi said.

A clinical clue suggestive of TAC upon physical examination, even in the absence of heart failure symptoms, is development of bilateral carpal tunnel syndrome in an older man. That’s because the same disease process that results in TAC can involve deposition of amyloid fibrils in peripheral nerves. Indeed, tafamidis is already approved in Europe and Japan under the trade name Vyndaqel as a treatment for familial amyloid polyneuropathy. For TAC, however, tafamidis remains investigational with fast-track status provided by both the Food and Drug Administration and the European Medicines Agency.

When TAC is suspected, it’s no longer necessary to subject patients to an onerous myocardial biopsy. Total body scintigraphy with bone tracers has been shown to be nearly as sensitive and specific as biopsy for the diagnosis.

Staging can now be done noninvasively as well. Investigators at the U.K. National Amyloidosis Centre recently reported that patients with TAC can be accurately staged using two biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR). In their series of 869 patients with TAC, median survival for those with stage I disease as defined by their protocol was 69 months, compared with 47 months for stage II disease and 24 months for those with stage III disease. This simple U.K. staging system was then validated in a separate French cohort of TAC patients (Eur Heart J. 2018 Aug 7;39[30]:2799-806).
 

The ATTR-ACT trial

Dr. Rapezzi reported on 441 patients with TAC who were randomized to oral tafamidis at either 20 mg or 80 mg per day or placebo and followed prospectively for 30 months in the 13-country, double-blind, phase 3 trial. At 30 months, all-cause mortality was 29.5% in patients who received tafamidis, compared with 42.9% in controls, for a 30% relative risk reduction. The rate of cardiovascular hospitalizations was 0.48 per year with tafamidis, compared with 0.70 per year with placebo, for a 38% relative risk reduction. The mortality benefit didn’t achieve significance until 15-18 months into the trial, as to be expected given tafamidis’ mechanism of action, which involves binding to transthyretin, gradually stabilizing it, and curbing amyloid fibril deposition.

Of note, the benefit was similar regardless of the dose used and whether patients had hereditary or wild type TAC.

Tafamidis proved safe and well tolerated, with a side-effect profile similar to placebo. While diarrhea and urinary tract infections have been an issue in tafamidis-treated patients with familial amyloid polyneuropathy, these adverse events were actually less common in TAC patients who received tafamidis than with placebo, according to Dr. Rapezzi.

A key point, the cardiologist emphasized, is that the benefits of active treatment were greatest in patients with earlier-stage disease. Therefore it’s vital that the diagnosis of TAC be made early, with prompt initiation of treatment to follow, in order to catch the disease at a more reversible stage. That could mean there will be a whole lot more bone scintigraphy being done in patients with unexplained nonischemic heart failure.

Dr. Rapezzi reported receiving research grants, speaker honoraria, and consulting fees from Pfizer, which sponsored the ATTR-ACT trial. Simultaneous with his presentation in Munich, the study results were published online at NEJM.org (doi: 10.1056/NEJMoa1805689). Dr. George reported no financial conflicts.

[email protected]

MUNICH – The big news in the field of heart failure at the annual congress of the European Society of Cardiology concerned an obscure form of the disease traditionally considered rare: transthyretin amyloid cardiomyopathy (TAC).

Bruce Jancin/MDedge News

It turns out that TAC is far more common than previously recognized; it can now be diagnosed and staged noninvasively; and – most important of all – there is for the first time an effective disease-modifying treatment in the form of a novel oral drug called tafamidis, as demonstrated in the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT) presented at the meeting.

“This is the first phase 3 trial that can offer a chance for people with a terrible, severe disease. And within the last year, while the trial was being conducted, it became clear that this disease is much more underdiagnosed than rare,” said Claudio Rapezzi, MD, ATTR-ACT principal investigator and director of the school of cardiovascular diseases at the University of Bologna, Italy.

ATTR-ACT participants randomized to tafamidis showed significant reductions in all-cause mortality and cardiovascular hospitalizations, compared with placebo-treated controls at 30 months follow-up. They also experienced significantly lesser declines in both quality of life as reflected in Kansas City Cardiomyopathy Questionnaire scores and in physical function as captured in 6-minute walk distance.

Bruce Jancin/MDedge News

Designated discussant Jacob George, MD, was over the moon regarding the results.

“This is a pioneering, game-changing trial that is likely to transform the way we diagnose and treat patients with cardiac amyloidosis,” said Dr. George of Kaplan Medical Center in Rehovot, Israel.

“We’re now in an era that, to my opinion, any patient with nonischemic unexplained heart failure should be screened for the presence of amyloidosis because, first, we now know how to prognosticate these patients, and second, we can offer them a real disease-modifying agent,” he added.
 

An underdiagnosed disease

Transthyretin amyloid cardiomyopathy occurs when transthyretin, a transport protein, becomes destabilized and misfolds, promoting deposition of amyloid fibrils in the myocardium. This results in progressive ventricular wall thickening and stiffness, manifest as restrictive cardiomyopathy and progressive heart failure. The cause of transthyretin destabilization can be either autosomal dominant inheritance of any of more than 100 pathogenic mutations in the transthyretin gene identified to date or a spontaneous wild type protein.

Think of TAC as a sort of dementia of the heart. As Dr. George noted, the cardiac disease bears “remarkable similarities” to Alzheimer’s disease, with both conditions entailing extracellular deposition of amyloid.

In the heritable form of TAC, patients typically present with heart failure symptoms at about age 50-55, while the wild type form becomes symptomatic much later at a mean age of about 75. Average survival from time of diagnosis is only about 3 years.

Recent studies from multiple centers have reported that the prevalence of TAC was 16% in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis, 13% among patients with heart failure with preserved ejection fraction, and 5% in patients who had been presumed to have hypertrophic cardiomyopathy: So, not a rare condition.

“In our clinic, vast and surprising numbers of patients with unexplained nonischemic heart failure are scan positive [for TAC],” according to Dr. George.
 

Breakthroughs in diagnosis and staging

The echocardiographic red flag for TAC in a patient with heart failure symptoms is symmetric hypertrophy with a normal end-diastolic volume and thickened ventricles. The end-diastolic interventricular septal wall thickness is typically about 15 mm. The left ventricular ejection fraction is typically in the normal range, “but the clue is not the preservation of the ejection fraction, it’s the [normal] quality of the volume,” Dr. Rapezzi said.

A clinical clue suggestive of TAC upon physical examination, even in the absence of heart failure symptoms, is development of bilateral carpal tunnel syndrome in an older man. That’s because the same disease process that results in TAC can involve deposition of amyloid fibrils in peripheral nerves. Indeed, tafamidis is already approved in Europe and Japan under the trade name Vyndaqel as a treatment for familial amyloid polyneuropathy. For TAC, however, tafamidis remains investigational with fast-track status provided by both the Food and Drug Administration and the European Medicines Agency.

When TAC is suspected, it’s no longer necessary to subject patients to an onerous myocardial biopsy. Total body scintigraphy with bone tracers has been shown to be nearly as sensitive and specific as biopsy for the diagnosis.

Staging can now be done noninvasively as well. Investigators at the U.K. National Amyloidosis Centre recently reported that patients with TAC can be accurately staged using two biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR). In their series of 869 patients with TAC, median survival for those with stage I disease as defined by their protocol was 69 months, compared with 47 months for stage II disease and 24 months for those with stage III disease. This simple U.K. staging system was then validated in a separate French cohort of TAC patients (Eur Heart J. 2018 Aug 7;39[30]:2799-806).
 

The ATTR-ACT trial

Dr. Rapezzi reported on 441 patients with TAC who were randomized to oral tafamidis at either 20 mg or 80 mg per day or placebo and followed prospectively for 30 months in the 13-country, double-blind, phase 3 trial. At 30 months, all-cause mortality was 29.5% in patients who received tafamidis, compared with 42.9% in controls, for a 30% relative risk reduction. The rate of cardiovascular hospitalizations was 0.48 per year with tafamidis, compared with 0.70 per year with placebo, for a 38% relative risk reduction. The mortality benefit didn’t achieve significance until 15-18 months into the trial, as to be expected given tafamidis’ mechanism of action, which involves binding to transthyretin, gradually stabilizing it, and curbing amyloid fibril deposition.

Of note, the benefit was similar regardless of the dose used and whether patients had hereditary or wild type TAC.

Tafamidis proved safe and well tolerated, with a side-effect profile similar to placebo. While diarrhea and urinary tract infections have been an issue in tafamidis-treated patients with familial amyloid polyneuropathy, these adverse events were actually less common in TAC patients who received tafamidis than with placebo, according to Dr. Rapezzi.

A key point, the cardiologist emphasized, is that the benefits of active treatment were greatest in patients with earlier-stage disease. Therefore it’s vital that the diagnosis of TAC be made early, with prompt initiation of treatment to follow, in order to catch the disease at a more reversible stage. That could mean there will be a whole lot more bone scintigraphy being done in patients with unexplained nonischemic heart failure.

Dr. Rapezzi reported receiving research grants, speaker honoraria, and consulting fees from Pfizer, which sponsored the ATTR-ACT trial. Simultaneous with his presentation in Munich, the study results were published online at NEJM.org (doi: 10.1056/NEJMoa1805689). Dr. George reported no financial conflicts.

[email protected]

MUNICH – The big news in the field of heart failure at the annual congress of the European Society of Cardiology concerned an obscure form of the disease traditionally considered rare: transthyretin amyloid cardiomyopathy (TAC).

Bruce Jancin/MDedge News

It turns out that TAC is far more common than previously recognized; it can now be diagnosed and staged noninvasively; and – most important of all – there is for the first time an effective disease-modifying treatment in the form of a novel oral drug called tafamidis, as demonstrated in the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT) presented at the meeting.

“This is the first phase 3 trial that can offer a chance for people with a terrible, severe disease. And within the last year, while the trial was being conducted, it became clear that this disease is much more underdiagnosed than rare,” said Claudio Rapezzi, MD, ATTR-ACT principal investigator and director of the school of cardiovascular diseases at the University of Bologna, Italy.

ATTR-ACT participants randomized to tafamidis showed significant reductions in all-cause mortality and cardiovascular hospitalizations, compared with placebo-treated controls at 30 months follow-up. They also experienced significantly lesser declines in both quality of life as reflected in Kansas City Cardiomyopathy Questionnaire scores and in physical function as captured in 6-minute walk distance.

Bruce Jancin/MDedge News

Designated discussant Jacob George, MD, was over the moon regarding the results.

“This is a pioneering, game-changing trial that is likely to transform the way we diagnose and treat patients with cardiac amyloidosis,” said Dr. George of Kaplan Medical Center in Rehovot, Israel.

“We’re now in an era that, to my opinion, any patient with nonischemic unexplained heart failure should be screened for the presence of amyloidosis because, first, we now know how to prognosticate these patients, and second, we can offer them a real disease-modifying agent,” he added.
 

An underdiagnosed disease

Transthyretin amyloid cardiomyopathy occurs when transthyretin, a transport protein, becomes destabilized and misfolds, promoting deposition of amyloid fibrils in the myocardium. This results in progressive ventricular wall thickening and stiffness, manifest as restrictive cardiomyopathy and progressive heart failure. The cause of transthyretin destabilization can be either autosomal dominant inheritance of any of more than 100 pathogenic mutations in the transthyretin gene identified to date or a spontaneous wild type protein.

Think of TAC as a sort of dementia of the heart. As Dr. George noted, the cardiac disease bears “remarkable similarities” to Alzheimer’s disease, with both conditions entailing extracellular deposition of amyloid.

In the heritable form of TAC, patients typically present with heart failure symptoms at about age 50-55, while the wild type form becomes symptomatic much later at a mean age of about 75. Average survival from time of diagnosis is only about 3 years.

Recent studies from multiple centers have reported that the prevalence of TAC was 16% in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis, 13% among patients with heart failure with preserved ejection fraction, and 5% in patients who had been presumed to have hypertrophic cardiomyopathy: So, not a rare condition.

“In our clinic, vast and surprising numbers of patients with unexplained nonischemic heart failure are scan positive [for TAC],” according to Dr. George.
 

Breakthroughs in diagnosis and staging

The echocardiographic red flag for TAC in a patient with heart failure symptoms is symmetric hypertrophy with a normal end-diastolic volume and thickened ventricles. The end-diastolic interventricular septal wall thickness is typically about 15 mm. The left ventricular ejection fraction is typically in the normal range, “but the clue is not the preservation of the ejection fraction, it’s the [normal] quality of the volume,” Dr. Rapezzi said.

A clinical clue suggestive of TAC upon physical examination, even in the absence of heart failure symptoms, is development of bilateral carpal tunnel syndrome in an older man. That’s because the same disease process that results in TAC can involve deposition of amyloid fibrils in peripheral nerves. Indeed, tafamidis is already approved in Europe and Japan under the trade name Vyndaqel as a treatment for familial amyloid polyneuropathy. For TAC, however, tafamidis remains investigational with fast-track status provided by both the Food and Drug Administration and the European Medicines Agency.

When TAC is suspected, it’s no longer necessary to subject patients to an onerous myocardial biopsy. Total body scintigraphy with bone tracers has been shown to be nearly as sensitive and specific as biopsy for the diagnosis.

Staging can now be done noninvasively as well. Investigators at the U.K. National Amyloidosis Centre recently reported that patients with TAC can be accurately staged using two biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR). In their series of 869 patients with TAC, median survival for those with stage I disease as defined by their protocol was 69 months, compared with 47 months for stage II disease and 24 months for those with stage III disease. This simple U.K. staging system was then validated in a separate French cohort of TAC patients (Eur Heart J. 2018 Aug 7;39[30]:2799-806).
 

The ATTR-ACT trial

Dr. Rapezzi reported on 441 patients with TAC who were randomized to oral tafamidis at either 20 mg or 80 mg per day or placebo and followed prospectively for 30 months in the 13-country, double-blind, phase 3 trial. At 30 months, all-cause mortality was 29.5% in patients who received tafamidis, compared with 42.9% in controls, for a 30% relative risk reduction. The rate of cardiovascular hospitalizations was 0.48 per year with tafamidis, compared with 0.70 per year with placebo, for a 38% relative risk reduction. The mortality benefit didn’t achieve significance until 15-18 months into the trial, as to be expected given tafamidis’ mechanism of action, which involves binding to transthyretin, gradually stabilizing it, and curbing amyloid fibril deposition.

Of note, the benefit was similar regardless of the dose used and whether patients had hereditary or wild type TAC.

Tafamidis proved safe and well tolerated, with a side-effect profile similar to placebo. While diarrhea and urinary tract infections have been an issue in tafamidis-treated patients with familial amyloid polyneuropathy, these adverse events were actually less common in TAC patients who received tafamidis than with placebo, according to Dr. Rapezzi.

A key point, the cardiologist emphasized, is that the benefits of active treatment were greatest in patients with earlier-stage disease. Therefore it’s vital that the diagnosis of TAC be made early, with prompt initiation of treatment to follow, in order to catch the disease at a more reversible stage. That could mean there will be a whole lot more bone scintigraphy being done in patients with unexplained nonischemic heart failure.

Dr. Rapezzi reported receiving research grants, speaker honoraria, and consulting fees from Pfizer, which sponsored the ATTR-ACT trial. Simultaneous with his presentation in Munich, the study results were published online at NEJM.org (doi: 10.1056/NEJMoa1805689). Dr. George reported no financial conflicts.

[email protected]

The United States has seen a decline in fatal myocardial infarctions, largely thanks to early detection of coronary artery disease. Current guidelines on assessment of cardiovascular risk still rely on the traditional 10-year risk model in clinical practice. However, the predictive value of this approach is only moderate, and many coronary events occur in people considered to be at low or intermediate risk.

See related editorial

Coronary artery calcium scoring has emerged as a means of risk stratification by direct measurement of disease. Primary care providers are either using it or are seeing it used by consulting physicians, and its relatively low cost and ease of performance have contributed to its widespread use. However, downstream costs, radiation exposure, and lack of randomized controlled trials have raised concerns.

This article reviews the usefulness and pitfalls of coronary artery calcium scoring, providing a better understanding of the test, its limitations, and the interpretation of results.

ATHEROSCLEROSIS AND CALCIUM

As the calcium deposits grow, they can be detected by imaging tests such as computed tomography (CT), and quantified to assess the extent of disease.⁴

CALCIFICATION AND CORONARY ARTERY DISEASE

Coronary calcification occurs almost exclusively in atherosclerosis. Several autopsy studies^5,6 and histopathologic studies⁷ have shown a direct relationship between the extent of calcification and atherosclerotic disease.

Sangiorgi et al⁷ performed a histologic analysis of 723 coronary artery segments. The amount of calcium correlated well with the area of plaque:

• r = 0.89, P < .0001 in the left anterior descending artery
• r = 0.7, P < .001 in the left circumflex artery
• r = 0.89, P < .0001 in the right coronary artery.

Coronary artery calcium has also been associated with obstructive coronary artery disease in studies using intravascular ultrasonography and optical coherence tomography.^8,9

TECHNICAL INFORMATION ABOUT THE TEST

First-generation CT scanners used for calcium scoring in the 1980s were electron-beam systems in which a stationary x-ray tube generated an oscillating electron beam, which was reflected around the patient table.¹⁰ A single, stationary detector ring captured the images.

These systems have been replaced by multidetector scanners, in which the x-ray tube and multiple rows of detectors are combined in a gantry that rotates at high speed around the patient.

Coronary calcium is measured by noncontrast CT of the heart. Thus, there is no risk of contrast-induced nephropathy or allergic reactions. Images are acquired while the patient holds his or her breath for 3 to 5 seconds. Electrocardiographic gating is used to reduce motion artifact.^11,12 With modern scanners, the effective radiation dose associated with calcium testing is as low as 0.5 to 1.5 mSv,^13,14 ie, about the same dose as that with mammography. The entire test takes 10 to 15 minutes.

The results fall into 4 categories, which correlate with the severity of coronary artery disease, ranging from no significant disease to severe disease (Table 1). Other scores, which are not commonly used, include the calcium volume score¹⁶ and the calcium mass score.¹⁷Figure 2 shows a screenshot from a coronary artery calcium scoring program. 

Early multicenter studies evaluated the utility of calcium scoring to predict coronary stenosis in patients who underwent both cardiac CT and coronary angiography. The sensitivity of calcium scoring for angiographically significant disease was high (95%), but its specificity was low (about 44%).¹⁸

Budoff et al,¹⁹ reviewing these and subsequent results, concluded that the value of calcium scoring is its high negative predictive value (about 98%); a negative score (no calcification) is strongly associated with the absence of obstructive coronary disease.

Blaha et al²⁰ concluded that a score of 0 would indicate that the patient had a low risk of cardiovascular disease. A test with these characteristics is helpful in excluding cardiovascular disease or at least in determining that it is less likely to be present in a patient deemed to be at intermediate risk.

CALCIUM SCORING AS A PROGNOSTIC TOOL

Early on, investigators recognized the value of calcium scoring in predicting the risk of future cardiovascular events and death.^21–25

Predicting cardiovascular events

Pletcher et al21 performed a meta-analysis of studies that measured calcification in asymptomatic patients with subsequent follow-up. The summary-adjusted relative risk of cardiac events such as myocardial infarction, coronary artery revascularization, and coronary heart disease-related death rose with the calcium score:

• 2.1 (95% confidence interval [CI] 1.6–2.9) with a score of 1 to 100
• 4.2 (95% CI 2.5–7.2) with scores of 101 to 400
• 7.2 (95% CI 3.9-13.0) with scores greater than 400.

The meta-analysis was limited in that it included only 4 studies, which were observational.

Kavousi et al,²² in a subsequent meta-analysis of 6,739 women at low risk of atherosclerotic cardiovascular disease based on the American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equation (10-year risk < 7.5%), found that 36.1% had calcium scores greater than 0. Compared with those whose score was 0, those with higher scores had a higher risk of atherosclerotic cardiovascular disease events. The incidence rates per 1,000 person-years were 1.41 vs 4.33 (relative risk 2.92, 95% CI 2.02–3.83; multivariable-adjusted hazard ratio 2.04, 95% CI 1.44–2.90). This study was limited because the population was mostly of European descent, making it less generalizable to non-European populations.

Calcium scoring has also been shown to be a strong predictor of incident cardiovascular events across different races beyond traditional risk factors such as hypertension, hyperlipidemia, and tobacco use.

Detrano et al,²³ in a study of 6,722 patients with diverse ethnic backgrounds, found that the adjusted risk of a coronary event was increased by a factor of 7.73 for calcium scores between 101 and 300 and by a factor of 9.67 for scores above 300 (P < .001). A limitation of this study was that the patients and physicians were informed of the scores, which could have led to bias.

Carr et al²⁴ found an association between calcium and coronary heart disease in a younger population (ages 32–46). In 12.5 years of follow-up, the hazard ratio for cardiovascular events increased exponentially with the calcium score:

• 2.6 (95% CI 1.0–5.7, P = .03) with calcium scores of 1 through 19
• 9.8 (95% CI 4.5–20.5, P < .001) with scores greater than 100.

Predicting mortality

Budoff et al,²⁵ in an observational study of 25,253 patients, found coronary calcium to be an independent predictor of mortality in a multivariable model controlling for age, sex, ethnicity, and cardiac risk factors (model chi-square = 2,017, P < .0001). However, most of the patients were already known to have cardiac risk factors, making the study findings less generalizable to the general population.

Nasir et al²⁶ found that mortality rates rose with the calcium score in a study with 44,052 participants. The annualized mortality rates per 1,000 person-years were:

• 0.87 (95% CI 0.72–1.06) with a score of 0
• 2.97 (95% CI 2.61–3.37) with scores of 1–100
• 6.90 (95% CI 6.02–7.90) with scores of 101–400
• 17.68 (95% CI 5.93–19.62) with scores higher than 400.

The mortality rate also rose with the number of traditional risk factors present, ie, current tobacco use, dyslipidemia, diabetes mellitus, hypertension, and family history of coronary artery disease. Interestingly, those with no risk factors but a calcium score greater than 400 had a higher mortality rate than those with no coronary calcium but more than 3 risk factors (16.89 per 1,000 person-years vs 2.72 per 1,000 person years). As in the previous study, the patient population that was analyzed was at high risk and therefore the findings are not generalizable.

Shaw et al²⁷ found that patients without symptoms but with elevated coronary calcium scores had higher all-cause mortality rates at 15 years than those with a score of 0. The difference remained significant after Cox regression was performed, adjusting for traditional risk factors.

Current guidelines on assessing risk still rely on the traditional 10-year risk model in clinical practice.²⁵ Patients are thus classified as being at low, intermediate, or high risk based on their probability of developing a cardiovascular event or cardiovascular disease-related death in the subsequent 10 years.

However, the predictive value of this approach is only moderate,²⁸ and a significant number of cardiovascular events, including sudden cardiac death, occur in people who were believed to be at low or intermediate risk according to traditional risk factor-based predictions. Because risk scores are strongly influenced by age,²⁹ they are least reliable in young adults.³⁰

Akosah et al³¹ reviewed the records of 222 young adults (women age 55 or younger, men age 65 or younger) who presented with their first myocardial infarction, and found that only 25% would have qualified for primary prevention pharmacologic treatments according to the National Cholesterol Education Program III guidelines.^32,33 Similar findings have been reported regarding previous versions of the risk scores.³³

Thus, risk predictions based exclusively on traditional risk factors are not sensitive for detecting young individuals at increased risk, and lead to late treatment of young adults with atherosclerosis, which may be a less effective strategy.³⁴

The reliance on age in risk algorithms also results in low specificity in elderly adults. Using risk scores, elderly adults are systematically stratified in higher risk categories, expanding the indication for statin therapy to almost all men age 65 or older regardless of their actual vascular health, according to current clinical practice guidelines.^35,36

Risk scores are based on self-reported history and single-day measurements, since this kind of information is readily available to the physician in the clinic. Moreover, our knowledge about genetic and epigenetic factors associated with the development of atherosclerosis is still in its infancy, with current guidelines not supporting genetic testing as part of cardiovascular risk assessment.³⁷ Thus, a reliable measure of an individual’s lifelong exposure to a number of environmental and genetic factors that may affect cardiovascular health appears unfeasible.

Atherosclerosis is a process in which interactions between genetic, epigenetic, environmental, and traditional risk factors result in subclinical inflammation that could develop into clinically significant disease. Therefore, subclinical coronary atherosclerosis has been shown to be a strong predictor of future incident cardiovascular disease events and death. Thus, alternative approaches that directly measure disease, such as calcium scoring, may help further refine risk stratification of cardiovascular disease.

The MESA trial (Multi-Ethnic Study of Atherosclerosis), for instance, in 6,814 participants, found coronary calcium to provide better discrimination and risk reclassification than the ankle-brachial index, high sensitivity C-reactive protein level, and family history.³⁸ Coronary calcium also had the highest incremental improvement of the area under the receiver operating curve when added to the Framingham Risk Score (0.623 vs 0.784).

Reclassifying cardiovascular risk also has implications regarding whether to start therapies such as statins and aspirin.

For considering statin therapy

Nasir et al³⁹ showed that, in patients eligible for statin therapy by the pooled cohort equation, the absence of coronary artery calcium reclassified approximately one-half of candidates as not eligible for statin therapy. The number needed to treat to prevent an atherosclerotic cardiovascular event in the population who were recommended a statin was 64 with a calcium score of 0, and 24 with a calcium score greater than 100. In the population for whom a statin was considered, the number needed to treat was 223 with a calcium score of 0 and 46 for those with a score greater than 100. Moreover, 57% of intermediate-risk patients and 41% of high-risk patients based on the Framingham Risk Score were found to have a calcium score of 0, implying that these patients may actually be at a lower risk.

The Society of Cardiovascular Computed Tomography guidelines⁴⁰ say that statin therapy can be considered in patients who have a calcium score greater than 0.

For considering aspirin therapy

Miedema et al⁴¹ studied the role of coronary artery calcium in guiding aspirin therapy in 4,229 participants in the MESA trial who were not taking aspirin at baseline. Those with a calcium score higher than 100 had a number needed to treat of 173 in the group with a Framingham Risk Score less than 10% and 92 with a Framingham Risk Score of 10% or higher. The estimated number needed to harm for a major bleeding event was 442. For those who had a score of 0, the estimated number needed to treat was 2,036 for a Framingham Risk Score less than 10% and 808 for a Framingham Risk Score of 10% or higher, with an estimated number needed to harm of 442 for a major bleeding event.

The Society of Cardiovascular Computed Tomography guidelines⁴⁰ recommend considering aspirin therapy for patients with a coronary calcium score of more than 100.

McClelland et al⁴² developed a MESA risk score to predict 10-year risk of coronary heart disease using the traditional risk factors along with coronary calcium. The score was validated externally with 2 separate longitudinal studies. Thus, this may serve as another tool to help providers further risk-stratify patients.

COST-EFFECTIVENESS OF THE TEST

As coronary calcium measurement began to be widely used, concerns were raised about the lack of data on its cost-effectiveness.

Cost-effectiveness depends not only on patient selection but also on the cost of therapy. For example, if the cost of a generic statin is $85 per year, then calcium scoring would not be beneficial. However, if the cost of a statin is more than $200, then calcium scoring would be much more cost-effective, offering a way to avoid treating some patients who do not need to be treated.⁴³

Hong et al⁴³ showed that coronary calcium testing was cost-effective when the patient and physician share decision-making about initiating statin therapy. This is especially important if the patient has financial limitations, is concerned about side effects, or wants to avoid taking unnecessary medications.

According to some reports, $8.5 billion is spent annually for low-value care.⁴⁴ Many of the 80 million CT scans performed annually in the United States are believed to be unnecessary and may lead to additional testing to investigate incidental findings.⁴⁵

Growing use of coronary calcium measurement has raised similar concerns about radiation exposure, healthcare costs, and increased downstream testing triggered by the detection of incidental noncardiac findings. For instance, Onuma et al⁴⁶ reported that, in 503 patients undergoing CT to evaluate coronary artery disease, noncardiac findings were seen in 58.1% of them, but only 22.7% of the 503 had clinically significant findings.

Some of these concerns have been addressed. Modern scanners can acquire images in only a few seconds, entailing lower radiation doses than in the past.^13,14 The cost of the test is currently less than $100 in many US metropolitan areas.⁴⁷ However, further studies are needed to adequately and cost-effectively guide follow-up imaging of incidental noncardiac findings.⁴⁸

An important limitation of calcium scoring for risk assessment is that no randomized controlled trial has evaluated the impact of preventive interventions guided by calcium scores on hard event outcomes. It can be argued that there have been plenty of observational studies that have shown the benefit of coronary calcium scoring when judiciously done in the appropriate population.⁴⁹ Similarly, no randomized controlled trial has tested the pooled cohort equation and the application of statins based on its use with the current guidelines. The feasibility and cost of a large randomized controlled trial to assess outcomes after coronary artery calcium measurement must also be considered.

Another limitation of coronary calcium scoring is that it cannot rule out the presence of noncalcified atherosclerotic plaque, which often is more unstable and prone to rupture.

In addition, calcification in the coronary vascular bed (even if severe) does not necessarily mean there is clinically relevant coronary stenosis. For instance, an asymptomatic patient could have a coronary artery calcium score higher than 100 and then get a coronary angiogram that reveals only a 30% lesion in the left anterior descending coronary artery. This is because accumulation of (calcified) plaque in the vessel wall is accommodated by expansion of vessel diameter, maintaining luminal dimensions (positive remodeling). By definition, this patient does have coronary artery disease but would be best served by medical management. This could have been determined without an invasive test in an otherwise asymptomatic patient. Thus, performing coronary angiography based on a coronary artery calcium score alone would not have changed this patient’s management and may have exposed the patient to risks of procedural complications, in addition to extra healthcare costs. Therefore, the presence or absence of symptoms should guide the clinician on whether to pursue stress testing for invasive coronary angiography based on the appropriate use criteria.^50,51

WHO SHOULD BE TESTED?

In the ACC/AHA 2013 guidelines,³⁷ coronary calcium scoring has a class IIB recommendation in scenarios where it may appear that the risk-based treatment decision is uncertain after formal risk estimation has been done. As discussed above, a score higher than 100 could be a rationale for starting aspirin therapy, and a score higher than 0 for statin therapy. The current guidelines also mention that the coronary calcium score is comparable to other predictors such as the C-reactive protein level and the ankle-brachial index.

Compared with the ACC/AHA guidelines, the 2016 Society of Cardiovascular Computed Tomography guidelines and expert consensus recently have added more specifics in terms of using this test for asymptomatic patients at intermediate risk (10-year risk of atherosclerotic cardiovascular disease 5%–20%) and in selected patients with a family history of premature coronary artery disease and 10-year risk less than 5%.^40,52 The 2010 ACC/AHA guidelines were more specific, offering a class IIA recommendation for patients who were at intermediate risk (Framingham Risk Score 10%–20%).⁵³

The ACC/AHA cited cost and radiation exposure as reasons they did not give coronary calcium measurement a stronger recommendation.³⁷ However, as data continue to come in, the guidelines may change, especially since low-dose radiation tools are being used for cancer screening (lungs and breast) and since the cost has declined over the past decade.

OUR APPROACH

Given the negative predictive value of the coronary calcium score, our approach has been to use this test in asymptomatic patients who are found to be at intermediate risk of atherosclerotic cardiovascular disease based on the ACC/AHA risk calculation and are reluctant to start pharmacologic therapy, or who want a more personalized measure of coronary artery disease. This is preceded by a lengthy patient-physician discussion about the risks and benefits of the test.⁵⁴

The patient’s risk can then be further clarified and possibly reclassified as either low or high if it doesn’t remain intermediate. A discussion can then take place on potentially starting pharmacologic therapy, intensive lifestyle modifications, or both.^54,55 If an electronic medical record is available, CT results can be shown to the patient in the office to point out coronary calcifications. Seeing the lesions may serve an as additional motivating factor as patients embark on primary preventive efforts.⁵⁶

Below, we describe cases of what we would consider appropriate and inappropriate use of coronary artery calcium scoring.

A 55-year-old man presents for an annual physical and is found to have a 10-year risk of atherosclerotic cardiovascular disease of 7%, placing him in the intermediate-risk category. Despite an extensive conversation about lifestyle modifications and pharmacologic therapy, he is reluctant to initiate these measures. He is otherwise asymptomatic. Would calcium scoring be reasonable?

Yes, it would be reasonable to perform coronary artery calcium scoring in an otherwise asymptomatic man to help reclassify his risk for a coronary vascular event. The objective data provided by the test could motivate the patient to undertake primary prevention efforts or, if his score is 0, to show that he may not need drug therapy.

Example 2

A 55-year-old man who has a family history of coronary artery disease, is an active smoker, and has diabetes mellitus presents to the clinic with 2 months of exertional chest pain that resolves with rest. Would coronary artery calcium scoring be reasonable?

This patient is symptomatic and is at high risk of coronary artery disease. Statin therapy is already indicated in the AHA/ACC guidelines, since he has diabetes. Therefore, calcium scoring would not be helpful, as it would not change this patient’s management. Instead, he would be best served by stress testing or coronary angiography based on the stability of his symptoms and cardiac biomarkers.

Example 3

A 30-year-old woman with no medical history presents with on-and-off chest pain at both exertion and rest. Her electrocardiogram is unremarkable, and cardiac enzyme tests are negative. Would coronary calcium scoring be reasonable?

This young patient’s story is not typical for coronary artery disease. Therefore, she has a low pretest probability of obstructive coronary artery disease. Moreover, calcium scoring may not be helpful because at her young age there has not been enough time for calcification to develop (median age is the fifth decade of life). Thus, she would be exposed to radiation unnecessarily at a young age.

What to do with an elevated calcium score?

Coronary artery calcification is now being incidentally detected as patients undergo CT for other reasons such as screening for lung cancer based on the US Preventive Services Task Force guidelines. Patients may also get the test done on their own and then present to a provider with an elevated score.

It is important to consider the entire clinical scenario in such patients and not just the score. If a patient presents with an elevated calcium score but has no symptoms and falls in the intermediate-risk group, there is evidence to suggest that he or she should be started on statin or aspirin therapy or both.

As mentioned above, an abnormal test result does not mean that the patient should undergo more-invasive testing such as cardiac catheterization or even stress testing, especially if he or she has no symptoms. However, if the patient is symptomatic, then further cardiac evaluation would be recommended.

SUMMARY

Measuring coronary artery calcium has been found to be valuable in detecting coronary artery disease and in predicting cardiovascular events and death. The test is relatively easy to perform, with newer technology allowing for less radiation and cost. It serves as a more personalized measure of disease and can help facilitate patient-physician discussions about starting pharmacologic therapy, especially if a patient is reluctant.

Currently, coronary calcium scoring has a class IIB recommendation in scenarios in which the risk-based treatment decision is uncertain after formal risk estimation has been done according to the ACC/AHA guideline. The Society of Cardiovascular Computed Tomography guideline and expert consensus documents are more specific in recommending the test in asymptomatic patients in the intermediate-risk group.

Limitations of calcium scoring include the possibility of unnecessary cardiovascular testing such as cardiac catheterization or stress testing being driven by the calcium score alone, as well as the impact of incidental findings. With increased reporting of the coronary calcium score in patients undergoing CT for lung cancer screening, the score should be interpreted in view of the entire clinical scenario.

The United States has seen a decline in fatal myocardial infarctions, largely thanks to early detection of coronary artery disease. Current guidelines on assessment of cardiovascular risk still rely on the traditional 10-year risk model in clinical practice. However, the predictive value of this approach is only moderate, and many coronary events occur in people considered to be at low or intermediate risk.

See related editorial

Coronary artery calcium scoring has emerged as a means of risk stratification by direct measurement of disease. Primary care providers are either using it or are seeing it used by consulting physicians, and its relatively low cost and ease of performance have contributed to its widespread use. However, downstream costs, radiation exposure, and lack of randomized controlled trials have raised concerns.

This article reviews the usefulness and pitfalls of coronary artery calcium scoring, providing a better understanding of the test, its limitations, and the interpretation of results.

ATHEROSCLEROSIS AND CALCIUM

As the calcium deposits grow, they can be detected by imaging tests such as computed tomography (CT), and quantified to assess the extent of disease.⁴

CALCIFICATION AND CORONARY ARTERY DISEASE

Coronary calcification occurs almost exclusively in atherosclerosis. Several autopsy studies^5,6 and histopathologic studies⁷ have shown a direct relationship between the extent of calcification and atherosclerotic disease.

Sangiorgi et al⁷ performed a histologic analysis of 723 coronary artery segments. The amount of calcium correlated well with the area of plaque:

• r = 0.89, P < .0001 in the left anterior descending artery
• r = 0.7, P < .001 in the left circumflex artery
• r = 0.89, P < .0001 in the right coronary artery.

Coronary artery calcium has also been associated with obstructive coronary artery disease in studies using intravascular ultrasonography and optical coherence tomography.^8,9

TECHNICAL INFORMATION ABOUT THE TEST

First-generation CT scanners used for calcium scoring in the 1980s were electron-beam systems in which a stationary x-ray tube generated an oscillating electron beam, which was reflected around the patient table.¹⁰ A single, stationary detector ring captured the images.

These systems have been replaced by multidetector scanners, in which the x-ray tube and multiple rows of detectors are combined in a gantry that rotates at high speed around the patient.

Coronary calcium is measured by noncontrast CT of the heart. Thus, there is no risk of contrast-induced nephropathy or allergic reactions. Images are acquired while the patient holds his or her breath for 3 to 5 seconds. Electrocardiographic gating is used to reduce motion artifact.^11,12 With modern scanners, the effective radiation dose associated with calcium testing is as low as 0.5 to 1.5 mSv,^13,14 ie, about the same dose as that with mammography. The entire test takes 10 to 15 minutes.

The results fall into 4 categories, which correlate with the severity of coronary artery disease, ranging from no significant disease to severe disease (Table 1). Other scores, which are not commonly used, include the calcium volume score¹⁶ and the calcium mass score.¹⁷Figure 2 shows a screenshot from a coronary artery calcium scoring program. 

Early multicenter studies evaluated the utility of calcium scoring to predict coronary stenosis in patients who underwent both cardiac CT and coronary angiography. The sensitivity of calcium scoring for angiographically significant disease was high (95%), but its specificity was low (about 44%).¹⁸

Budoff et al,¹⁹ reviewing these and subsequent results, concluded that the value of calcium scoring is its high negative predictive value (about 98%); a negative score (no calcification) is strongly associated with the absence of obstructive coronary disease.

Blaha et al²⁰ concluded that a score of 0 would indicate that the patient had a low risk of cardiovascular disease. A test with these characteristics is helpful in excluding cardiovascular disease or at least in determining that it is less likely to be present in a patient deemed to be at intermediate risk.

CALCIUM SCORING AS A PROGNOSTIC TOOL

Early on, investigators recognized the value of calcium scoring in predicting the risk of future cardiovascular events and death.^21–25

Predicting cardiovascular events

Pletcher et al21 performed a meta-analysis of studies that measured calcification in asymptomatic patients with subsequent follow-up. The summary-adjusted relative risk of cardiac events such as myocardial infarction, coronary artery revascularization, and coronary heart disease-related death rose with the calcium score:

• 2.1 (95% confidence interval [CI] 1.6–2.9) with a score of 1 to 100
• 4.2 (95% CI 2.5–7.2) with scores of 101 to 400
• 7.2 (95% CI 3.9-13.0) with scores greater than 400.

The meta-analysis was limited in that it included only 4 studies, which were observational.

Kavousi et al,²² in a subsequent meta-analysis of 6,739 women at low risk of atherosclerotic cardiovascular disease based on the American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equation (10-year risk < 7.5%), found that 36.1% had calcium scores greater than 0. Compared with those whose score was 0, those with higher scores had a higher risk of atherosclerotic cardiovascular disease events. The incidence rates per 1,000 person-years were 1.41 vs 4.33 (relative risk 2.92, 95% CI 2.02–3.83; multivariable-adjusted hazard ratio 2.04, 95% CI 1.44–2.90). This study was limited because the population was mostly of European descent, making it less generalizable to non-European populations.

Calcium scoring has also been shown to be a strong predictor of incident cardiovascular events across different races beyond traditional risk factors such as hypertension, hyperlipidemia, and tobacco use.

Detrano et al,²³ in a study of 6,722 patients with diverse ethnic backgrounds, found that the adjusted risk of a coronary event was increased by a factor of 7.73 for calcium scores between 101 and 300 and by a factor of 9.67 for scores above 300 (P < .001). A limitation of this study was that the patients and physicians were informed of the scores, which could have led to bias.

Carr et al²⁴ found an association between calcium and coronary heart disease in a younger population (ages 32–46). In 12.5 years of follow-up, the hazard ratio for cardiovascular events increased exponentially with the calcium score:

• 2.6 (95% CI 1.0–5.7, P = .03) with calcium scores of 1 through 19
• 9.8 (95% CI 4.5–20.5, P < .001) with scores greater than 100.

Predicting mortality

Budoff et al,²⁵ in an observational study of 25,253 patients, found coronary calcium to be an independent predictor of mortality in a multivariable model controlling for age, sex, ethnicity, and cardiac risk factors (model chi-square = 2,017, P < .0001). However, most of the patients were already known to have cardiac risk factors, making the study findings less generalizable to the general population.

Nasir et al²⁶ found that mortality rates rose with the calcium score in a study with 44,052 participants. The annualized mortality rates per 1,000 person-years were:

• 0.87 (95% CI 0.72–1.06) with a score of 0
• 2.97 (95% CI 2.61–3.37) with scores of 1–100
• 6.90 (95% CI 6.02–7.90) with scores of 101–400
• 17.68 (95% CI 5.93–19.62) with scores higher than 400.

The mortality rate also rose with the number of traditional risk factors present, ie, current tobacco use, dyslipidemia, diabetes mellitus, hypertension, and family history of coronary artery disease. Interestingly, those with no risk factors but a calcium score greater than 400 had a higher mortality rate than those with no coronary calcium but more than 3 risk factors (16.89 per 1,000 person-years vs 2.72 per 1,000 person years). As in the previous study, the patient population that was analyzed was at high risk and therefore the findings are not generalizable.

Shaw et al²⁷ found that patients without symptoms but with elevated coronary calcium scores had higher all-cause mortality rates at 15 years than those with a score of 0. The difference remained significant after Cox regression was performed, adjusting for traditional risk factors.

Current guidelines on assessing risk still rely on the traditional 10-year risk model in clinical practice.²⁵ Patients are thus classified as being at low, intermediate, or high risk based on their probability of developing a cardiovascular event or cardiovascular disease-related death in the subsequent 10 years.

However, the predictive value of this approach is only moderate,²⁸ and a significant number of cardiovascular events, including sudden cardiac death, occur in people who were believed to be at low or intermediate risk according to traditional risk factor-based predictions. Because risk scores are strongly influenced by age,²⁹ they are least reliable in young adults.³⁰

Akosah et al³¹ reviewed the records of 222 young adults (women age 55 or younger, men age 65 or younger) who presented with their first myocardial infarction, and found that only 25% would have qualified for primary prevention pharmacologic treatments according to the National Cholesterol Education Program III guidelines.^32,33 Similar findings have been reported regarding previous versions of the risk scores.³³

Thus, risk predictions based exclusively on traditional risk factors are not sensitive for detecting young individuals at increased risk, and lead to late treatment of young adults with atherosclerosis, which may be a less effective strategy.³⁴

The reliance on age in risk algorithms also results in low specificity in elderly adults. Using risk scores, elderly adults are systematically stratified in higher risk categories, expanding the indication for statin therapy to almost all men age 65 or older regardless of their actual vascular health, according to current clinical practice guidelines.^35,36

Risk scores are based on self-reported history and single-day measurements, since this kind of information is readily available to the physician in the clinic. Moreover, our knowledge about genetic and epigenetic factors associated with the development of atherosclerosis is still in its infancy, with current guidelines not supporting genetic testing as part of cardiovascular risk assessment.³⁷ Thus, a reliable measure of an individual’s lifelong exposure to a number of environmental and genetic factors that may affect cardiovascular health appears unfeasible.

Atherosclerosis is a process in which interactions between genetic, epigenetic, environmental, and traditional risk factors result in subclinical inflammation that could develop into clinically significant disease. Therefore, subclinical coronary atherosclerosis has been shown to be a strong predictor of future incident cardiovascular disease events and death. Thus, alternative approaches that directly measure disease, such as calcium scoring, may help further refine risk stratification of cardiovascular disease.

The MESA trial (Multi-Ethnic Study of Atherosclerosis), for instance, in 6,814 participants, found coronary calcium to provide better discrimination and risk reclassification than the ankle-brachial index, high sensitivity C-reactive protein level, and family history.³⁸ Coronary calcium also had the highest incremental improvement of the area under the receiver operating curve when added to the Framingham Risk Score (0.623 vs 0.784).

Reclassifying cardiovascular risk also has implications regarding whether to start therapies such as statins and aspirin.

For considering statin therapy

Nasir et al³⁹ showed that, in patients eligible for statin therapy by the pooled cohort equation, the absence of coronary artery calcium reclassified approximately one-half of candidates as not eligible for statin therapy. The number needed to treat to prevent an atherosclerotic cardiovascular event in the population who were recommended a statin was 64 with a calcium score of 0, and 24 with a calcium score greater than 100. In the population for whom a statin was considered, the number needed to treat was 223 with a calcium score of 0 and 46 for those with a score greater than 100. Moreover, 57% of intermediate-risk patients and 41% of high-risk patients based on the Framingham Risk Score were found to have a calcium score of 0, implying that these patients may actually be at a lower risk.

The Society of Cardiovascular Computed Tomography guidelines⁴⁰ say that statin therapy can be considered in patients who have a calcium score greater than 0.

For considering aspirin therapy

Miedema et al⁴¹ studied the role of coronary artery calcium in guiding aspirin therapy in 4,229 participants in the MESA trial who were not taking aspirin at baseline. Those with a calcium score higher than 100 had a number needed to treat of 173 in the group with a Framingham Risk Score less than 10% and 92 with a Framingham Risk Score of 10% or higher. The estimated number needed to harm for a major bleeding event was 442. For those who had a score of 0, the estimated number needed to treat was 2,036 for a Framingham Risk Score less than 10% and 808 for a Framingham Risk Score of 10% or higher, with an estimated number needed to harm of 442 for a major bleeding event.

The Society of Cardiovascular Computed Tomography guidelines⁴⁰ recommend considering aspirin therapy for patients with a coronary calcium score of more than 100.

McClelland et al⁴² developed a MESA risk score to predict 10-year risk of coronary heart disease using the traditional risk factors along with coronary calcium. The score was validated externally with 2 separate longitudinal studies. Thus, this may serve as another tool to help providers further risk-stratify patients.

COST-EFFECTIVENESS OF THE TEST

As coronary calcium measurement began to be widely used, concerns were raised about the lack of data on its cost-effectiveness.

Cost-effectiveness depends not only on patient selection but also on the cost of therapy. For example, if the cost of a generic statin is $85 per year, then calcium scoring would not be beneficial. However, if the cost of a statin is more than $200, then calcium scoring would be much more cost-effective, offering a way to avoid treating some patients who do not need to be treated.⁴³

Hong et al⁴³ showed that coronary calcium testing was cost-effective when the patient and physician share decision-making about initiating statin therapy. This is especially important if the patient has financial limitations, is concerned about side effects, or wants to avoid taking unnecessary medications.

According to some reports, $8.5 billion is spent annually for low-value care.⁴⁴ Many of the 80 million CT scans performed annually in the United States are believed to be unnecessary and may lead to additional testing to investigate incidental findings.⁴⁵

Growing use of coronary calcium measurement has raised similar concerns about radiation exposure, healthcare costs, and increased downstream testing triggered by the detection of incidental noncardiac findings. For instance, Onuma et al⁴⁶ reported that, in 503 patients undergoing CT to evaluate coronary artery disease, noncardiac findings were seen in 58.1% of them, but only 22.7% of the 503 had clinically significant findings.

Some of these concerns have been addressed. Modern scanners can acquire images in only a few seconds, entailing lower radiation doses than in the past.^13,14 The cost of the test is currently less than $100 in many US metropolitan areas.⁴⁷ However, further studies are needed to adequately and cost-effectively guide follow-up imaging of incidental noncardiac findings.⁴⁸

An important limitation of calcium scoring for risk assessment is that no randomized controlled trial has evaluated the impact of preventive interventions guided by calcium scores on hard event outcomes. It can be argued that there have been plenty of observational studies that have shown the benefit of coronary calcium scoring when judiciously done in the appropriate population.⁴⁹ Similarly, no randomized controlled trial has tested the pooled cohort equation and the application of statins based on its use with the current guidelines. The feasibility and cost of a large randomized controlled trial to assess outcomes after coronary artery calcium measurement must also be considered.

Another limitation of coronary calcium scoring is that it cannot rule out the presence of noncalcified atherosclerotic plaque, which often is more unstable and prone to rupture.

In addition, calcification in the coronary vascular bed (even if severe) does not necessarily mean there is clinically relevant coronary stenosis. For instance, an asymptomatic patient could have a coronary artery calcium score higher than 100 and then get a coronary angiogram that reveals only a 30% lesion in the left anterior descending coronary artery. This is because accumulation of (calcified) plaque in the vessel wall is accommodated by expansion of vessel diameter, maintaining luminal dimensions (positive remodeling). By definition, this patient does have coronary artery disease but would be best served by medical management. This could have been determined without an invasive test in an otherwise asymptomatic patient. Thus, performing coronary angiography based on a coronary artery calcium score alone would not have changed this patient’s management and may have exposed the patient to risks of procedural complications, in addition to extra healthcare costs. Therefore, the presence or absence of symptoms should guide the clinician on whether to pursue stress testing for invasive coronary angiography based on the appropriate use criteria.^50,51

WHO SHOULD BE TESTED?

In the ACC/AHA 2013 guidelines,³⁷ coronary calcium scoring has a class IIB recommendation in scenarios where it may appear that the risk-based treatment decision is uncertain after formal risk estimation has been done. As discussed above, a score higher than 100 could be a rationale for starting aspirin therapy, and a score higher than 0 for statin therapy. The current guidelines also mention that the coronary calcium score is comparable to other predictors such as the C-reactive protein level and the ankle-brachial index.

Compared with the ACC/AHA guidelines, the 2016 Society of Cardiovascular Computed Tomography guidelines and expert consensus recently have added more specifics in terms of using this test for asymptomatic patients at intermediate risk (10-year risk of atherosclerotic cardiovascular disease 5%–20%) and in selected patients with a family history of premature coronary artery disease and 10-year risk less than 5%.^40,52 The 2010 ACC/AHA guidelines were more specific, offering a class IIA recommendation for patients who were at intermediate risk (Framingham Risk Score 10%–20%).⁵³

The ACC/AHA cited cost and radiation exposure as reasons they did not give coronary calcium measurement a stronger recommendation.³⁷ However, as data continue to come in, the guidelines may change, especially since low-dose radiation tools are being used for cancer screening (lungs and breast) and since the cost has declined over the past decade.

OUR APPROACH

Given the negative predictive value of the coronary calcium score, our approach has been to use this test in asymptomatic patients who are found to be at intermediate risk of atherosclerotic cardiovascular disease based on the ACC/AHA risk calculation and are reluctant to start pharmacologic therapy, or who want a more personalized measure of coronary artery disease. This is preceded by a lengthy patient-physician discussion about the risks and benefits of the test.⁵⁴

The patient’s risk can then be further clarified and possibly reclassified as either low or high if it doesn’t remain intermediate. A discussion can then take place on potentially starting pharmacologic therapy, intensive lifestyle modifications, or both.^54,55 If an electronic medical record is available, CT results can be shown to the patient in the office to point out coronary calcifications. Seeing the lesions may serve an as additional motivating factor as patients embark on primary preventive efforts.⁵⁶

Below, we describe cases of what we would consider appropriate and inappropriate use of coronary artery calcium scoring.

A 55-year-old man presents for an annual physical and is found to have a 10-year risk of atherosclerotic cardiovascular disease of 7%, placing him in the intermediate-risk category. Despite an extensive conversation about lifestyle modifications and pharmacologic therapy, he is reluctant to initiate these measures. He is otherwise asymptomatic. Would calcium scoring be reasonable?

Yes, it would be reasonable to perform coronary artery calcium scoring in an otherwise asymptomatic man to help reclassify his risk for a coronary vascular event. The objective data provided by the test could motivate the patient to undertake primary prevention efforts or, if his score is 0, to show that he may not need drug therapy.

Example 2

A 55-year-old man who has a family history of coronary artery disease, is an active smoker, and has diabetes mellitus presents to the clinic with 2 months of exertional chest pain that resolves with rest. Would coronary artery calcium scoring be reasonable?

This patient is symptomatic and is at high risk of coronary artery disease. Statin therapy is already indicated in the AHA/ACC guidelines, since he has diabetes. Therefore, calcium scoring would not be helpful, as it would not change this patient’s management. Instead, he would be best served by stress testing or coronary angiography based on the stability of his symptoms and cardiac biomarkers.

Example 3

A 30-year-old woman with no medical history presents with on-and-off chest pain at both exertion and rest. Her electrocardiogram is unremarkable, and cardiac enzyme tests are negative. Would coronary calcium scoring be reasonable?

This young patient’s story is not typical for coronary artery disease. Therefore, she has a low pretest probability of obstructive coronary artery disease. Moreover, calcium scoring may not be helpful because at her young age there has not been enough time for calcification to develop (median age is the fifth decade of life). Thus, she would be exposed to radiation unnecessarily at a young age.

What to do with an elevated calcium score?

Coronary artery calcification is now being incidentally detected as patients undergo CT for other reasons such as screening for lung cancer based on the US Preventive Services Task Force guidelines. Patients may also get the test done on their own and then present to a provider with an elevated score.

It is important to consider the entire clinical scenario in such patients and not just the score. If a patient presents with an elevated calcium score but has no symptoms and falls in the intermediate-risk group, there is evidence to suggest that he or she should be started on statin or aspirin therapy or both.

As mentioned above, an abnormal test result does not mean that the patient should undergo more-invasive testing such as cardiac catheterization or even stress testing, especially if he or she has no symptoms. However, if the patient is symptomatic, then further cardiac evaluation would be recommended.

SUMMARY

Measuring coronary artery calcium has been found to be valuable in detecting coronary artery disease and in predicting cardiovascular events and death. The test is relatively easy to perform, with newer technology allowing for less radiation and cost. It serves as a more personalized measure of disease and can help facilitate patient-physician discussions about starting pharmacologic therapy, especially if a patient is reluctant.

Currently, coronary calcium scoring has a class IIB recommendation in scenarios in which the risk-based treatment decision is uncertain after formal risk estimation has been done according to the ACC/AHA guideline. The Society of Cardiovascular Computed Tomography guideline and expert consensus documents are more specific in recommending the test in asymptomatic patients in the intermediate-risk group.

Limitations of calcium scoring include the possibility of unnecessary cardiovascular testing such as cardiac catheterization or stress testing being driven by the calcium score alone, as well as the impact of incidental findings. With increased reporting of the coronary calcium score in patients undergoing CT for lung cancer screening, the score should be interpreted in view of the entire clinical scenario.

The United States has seen a decline in fatal myocardial infarctions, largely thanks to early detection of coronary artery disease. Current guidelines on assessment of cardiovascular risk still rely on the traditional 10-year risk model in clinical practice. However, the predictive value of this approach is only moderate, and many coronary events occur in people considered to be at low or intermediate risk.

See related editorial

Coronary artery calcium scoring has emerged as a means of risk stratification by direct measurement of disease. Primary care providers are either using it or are seeing it used by consulting physicians, and its relatively low cost and ease of performance have contributed to its widespread use. However, downstream costs, radiation exposure, and lack of randomized controlled trials have raised concerns.

This article reviews the usefulness and pitfalls of coronary artery calcium scoring, providing a better understanding of the test, its limitations, and the interpretation of results.

ATHEROSCLEROSIS AND CALCIUM

As the calcium deposits grow, they can be detected by imaging tests such as computed tomography (CT), and quantified to assess the extent of disease.⁴

CALCIFICATION AND CORONARY ARTERY DISEASE

Coronary calcification occurs almost exclusively in atherosclerosis. Several autopsy studies^5,6 and histopathologic studies⁷ have shown a direct relationship between the extent of calcification and atherosclerotic disease.

Sangiorgi et al⁷ performed a histologic analysis of 723 coronary artery segments. The amount of calcium correlated well with the area of plaque:

• r = 0.89, P < .0001 in the left anterior descending artery
• r = 0.7, P < .001 in the left circumflex artery
• r = 0.89, P < .0001 in the right coronary artery.

Coronary artery calcium has also been associated with obstructive coronary artery disease in studies using intravascular ultrasonography and optical coherence tomography.^8,9

TECHNICAL INFORMATION ABOUT THE TEST

First-generation CT scanners used for calcium scoring in the 1980s were electron-beam systems in which a stationary x-ray tube generated an oscillating electron beam, which was reflected around the patient table.¹⁰ A single, stationary detector ring captured the images.

These systems have been replaced by multidetector scanners, in which the x-ray tube and multiple rows of detectors are combined in a gantry that rotates at high speed around the patient.

Coronary calcium is measured by noncontrast CT of the heart. Thus, there is no risk of contrast-induced nephropathy or allergic reactions. Images are acquired while the patient holds his or her breath for 3 to 5 seconds. Electrocardiographic gating is used to reduce motion artifact.^11,12 With modern scanners, the effective radiation dose associated with calcium testing is as low as 0.5 to 1.5 mSv,^13,14 ie, about the same dose as that with mammography. The entire test takes 10 to 15 minutes.

The results fall into 4 categories, which correlate with the severity of coronary artery disease, ranging from no significant disease to severe disease (Table 1). Other scores, which are not commonly used, include the calcium volume score¹⁶ and the calcium mass score.¹⁷Figure 2 shows a screenshot from a coronary artery calcium scoring program. 

Early multicenter studies evaluated the utility of calcium scoring to predict coronary stenosis in patients who underwent both cardiac CT and coronary angiography. The sensitivity of calcium scoring for angiographically significant disease was high (95%), but its specificity was low (about 44%).¹⁸

Budoff et al,¹⁹ reviewing these and subsequent results, concluded that the value of calcium scoring is its high negative predictive value (about 98%); a negative score (no calcification) is strongly associated with the absence of obstructive coronary disease.

Blaha et al²⁰ concluded that a score of 0 would indicate that the patient had a low risk of cardiovascular disease. A test with these characteristics is helpful in excluding cardiovascular disease or at least in determining that it is less likely to be present in a patient deemed to be at intermediate risk.

CALCIUM SCORING AS A PROGNOSTIC TOOL

Early on, investigators recognized the value of calcium scoring in predicting the risk of future cardiovascular events and death.^21–25

Predicting cardiovascular events

Pletcher et al21 performed a meta-analysis of studies that measured calcification in asymptomatic patients with subsequent follow-up. The summary-adjusted relative risk of cardiac events such as myocardial infarction, coronary artery revascularization, and coronary heart disease-related death rose with the calcium score:

• 2.1 (95% confidence interval [CI] 1.6–2.9) with a score of 1 to 100
• 4.2 (95% CI 2.5–7.2) with scores of 101 to 400
• 7.2 (95% CI 3.9-13.0) with scores greater than 400.

The meta-analysis was limited in that it included only 4 studies, which were observational.

Kavousi et al,²² in a subsequent meta-analysis of 6,739 women at low risk of atherosclerotic cardiovascular disease based on the American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equation (10-year risk < 7.5%), found that 36.1% had calcium scores greater than 0. Compared with those whose score was 0, those with higher scores had a higher risk of atherosclerotic cardiovascular disease events. The incidence rates per 1,000 person-years were 1.41 vs 4.33 (relative risk 2.92, 95% CI 2.02–3.83; multivariable-adjusted hazard ratio 2.04, 95% CI 1.44–2.90). This study was limited because the population was mostly of European descent, making it less generalizable to non-European populations.

Calcium scoring has also been shown to be a strong predictor of incident cardiovascular events across different races beyond traditional risk factors such as hypertension, hyperlipidemia, and tobacco use.

Detrano et al,²³ in a study of 6,722 patients with diverse ethnic backgrounds, found that the adjusted risk of a coronary event was increased by a factor of 7.73 for calcium scores between 101 and 300 and by a factor of 9.67 for scores above 300 (P < .001). A limitation of this study was that the patients and physicians were informed of the scores, which could have led to bias.

Carr et al²⁴ found an association between calcium and coronary heart disease in a younger population (ages 32–46). In 12.5 years of follow-up, the hazard ratio for cardiovascular events increased exponentially with the calcium score:

• 2.6 (95% CI 1.0–5.7, P = .03) with calcium scores of 1 through 19
• 9.8 (95% CI 4.5–20.5, P < .001) with scores greater than 100.

Predicting mortality

Budoff et al,²⁵ in an observational study of 25,253 patients, found coronary calcium to be an independent predictor of mortality in a multivariable model controlling for age, sex, ethnicity, and cardiac risk factors (model chi-square = 2,017, P < .0001). However, most of the patients were already known to have cardiac risk factors, making the study findings less generalizable to the general population.

Nasir et al²⁶ found that mortality rates rose with the calcium score in a study with 44,052 participants. The annualized mortality rates per 1,000 person-years were:

• 0.87 (95% CI 0.72–1.06) with a score of 0
• 2.97 (95% CI 2.61–3.37) with scores of 1–100
• 6.90 (95% CI 6.02–7.90) with scores of 101–400
• 17.68 (95% CI 5.93–19.62) with scores higher than 400.

The mortality rate also rose with the number of traditional risk factors present, ie, current tobacco use, dyslipidemia, diabetes mellitus, hypertension, and family history of coronary artery disease. Interestingly, those with no risk factors but a calcium score greater than 400 had a higher mortality rate than those with no coronary calcium but more than 3 risk factors (16.89 per 1,000 person-years vs 2.72 per 1,000 person years). As in the previous study, the patient population that was analyzed was at high risk and therefore the findings are not generalizable.

Shaw et al²⁷ found that patients without symptoms but with elevated coronary calcium scores had higher all-cause mortality rates at 15 years than those with a score of 0. The difference remained significant after Cox regression was performed, adjusting for traditional risk factors.

Current guidelines on assessing risk still rely on the traditional 10-year risk model in clinical practice.²⁵ Patients are thus classified as being at low, intermediate, or high risk based on their probability of developing a cardiovascular event or cardiovascular disease-related death in the subsequent 10 years.

However, the predictive value of this approach is only moderate,²⁸ and a significant number of cardiovascular events, including sudden cardiac death, occur in people who were believed to be at low or intermediate risk according to traditional risk factor-based predictions. Because risk scores are strongly influenced by age,²⁹ they are least reliable in young adults.³⁰

Akosah et al³¹ reviewed the records of 222 young adults (women age 55 or younger, men age 65 or younger) who presented with their first myocardial infarction, and found that only 25% would have qualified for primary prevention pharmacologic treatments according to the National Cholesterol Education Program III guidelines.^32,33 Similar findings have been reported regarding previous versions of the risk scores.³³

Thus, risk predictions based exclusively on traditional risk factors are not sensitive for detecting young individuals at increased risk, and lead to late treatment of young adults with atherosclerosis, which may be a less effective strategy.³⁴

The reliance on age in risk algorithms also results in low specificity in elderly adults. Using risk scores, elderly adults are systematically stratified in higher risk categories, expanding the indication for statin therapy to almost all men age 65 or older regardless of their actual vascular health, according to current clinical practice guidelines.^35,36

Risk scores are based on self-reported history and single-day measurements, since this kind of information is readily available to the physician in the clinic. Moreover, our knowledge about genetic and epigenetic factors associated with the development of atherosclerosis is still in its infancy, with current guidelines not supporting genetic testing as part of cardiovascular risk assessment.³⁷ Thus, a reliable measure of an individual’s lifelong exposure to a number of environmental and genetic factors that may affect cardiovascular health appears unfeasible.

Atherosclerosis is a process in which interactions between genetic, epigenetic, environmental, and traditional risk factors result in subclinical inflammation that could develop into clinically significant disease. Therefore, subclinical coronary atherosclerosis has been shown to be a strong predictor of future incident cardiovascular disease events and death. Thus, alternative approaches that directly measure disease, such as calcium scoring, may help further refine risk stratification of cardiovascular disease.

The MESA trial (Multi-Ethnic Study of Atherosclerosis), for instance, in 6,814 participants, found coronary calcium to provide better discrimination and risk reclassification than the ankle-brachial index, high sensitivity C-reactive protein level, and family history.³⁸ Coronary calcium also had the highest incremental improvement of the area under the receiver operating curve when added to the Framingham Risk Score (0.623 vs 0.784).

Reclassifying cardiovascular risk also has implications regarding whether to start therapies such as statins and aspirin.

For considering statin therapy

Nasir et al³⁹ showed that, in patients eligible for statin therapy by the pooled cohort equation, the absence of coronary artery calcium reclassified approximately one-half of candidates as not eligible for statin therapy. The number needed to treat to prevent an atherosclerotic cardiovascular event in the population who were recommended a statin was 64 with a calcium score of 0, and 24 with a calcium score greater than 100. In the population for whom a statin was considered, the number needed to treat was 223 with a calcium score of 0 and 46 for those with a score greater than 100. Moreover, 57% of intermediate-risk patients and 41% of high-risk patients based on the Framingham Risk Score were found to have a calcium score of 0, implying that these patients may actually be at a lower risk.

The Society of Cardiovascular Computed Tomography guidelines⁴⁰ say that statin therapy can be considered in patients who have a calcium score greater than 0.

For considering aspirin therapy

Miedema et al⁴¹ studied the role of coronary artery calcium in guiding aspirin therapy in 4,229 participants in the MESA trial who were not taking aspirin at baseline. Those with a calcium score higher than 100 had a number needed to treat of 173 in the group with a Framingham Risk Score less than 10% and 92 with a Framingham Risk Score of 10% or higher. The estimated number needed to harm for a major bleeding event was 442. For those who had a score of 0, the estimated number needed to treat was 2,036 for a Framingham Risk Score less than 10% and 808 for a Framingham Risk Score of 10% or higher, with an estimated number needed to harm of 442 for a major bleeding event.

The Society of Cardiovascular Computed Tomography guidelines⁴⁰ recommend considering aspirin therapy for patients with a coronary calcium score of more than 100.

McClelland et al⁴² developed a MESA risk score to predict 10-year risk of coronary heart disease using the traditional risk factors along with coronary calcium. The score was validated externally with 2 separate longitudinal studies. Thus, this may serve as another tool to help providers further risk-stratify patients.

COST-EFFECTIVENESS OF THE TEST

As coronary calcium measurement began to be widely used, concerns were raised about the lack of data on its cost-effectiveness.

Cost-effectiveness depends not only on patient selection but also on the cost of therapy. For example, if the cost of a generic statin is $85 per year, then calcium scoring would not be beneficial. However, if the cost of a statin is more than $200, then calcium scoring would be much more cost-effective, offering a way to avoid treating some patients who do not need to be treated.⁴³

Hong et al⁴³ showed that coronary calcium testing was cost-effective when the patient and physician share decision-making about initiating statin therapy. This is especially important if the patient has financial limitations, is concerned about side effects, or wants to avoid taking unnecessary medications.

According to some reports, $8.5 billion is spent annually for low-value care.⁴⁴ Many of the 80 million CT scans performed annually in the United States are believed to be unnecessary and may lead to additional testing to investigate incidental findings.⁴⁵

Growing use of coronary calcium measurement has raised similar concerns about radiation exposure, healthcare costs, and increased downstream testing triggered by the detection of incidental noncardiac findings. For instance, Onuma et al⁴⁶ reported that, in 503 patients undergoing CT to evaluate coronary artery disease, noncardiac findings were seen in 58.1% of them, but only 22.7% of the 503 had clinically significant findings.

Some of these concerns have been addressed. Modern scanners can acquire images in only a few seconds, entailing lower radiation doses than in the past.^13,14 The cost of the test is currently less than $100 in many US metropolitan areas.⁴⁷ However, further studies are needed to adequately and cost-effectively guide follow-up imaging of incidental noncardiac findings.⁴⁸

An important limitation of calcium scoring for risk assessment is that no randomized controlled trial has evaluated the impact of preventive interventions guided by calcium scores on hard event outcomes. It can be argued that there have been plenty of observational studies that have shown the benefit of coronary calcium scoring when judiciously done in the appropriate population.⁴⁹ Similarly, no randomized controlled trial has tested the pooled cohort equation and the application of statins based on its use with the current guidelines. The feasibility and cost of a large randomized controlled trial to assess outcomes after coronary artery calcium measurement must also be considered.

Another limitation of coronary calcium scoring is that it cannot rule out the presence of noncalcified atherosclerotic plaque, which often is more unstable and prone to rupture.

In addition, calcification in the coronary vascular bed (even if severe) does not necessarily mean there is clinically relevant coronary stenosis. For instance, an asymptomatic patient could have a coronary artery calcium score higher than 100 and then get a coronary angiogram that reveals only a 30% lesion in the left anterior descending coronary artery. This is because accumulation of (calcified) plaque in the vessel wall is accommodated by expansion of vessel diameter, maintaining luminal dimensions (positive remodeling). By definition, this patient does have coronary artery disease but would be best served by medical management. This could have been determined without an invasive test in an otherwise asymptomatic patient. Thus, performing coronary angiography based on a coronary artery calcium score alone would not have changed this patient’s management and may have exposed the patient to risks of procedural complications, in addition to extra healthcare costs. Therefore, the presence or absence of symptoms should guide the clinician on whether to pursue stress testing for invasive coronary angiography based on the appropriate use criteria.^50,51

WHO SHOULD BE TESTED?

In the ACC/AHA 2013 guidelines,³⁷ coronary calcium scoring has a class IIB recommendation in scenarios where it may appear that the risk-based treatment decision is uncertain after formal risk estimation has been done. As discussed above, a score higher than 100 could be a rationale for starting aspirin therapy, and a score higher than 0 for statin therapy. The current guidelines also mention that the coronary calcium score is comparable to other predictors such as the C-reactive protein level and the ankle-brachial index.

Compared with the ACC/AHA guidelines, the 2016 Society of Cardiovascular Computed Tomography guidelines and expert consensus recently have added more specifics in terms of using this test for asymptomatic patients at intermediate risk (10-year risk of atherosclerotic cardiovascular disease 5%–20%) and in selected patients with a family history of premature coronary artery disease and 10-year risk less than 5%.^40,52 The 2010 ACC/AHA guidelines were more specific, offering a class IIA recommendation for patients who were at intermediate risk (Framingham Risk Score 10%–20%).⁵³

The ACC/AHA cited cost and radiation exposure as reasons they did not give coronary calcium measurement a stronger recommendation.³⁷ However, as data continue to come in, the guidelines may change, especially since low-dose radiation tools are being used for cancer screening (lungs and breast) and since the cost has declined over the past decade.

OUR APPROACH

Given the negative predictive value of the coronary calcium score, our approach has been to use this test in asymptomatic patients who are found to be at intermediate risk of atherosclerotic cardiovascular disease based on the ACC/AHA risk calculation and are reluctant to start pharmacologic therapy, or who want a more personalized measure of coronary artery disease. This is preceded by a lengthy patient-physician discussion about the risks and benefits of the test.⁵⁴

The patient’s risk can then be further clarified and possibly reclassified as either low or high if it doesn’t remain intermediate. A discussion can then take place on potentially starting pharmacologic therapy, intensive lifestyle modifications, or both.^54,55 If an electronic medical record is available, CT results can be shown to the patient in the office to point out coronary calcifications. Seeing the lesions may serve an as additional motivating factor as patients embark on primary preventive efforts.⁵⁶

Below, we describe cases of what we would consider appropriate and inappropriate use of coronary artery calcium scoring.

A 55-year-old man presents for an annual physical and is found to have a 10-year risk of atherosclerotic cardiovascular disease of 7%, placing him in the intermediate-risk category. Despite an extensive conversation about lifestyle modifications and pharmacologic therapy, he is reluctant to initiate these measures. He is otherwise asymptomatic. Would calcium scoring be reasonable?

Yes, it would be reasonable to perform coronary artery calcium scoring in an otherwise asymptomatic man to help reclassify his risk for a coronary vascular event. The objective data provided by the test could motivate the patient to undertake primary prevention efforts or, if his score is 0, to show that he may not need drug therapy.

Example 2

A 55-year-old man who has a family history of coronary artery disease, is an active smoker, and has diabetes mellitus presents to the clinic with 2 months of exertional chest pain that resolves with rest. Would coronary artery calcium scoring be reasonable?

This patient is symptomatic and is at high risk of coronary artery disease. Statin therapy is already indicated in the AHA/ACC guidelines, since he has diabetes. Therefore, calcium scoring would not be helpful, as it would not change this patient’s management. Instead, he would be best served by stress testing or coronary angiography based on the stability of his symptoms and cardiac biomarkers.

Example 3

A 30-year-old woman with no medical history presents with on-and-off chest pain at both exertion and rest. Her electrocardiogram is unremarkable, and cardiac enzyme tests are negative. Would coronary calcium scoring be reasonable?

This young patient’s story is not typical for coronary artery disease. Therefore, she has a low pretest probability of obstructive coronary artery disease. Moreover, calcium scoring may not be helpful because at her young age there has not been enough time for calcification to develop (median age is the fifth decade of life). Thus, she would be exposed to radiation unnecessarily at a young age.

What to do with an elevated calcium score?

Coronary artery calcification is now being incidentally detected as patients undergo CT for other reasons such as screening for lung cancer based on the US Preventive Services Task Force guidelines. Patients may also get the test done on their own and then present to a provider with an elevated score.

It is important to consider the entire clinical scenario in such patients and not just the score. If a patient presents with an elevated calcium score but has no symptoms and falls in the intermediate-risk group, there is evidence to suggest that he or she should be started on statin or aspirin therapy or both.

As mentioned above, an abnormal test result does not mean that the patient should undergo more-invasive testing such as cardiac catheterization or even stress testing, especially if he or she has no symptoms. However, if the patient is symptomatic, then further cardiac evaluation would be recommended.

SUMMARY

Measuring coronary artery calcium has been found to be valuable in detecting coronary artery disease and in predicting cardiovascular events and death. The test is relatively easy to perform, with newer technology allowing for less radiation and cost. It serves as a more personalized measure of disease and can help facilitate patient-physician discussions about starting pharmacologic therapy, especially if a patient is reluctant.

Currently, coronary calcium scoring has a class IIB recommendation in scenarios in which the risk-based treatment decision is uncertain after formal risk estimation has been done according to the ACC/AHA guideline. The Society of Cardiovascular Computed Tomography guideline and expert consensus documents are more specific in recommending the test in asymptomatic patients in the intermediate-risk group.

Limitations of calcium scoring include the possibility of unnecessary cardiovascular testing such as cardiac catheterization or stress testing being driven by the calcium score alone, as well as the impact of incidental findings. With increased reporting of the coronary calcium score in patients undergoing CT for lung cancer screening, the score should be interpreted in view of the entire clinical scenario.

A 60-year-old man with hypertension and persistent atrial fibrillation refractory to radiofrequency ablation was brought to the hospital in status epilepticus requiring intubation. His wife said that during the past month he had experienced a number of episodic seizures, but due to his busy work schedule he had not sought medical attention. He had also been hospitalized 3 times during the past week for chills, tremors, and fevers with temperatures up to 101°F (38.3°C), and his symptoms had been ascribed to the amiodarone he had been taking for the past 11 days for atrial fibrillation. The amiodarone dose had been decreased to half a tablet after the first 7 days, but his symptoms had continued.

When the patient was able to speak, he denied intravenous drug abuse and claimed to be up to date with vaccinations. Colonoscopy 10 years earlier had been negative. He has no pets, but says that there are stray cats around his home and that he has had contact with cat feces while gardening. He works as a diesel mechanic and is exposed to motor oil and diesel fuel, but denies any direct exposure to carcinogenic chemicals.

On admission, his temperature was 37.7°C (99.9°F), blood pressure 92/69 mm Hg, heart rate 96 beats per minute, respiratory rate 21 per minute, and oxygen saturation 95% on room air and 100% on oxygen at 2 L per minute.

Decerebrate posturing and forced left visual gaze deviation was observed. Oral examination revealed severe decay of multiple teeth, with some teeth broken down to the level of the gingiva, and moderate generalized periodontal disease with heavy plaque and calculi in the gingiva.

The differential diagnosis for intracranial ring-enhancing lesions includes metastasis, abscess, infection in an immunocompromised state (eg, toxoplasmosis), glioblastoma, subacute infarct, neurocysticercosis, lymphoma, demyelination, and resolving hematoma. In our patient, further testing to narrow the differential included lumbar puncture, with results within normal limits, and transthoracic echocardiography, which was negative for endocarditis. A biopsy obtained by craniotomy confirmed the diagnosis of abscess surrounded by reactive glioses.

During his hospitalization, the patient’s antiseizure regimen was lorazepam 1 to 2 mg as needed, levetiracetam 1,500 mg twice daily, and fosphenytoin infusion at 100 mg phenytoin sodium equivalents per minute. Initial antibiotic therapy included ampicillin 2 g intravenously (IV) 4 times daily.

Because of persistent nocturnal fevers with temperatures ranging from 37.8°C (100°F) to 41.2°C (106.2°F), antibiotic coverage was broadened to meropenem 2 g IV every 8 hours. Testing for Toxoplasma gondii, human immunodeficiency virus, and JC polyomavirus was negative. Cerebrospinal fluid culture and abscess cultures were also negative. Blood cultures were eventually positive for Peptostreptococcus micros and Streptococcus constellatus. Based on review of culture results, antibiotic therapy was switched to ceftriaxone 2 g IV twice daily and metronidazole 500 mg IV 3 times daily.

For the dental infection, the patient underwent surgical irrigation and debridement with full dental extraction for multiple dental abscesses.

His regimen for seizure control was changed to phenytoin and valproic acid, and he was discharged in stable condition on the following drug regimen: ceftriaxone 2 g IV twice daily, metronidazole 500 mg IV 3 times daily for 6 weeks, levetiracetam 1,500 mg twice daily, and valproic acid 750 mg 3 times daily.

At a 3-month follow-up visit, he reported no seizure-like activity but demonstrated persistent neurologic deficits (dysdiadocho­kinesia and mild ataxia).

A LESS COMMON CAUSE OF BRAIN ABSCESS

In the United States, 1,500 to 2,000 cases of brain abscess are diagnosed every year, and this condition is responsible for an estimated 1 in 10,000 hospitalizations. Most patients hospitalized are men over age 60 or children. Most patients with hematogenous or embolic spread of infection from a primary infection source are immunocompromised.

However, the lesions in our patient were not from compromised immunity, but rather from septic hematogenous spread of an odontogenic infection. Odontogenic bacteria are a common cause of pyogenic orofascial infection, including periapical abscess and infection of adjoining fascial spaces of the head and neck.¹

P micros and S constellatus have been commonly found in many types of odontogenic infection, including dentoalveolar infection, periodontitis, and pericoronitis.² Our patient was found to have several periodontal abscesses with bacteremia and spread to the brain. Although transthoracic echocardiography was negative for vegetations or patent foramen ovale, the quality and location of the brain abscesses suggested embolic spread of infection. Most of the suspected septic emboli were in the right hemisphere, consistent with patterns seen with cardioembolic phenomena, and a number of lesions appeared to be within the distribution of the right anterior cerebral artery and the middle cerebral artery.

Empiric antibiotic therapy for local odontogenic infection includes amoxicillin with clavulanic acid and metronidazole.¹ Our patient’s treatment with ceftriaxone and metronidazole was based on the species and sensitivities of the bacteria in blood cultures.

Surgical irrigation with debridement is considered first-line therapy for local dental infection, with antimicrobials as adjunctive therapy. Initiation of antibiotic therapy before surgery has been associated with a shortened duration of infection and a reduced risk of bacteremia.³

First-line therapy for cerebral abscess is typically antibiotics, specifically ceftriaxone and metronidazole as in our patient. Ceftriaxone is selected for coverage against streptococci, enterobacteriacae, and most common anaerobes, whereas metronidazole is chosen for its efficacy against Bacteroides fragilis.

Computed tomography-guided stereotactic aspiration and open drainage are viable options for solitary and surgically accessible abscesses—typically those greater than 2 cm. Our patient had multiple small septic emboli in the right hemisphere, with the largest lesion measuring 1.5 cm, thus limiting the effectiveness of surgical intervention.

Some patients with mass effect or other evidence of increased intracranial pressure may benefit from high doses of a corticosteroid such as dexamethasone. However, since our patient had no clinical or diagnostic findings suggesting elevated intracranial pressure, we opted for nonsurgical management of the brain abscesses, with 6 weeks of intravenous antibiotics, an antiseizure regimen, and plans for repeat imaging in the outpatient setting.

A 60-year-old man with hypertension and persistent atrial fibrillation refractory to radiofrequency ablation was brought to the hospital in status epilepticus requiring intubation. His wife said that during the past month he had experienced a number of episodic seizures, but due to his busy work schedule he had not sought medical attention. He had also been hospitalized 3 times during the past week for chills, tremors, and fevers with temperatures up to 101°F (38.3°C), and his symptoms had been ascribed to the amiodarone he had been taking for the past 11 days for atrial fibrillation. The amiodarone dose had been decreased to half a tablet after the first 7 days, but his symptoms had continued.

When the patient was able to speak, he denied intravenous drug abuse and claimed to be up to date with vaccinations. Colonoscopy 10 years earlier had been negative. He has no pets, but says that there are stray cats around his home and that he has had contact with cat feces while gardening. He works as a diesel mechanic and is exposed to motor oil and diesel fuel, but denies any direct exposure to carcinogenic chemicals.

On admission, his temperature was 37.7°C (99.9°F), blood pressure 92/69 mm Hg, heart rate 96 beats per minute, respiratory rate 21 per minute, and oxygen saturation 95% on room air and 100% on oxygen at 2 L per minute.

Decerebrate posturing and forced left visual gaze deviation was observed. Oral examination revealed severe decay of multiple teeth, with some teeth broken down to the level of the gingiva, and moderate generalized periodontal disease with heavy plaque and calculi in the gingiva.

The differential diagnosis for intracranial ring-enhancing lesions includes metastasis, abscess, infection in an immunocompromised state (eg, toxoplasmosis), glioblastoma, subacute infarct, neurocysticercosis, lymphoma, demyelination, and resolving hematoma. In our patient, further testing to narrow the differential included lumbar puncture, with results within normal limits, and transthoracic echocardiography, which was negative for endocarditis. A biopsy obtained by craniotomy confirmed the diagnosis of abscess surrounded by reactive glioses.

During his hospitalization, the patient’s antiseizure regimen was lorazepam 1 to 2 mg as needed, levetiracetam 1,500 mg twice daily, and fosphenytoin infusion at 100 mg phenytoin sodium equivalents per minute. Initial antibiotic therapy included ampicillin 2 g intravenously (IV) 4 times daily.

Because of persistent nocturnal fevers with temperatures ranging from 37.8°C (100°F) to 41.2°C (106.2°F), antibiotic coverage was broadened to meropenem 2 g IV every 8 hours. Testing for Toxoplasma gondii, human immunodeficiency virus, and JC polyomavirus was negative. Cerebrospinal fluid culture and abscess cultures were also negative. Blood cultures were eventually positive for Peptostreptococcus micros and Streptococcus constellatus. Based on review of culture results, antibiotic therapy was switched to ceftriaxone 2 g IV twice daily and metronidazole 500 mg IV 3 times daily.

For the dental infection, the patient underwent surgical irrigation and debridement with full dental extraction for multiple dental abscesses.

His regimen for seizure control was changed to phenytoin and valproic acid, and he was discharged in stable condition on the following drug regimen: ceftriaxone 2 g IV twice daily, metronidazole 500 mg IV 3 times daily for 6 weeks, levetiracetam 1,500 mg twice daily, and valproic acid 750 mg 3 times daily.

At a 3-month follow-up visit, he reported no seizure-like activity but demonstrated persistent neurologic deficits (dysdiadocho­kinesia and mild ataxia).

A LESS COMMON CAUSE OF BRAIN ABSCESS

In the United States, 1,500 to 2,000 cases of brain abscess are diagnosed every year, and this condition is responsible for an estimated 1 in 10,000 hospitalizations. Most patients hospitalized are men over age 60 or children. Most patients with hematogenous or embolic spread of infection from a primary infection source are immunocompromised.

However, the lesions in our patient were not from compromised immunity, but rather from septic hematogenous spread of an odontogenic infection. Odontogenic bacteria are a common cause of pyogenic orofascial infection, including periapical abscess and infection of adjoining fascial spaces of the head and neck.¹

P micros and S constellatus have been commonly found in many types of odontogenic infection, including dentoalveolar infection, periodontitis, and pericoronitis.² Our patient was found to have several periodontal abscesses with bacteremia and spread to the brain. Although transthoracic echocardiography was negative for vegetations or patent foramen ovale, the quality and location of the brain abscesses suggested embolic spread of infection. Most of the suspected septic emboli were in the right hemisphere, consistent with patterns seen with cardioembolic phenomena, and a number of lesions appeared to be within the distribution of the right anterior cerebral artery and the middle cerebral artery.

Empiric antibiotic therapy for local odontogenic infection includes amoxicillin with clavulanic acid and metronidazole.¹ Our patient’s treatment with ceftriaxone and metronidazole was based on the species and sensitivities of the bacteria in blood cultures.

Surgical irrigation with debridement is considered first-line therapy for local dental infection, with antimicrobials as adjunctive therapy. Initiation of antibiotic therapy before surgery has been associated with a shortened duration of infection and a reduced risk of bacteremia.³

First-line therapy for cerebral abscess is typically antibiotics, specifically ceftriaxone and metronidazole as in our patient. Ceftriaxone is selected for coverage against streptococci, enterobacteriacae, and most common anaerobes, whereas metronidazole is chosen for its efficacy against Bacteroides fragilis.

Computed tomography-guided stereotactic aspiration and open drainage are viable options for solitary and surgically accessible abscesses—typically those greater than 2 cm. Our patient had multiple small septic emboli in the right hemisphere, with the largest lesion measuring 1.5 cm, thus limiting the effectiveness of surgical intervention.

Some patients with mass effect or other evidence of increased intracranial pressure may benefit from high doses of a corticosteroid such as dexamethasone. However, since our patient had no clinical or diagnostic findings suggesting elevated intracranial pressure, we opted for nonsurgical management of the brain abscesses, with 6 weeks of intravenous antibiotics, an antiseizure regimen, and plans for repeat imaging in the outpatient setting.

A 60-year-old man with hypertension and persistent atrial fibrillation refractory to radiofrequency ablation was brought to the hospital in status epilepticus requiring intubation. His wife said that during the past month he had experienced a number of episodic seizures, but due to his busy work schedule he had not sought medical attention. He had also been hospitalized 3 times during the past week for chills, tremors, and fevers with temperatures up to 101°F (38.3°C), and his symptoms had been ascribed to the amiodarone he had been taking for the past 11 days for atrial fibrillation. The amiodarone dose had been decreased to half a tablet after the first 7 days, but his symptoms had continued.

When the patient was able to speak, he denied intravenous drug abuse and claimed to be up to date with vaccinations. Colonoscopy 10 years earlier had been negative. He has no pets, but says that there are stray cats around his home and that he has had contact with cat feces while gardening. He works as a diesel mechanic and is exposed to motor oil and diesel fuel, but denies any direct exposure to carcinogenic chemicals.

On admission, his temperature was 37.7°C (99.9°F), blood pressure 92/69 mm Hg, heart rate 96 beats per minute, respiratory rate 21 per minute, and oxygen saturation 95% on room air and 100% on oxygen at 2 L per minute.

Decerebrate posturing and forced left visual gaze deviation was observed. Oral examination revealed severe decay of multiple teeth, with some teeth broken down to the level of the gingiva, and moderate generalized periodontal disease with heavy plaque and calculi in the gingiva.

The differential diagnosis for intracranial ring-enhancing lesions includes metastasis, abscess, infection in an immunocompromised state (eg, toxoplasmosis), glioblastoma, subacute infarct, neurocysticercosis, lymphoma, demyelination, and resolving hematoma. In our patient, further testing to narrow the differential included lumbar puncture, with results within normal limits, and transthoracic echocardiography, which was negative for endocarditis. A biopsy obtained by craniotomy confirmed the diagnosis of abscess surrounded by reactive glioses.

During his hospitalization, the patient’s antiseizure regimen was lorazepam 1 to 2 mg as needed, levetiracetam 1,500 mg twice daily, and fosphenytoin infusion at 100 mg phenytoin sodium equivalents per minute. Initial antibiotic therapy included ampicillin 2 g intravenously (IV) 4 times daily.

Because of persistent nocturnal fevers with temperatures ranging from 37.8°C (100°F) to 41.2°C (106.2°F), antibiotic coverage was broadened to meropenem 2 g IV every 8 hours. Testing for Toxoplasma gondii, human immunodeficiency virus, and JC polyomavirus was negative. Cerebrospinal fluid culture and abscess cultures were also negative. Blood cultures were eventually positive for Peptostreptococcus micros and Streptococcus constellatus. Based on review of culture results, antibiotic therapy was switched to ceftriaxone 2 g IV twice daily and metronidazole 500 mg IV 3 times daily.

For the dental infection, the patient underwent surgical irrigation and debridement with full dental extraction for multiple dental abscesses.

His regimen for seizure control was changed to phenytoin and valproic acid, and he was discharged in stable condition on the following drug regimen: ceftriaxone 2 g IV twice daily, metronidazole 500 mg IV 3 times daily for 6 weeks, levetiracetam 1,500 mg twice daily, and valproic acid 750 mg 3 times daily.

At a 3-month follow-up visit, he reported no seizure-like activity but demonstrated persistent neurologic deficits (dysdiadocho­kinesia and mild ataxia).

A LESS COMMON CAUSE OF BRAIN ABSCESS

In the United States, 1,500 to 2,000 cases of brain abscess are diagnosed every year, and this condition is responsible for an estimated 1 in 10,000 hospitalizations. Most patients hospitalized are men over age 60 or children. Most patients with hematogenous or embolic spread of infection from a primary infection source are immunocompromised.

However, the lesions in our patient were not from compromised immunity, but rather from septic hematogenous spread of an odontogenic infection. Odontogenic bacteria are a common cause of pyogenic orofascial infection, including periapical abscess and infection of adjoining fascial spaces of the head and neck.¹

P micros and S constellatus have been commonly found in many types of odontogenic infection, including dentoalveolar infection, periodontitis, and pericoronitis.² Our patient was found to have several periodontal abscesses with bacteremia and spread to the brain. Although transthoracic echocardiography was negative for vegetations or patent foramen ovale, the quality and location of the brain abscesses suggested embolic spread of infection. Most of the suspected septic emboli were in the right hemisphere, consistent with patterns seen with cardioembolic phenomena, and a number of lesions appeared to be within the distribution of the right anterior cerebral artery and the middle cerebral artery.

Empiric antibiotic therapy for local odontogenic infection includes amoxicillin with clavulanic acid and metronidazole.¹ Our patient’s treatment with ceftriaxone and metronidazole was based on the species and sensitivities of the bacteria in blood cultures.

Surgical irrigation with debridement is considered first-line therapy for local dental infection, with antimicrobials as adjunctive therapy. Initiation of antibiotic therapy before surgery has been associated with a shortened duration of infection and a reduced risk of bacteremia.³

First-line therapy for cerebral abscess is typically antibiotics, specifically ceftriaxone and metronidazole as in our patient. Ceftriaxone is selected for coverage against streptococci, enterobacteriacae, and most common anaerobes, whereas metronidazole is chosen for its efficacy against Bacteroides fragilis.

Computed tomography-guided stereotactic aspiration and open drainage are viable options for solitary and surgically accessible abscesses—typically those greater than 2 cm. Our patient had multiple small septic emboli in the right hemisphere, with the largest lesion measuring 1.5 cm, thus limiting the effectiveness of surgical intervention.

Some patients with mass effect or other evidence of increased intracranial pressure may benefit from high doses of a corticosteroid such as dexamethasone. However, since our patient had no clinical or diagnostic findings suggesting elevated intracranial pressure, we opted for nonsurgical management of the brain abscesses, with 6 weeks of intravenous antibiotics, an antiseizure regimen, and plans for repeat imaging in the outpatient setting.

In 1984, Jim Fixx, who wrote The Complete Book of Running,¹ went out for his daily run and died of a massive heart attack. He was 48. Unbeknownst to him, he had 3-vessel coronary artery disease.

See related article

His case illustrates the difficulty of diagnosing coronary artery disease in patients who have no symptoms of it. For many, the initial presentation is myocardial infarction or death. Until recently, there was no reliable way to diagnose subclinical coronary artery disease other than angiography, and there is still no way to rule it out. As a result, physicians have concentrated less on diagnosing subclinical disease and more on assessing the risk of myocardial infarction.

ASSESSING RISK

The risk factors for coronary artery disease (age, male sex, smoking, hypertension, and cholesterol) have been well known for half a century. By combining risk factors with the appropriate weighting, it is possible to predict an individual’s risk of a myocardial infarction. 

In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines applied this risk-based approach to prescribing statins for primary prevention.² Instead of focusing on low-density lipoprotein cholesterol concentration, which by itself is a poor predictor of myocardial infarction, they recommended using the Pooled Cohort Equation³ to determine the risk of a cardiovascular event within 10 years. For patients at high risk (> 7.5%), the benefits of a statin generally outweigh the harms. For those at low risk (< 5%), the opposite is true. For patients in between, there is room for shared decision-making.

Debate has focused on the predictive accuracy of the equation, the threshold for treatment, and the fact that almost all men over 60 qualify for treatment.⁴ These objections stem from the focus on risk rather than on diagnosis of the underlying disease.

Because one-third of “high-risk” patients never develop cardiovascular disease,⁵ the risk-based approach necessitates overtreatment. Those without disease cannot benefit from treatment but nonetheless suffer its side effects, cost, and inconvenience. Raising treatment thresholds (eg, treating only patients whose 10-year risk exceeds 10%) improves the ratio of patients with disease to those without but also misses diseased patients who have few risk factors. “Low risk” is not “no risk.”

TESTING FOR DISEASE IN THOSE AT INTERMEDIATE RISK

Diagnostic testing is preferred if such testing is safe and inexpensive.

In this issue of Cleveland Clinic Journal of Medicine, Parikh and colleagues⁶ review coronary artery calcium scoring, a diagnostic test for coronary artery disease. They conclude that calcium scoring is strongly predictive but should be reserved for patients at intermediate risk to help them decide about treatment. This is clearly the right approach, but the authors leave the term “intermediate” undefined, and their clinical examples offer little guidance as to where the borders lie.

The ACC/AHA guidelines specify a narrow intermediate range (5.0%–7.4%). For these patients, calcium scoring could reclassify most as being at high or low risk, helping to clarify whether statins are indicated.

However, only 12% of patients fall into this category.⁷ What about patients at higher risk? Could they be reclassified as being at low risk if their calcium score was 0?⁸ Conversely, could some low-risk patients discover that they are at high risk and perhaps take action?

The ACC/AHA guidelines recommend against calcium scoring in these circumstances. One concern was that calcium scoring had not been tested with the Pooled Cohort Equation. Another concern related to cost and radiation exposure, but as Parikh et al point out, the cost has now fallen to less than $100, and radiation exposure is similar to that with mammography.

Who, then, should we test? For patients at high or low risk according to the Pooled Cohort Equation, 2 questions determine whether calcium scoring is warranted: how much would an extremely high or low score (ie, 0 or > 400) change the risk of an event, and how likely is an extreme score?

The first question relates to the usefulness of the test, the second to its cost-effectiveness. If even an extreme score cannot move a patient’s risk into or out of the treatment range, then testing is unwarranted. At the same time, if few patients have an extreme score, then cost per test that changes practice will be high.

Because calcium scoring is a direct test for disease, it is extremely predictive. When added to risk-factor models, it substantially improves discrimination⁹ and exhibits excellent calibration.¹⁰ This is true whether the outcome is a major cardiovascular event or death from any cause.

But the calcium score is not strong enough to override all other risk factors. A patient with a predicted 10-year risk of 18% according to the Pooled Cohort Equation and a calcium score of 0 could be reclassified as being at low risk, but a patient with a 10-year predicted risk of 35% could not. The same is true for patients at low risk. A patient with a 4% risk and a calcium score higher than 400 would be reclassified as being at high risk, but not a patient with a 1% risk.

Extreme calcium scores are common, especially in patients at high risk. In the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, 45% of patients with a 10-year predicted risk of 7.5% to 20% had a calcium score of 0, reclassifying them into the low-risk category.¹¹ Even if the predicted risk was greater than 20%, 1 in 4 patients had a score of 0. In contrast, if the 10-year predicted risk was below 5%, one-fifth of patients had a calcium score greater than 0, but only 4% had a score greater than 100.

Nevertheless, patients in the low-risk category whose baseline risk is close to 5% may wish to undergo calcium scoring, because a positive test opens the door to a potentially lifesaving treatment. In general, the closer patients are to the treatment threshold, the more likely they are to be reclassified by calcium scoring.

The Society for Cardiovascular Computed Tomography currently recommends coronary artery calcium scoring for patients whose 10-year risk is between 5% and 20%.¹² These numbers are easy to remember and a reasonable approximation of the number of patients likely to benefit from testing.

COMBINING CALCIUM SCORING WITH TRADITIONAL RISK FACTORS

Primary care physicians interested in more exact personalized medicine can use a risk calculator derived from the MESA cohort.¹³ Based on 10-year outcomes for 6,814 participants, Blaha et al8 derived and validated this risk-prediction tool incorporating all the elements of the Pooled Cohort Equation in addition to family history, race, and calcium score.

The tool offered good discrimination and calibration when validated against 2 external cohorts (the Heinz Nixdorf Recall Study and the Dallas Heart Study).¹⁰ The C statistics were 0.78 and 0.82, with 10-year risk predicted by the tool within half a percent of the observed event rate in each cohort.

The online calculator displays the 10-year risk based on risk factors alone or including a calcium score, allowing the clinician to gauge the value of testing. For example, a 70-year-old nonsmoking white man with a total cholesterol level of 240 mg/dL, high-density lipo­protein cholesterol 40 mg/dL, and systolic blood pressure 130 mm Hg on amlodipine has a 15.2% 10-year risk (well above the 7.5% threshold for statin therapy). However, if his calcium score is 0, his risk falls to 4.3% (well below the threshold). Sharing such information with patients could help them to decide whether to undergo coronary artery calcium scoring.

Ultimately, the decision to take a statin for primary prevention of coronary artery disease is a personal one. It involves weighing risks, benefits, and preferences. Physicians can facilitate the process by providing information and guidance. Patients are best served by having the most accurate information. In many cases, that information should include calcium scoring.

In 1984, Jim Fixx, who wrote The Complete Book of Running,¹ went out for his daily run and died of a massive heart attack. He was 48. Unbeknownst to him, he had 3-vessel coronary artery disease.

See related article

His case illustrates the difficulty of diagnosing coronary artery disease in patients who have no symptoms of it. For many, the initial presentation is myocardial infarction or death. Until recently, there was no reliable way to diagnose subclinical coronary artery disease other than angiography, and there is still no way to rule it out. As a result, physicians have concentrated less on diagnosing subclinical disease and more on assessing the risk of myocardial infarction.

ASSESSING RISK

The risk factors for coronary artery disease (age, male sex, smoking, hypertension, and cholesterol) have been well known for half a century. By combining risk factors with the appropriate weighting, it is possible to predict an individual’s risk of a myocardial infarction. 

In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines applied this risk-based approach to prescribing statins for primary prevention.² Instead of focusing on low-density lipoprotein cholesterol concentration, which by itself is a poor predictor of myocardial infarction, they recommended using the Pooled Cohort Equation³ to determine the risk of a cardiovascular event within 10 years. For patients at high risk (> 7.5%), the benefits of a statin generally outweigh the harms. For those at low risk (< 5%), the opposite is true. For patients in between, there is room for shared decision-making.

Debate has focused on the predictive accuracy of the equation, the threshold for treatment, and the fact that almost all men over 60 qualify for treatment.⁴ These objections stem from the focus on risk rather than on diagnosis of the underlying disease.

Because one-third of “high-risk” patients never develop cardiovascular disease,⁵ the risk-based approach necessitates overtreatment. Those without disease cannot benefit from treatment but nonetheless suffer its side effects, cost, and inconvenience. Raising treatment thresholds (eg, treating only patients whose 10-year risk exceeds 10%) improves the ratio of patients with disease to those without but also misses diseased patients who have few risk factors. “Low risk” is not “no risk.”

TESTING FOR DISEASE IN THOSE AT INTERMEDIATE RISK

Diagnostic testing is preferred if such testing is safe and inexpensive.

In this issue of Cleveland Clinic Journal of Medicine, Parikh and colleagues⁶ review coronary artery calcium scoring, a diagnostic test for coronary artery disease. They conclude that calcium scoring is strongly predictive but should be reserved for patients at intermediate risk to help them decide about treatment. This is clearly the right approach, but the authors leave the term “intermediate” undefined, and their clinical examples offer little guidance as to where the borders lie.

The ACC/AHA guidelines specify a narrow intermediate range (5.0%–7.4%). For these patients, calcium scoring could reclassify most as being at high or low risk, helping to clarify whether statins are indicated.

However, only 12% of patients fall into this category.⁷ What about patients at higher risk? Could they be reclassified as being at low risk if their calcium score was 0?⁸ Conversely, could some low-risk patients discover that they are at high risk and perhaps take action?

The ACC/AHA guidelines recommend against calcium scoring in these circumstances. One concern was that calcium scoring had not been tested with the Pooled Cohort Equation. Another concern related to cost and radiation exposure, but as Parikh et al point out, the cost has now fallen to less than $100, and radiation exposure is similar to that with mammography.

Who, then, should we test? For patients at high or low risk according to the Pooled Cohort Equation, 2 questions determine whether calcium scoring is warranted: how much would an extremely high or low score (ie, 0 or > 400) change the risk of an event, and how likely is an extreme score?

The first question relates to the usefulness of the test, the second to its cost-effectiveness. If even an extreme score cannot move a patient’s risk into or out of the treatment range, then testing is unwarranted. At the same time, if few patients have an extreme score, then cost per test that changes practice will be high.

Because calcium scoring is a direct test for disease, it is extremely predictive. When added to risk-factor models, it substantially improves discrimination⁹ and exhibits excellent calibration.¹⁰ This is true whether the outcome is a major cardiovascular event or death from any cause.

But the calcium score is not strong enough to override all other risk factors. A patient with a predicted 10-year risk of 18% according to the Pooled Cohort Equation and a calcium score of 0 could be reclassified as being at low risk, but a patient with a 10-year predicted risk of 35% could not. The same is true for patients at low risk. A patient with a 4% risk and a calcium score higher than 400 would be reclassified as being at high risk, but not a patient with a 1% risk.

Extreme calcium scores are common, especially in patients at high risk. In the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, 45% of patients with a 10-year predicted risk of 7.5% to 20% had a calcium score of 0, reclassifying them into the low-risk category.¹¹ Even if the predicted risk was greater than 20%, 1 in 4 patients had a score of 0. In contrast, if the 10-year predicted risk was below 5%, one-fifth of patients had a calcium score greater than 0, but only 4% had a score greater than 100.

Nevertheless, patients in the low-risk category whose baseline risk is close to 5% may wish to undergo calcium scoring, because a positive test opens the door to a potentially lifesaving treatment. In general, the closer patients are to the treatment threshold, the more likely they are to be reclassified by calcium scoring.

The Society for Cardiovascular Computed Tomography currently recommends coronary artery calcium scoring for patients whose 10-year risk is between 5% and 20%.¹² These numbers are easy to remember and a reasonable approximation of the number of patients likely to benefit from testing.

COMBINING CALCIUM SCORING WITH TRADITIONAL RISK FACTORS

Primary care physicians interested in more exact personalized medicine can use a risk calculator derived from the MESA cohort.¹³ Based on 10-year outcomes for 6,814 participants, Blaha et al8 derived and validated this risk-prediction tool incorporating all the elements of the Pooled Cohort Equation in addition to family history, race, and calcium score.

The tool offered good discrimination and calibration when validated against 2 external cohorts (the Heinz Nixdorf Recall Study and the Dallas Heart Study).¹⁰ The C statistics were 0.78 and 0.82, with 10-year risk predicted by the tool within half a percent of the observed event rate in each cohort.

The online calculator displays the 10-year risk based on risk factors alone or including a calcium score, allowing the clinician to gauge the value of testing. For example, a 70-year-old nonsmoking white man with a total cholesterol level of 240 mg/dL, high-density lipo­protein cholesterol 40 mg/dL, and systolic blood pressure 130 mm Hg on amlodipine has a 15.2% 10-year risk (well above the 7.5% threshold for statin therapy). However, if his calcium score is 0, his risk falls to 4.3% (well below the threshold). Sharing such information with patients could help them to decide whether to undergo coronary artery calcium scoring.

Ultimately, the decision to take a statin for primary prevention of coronary artery disease is a personal one. It involves weighing risks, benefits, and preferences. Physicians can facilitate the process by providing information and guidance. Patients are best served by having the most accurate information. In many cases, that information should include calcium scoring.

In 1984, Jim Fixx, who wrote The Complete Book of Running,¹ went out for his daily run and died of a massive heart attack. He was 48. Unbeknownst to him, he had 3-vessel coronary artery disease.

See related article

His case illustrates the difficulty of diagnosing coronary artery disease in patients who have no symptoms of it. For many, the initial presentation is myocardial infarction or death. Until recently, there was no reliable way to diagnose subclinical coronary artery disease other than angiography, and there is still no way to rule it out. As a result, physicians have concentrated less on diagnosing subclinical disease and more on assessing the risk of myocardial infarction.

ASSESSING RISK

The risk factors for coronary artery disease (age, male sex, smoking, hypertension, and cholesterol) have been well known for half a century. By combining risk factors with the appropriate weighting, it is possible to predict an individual’s risk of a myocardial infarction. 

In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines applied this risk-based approach to prescribing statins for primary prevention.² Instead of focusing on low-density lipoprotein cholesterol concentration, which by itself is a poor predictor of myocardial infarction, they recommended using the Pooled Cohort Equation³ to determine the risk of a cardiovascular event within 10 years. For patients at high risk (> 7.5%), the benefits of a statin generally outweigh the harms. For those at low risk (< 5%), the opposite is true. For patients in between, there is room for shared decision-making.

Debate has focused on the predictive accuracy of the equation, the threshold for treatment, and the fact that almost all men over 60 qualify for treatment.⁴ These objections stem from the focus on risk rather than on diagnosis of the underlying disease.

Because one-third of “high-risk” patients never develop cardiovascular disease,⁵ the risk-based approach necessitates overtreatment. Those without disease cannot benefit from treatment but nonetheless suffer its side effects, cost, and inconvenience. Raising treatment thresholds (eg, treating only patients whose 10-year risk exceeds 10%) improves the ratio of patients with disease to those without but also misses diseased patients who have few risk factors. “Low risk” is not “no risk.”

TESTING FOR DISEASE IN THOSE AT INTERMEDIATE RISK

Diagnostic testing is preferred if such testing is safe and inexpensive.

In this issue of Cleveland Clinic Journal of Medicine, Parikh and colleagues⁶ review coronary artery calcium scoring, a diagnostic test for coronary artery disease. They conclude that calcium scoring is strongly predictive but should be reserved for patients at intermediate risk to help them decide about treatment. This is clearly the right approach, but the authors leave the term “intermediate” undefined, and their clinical examples offer little guidance as to where the borders lie.

The ACC/AHA guidelines specify a narrow intermediate range (5.0%–7.4%). For these patients, calcium scoring could reclassify most as being at high or low risk, helping to clarify whether statins are indicated.

However, only 12% of patients fall into this category.⁷ What about patients at higher risk? Could they be reclassified as being at low risk if their calcium score was 0?⁸ Conversely, could some low-risk patients discover that they are at high risk and perhaps take action?

The ACC/AHA guidelines recommend against calcium scoring in these circumstances. One concern was that calcium scoring had not been tested with the Pooled Cohort Equation. Another concern related to cost and radiation exposure, but as Parikh et al point out, the cost has now fallen to less than $100, and radiation exposure is similar to that with mammography.

Who, then, should we test? For patients at high or low risk according to the Pooled Cohort Equation, 2 questions determine whether calcium scoring is warranted: how much would an extremely high or low score (ie, 0 or > 400) change the risk of an event, and how likely is an extreme score?

The first question relates to the usefulness of the test, the second to its cost-effectiveness. If even an extreme score cannot move a patient’s risk into or out of the treatment range, then testing is unwarranted. At the same time, if few patients have an extreme score, then cost per test that changes practice will be high.

Because calcium scoring is a direct test for disease, it is extremely predictive. When added to risk-factor models, it substantially improves discrimination⁹ and exhibits excellent calibration.¹⁰ This is true whether the outcome is a major cardiovascular event or death from any cause.

But the calcium score is not strong enough to override all other risk factors. A patient with a predicted 10-year risk of 18% according to the Pooled Cohort Equation and a calcium score of 0 could be reclassified as being at low risk, but a patient with a 10-year predicted risk of 35% could not. The same is true for patients at low risk. A patient with a 4% risk and a calcium score higher than 400 would be reclassified as being at high risk, but not a patient with a 1% risk.

Extreme calcium scores are common, especially in patients at high risk. In the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, 45% of patients with a 10-year predicted risk of 7.5% to 20% had a calcium score of 0, reclassifying them into the low-risk category.¹¹ Even if the predicted risk was greater than 20%, 1 in 4 patients had a score of 0. In contrast, if the 10-year predicted risk was below 5%, one-fifth of patients had a calcium score greater than 0, but only 4% had a score greater than 100.

Nevertheless, patients in the low-risk category whose baseline risk is close to 5% may wish to undergo calcium scoring, because a positive test opens the door to a potentially lifesaving treatment. In general, the closer patients are to the treatment threshold, the more likely they are to be reclassified by calcium scoring.

The Society for Cardiovascular Computed Tomography currently recommends coronary artery calcium scoring for patients whose 10-year risk is between 5% and 20%.¹² These numbers are easy to remember and a reasonable approximation of the number of patients likely to benefit from testing.

COMBINING CALCIUM SCORING WITH TRADITIONAL RISK FACTORS

Primary care physicians interested in more exact personalized medicine can use a risk calculator derived from the MESA cohort.¹³ Based on 10-year outcomes for 6,814 participants, Blaha et al8 derived and validated this risk-prediction tool incorporating all the elements of the Pooled Cohort Equation in addition to family history, race, and calcium score.

The tool offered good discrimination and calibration when validated against 2 external cohorts (the Heinz Nixdorf Recall Study and the Dallas Heart Study).¹⁰ The C statistics were 0.78 and 0.82, with 10-year risk predicted by the tool within half a percent of the observed event rate in each cohort.

The online calculator displays the 10-year risk based on risk factors alone or including a calcium score, allowing the clinician to gauge the value of testing. For example, a 70-year-old nonsmoking white man with a total cholesterol level of 240 mg/dL, high-density lipo­protein cholesterol 40 mg/dL, and systolic blood pressure 130 mm Hg on amlodipine has a 15.2% 10-year risk (well above the 7.5% threshold for statin therapy). However, if his calcium score is 0, his risk falls to 4.3% (well below the threshold). Sharing such information with patients could help them to decide whether to undergo coronary artery calcium scoring.

Ultimately, the decision to take a statin for primary prevention of coronary artery disease is a personal one. It involves weighing risks, benefits, and preferences. Physicians can facilitate the process by providing information and guidance. Patients are best served by having the most accurate information. In many cases, that information should include calcium scoring.

MUNICH – The worldwide cardiology community’s newly revised universal definition of an MI refines the way that cardiologists distinguish between myocardial infarction and myocardial injury, said Joseph S. Alpert, MD, one of the two chairs of the definition-writing panel.

“We had three previous definitions, but there is still a lot of confusion [about distinguishing] between injury and infarction. We definitely hope that this fourth definition will further help people distinguish the two and help people determine whether or not a patient has an MI,” said Dr. Alpert following a session at the annual congress of the European Society of Cardiology that introduced some of the key elements of the new revision.

Days before the ESC congress, a task force formed by the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and the World Heart Federation released the Fourth Universal Definition of Myocardial Infarction (2018) (J Am Coll Cardiol. 2018 Aug 24. doi: 10.1016/j.jacc.2018.08.1038), which follows the series of three prior MI definitions that these groups have issued since the first iteration came out in 2007 (J Am Coll Cardiol. 2007;50[22]:2173-95).

The new revision includes 5 “new concepts,” 14 updated concepts, and 6 new sections since the third universal definition from 2012. The change that topped Dr. Alpert’s list of key messages was the need to determine whether a rise in cardiac troponin, a key biomarker of cardiac damage, resulted from infarction or injury.

These two alternative diagnoses mean “a very different outlook for patients. Treatment is different, and their prognosis is different. It’s important to make the distinction,” said Dr. Alpert, professor of medicine at the University of Arizona in Tucson.

The new changes to making an MI diagnosis will likely help drive a couple of important changes in the way U.S. patients with suspected myocardial injury or infarction get assessed, he said in an interview. The first change will be wide uptake of high sensitivity cardiac troponin (hscTn) assays over the next 5 years or so, as the ability to measure this key diagnostic biomarker progresses from its initial Food and Drug Administration approval for the U.S. market in 2017 to “close to 100% of U.S. hospitals using it,” he predicted. A big issue that is currently slowing even quicker adoption of hscTn is that many hospitals, including the one where Dr. Alpert practices, still have laboratory contracts in place that tether them to older troponin-testing technologies and make it economically unfeasible to change until their contracts expire. The contract in place where Dr. Alpert practices runs out in 2019, and soon after that happens he expects to gain the ability to order a hscTn test.

The new, fourth definition says that hscTn is “recommended for routine clinical use,” but routine U.S. use “won’t be immediate because many hospitals will put in hscTn only when their old contract runs out,” he said.

Another practice-changing impact from the fourth definition may be expanded U.S. availability and use of MR imaging, which the fourth definition identified as the most informative and versatile of the several imaging options used to confirm or rule out an MI.

Cardiac MR “provides both functional and tissue characterization. It’s the technique with the most potential,” able to noninvasively identify “both the nature and extent of myocardial damage,” explained Chiara Bucciarelli-Ducci, MD, a cardiologist and imaging specialist at the Bristol (England) Heart Institute. A single cardiac MR scan “gives many answers,” said Dr. Bucciarelli-Ducci, who also served on the fourth definition task force and spoke at the session about the document’s revised imaging recommendations.

Mitchel L. Zoler/MDedge News

“In the setting of acute MI, cardiac MR can also be used to assess the presence and extent of myocardium at risk (myocardial edema), myocardial salvage, microvascular obstruction, intramyocardial hemorrhage, and infarct size, all markers of myocardial injury that have prognostic value,” according to the fourth definition. “In patients with possible acute MI but unobstructed coronary arteries, cardiac MR can help to diagnose alternative conditions such as myocarditis, Takotsubo syndrome, embolic infarction, or MI with spontaneous recanalization.”

“What’s turning out is that, a large number of patients with chest pain have an infection and not an MI, and cardiac MR can distinguish inflammation and myocarditis from infarction. We’re now doing a lot more MRs,” Dr. Alpert said. Although MR capability is not as widely available today as other imaging methods, like echocardiography and CT, over the next 5 years that will likely change, he said. But Dr. Alpert cautioned that not every patient with a suspected MI needs MR assessment. It’s best focused for selected patients with an uncertain diagnosis based on the core indicators of disease: history, ECG, changes in hscTn levels over time, and a chest x-ray. “MR is for when there are questions,” he said. When patients present with classic MI signs and symptoms the diagnosis can depend just on the basics, perhaps supplemented with a more widely available imaging method like echocardiography to look for wall motion abnormalities, he said. “If echo shows good left ventricular function you probably don’t need MR.” he said.

CT coronary angiography (CTCA) is another useful diagnostic tool, and right now is more widely available than MR. CTCA “may be used to diagnose coronary artery disease in patients with an acute coronary syndrome event in the emergency department or chest pain unit, particularly in low- to intermediate-risk patients with normal hscTn at presentation,” said the fourth definition. But Dr. Alpert cited the radiation dose from CT as a limiting factor. “We have patients who get repeat CT scans, and we know that increases their cancer risk. There is no such thing as a totally safe dose of radiation.” Lack of radiation exposure is another feature that makes MR imaging attractive.

Dr. Alpert had no disclosures. Dr. Bucciarelli-Ducci has had a financial relationship with Circle Cardiovascular Imaging.

[email protected]


 

MUNICH – The worldwide cardiology community’s newly revised universal definition of an MI refines the way that cardiologists distinguish between myocardial infarction and myocardial injury, said Joseph S. Alpert, MD, one of the two chairs of the definition-writing panel.

“We had three previous definitions, but there is still a lot of confusion [about distinguishing] between injury and infarction. We definitely hope that this fourth definition will further help people distinguish the two and help people determine whether or not a patient has an MI,” said Dr. Alpert following a session at the annual congress of the European Society of Cardiology that introduced some of the key elements of the new revision.

Days before the ESC congress, a task force formed by the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and the World Heart Federation released the Fourth Universal Definition of Myocardial Infarction (2018) (J Am Coll Cardiol. 2018 Aug 24. doi: 10.1016/j.jacc.2018.08.1038), which follows the series of three prior MI definitions that these groups have issued since the first iteration came out in 2007 (J Am Coll Cardiol. 2007;50[22]:2173-95).

The new revision includes 5 “new concepts,” 14 updated concepts, and 6 new sections since the third universal definition from 2012. The change that topped Dr. Alpert’s list of key messages was the need to determine whether a rise in cardiac troponin, a key biomarker of cardiac damage, resulted from infarction or injury.

These two alternative diagnoses mean “a very different outlook for patients. Treatment is different, and their prognosis is different. It’s important to make the distinction,” said Dr. Alpert, professor of medicine at the University of Arizona in Tucson.

The new changes to making an MI diagnosis will likely help drive a couple of important changes in the way U.S. patients with suspected myocardial injury or infarction get assessed, he said in an interview. The first change will be wide uptake of high sensitivity cardiac troponin (hscTn) assays over the next 5 years or so, as the ability to measure this key diagnostic biomarker progresses from its initial Food and Drug Administration approval for the U.S. market in 2017 to “close to 100% of U.S. hospitals using it,” he predicted. A big issue that is currently slowing even quicker adoption of hscTn is that many hospitals, including the one where Dr. Alpert practices, still have laboratory contracts in place that tether them to older troponin-testing technologies and make it economically unfeasible to change until their contracts expire. The contract in place where Dr. Alpert practices runs out in 2019, and soon after that happens he expects to gain the ability to order a hscTn test.

The new, fourth definition says that hscTn is “recommended for routine clinical use,” but routine U.S. use “won’t be immediate because many hospitals will put in hscTn only when their old contract runs out,” he said.

Another practice-changing impact from the fourth definition may be expanded U.S. availability and use of MR imaging, which the fourth definition identified as the most informative and versatile of the several imaging options used to confirm or rule out an MI.

Cardiac MR “provides both functional and tissue characterization. It’s the technique with the most potential,” able to noninvasively identify “both the nature and extent of myocardial damage,” explained Chiara Bucciarelli-Ducci, MD, a cardiologist and imaging specialist at the Bristol (England) Heart Institute. A single cardiac MR scan “gives many answers,” said Dr. Bucciarelli-Ducci, who also served on the fourth definition task force and spoke at the session about the document’s revised imaging recommendations.

Mitchel L. Zoler/MDedge News

“In the setting of acute MI, cardiac MR can also be used to assess the presence and extent of myocardium at risk (myocardial edema), myocardial salvage, microvascular obstruction, intramyocardial hemorrhage, and infarct size, all markers of myocardial injury that have prognostic value,” according to the fourth definition. “In patients with possible acute MI but unobstructed coronary arteries, cardiac MR can help to diagnose alternative conditions such as myocarditis, Takotsubo syndrome, embolic infarction, or MI with spontaneous recanalization.”

“What’s turning out is that, a large number of patients with chest pain have an infection and not an MI, and cardiac MR can distinguish inflammation and myocarditis from infarction. We’re now doing a lot more MRs,” Dr. Alpert said. Although MR capability is not as widely available today as other imaging methods, like echocardiography and CT, over the next 5 years that will likely change, he said. But Dr. Alpert cautioned that not every patient with a suspected MI needs MR assessment. It’s best focused for selected patients with an uncertain diagnosis based on the core indicators of disease: history, ECG, changes in hscTn levels over time, and a chest x-ray. “MR is for when there are questions,” he said. When patients present with classic MI signs and symptoms the diagnosis can depend just on the basics, perhaps supplemented with a more widely available imaging method like echocardiography to look for wall motion abnormalities, he said. “If echo shows good left ventricular function you probably don’t need MR.” he said.

CT coronary angiography (CTCA) is another useful diagnostic tool, and right now is more widely available than MR. CTCA “may be used to diagnose coronary artery disease in patients with an acute coronary syndrome event in the emergency department or chest pain unit, particularly in low- to intermediate-risk patients with normal hscTn at presentation,” said the fourth definition. But Dr. Alpert cited the radiation dose from CT as a limiting factor. “We have patients who get repeat CT scans, and we know that increases their cancer risk. There is no such thing as a totally safe dose of radiation.” Lack of radiation exposure is another feature that makes MR imaging attractive.

Dr. Alpert had no disclosures. Dr. Bucciarelli-Ducci has had a financial relationship with Circle Cardiovascular Imaging.

[email protected]


 

MUNICH – The worldwide cardiology community’s newly revised universal definition of an MI refines the way that cardiologists distinguish between myocardial infarction and myocardial injury, said Joseph S. Alpert, MD, one of the two chairs of the definition-writing panel.

“We had three previous definitions, but there is still a lot of confusion [about distinguishing] between injury and infarction. We definitely hope that this fourth definition will further help people distinguish the two and help people determine whether or not a patient has an MI,” said Dr. Alpert following a session at the annual congress of the European Society of Cardiology that introduced some of the key elements of the new revision.

Days before the ESC congress, a task force formed by the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and the World Heart Federation released the Fourth Universal Definition of Myocardial Infarction (2018) (J Am Coll Cardiol. 2018 Aug 24. doi: 10.1016/j.jacc.2018.08.1038), which follows the series of three prior MI definitions that these groups have issued since the first iteration came out in 2007 (J Am Coll Cardiol. 2007;50[22]:2173-95).

The new revision includes 5 “new concepts,” 14 updated concepts, and 6 new sections since the third universal definition from 2012. The change that topped Dr. Alpert’s list of key messages was the need to determine whether a rise in cardiac troponin, a key biomarker of cardiac damage, resulted from infarction or injury.

These two alternative diagnoses mean “a very different outlook for patients. Treatment is different, and their prognosis is different. It’s important to make the distinction,” said Dr. Alpert, professor of medicine at the University of Arizona in Tucson.

The new changes to making an MI diagnosis will likely help drive a couple of important changes in the way U.S. patients with suspected myocardial injury or infarction get assessed, he said in an interview. The first change will be wide uptake of high sensitivity cardiac troponin (hscTn) assays over the next 5 years or so, as the ability to measure this key diagnostic biomarker progresses from its initial Food and Drug Administration approval for the U.S. market in 2017 to “close to 100% of U.S. hospitals using it,” he predicted. A big issue that is currently slowing even quicker adoption of hscTn is that many hospitals, including the one where Dr. Alpert practices, still have laboratory contracts in place that tether them to older troponin-testing technologies and make it economically unfeasible to change until their contracts expire. The contract in place where Dr. Alpert practices runs out in 2019, and soon after that happens he expects to gain the ability to order a hscTn test.

The new, fourth definition says that hscTn is “recommended for routine clinical use,” but routine U.S. use “won’t be immediate because many hospitals will put in hscTn only when their old contract runs out,” he said.

Another practice-changing impact from the fourth definition may be expanded U.S. availability and use of MR imaging, which the fourth definition identified as the most informative and versatile of the several imaging options used to confirm or rule out an MI.

Cardiac MR “provides both functional and tissue characterization. It’s the technique with the most potential,” able to noninvasively identify “both the nature and extent of myocardial damage,” explained Chiara Bucciarelli-Ducci, MD, a cardiologist and imaging specialist at the Bristol (England) Heart Institute. A single cardiac MR scan “gives many answers,” said Dr. Bucciarelli-Ducci, who also served on the fourth definition task force and spoke at the session about the document’s revised imaging recommendations.

Mitchel L. Zoler/MDedge News

“In the setting of acute MI, cardiac MR can also be used to assess the presence and extent of myocardium at risk (myocardial edema), myocardial salvage, microvascular obstruction, intramyocardial hemorrhage, and infarct size, all markers of myocardial injury that have prognostic value,” according to the fourth definition. “In patients with possible acute MI but unobstructed coronary arteries, cardiac MR can help to diagnose alternative conditions such as myocarditis, Takotsubo syndrome, embolic infarction, or MI with spontaneous recanalization.”

“What’s turning out is that, a large number of patients with chest pain have an infection and not an MI, and cardiac MR can distinguish inflammation and myocarditis from infarction. We’re now doing a lot more MRs,” Dr. Alpert said. Although MR capability is not as widely available today as other imaging methods, like echocardiography and CT, over the next 5 years that will likely change, he said. But Dr. Alpert cautioned that not every patient with a suspected MI needs MR assessment. It’s best focused for selected patients with an uncertain diagnosis based on the core indicators of disease: history, ECG, changes in hscTn levels over time, and a chest x-ray. “MR is for when there are questions,” he said. When patients present with classic MI signs and symptoms the diagnosis can depend just on the basics, perhaps supplemented with a more widely available imaging method like echocardiography to look for wall motion abnormalities, he said. “If echo shows good left ventricular function you probably don’t need MR.” he said.

CT coronary angiography (CTCA) is another useful diagnostic tool, and right now is more widely available than MR. CTCA “may be used to diagnose coronary artery disease in patients with an acute coronary syndrome event in the emergency department or chest pain unit, particularly in low- to intermediate-risk patients with normal hscTn at presentation,” said the fourth definition. But Dr. Alpert cited the radiation dose from CT as a limiting factor. “We have patients who get repeat CT scans, and we know that increases their cancer risk. There is no such thing as a totally safe dose of radiation.” Lack of radiation exposure is another feature that makes MR imaging attractive.

Dr. Alpert had no disclosures. Dr. Bucciarelli-Ducci has had a financial relationship with Circle Cardiovascular Imaging.

[email protected]


 

MUNICH – The use of coronary computed tomographic angiography (CTA) in patients with stable chest pain reduced the risk of nonfatal heart attack or cardiovascular death by 41% over 5 years.

Although the absolute numbers were small – 48 clinical events in the intervention group and 81 among patients who had standard care – the difference was significant and wasn’t associated with any increase in invasive coronary procedures, David E. Newby, MD, said at the annual congress of the European Society of Cardiology.

The study, presented August 25, was published simultaneously in the New England Journal of Medicine (NEJM 2018; DOI: 10.1056/NEJMoa1805971

The data suggest that 63 patients with stable chest pain would need to undergo CTA to prevent one fatal or nonfatal myocardial infarction over 5 years, said Dr. Newby, the BHF John Wheatley professor of cardiology at the University of Edinburgh, Scotland.

He presented 5-year results of the SCOT-HEART study, an open-label trial that randomized 4,146 patients with stable chest pain to standard care plus CTA, or standard care alone. The primary endpoint was nonfatal myocardial infarction or death from coronary heart disease at 5 years. The 3-year results were previously reported.

“This is one of the most impactful studies in cardiovascular medicine. It’s a groundbreaking trial,” commented Todd C. Villines, MD, a designated discussant for the report at the meeting. SCOT-HEART “looked at the additive value of CTA compared with usual care using functional testing with an exercise stress test. It showed that when you visualize coronary atherosclerosis [with CTA] and change medical management based on whether or not plaque is present it drove a significant decrease in MIs,” noted Dr. Villines, a cardiologist affiliated with Georgetown University Medical School in Washington, and immediate past president of the Society of Cardiovascular CT.

Patients were recruited from 12 cardiology centers across Scotland and followed for a mean of 4.8 years, amassing 20,254 patient-years of follow-up. They were a mean of 57 years old; 41% had nonanginal chest pain, 35% typical angina, and 24% atypical angina About half were current or former smokers, a third had hypertension, and half had hypercholesterolemia. Resting EEG was normal in 85%.

Patients who underwent CTA were more likely to start preventive therapies (19% vs. 14.7%; odds ratio, 1.4) and antianginal therapies (13% vs. 10.7%; hazard ratio, 1.27). And although there were more revascularizations in that group early on, the numbers were similar by the end of follow-up (13.5% vs. 13%). After 12 months, CTA patients were 30% less likely to undergo invasive coronary angiography (HR, 0.70) and 41% less likely to undergo a coronary revascularization (HR, 0.59).

“This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies,” Dr. Newby and colleagues wrote in the NEJM paper.

The composite clinical endpoint occurred in 2.3% of the CTA group and 3.9% of the standard care group – a significant risk differential of 41% (HR, 0.59). The primary driver of this benefit was a significantly lower rate of nonfatal myocardial infarction (HR, 0.60) among CTA patients.

There was no evidence of a subgroup effect, Dr. Newby noted. Among the 48 CTA patients who experienced a clinical event, 22 had obstructive disease, 17 had nonobstructive disease, and three had normal coronary arteries (six patients assigned to the procedure didn’t return for it).

There was a slightly higher event rate among patients with possible angina than among those with nonanginal pain (3.1% vs. 1.8%), but the 5-year difference between the treatment groups was not significantly different.

“Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group,” Dr. Newby noted. “Patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies and may have greater motivation to implement healthy lifestyle modification.”

“The SCOT-HEART data solidify coronary CTA as the best first-line test for patients without established coronary disease,” especially now that a report documented that clinicians worldwide are performing coronary CTA using lower levels of radiation exposure to patients, commented Dr. Villines in an interview. During the same session where Dr. Newby reported the SCOT-HEART results, an international team of researchers reported results of a survey of CTA methods used at 61 centers in 32 countries, including several U.S. sites. The results from the survey showed that in 2017 patients undergoing coronary CTA received a median radiation dose of 2.7 mSv and a median dose-length product of 195 mGy*cm, both representing a 78% relative reduction compared with the median doses received during CTA when a similar survey ran in 2007 (Eur Heart J. 2018 Aug 25; doi:10.1093/eurheartj/ehy546).

In contrast, for patients with established coronary artery disease functional tests using stress imaging remain best, Dr. Villines said. “What SCOT-HEART said was that when you use coronary CTA in a population without established coronary disease you can identify not only whether the patient has obstructive disease but do they have coronary atherosclerosis, and that is prognostic and valuable. You miss that with functional testing.”

The Chief Scientist Office of the Scottish Government funded the study. Dr. Newby has received grants from Seimens. Dr. Villines had no relevant commercial disclosures.

Updated 8/27/18: Mitchel L. Zoler contributed commentary by Dr. Todd C. Villines, and additional data and discussion from the presentation, to this article.

[email protected]

SOURCE: Newby DE et al. NEJM 2018; DOI: 10.1056/NEJMoa1805971.

MUNICH – The use of coronary computed tomographic angiography (CTA) in patients with stable chest pain reduced the risk of nonfatal heart attack or cardiovascular death by 41% over 5 years.

Although the absolute numbers were small – 48 clinical events in the intervention group and 81 among patients who had standard care – the difference was significant and wasn’t associated with any increase in invasive coronary procedures, David E. Newby, MD, said at the annual congress of the European Society of Cardiology.

The study, presented August 25, was published simultaneously in the New England Journal of Medicine (NEJM 2018; DOI: 10.1056/NEJMoa1805971

The data suggest that 63 patients with stable chest pain would need to undergo CTA to prevent one fatal or nonfatal myocardial infarction over 5 years, said Dr. Newby, the BHF John Wheatley professor of cardiology at the University of Edinburgh, Scotland.

He presented 5-year results of the SCOT-HEART study, an open-label trial that randomized 4,146 patients with stable chest pain to standard care plus CTA, or standard care alone. The primary endpoint was nonfatal myocardial infarction or death from coronary heart disease at 5 years. The 3-year results were previously reported.

“This is one of the most impactful studies in cardiovascular medicine. It’s a groundbreaking trial,” commented Todd C. Villines, MD, a designated discussant for the report at the meeting. SCOT-HEART “looked at the additive value of CTA compared with usual care using functional testing with an exercise stress test. It showed that when you visualize coronary atherosclerosis [with CTA] and change medical management based on whether or not plaque is present it drove a significant decrease in MIs,” noted Dr. Villines, a cardiologist affiliated with Georgetown University Medical School in Washington, and immediate past president of the Society of Cardiovascular CT.

Patients were recruited from 12 cardiology centers across Scotland and followed for a mean of 4.8 years, amassing 20,254 patient-years of follow-up. They were a mean of 57 years old; 41% had nonanginal chest pain, 35% typical angina, and 24% atypical angina About half were current or former smokers, a third had hypertension, and half had hypercholesterolemia. Resting EEG was normal in 85%.

Patients who underwent CTA were more likely to start preventive therapies (19% vs. 14.7%; odds ratio, 1.4) and antianginal therapies (13% vs. 10.7%; hazard ratio, 1.27). And although there were more revascularizations in that group early on, the numbers were similar by the end of follow-up (13.5% vs. 13%). After 12 months, CTA patients were 30% less likely to undergo invasive coronary angiography (HR, 0.70) and 41% less likely to undergo a coronary revascularization (HR, 0.59).

“This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies,” Dr. Newby and colleagues wrote in the NEJM paper.

The composite clinical endpoint occurred in 2.3% of the CTA group and 3.9% of the standard care group – a significant risk differential of 41% (HR, 0.59). The primary driver of this benefit was a significantly lower rate of nonfatal myocardial infarction (HR, 0.60) among CTA patients.

There was no evidence of a subgroup effect, Dr. Newby noted. Among the 48 CTA patients who experienced a clinical event, 22 had obstructive disease, 17 had nonobstructive disease, and three had normal coronary arteries (six patients assigned to the procedure didn’t return for it).

There was a slightly higher event rate among patients with possible angina than among those with nonanginal pain (3.1% vs. 1.8%), but the 5-year difference between the treatment groups was not significantly different.

“Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group,” Dr. Newby noted. “Patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies and may have greater motivation to implement healthy lifestyle modification.”

“The SCOT-HEART data solidify coronary CTA as the best first-line test for patients without established coronary disease,” especially now that a report documented that clinicians worldwide are performing coronary CTA using lower levels of radiation exposure to patients, commented Dr. Villines in an interview. During the same session where Dr. Newby reported the SCOT-HEART results, an international team of researchers reported results of a survey of CTA methods used at 61 centers in 32 countries, including several U.S. sites. The results from the survey showed that in 2017 patients undergoing coronary CTA received a median radiation dose of 2.7 mSv and a median dose-length product of 195 mGy*cm, both representing a 78% relative reduction compared with the median doses received during CTA when a similar survey ran in 2007 (Eur Heart J. 2018 Aug 25; doi:10.1093/eurheartj/ehy546).

In contrast, for patients with established coronary artery disease functional tests using stress imaging remain best, Dr. Villines said. “What SCOT-HEART said was that when you use coronary CTA in a population without established coronary disease you can identify not only whether the patient has obstructive disease but do they have coronary atherosclerosis, and that is prognostic and valuable. You miss that with functional testing.”

The Chief Scientist Office of the Scottish Government funded the study. Dr. Newby has received grants from Seimens. Dr. Villines had no relevant commercial disclosures.

Updated 8/27/18: Mitchel L. Zoler contributed commentary by Dr. Todd C. Villines, and additional data and discussion from the presentation, to this article.

[email protected]

SOURCE: Newby DE et al. NEJM 2018; DOI: 10.1056/NEJMoa1805971.

MUNICH – The use of coronary computed tomographic angiography (CTA) in patients with stable chest pain reduced the risk of nonfatal heart attack or cardiovascular death by 41% over 5 years.

Although the absolute numbers were small – 48 clinical events in the intervention group and 81 among patients who had standard care – the difference was significant and wasn’t associated with any increase in invasive coronary procedures, David E. Newby, MD, said at the annual congress of the European Society of Cardiology.

The study, presented August 25, was published simultaneously in the New England Journal of Medicine (NEJM 2018; DOI: 10.1056/NEJMoa1805971

The data suggest that 63 patients with stable chest pain would need to undergo CTA to prevent one fatal or nonfatal myocardial infarction over 5 years, said Dr. Newby, the BHF John Wheatley professor of cardiology at the University of Edinburgh, Scotland.

He presented 5-year results of the SCOT-HEART study, an open-label trial that randomized 4,146 patients with stable chest pain to standard care plus CTA, or standard care alone. The primary endpoint was nonfatal myocardial infarction or death from coronary heart disease at 5 years. The 3-year results were previously reported.

“This is one of the most impactful studies in cardiovascular medicine. It’s a groundbreaking trial,” commented Todd C. Villines, MD, a designated discussant for the report at the meeting. SCOT-HEART “looked at the additive value of CTA compared with usual care using functional testing with an exercise stress test. It showed that when you visualize coronary atherosclerosis [with CTA] and change medical management based on whether or not plaque is present it drove a significant decrease in MIs,” noted Dr. Villines, a cardiologist affiliated with Georgetown University Medical School in Washington, and immediate past president of the Society of Cardiovascular CT.

Patients were recruited from 12 cardiology centers across Scotland and followed for a mean of 4.8 years, amassing 20,254 patient-years of follow-up. They were a mean of 57 years old; 41% had nonanginal chest pain, 35% typical angina, and 24% atypical angina About half were current or former smokers, a third had hypertension, and half had hypercholesterolemia. Resting EEG was normal in 85%.

Patients who underwent CTA were more likely to start preventive therapies (19% vs. 14.7%; odds ratio, 1.4) and antianginal therapies (13% vs. 10.7%; hazard ratio, 1.27). And although there were more revascularizations in that group early on, the numbers were similar by the end of follow-up (13.5% vs. 13%). After 12 months, CTA patients were 30% less likely to undergo invasive coronary angiography (HR, 0.70) and 41% less likely to undergo a coronary revascularization (HR, 0.59).

“This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies,” Dr. Newby and colleagues wrote in the NEJM paper.

The composite clinical endpoint occurred in 2.3% of the CTA group and 3.9% of the standard care group – a significant risk differential of 41% (HR, 0.59). The primary driver of this benefit was a significantly lower rate of nonfatal myocardial infarction (HR, 0.60) among CTA patients.

There was no evidence of a subgroup effect, Dr. Newby noted. Among the 48 CTA patients who experienced a clinical event, 22 had obstructive disease, 17 had nonobstructive disease, and three had normal coronary arteries (six patients assigned to the procedure didn’t return for it).

There was a slightly higher event rate among patients with possible angina than among those with nonanginal pain (3.1% vs. 1.8%), but the 5-year difference between the treatment groups was not significantly different.

“Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group,” Dr. Newby noted. “Patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies and may have greater motivation to implement healthy lifestyle modification.”

“The SCOT-HEART data solidify coronary CTA as the best first-line test for patients without established coronary disease,” especially now that a report documented that clinicians worldwide are performing coronary CTA using lower levels of radiation exposure to patients, commented Dr. Villines in an interview. During the same session where Dr. Newby reported the SCOT-HEART results, an international team of researchers reported results of a survey of CTA methods used at 61 centers in 32 countries, including several U.S. sites. The results from the survey showed that in 2017 patients undergoing coronary CTA received a median radiation dose of 2.7 mSv and a median dose-length product of 195 mGy*cm, both representing a 78% relative reduction compared with the median doses received during CTA when a similar survey ran in 2007 (Eur Heart J. 2018 Aug 25; doi:10.1093/eurheartj/ehy546).

In contrast, for patients with established coronary artery disease functional tests using stress imaging remain best, Dr. Villines said. “What SCOT-HEART said was that when you use coronary CTA in a population without established coronary disease you can identify not only whether the patient has obstructive disease but do they have coronary atherosclerosis, and that is prognostic and valuable. You miss that with functional testing.”

The Chief Scientist Office of the Scottish Government funded the study. Dr. Newby has received grants from Seimens. Dr. Villines had no relevant commercial disclosures.

Updated 8/27/18: Mitchel L. Zoler contributed commentary by Dr. Todd C. Villines, and additional data and discussion from the presentation, to this article.

[email protected]

SOURCE: Newby DE et al. NEJM 2018; DOI: 10.1056/NEJMoa1805971.

ATLANTA – It’s possible to reduce chest x-rays for routine pediatric asthma exacerbations in the ED, but accomplishing this goal takes more than a new clinical practice guideline, according to a quality improvement team at the Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn.

M. Alexander Otto/MDedge News

The team eventually reduced the chest x-ray rate for pediatric asthma exacerbations from 30% to 15% without increasing 3-day all-cause readmissions, but it took some sleuthing in the ED and good relations with staff. “We were way out in left field when we started this. Working in silos is never ideal,” said senior project member David Johnson, MD, a pediatric hospitalist and assistant professor of pediatrics at Vanderbilt.

It’s been known for a while that chest x-rays are almost always a waste of time and money for asthma exacerbations, and national guidelines recommend against them. X-rays don’t improve outcomes and needlessly expose children to radiation.

In 2014, some of the providers at Vanderbilt, which has about 1,700 asthma encounters a year, realized that the institution’s 30% x-ray rate was a problem. The quality improvement team hoped a new guideline would address the issue, but that didn’t happen. “We roll out clinical practice guidelines” from on high, “and think people will magically change their behavior,” but they don’t, Dr. Johnson said at the annual Pediatric Hospital Medicine meeting.

The guideline was not being fully implemented. So the team asked the ED what was the standard procedure for a child presenting with asthma exacerbation. It turned out that the ED had a dyspnea order set that the team ”had no idea existed.” Chest x-rays were at the top of the list; next came blood gases, ventilation-perfusion scans, and leg Dopplers, he said.

The investigators tried to get rid of the whole order set but were unsuccessful. The ED department did, however, let the team eliminate chest x-rays in the default order set in July 2015. That helped, but more changes were needed.

The next conversation was to figure out why x-rays were being ordered in the first place. ED staff said they were worried about missing something, especially pneumonia. They also thought they were helping hospitalists by getting x-rays before sending kids to the ward even though, in reality, it didn’t matter whether x-rays were done a few hours later on the floor. ED providers also said that ill-appearing children often got better after a few hours but were kept back from discharge because x-ray results were still pending and that sometimes these results revealed problems at 3 a.m. that had nothing to do with why the patients were in the ED but still required a work-up.

This discussion opened a door. The ED staff didn’t want to order unnecessary x-rays, either. That led to talks about letting kids declare themselves a bit before x-rays were ordered. ED staff liked the idea, so the guidelines were updated in early 2016 to say that chest x-rays should only be ordered if there is persistent severe respiratory distress with hypoxia, there are focal findings that don’t improve after 12 hours of treatment, or there were concerns for pneumomediastinum or collapsed lung. The updated guidelines were posted in work areas and brought home by resident education. A reminder was added to the electronic medical record system that popped up when someone tried to order a chest x-ray for an child with asthma.

It worked. Chest x-ray rates in asthma fell to 15%, and have remained there since.

“We gave them permission to take their foot off the throttle and wait a little bit, and we don’t have more kids bouncing back from reduced x-rays.” The approach is “probably generalizable everywhere,” Dr. Johnson said.

It was essential that an ED fellow, Caroline Watnick, MD, led the effort and eventually bridged the gap between hospitalists and ED providers. In the end, “the change wasn’t something from the outside,” Dr. Johnson said.

There was no industry funding, and Dr. Johnson didn’t have any disclosures. The Pediatric Hospital Medicine meeting is sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

ATLANTA – It’s possible to reduce chest x-rays for routine pediatric asthma exacerbations in the ED, but accomplishing this goal takes more than a new clinical practice guideline, according to a quality improvement team at the Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn.

M. Alexander Otto/MDedge News

The team eventually reduced the chest x-ray rate for pediatric asthma exacerbations from 30% to 15% without increasing 3-day all-cause readmissions, but it took some sleuthing in the ED and good relations with staff. “We were way out in left field when we started this. Working in silos is never ideal,” said senior project member David Johnson, MD, a pediatric hospitalist and assistant professor of pediatrics at Vanderbilt.

It’s been known for a while that chest x-rays are almost always a waste of time and money for asthma exacerbations, and national guidelines recommend against them. X-rays don’t improve outcomes and needlessly expose children to radiation.

In 2014, some of the providers at Vanderbilt, which has about 1,700 asthma encounters a year, realized that the institution’s 30% x-ray rate was a problem. The quality improvement team hoped a new guideline would address the issue, but that didn’t happen. “We roll out clinical practice guidelines” from on high, “and think people will magically change their behavior,” but they don’t, Dr. Johnson said at the annual Pediatric Hospital Medicine meeting.

The guideline was not being fully implemented. So the team asked the ED what was the standard procedure for a child presenting with asthma exacerbation. It turned out that the ED had a dyspnea order set that the team ”had no idea existed.” Chest x-rays were at the top of the list; next came blood gases, ventilation-perfusion scans, and leg Dopplers, he said.

The investigators tried to get rid of the whole order set but were unsuccessful. The ED department did, however, let the team eliminate chest x-rays in the default order set in July 2015. That helped, but more changes were needed.

The next conversation was to figure out why x-rays were being ordered in the first place. ED staff said they were worried about missing something, especially pneumonia. They also thought they were helping hospitalists by getting x-rays before sending kids to the ward even though, in reality, it didn’t matter whether x-rays were done a few hours later on the floor. ED providers also said that ill-appearing children often got better after a few hours but were kept back from discharge because x-ray results were still pending and that sometimes these results revealed problems at 3 a.m. that had nothing to do with why the patients were in the ED but still required a work-up.

This discussion opened a door. The ED staff didn’t want to order unnecessary x-rays, either. That led to talks about letting kids declare themselves a bit before x-rays were ordered. ED staff liked the idea, so the guidelines were updated in early 2016 to say that chest x-rays should only be ordered if there is persistent severe respiratory distress with hypoxia, there are focal findings that don’t improve after 12 hours of treatment, or there were concerns for pneumomediastinum or collapsed lung. The updated guidelines were posted in work areas and brought home by resident education. A reminder was added to the electronic medical record system that popped up when someone tried to order a chest x-ray for an child with asthma.

It worked. Chest x-ray rates in asthma fell to 15%, and have remained there since.

“We gave them permission to take their foot off the throttle and wait a little bit, and we don’t have more kids bouncing back from reduced x-rays.” The approach is “probably generalizable everywhere,” Dr. Johnson said.

It was essential that an ED fellow, Caroline Watnick, MD, led the effort and eventually bridged the gap between hospitalists and ED providers. In the end, “the change wasn’t something from the outside,” Dr. Johnson said.

There was no industry funding, and Dr. Johnson didn’t have any disclosures. The Pediatric Hospital Medicine meeting is sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

ATLANTA – It’s possible to reduce chest x-rays for routine pediatric asthma exacerbations in the ED, but accomplishing this goal takes more than a new clinical practice guideline, according to a quality improvement team at the Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn.

M. Alexander Otto/MDedge News

The team eventually reduced the chest x-ray rate for pediatric asthma exacerbations from 30% to 15% without increasing 3-day all-cause readmissions, but it took some sleuthing in the ED and good relations with staff. “We were way out in left field when we started this. Working in silos is never ideal,” said senior project member David Johnson, MD, a pediatric hospitalist and assistant professor of pediatrics at Vanderbilt.

It’s been known for a while that chest x-rays are almost always a waste of time and money for asthma exacerbations, and national guidelines recommend against them. X-rays don’t improve outcomes and needlessly expose children to radiation.

In 2014, some of the providers at Vanderbilt, which has about 1,700 asthma encounters a year, realized that the institution’s 30% x-ray rate was a problem. The quality improvement team hoped a new guideline would address the issue, but that didn’t happen. “We roll out clinical practice guidelines” from on high, “and think people will magically change their behavior,” but they don’t, Dr. Johnson said at the annual Pediatric Hospital Medicine meeting.

The guideline was not being fully implemented. So the team asked the ED what was the standard procedure for a child presenting with asthma exacerbation. It turned out that the ED had a dyspnea order set that the team ”had no idea existed.” Chest x-rays were at the top of the list; next came blood gases, ventilation-perfusion scans, and leg Dopplers, he said.

The investigators tried to get rid of the whole order set but were unsuccessful. The ED department did, however, let the team eliminate chest x-rays in the default order set in July 2015. That helped, but more changes were needed.

The next conversation was to figure out why x-rays were being ordered in the first place. ED staff said they were worried about missing something, especially pneumonia. They also thought they were helping hospitalists by getting x-rays before sending kids to the ward even though, in reality, it didn’t matter whether x-rays were done a few hours later on the floor. ED providers also said that ill-appearing children often got better after a few hours but were kept back from discharge because x-ray results were still pending and that sometimes these results revealed problems at 3 a.m. that had nothing to do with why the patients were in the ED but still required a work-up.

This discussion opened a door. The ED staff didn’t want to order unnecessary x-rays, either. That led to talks about letting kids declare themselves a bit before x-rays were ordered. ED staff liked the idea, so the guidelines were updated in early 2016 to say that chest x-rays should only be ordered if there is persistent severe respiratory distress with hypoxia, there are focal findings that don’t improve after 12 hours of treatment, or there were concerns for pneumomediastinum or collapsed lung. The updated guidelines were posted in work areas and brought home by resident education. A reminder was added to the electronic medical record system that popped up when someone tried to order a chest x-ray for an child with asthma.

It worked. Chest x-ray rates in asthma fell to 15%, and have remained there since.

“We gave them permission to take their foot off the throttle and wait a little bit, and we don’t have more kids bouncing back from reduced x-rays.” The approach is “probably generalizable everywhere,” Dr. Johnson said.

It was essential that an ED fellow, Caroline Watnick, MD, led the effort and eventually bridged the gap between hospitalists and ED providers. In the end, “the change wasn’t something from the outside,” Dr. Johnson said.

There was no industry funding, and Dr. Johnson didn’t have any disclosures. The Pediatric Hospital Medicine meeting is sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

Neuroimaging may be appropriate only for specific types of patients with recurrent seizures who present at emergency departments because the scans are otherwise unlikely to prompt acute changes in treatment, a new multicenter study suggests.

Spotmatik/Thinkstock

“Going forward, our results should help ED providers determine which patients are more likely to derive benefit from neuroimaging and which patients are not likely to benefit,” lead author Martin Salinsky, MD, of Oregon Health & Science University, Portland, said in an interview. “They can be more selective in ordering scans and reduce the total number obtained.”

As the study authors noted in their report, published July 18 in Epilepsia, “head CT is generally considered a benign procedure. However, overuse is problematic.”

The scans are costly and expose patients to radiation equivalent to 10 chest x-rays, the authors wrote. Scans can complicate care by clogging ED work flow and producing false positives, and patients often seize while undergoing scans, creating even more complications, they added.

“There is very little information in the medical literature that would help guide ED providers in their decision of whether to obtain neuroimaging on a patient who presents with a recurrent seizure,” Dr. Salinsky said. “Without this information, the tendency is to be cautious and obtain scans in more patients.”

For the study, the researchers tracked 822 consecutive ED visits for nonindex – recurrent – epileptic seizures at Oregon Health & Science University and VA Portland Health Care medical centers. (Nonindex seizures accounted for 78% of the total seizures that prompted ED care.)

The study subjects were adults treated for seizure as the main complaint. Patients who had a history of seizures but hadn’t had one for at least 5 years were excluded.

Of the total nonindex seizures, 46% of those resulted in neuroimaging.

“The overall yield of neuroimaging in this patient group was 2%-3%,” Dr. Salinsky said, referring to the percentage of patients whose scans resulted in an acute change in management.

False positives due to imaging artifacts were subsequently discovered in 3 of the 11 patients whose neuroimaging prompted an acute change in management. When the false positives were removed, the yield of acute management changes prompted by neuroimaging decreased to 2.1% overall.

“Three clinical factors – acute head trauma, prolonged alteration of consciousness, and focal neurological examination [at presentation] – were associated with an increased yield of imaging,” he said. “Absent all three factors, the yield in our patients was zero.”

At the two medical centers, the percentages of patients with acute head trauma were 10% and 15%. Prolonged alteration of consciousness occurred in 6% at both centers, and focal neurological examination at presentation was observed in 12% and 14%.

A fourth factor, presentation with status epilepticus/acute repetitive seizures, “bordered on statistical significance and might have reached significance in a larger series,” the authors wrote.

As they put it, “these results support a more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at the time of presentation. ... without specific indications, ED neuroimaging for nonindex seizures is unlikely to result in an acute change in care.”

The study authors estimated that hundreds of millions of dollars could be saved annually in the United States if neuroimaging in these ED patients could be cut in half.

No study funding was reported, and the authors reported no relevant disclosures.

SOURCE: Salinsky M et al. Epilepsia. 2018 July 18. doi: 10.1111/epi.14518

Neuroimaging may be appropriate only for specific types of patients with recurrent seizures who present at emergency departments because the scans are otherwise unlikely to prompt acute changes in treatment, a new multicenter study suggests.

Spotmatik/Thinkstock

“Going forward, our results should help ED providers determine which patients are more likely to derive benefit from neuroimaging and which patients are not likely to benefit,” lead author Martin Salinsky, MD, of Oregon Health & Science University, Portland, said in an interview. “They can be more selective in ordering scans and reduce the total number obtained.”

As the study authors noted in their report, published July 18 in Epilepsia, “head CT is generally considered a benign procedure. However, overuse is problematic.”

The scans are costly and expose patients to radiation equivalent to 10 chest x-rays, the authors wrote. Scans can complicate care by clogging ED work flow and producing false positives, and patients often seize while undergoing scans, creating even more complications, they added.

“There is very little information in the medical literature that would help guide ED providers in their decision of whether to obtain neuroimaging on a patient who presents with a recurrent seizure,” Dr. Salinsky said. “Without this information, the tendency is to be cautious and obtain scans in more patients.”

For the study, the researchers tracked 822 consecutive ED visits for nonindex – recurrent – epileptic seizures at Oregon Health & Science University and VA Portland Health Care medical centers. (Nonindex seizures accounted for 78% of the total seizures that prompted ED care.)

The study subjects were adults treated for seizure as the main complaint. Patients who had a history of seizures but hadn’t had one for at least 5 years were excluded.

Of the total nonindex seizures, 46% of those resulted in neuroimaging.

“The overall yield of neuroimaging in this patient group was 2%-3%,” Dr. Salinsky said, referring to the percentage of patients whose scans resulted in an acute change in management.

False positives due to imaging artifacts were subsequently discovered in 3 of the 11 patients whose neuroimaging prompted an acute change in management. When the false positives were removed, the yield of acute management changes prompted by neuroimaging decreased to 2.1% overall.

“Three clinical factors – acute head trauma, prolonged alteration of consciousness, and focal neurological examination [at presentation] – were associated with an increased yield of imaging,” he said. “Absent all three factors, the yield in our patients was zero.”

At the two medical centers, the percentages of patients with acute head trauma were 10% and 15%. Prolonged alteration of consciousness occurred in 6% at both centers, and focal neurological examination at presentation was observed in 12% and 14%.

A fourth factor, presentation with status epilepticus/acute repetitive seizures, “bordered on statistical significance and might have reached significance in a larger series,” the authors wrote.

As they put it, “these results support a more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at the time of presentation. ... without specific indications, ED neuroimaging for nonindex seizures is unlikely to result in an acute change in care.”

The study authors estimated that hundreds of millions of dollars could be saved annually in the United States if neuroimaging in these ED patients could be cut in half.

No study funding was reported, and the authors reported no relevant disclosures.

SOURCE: Salinsky M et al. Epilepsia. 2018 July 18. doi: 10.1111/epi.14518

Neuroimaging may be appropriate only for specific types of patients with recurrent seizures who present at emergency departments because the scans are otherwise unlikely to prompt acute changes in treatment, a new multicenter study suggests.

Spotmatik/Thinkstock

“Going forward, our results should help ED providers determine which patients are more likely to derive benefit from neuroimaging and which patients are not likely to benefit,” lead author Martin Salinsky, MD, of Oregon Health & Science University, Portland, said in an interview. “They can be more selective in ordering scans and reduce the total number obtained.”

As the study authors noted in their report, published July 18 in Epilepsia, “head CT is generally considered a benign procedure. However, overuse is problematic.”

The scans are costly and expose patients to radiation equivalent to 10 chest x-rays, the authors wrote. Scans can complicate care by clogging ED work flow and producing false positives, and patients often seize while undergoing scans, creating even more complications, they added.

“There is very little information in the medical literature that would help guide ED providers in their decision of whether to obtain neuroimaging on a patient who presents with a recurrent seizure,” Dr. Salinsky said. “Without this information, the tendency is to be cautious and obtain scans in more patients.”

For the study, the researchers tracked 822 consecutive ED visits for nonindex – recurrent – epileptic seizures at Oregon Health & Science University and VA Portland Health Care medical centers. (Nonindex seizures accounted for 78% of the total seizures that prompted ED care.)

The study subjects were adults treated for seizure as the main complaint. Patients who had a history of seizures but hadn’t had one for at least 5 years were excluded.

Of the total nonindex seizures, 46% of those resulted in neuroimaging.

“The overall yield of neuroimaging in this patient group was 2%-3%,” Dr. Salinsky said, referring to the percentage of patients whose scans resulted in an acute change in management.

False positives due to imaging artifacts were subsequently discovered in 3 of the 11 patients whose neuroimaging prompted an acute change in management. When the false positives were removed, the yield of acute management changes prompted by neuroimaging decreased to 2.1% overall.

“Three clinical factors – acute head trauma, prolonged alteration of consciousness, and focal neurological examination [at presentation] – were associated with an increased yield of imaging,” he said. “Absent all three factors, the yield in our patients was zero.”

At the two medical centers, the percentages of patients with acute head trauma were 10% and 15%. Prolonged alteration of consciousness occurred in 6% at both centers, and focal neurological examination at presentation was observed in 12% and 14%.

A fourth factor, presentation with status epilepticus/acute repetitive seizures, “bordered on statistical significance and might have reached significance in a larger series,” the authors wrote.

As they put it, “these results support a more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at the time of presentation. ... without specific indications, ED neuroimaging for nonindex seizures is unlikely to result in an acute change in care.”

The study authors estimated that hundreds of millions of dollars could be saved annually in the United States if neuroimaging in these ED patients could be cut in half.

No study funding was reported, and the authors reported no relevant disclosures.

SOURCE: Salinsky M et al. Epilepsia. 2018 July 18. doi: 10.1111/epi.14518

Clinical question: What physician characteristics are associated with CT pulmonary angiogram (CTPA) diagnostic yield?

Background: Overuse of CTPAs for pulmonary embolism evaluation exposes patients to unnecessary testing and harmful ionizing radiation. Physician characteristics influence ordering practice. Identifying specific characteristics can provide an intervention for reducing overutilization.

Study design: Retrospective analysis.

Setting: Academic teaching hospital in Montreal, Canada.

Synopsis: Investigators reviewed 1,394 CTPAs ordered by 182 physicians at an academic teaching hospital during 2014-2016, with 199 (14.3%) positive studies and 1,195 (85.7%) negative studies. Physician years of experience, physician sex, and emergency medicine specialty were not associated with diagnostic yield. However, the diagnostic yield decreased with the total number of scans ordered per physician. For every 10 additional scans ordered, the odds of a positive test were reduced (odds ratio, 0.76; 95% confidence interval, 0.73-0.79). For physicians who ordered more than 50 studies, the percentage of positive studies was only 5%.

This study’s results show that overuse of CTPA is associated with decreased diagnostic yield. A limitation of the study was that pretest probabilities for pulmonary embolism could not be calculated because of inadequate charting, which would have determined whether CTPA was the appropriate test (as opposed to D-dimer).

Bottom line: Physicians who order higher numbers of CTPAs have lower diagnostic yields.

Citation: Chong J et al. Association of lower diagnostic yield with high users of CT pulmonary angiogram. JAMA Intern Med. 2018 Mar 1;178(3):412-3.

Dr. Komsoukaniants is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

Clinical question: What physician characteristics are associated with CT pulmonary angiogram (CTPA) diagnostic yield?

Background: Overuse of CTPAs for pulmonary embolism evaluation exposes patients to unnecessary testing and harmful ionizing radiation. Physician characteristics influence ordering practice. Identifying specific characteristics can provide an intervention for reducing overutilization.

Study design: Retrospective analysis.

Setting: Academic teaching hospital in Montreal, Canada.

Synopsis: Investigators reviewed 1,394 CTPAs ordered by 182 physicians at an academic teaching hospital during 2014-2016, with 199 (14.3%) positive studies and 1,195 (85.7%) negative studies. Physician years of experience, physician sex, and emergency medicine specialty were not associated with diagnostic yield. However, the diagnostic yield decreased with the total number of scans ordered per physician. For every 10 additional scans ordered, the odds of a positive test were reduced (odds ratio, 0.76; 95% confidence interval, 0.73-0.79). For physicians who ordered more than 50 studies, the percentage of positive studies was only 5%.

This study’s results show that overuse of CTPA is associated with decreased diagnostic yield. A limitation of the study was that pretest probabilities for pulmonary embolism could not be calculated because of inadequate charting, which would have determined whether CTPA was the appropriate test (as opposed to D-dimer).

Bottom line: Physicians who order higher numbers of CTPAs have lower diagnostic yields.

Citation: Chong J et al. Association of lower diagnostic yield with high users of CT pulmonary angiogram. JAMA Intern Med. 2018 Mar 1;178(3):412-3.

Dr. Komsoukaniants is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

Clinical question: What physician characteristics are associated with CT pulmonary angiogram (CTPA) diagnostic yield?

Background: Overuse of CTPAs for pulmonary embolism evaluation exposes patients to unnecessary testing and harmful ionizing radiation. Physician characteristics influence ordering practice. Identifying specific characteristics can provide an intervention for reducing overutilization.

Study design: Retrospective analysis.

Setting: Academic teaching hospital in Montreal, Canada.

Synopsis: Investigators reviewed 1,394 CTPAs ordered by 182 physicians at an academic teaching hospital during 2014-2016, with 199 (14.3%) positive studies and 1,195 (85.7%) negative studies. Physician years of experience, physician sex, and emergency medicine specialty were not associated with diagnostic yield. However, the diagnostic yield decreased with the total number of scans ordered per physician. For every 10 additional scans ordered, the odds of a positive test were reduced (odds ratio, 0.76; 95% confidence interval, 0.73-0.79). For physicians who ordered more than 50 studies, the percentage of positive studies was only 5%.

This study’s results show that overuse of CTPA is associated with decreased diagnostic yield. A limitation of the study was that pretest probabilities for pulmonary embolism could not be calculated because of inadequate charting, which would have determined whether CTPA was the appropriate test (as opposed to D-dimer).

Bottom line: Physicians who order higher numbers of CTPAs have lower diagnostic yields.

Citation: Chong J et al. Association of lower diagnostic yield with high users of CT pulmonary angiogram. JAMA Intern Med. 2018 Mar 1;178(3):412-3.

Dr. Komsoukaniants is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.