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AHA: PCI renal complications keep climbing
ORLANDO – Cases of contrast-induced nephropathy increased dramatically among Medicare patients undergoing percutaneous coronary intervention (PCI) during a recent 5-year period, despite the increased attention that has been drawn to the problem.
“These findings suggest that despite a longstanding focus on preventing CIN [contrast-induced nephropathy], the complication is increasing steadily and new efforts to reduce PCI-related CIN are warranted,” Dr. Phillip P. Brown said at the American Heart Association scientific sessions.
A fresh approach is a priority for Medicare, in part because new-onset renal failure requiring hemodialysis as a result of CIN increases health care costs substantially for the remainder of the patient’s life, noted Dr. Brown of Cardiac Data Solutions in Atlanta.
He presented a retrospective analysis of Medicare data files for 2009-2013. Among 1,552,960 Medicare beneficiaries who underwent PCI without valve surgery or coronary artery bypass graft surgery, 275,471 were admitted for nonelective PCI.
The rate of new hemodialysis as a complication of nonelective PCI increased by 24.8% annually during the study period, climbing to an incidence of 1.15% in 2013. Among patients admitted for elective PCI, the rate of new-onset renal failure requiring hemodialysis essentially doubled from 1% to 2% during the 5-year period.
The rate of new-onset acute renal failure as a complication of nonelective PCI increased by an average of 6.9% annually, reaching 7.67% in 2013. The increase in acute renal failure as a complication of elective PCI was even steeper: an average of 10.6% per year.
In addition to the rising rates of acute renal failure and need for dialysis as a complication of PCI, the proportion of patients who presented with prior dialysis or acute renal failure at admission for the procedure also rose year by year. In 2013, acute renal failure was present at admission in 6.12% of patients undergoing elective and 7.02% having nonelective PCI. Prior dialysis at admission was present in 2.61% and 0.94%, respectively.
Dr. Brown reported having no financial conflicts regarding this descriptive study.
ORLANDO – Cases of contrast-induced nephropathy increased dramatically among Medicare patients undergoing percutaneous coronary intervention (PCI) during a recent 5-year period, despite the increased attention that has been drawn to the problem.
“These findings suggest that despite a longstanding focus on preventing CIN [contrast-induced nephropathy], the complication is increasing steadily and new efforts to reduce PCI-related CIN are warranted,” Dr. Phillip P. Brown said at the American Heart Association scientific sessions.
A fresh approach is a priority for Medicare, in part because new-onset renal failure requiring hemodialysis as a result of CIN increases health care costs substantially for the remainder of the patient’s life, noted Dr. Brown of Cardiac Data Solutions in Atlanta.
He presented a retrospective analysis of Medicare data files for 2009-2013. Among 1,552,960 Medicare beneficiaries who underwent PCI without valve surgery or coronary artery bypass graft surgery, 275,471 were admitted for nonelective PCI.
The rate of new hemodialysis as a complication of nonelective PCI increased by 24.8% annually during the study period, climbing to an incidence of 1.15% in 2013. Among patients admitted for elective PCI, the rate of new-onset renal failure requiring hemodialysis essentially doubled from 1% to 2% during the 5-year period.
The rate of new-onset acute renal failure as a complication of nonelective PCI increased by an average of 6.9% annually, reaching 7.67% in 2013. The increase in acute renal failure as a complication of elective PCI was even steeper: an average of 10.6% per year.
In addition to the rising rates of acute renal failure and need for dialysis as a complication of PCI, the proportion of patients who presented with prior dialysis or acute renal failure at admission for the procedure also rose year by year. In 2013, acute renal failure was present at admission in 6.12% of patients undergoing elective and 7.02% having nonelective PCI. Prior dialysis at admission was present in 2.61% and 0.94%, respectively.
Dr. Brown reported having no financial conflicts regarding this descriptive study.
ORLANDO – Cases of contrast-induced nephropathy increased dramatically among Medicare patients undergoing percutaneous coronary intervention (PCI) during a recent 5-year period, despite the increased attention that has been drawn to the problem.
“These findings suggest that despite a longstanding focus on preventing CIN [contrast-induced nephropathy], the complication is increasing steadily and new efforts to reduce PCI-related CIN are warranted,” Dr. Phillip P. Brown said at the American Heart Association scientific sessions.
A fresh approach is a priority for Medicare, in part because new-onset renal failure requiring hemodialysis as a result of CIN increases health care costs substantially for the remainder of the patient’s life, noted Dr. Brown of Cardiac Data Solutions in Atlanta.
He presented a retrospective analysis of Medicare data files for 2009-2013. Among 1,552,960 Medicare beneficiaries who underwent PCI without valve surgery or coronary artery bypass graft surgery, 275,471 were admitted for nonelective PCI.
The rate of new hemodialysis as a complication of nonelective PCI increased by 24.8% annually during the study period, climbing to an incidence of 1.15% in 2013. Among patients admitted for elective PCI, the rate of new-onset renal failure requiring hemodialysis essentially doubled from 1% to 2% during the 5-year period.
The rate of new-onset acute renal failure as a complication of nonelective PCI increased by an average of 6.9% annually, reaching 7.67% in 2013. The increase in acute renal failure as a complication of elective PCI was even steeper: an average of 10.6% per year.
In addition to the rising rates of acute renal failure and need for dialysis as a complication of PCI, the proportion of patients who presented with prior dialysis or acute renal failure at admission for the procedure also rose year by year. In 2013, acute renal failure was present at admission in 6.12% of patients undergoing elective and 7.02% having nonelective PCI. Prior dialysis at admission was present in 2.61% and 0.94%, respectively.
Dr. Brown reported having no financial conflicts regarding this descriptive study.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point: Renal complication rates in Medicare patients undergoing PCI continue to rise dramatically.
Major finding: The combined rate of acute renal failure and need for hemodialysis as a complication of elective PCI in Medicare patients climbed by 18% per year during a recent 5-year period and by nearly 32% annually in those undergoing nonelective PCI.
Data source: A retrospective study of 1.5 million Medicare beneficiaries who underwent elective or nonelective PCI during 2009-2013.
Disclosures: The presenter of this study reported having no financial conflicts.
VIDEO: SPRINT is practice changer; good news for elderly patients
ORLANDO – Results from the SPRINT hypertension trial are “truly practice changing,” by “giving us definitive clinical-trial evidence that an additional 15-18 mm Hg lowering of systolic blood pressure, aiming for a target of less than 120 mm Hg, translates into” a significantly reduced composite cardiovascular-event endpoint as well as significantly reduced all-cause death, Dr. Gregg C. Fonarow said in an interview at the American Heart Association scientific sessions.
The significant, 27% relative reduction in all-cause mortality in SPRINT in patients targeted to a systolic blood pressure of less than 120 mm Hg was especially notable because an all-cause mortality benefit is not typically seen with other interventions, and because it “ultimately demonstrates that the benefits clearly outweigh the potential risks,” said Dr. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.
Dr. Fonarow acknowledged that results from SPRINT showed a more aggressive regimen also produced higher rates of certain important adverse effects, such as acute kidney injury. But the large incremental benefit in total mortality during the greater than 3 years of average follow-up showed the overwhelming net benefit from more aggressive antihypertensive treatment.
Less clear is whether the SPRINT results say anything about initiating antihypertensive treatment in a patients who resemble those enrolled in the trial and have an untreated systolic blood pressure of 130-139 mm Hg. While people like these could enter SPRINT, they constituted just under 10% of the enrolled population.
“The vast majority of patients in the trial met the conventional clinical definition of hypertension, with a systolic blood pressure of 140 mm Hg or greater and already on some treatment, and treating them to a systolic pressure of less than 120 mm Hg, usually by adding just one antihypertensive drug, translated into substantial clinical benefit,” Dr. Fonarow concluded. He also noted that a large subgroup, about 28% of enrolled patients, were at least 75 years old, and in these patients the more aggressive regimen was as safe and effective as in the entire study. “We have a spectacular result” for elderly patients, he said.
Dr. Fonarow had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ORLANDO – Results from the SPRINT hypertension trial are “truly practice changing,” by “giving us definitive clinical-trial evidence that an additional 15-18 mm Hg lowering of systolic blood pressure, aiming for a target of less than 120 mm Hg, translates into” a significantly reduced composite cardiovascular-event endpoint as well as significantly reduced all-cause death, Dr. Gregg C. Fonarow said in an interview at the American Heart Association scientific sessions.
The significant, 27% relative reduction in all-cause mortality in SPRINT in patients targeted to a systolic blood pressure of less than 120 mm Hg was especially notable because an all-cause mortality benefit is not typically seen with other interventions, and because it “ultimately demonstrates that the benefits clearly outweigh the potential risks,” said Dr. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.
Dr. Fonarow acknowledged that results from SPRINT showed a more aggressive regimen also produced higher rates of certain important adverse effects, such as acute kidney injury. But the large incremental benefit in total mortality during the greater than 3 years of average follow-up showed the overwhelming net benefit from more aggressive antihypertensive treatment.
Less clear is whether the SPRINT results say anything about initiating antihypertensive treatment in a patients who resemble those enrolled in the trial and have an untreated systolic blood pressure of 130-139 mm Hg. While people like these could enter SPRINT, they constituted just under 10% of the enrolled population.
“The vast majority of patients in the trial met the conventional clinical definition of hypertension, with a systolic blood pressure of 140 mm Hg or greater and already on some treatment, and treating them to a systolic pressure of less than 120 mm Hg, usually by adding just one antihypertensive drug, translated into substantial clinical benefit,” Dr. Fonarow concluded. He also noted that a large subgroup, about 28% of enrolled patients, were at least 75 years old, and in these patients the more aggressive regimen was as safe and effective as in the entire study. “We have a spectacular result” for elderly patients, he said.
Dr. Fonarow had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ORLANDO – Results from the SPRINT hypertension trial are “truly practice changing,” by “giving us definitive clinical-trial evidence that an additional 15-18 mm Hg lowering of systolic blood pressure, aiming for a target of less than 120 mm Hg, translates into” a significantly reduced composite cardiovascular-event endpoint as well as significantly reduced all-cause death, Dr. Gregg C. Fonarow said in an interview at the American Heart Association scientific sessions.
The significant, 27% relative reduction in all-cause mortality in SPRINT in patients targeted to a systolic blood pressure of less than 120 mm Hg was especially notable because an all-cause mortality benefit is not typically seen with other interventions, and because it “ultimately demonstrates that the benefits clearly outweigh the potential risks,” said Dr. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.
Dr. Fonarow acknowledged that results from SPRINT showed a more aggressive regimen also produced higher rates of certain important adverse effects, such as acute kidney injury. But the large incremental benefit in total mortality during the greater than 3 years of average follow-up showed the overwhelming net benefit from more aggressive antihypertensive treatment.
Less clear is whether the SPRINT results say anything about initiating antihypertensive treatment in a patients who resemble those enrolled in the trial and have an untreated systolic blood pressure of 130-139 mm Hg. While people like these could enter SPRINT, they constituted just under 10% of the enrolled population.
“The vast majority of patients in the trial met the conventional clinical definition of hypertension, with a systolic blood pressure of 140 mm Hg or greater and already on some treatment, and treating them to a systolic pressure of less than 120 mm Hg, usually by adding just one antihypertensive drug, translated into substantial clinical benefit,” Dr. Fonarow concluded. He also noted that a large subgroup, about 28% of enrolled patients, were at least 75 years old, and in these patients the more aggressive regimen was as safe and effective as in the entire study. “We have a spectacular result” for elderly patients, he said.
Dr. Fonarow had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: SPRINT results showed significant added benefit from treating selected patients with cardiovascular disease risk to a systolic blood pressure of less than 120 mm Hg.
AHA: Candesartan protects against cardiotoxicity in breast cancer patients in PRADA
ORLANDO – Concomitant treatment with candesartan protects against the early decline in left ventricular ejection fraction associated with adjunct therapy for early breast cancer.
That was the key finding in the PRADA trial (PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy), the largest study to date looking at prevention of cardiac dysfunction in a breast cancer population.
Another important finding in PRADA was that unlike the angiotensin receptor blocker candesartan (Atacand), metoprolol, a beta blocker, didn’t prevent the early drop in LVEF commonly seen in breast cancer patients treated with anthracyclines and trastuzumab (Herceptin), even though both classes of heart medications are cornerstones of the treatment of ischemic and hypertensive cardiomyopathy, Dr. Geeta Gulati reported at the American Heart Association scientific sessions.
Although the cardiotoxicity of certain breast cancer treatments is widely recognized and has spawned the emerging field of cardio-oncology, the literature in this area is weak. Indeed, a recent meta-analysis identified only four published randomized studies evaluating the possible cardioprotective role for beta blockers and angiotensin antagonists in patients undergoing anthracycline-based chemotherapy (Postgrad Med J doi:10.1136/ postgradmedj-2015-133535). None of the studies was double-blind, all relied upon echocardiographic assessment of changes in LVEF rather than gold-standard cardiac MRI, and the study sizes were small -- just 18-45 breast cancer patients.
Most problematic of all, the studies employed a variety of different definitions of cardiotoxicity, noted Dr. Gulati of Akershus University Hospital in Lorenskog, Norway.
In contrast, PRADA was a double-blind, placebo-controlled, 2 by 2 factorial design, single-center trial, which included 120 patients with early breast cancer. Participants were randomized to candesartan at a starting dose of 8 mg and target dose of 32 mg/day, metoprolol starting at 25 mg with a target of 100 mg/day, or placebo after breast cancer surgery but before the start of anthracycline-containing chemotherapy.
The primary endpoint was change in LVEF from baseline to completion of adjuvant therapy, a period as short as 10 weeks and as long as 64 weeks depending upon whether a woman also underwent courses of trastuzumab, taxanes, and/or radiation therapy.
The overall decline in LVEF was 2.6% in the placebo group and 0.6% in the candesartan group, a significant difference. Metoprolol didn’t put a dent in the LVEF decline.
“Observational studies show early reduction in LVEF is associated with increased risk of developing heart failure later. So if a sustained, long-term effect of angiotensin inhibition can be confirmed in larger multicenter trials, preventive therapy may be indicated as standard care for breast cancer patients,” Dr. Gulati said.
Discussant Dr. Bonnie Ky of the University of Pennsylvania, Philadelphia, called PRADA an important study that moves the field of cardio-oncology forward, yet it’s also a trial that raises more questions than it answers.
PRADA certainly addresses a major problem: “The incidence of heart failure and cardiomyopathy increases over time in breast cancer patients exposed to anthracyclines and trastuzumab. Because patients are living longer because of cancer chemotherapy, their risk of dying of cardiovascular disease actually exceeds that of recurrent cancer in the long term,” she observed.
The study has three major limitations that prevent its findings being implemented in routine clinical practice at this time, Dr. Ky said. One is its relatively small size, even though it’s far bigger than any previous study. Another limitation is that this was an extremely low-cardiovascular-risk patient cohort: the baseline prevalence of diabetes was only 1.5%, fewer than 7% of patients had hypertension, and the baseline LVEF was 63%. That may be why no one developed a substantial decrement in LVEF or actual heart failure.
And since the incidence of cardiomyopathy following breast cancer therapy is known to climb over time, reaching a cumulative 12% at 6 years followup in trastuzumab-treated patients and 20% in those who receive both anthracyclines and trastuzumab (J Natl Cancer Inst. 2012 Sep 5;104(17):1293-305), the lack of extended followup time in PRADA is a significant shortcoming, she added.
The important questions raised by PRADA, Dr. Ky continued, include whether carvedilol or another beta blocker would have generated a positive result where metoprolol failed. Also, should the target population for prevention of cardiotoxicity be more narrowly focused on those at higher baseline cardiovascular risk? And bearing in mind that change in LVEF is a surrogate endpoint, what might be a more clinically meaningful and valid outcome measure? What’s the effect of carvedilol and other cardioprotective medications on cardiac biomarkers in breast cancer patients? And the most important questions of all, she said: What would be the effects of longer followup time and extended therapy?
“This study highlights for us in the field of cardio-oncology the critical need to develop a robust consensus definition of cardiotoxicity and a methodology to identify high cardiovascular risk patients,” she concluded.
PRADA was funded primarily by the University of Oslo and the Norwegian Cancer Society. Dr. Gulati reported having no financial conflicts of interest. Dr. Ky reported receiving a research grant from Pfizer and serving as a consultant to Bristol Myers Squibb.
ORLANDO – Concomitant treatment with candesartan protects against the early decline in left ventricular ejection fraction associated with adjunct therapy for early breast cancer.
That was the key finding in the PRADA trial (PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy), the largest study to date looking at prevention of cardiac dysfunction in a breast cancer population.
Another important finding in PRADA was that unlike the angiotensin receptor blocker candesartan (Atacand), metoprolol, a beta blocker, didn’t prevent the early drop in LVEF commonly seen in breast cancer patients treated with anthracyclines and trastuzumab (Herceptin), even though both classes of heart medications are cornerstones of the treatment of ischemic and hypertensive cardiomyopathy, Dr. Geeta Gulati reported at the American Heart Association scientific sessions.
Although the cardiotoxicity of certain breast cancer treatments is widely recognized and has spawned the emerging field of cardio-oncology, the literature in this area is weak. Indeed, a recent meta-analysis identified only four published randomized studies evaluating the possible cardioprotective role for beta blockers and angiotensin antagonists in patients undergoing anthracycline-based chemotherapy (Postgrad Med J doi:10.1136/ postgradmedj-2015-133535). None of the studies was double-blind, all relied upon echocardiographic assessment of changes in LVEF rather than gold-standard cardiac MRI, and the study sizes were small -- just 18-45 breast cancer patients.
Most problematic of all, the studies employed a variety of different definitions of cardiotoxicity, noted Dr. Gulati of Akershus University Hospital in Lorenskog, Norway.
In contrast, PRADA was a double-blind, placebo-controlled, 2 by 2 factorial design, single-center trial, which included 120 patients with early breast cancer. Participants were randomized to candesartan at a starting dose of 8 mg and target dose of 32 mg/day, metoprolol starting at 25 mg with a target of 100 mg/day, or placebo after breast cancer surgery but before the start of anthracycline-containing chemotherapy.
The primary endpoint was change in LVEF from baseline to completion of adjuvant therapy, a period as short as 10 weeks and as long as 64 weeks depending upon whether a woman also underwent courses of trastuzumab, taxanes, and/or radiation therapy.
The overall decline in LVEF was 2.6% in the placebo group and 0.6% in the candesartan group, a significant difference. Metoprolol didn’t put a dent in the LVEF decline.
“Observational studies show early reduction in LVEF is associated with increased risk of developing heart failure later. So if a sustained, long-term effect of angiotensin inhibition can be confirmed in larger multicenter trials, preventive therapy may be indicated as standard care for breast cancer patients,” Dr. Gulati said.
Discussant Dr. Bonnie Ky of the University of Pennsylvania, Philadelphia, called PRADA an important study that moves the field of cardio-oncology forward, yet it’s also a trial that raises more questions than it answers.
PRADA certainly addresses a major problem: “The incidence of heart failure and cardiomyopathy increases over time in breast cancer patients exposed to anthracyclines and trastuzumab. Because patients are living longer because of cancer chemotherapy, their risk of dying of cardiovascular disease actually exceeds that of recurrent cancer in the long term,” she observed.
The study has three major limitations that prevent its findings being implemented in routine clinical practice at this time, Dr. Ky said. One is its relatively small size, even though it’s far bigger than any previous study. Another limitation is that this was an extremely low-cardiovascular-risk patient cohort: the baseline prevalence of diabetes was only 1.5%, fewer than 7% of patients had hypertension, and the baseline LVEF was 63%. That may be why no one developed a substantial decrement in LVEF or actual heart failure.
And since the incidence of cardiomyopathy following breast cancer therapy is known to climb over time, reaching a cumulative 12% at 6 years followup in trastuzumab-treated patients and 20% in those who receive both anthracyclines and trastuzumab (J Natl Cancer Inst. 2012 Sep 5;104(17):1293-305), the lack of extended followup time in PRADA is a significant shortcoming, she added.
The important questions raised by PRADA, Dr. Ky continued, include whether carvedilol or another beta blocker would have generated a positive result where metoprolol failed. Also, should the target population for prevention of cardiotoxicity be more narrowly focused on those at higher baseline cardiovascular risk? And bearing in mind that change in LVEF is a surrogate endpoint, what might be a more clinically meaningful and valid outcome measure? What’s the effect of carvedilol and other cardioprotective medications on cardiac biomarkers in breast cancer patients? And the most important questions of all, she said: What would be the effects of longer followup time and extended therapy?
“This study highlights for us in the field of cardio-oncology the critical need to develop a robust consensus definition of cardiotoxicity and a methodology to identify high cardiovascular risk patients,” she concluded.
PRADA was funded primarily by the University of Oslo and the Norwegian Cancer Society. Dr. Gulati reported having no financial conflicts of interest. Dr. Ky reported receiving a research grant from Pfizer and serving as a consultant to Bristol Myers Squibb.
ORLANDO – Concomitant treatment with candesartan protects against the early decline in left ventricular ejection fraction associated with adjunct therapy for early breast cancer.
That was the key finding in the PRADA trial (PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy), the largest study to date looking at prevention of cardiac dysfunction in a breast cancer population.
Another important finding in PRADA was that unlike the angiotensin receptor blocker candesartan (Atacand), metoprolol, a beta blocker, didn’t prevent the early drop in LVEF commonly seen in breast cancer patients treated with anthracyclines and trastuzumab (Herceptin), even though both classes of heart medications are cornerstones of the treatment of ischemic and hypertensive cardiomyopathy, Dr. Geeta Gulati reported at the American Heart Association scientific sessions.
Although the cardiotoxicity of certain breast cancer treatments is widely recognized and has spawned the emerging field of cardio-oncology, the literature in this area is weak. Indeed, a recent meta-analysis identified only four published randomized studies evaluating the possible cardioprotective role for beta blockers and angiotensin antagonists in patients undergoing anthracycline-based chemotherapy (Postgrad Med J doi:10.1136/ postgradmedj-2015-133535). None of the studies was double-blind, all relied upon echocardiographic assessment of changes in LVEF rather than gold-standard cardiac MRI, and the study sizes were small -- just 18-45 breast cancer patients.
Most problematic of all, the studies employed a variety of different definitions of cardiotoxicity, noted Dr. Gulati of Akershus University Hospital in Lorenskog, Norway.
In contrast, PRADA was a double-blind, placebo-controlled, 2 by 2 factorial design, single-center trial, which included 120 patients with early breast cancer. Participants were randomized to candesartan at a starting dose of 8 mg and target dose of 32 mg/day, metoprolol starting at 25 mg with a target of 100 mg/day, or placebo after breast cancer surgery but before the start of anthracycline-containing chemotherapy.
The primary endpoint was change in LVEF from baseline to completion of adjuvant therapy, a period as short as 10 weeks and as long as 64 weeks depending upon whether a woman also underwent courses of trastuzumab, taxanes, and/or radiation therapy.
The overall decline in LVEF was 2.6% in the placebo group and 0.6% in the candesartan group, a significant difference. Metoprolol didn’t put a dent in the LVEF decline.
“Observational studies show early reduction in LVEF is associated with increased risk of developing heart failure later. So if a sustained, long-term effect of angiotensin inhibition can be confirmed in larger multicenter trials, preventive therapy may be indicated as standard care for breast cancer patients,” Dr. Gulati said.
Discussant Dr. Bonnie Ky of the University of Pennsylvania, Philadelphia, called PRADA an important study that moves the field of cardio-oncology forward, yet it’s also a trial that raises more questions than it answers.
PRADA certainly addresses a major problem: “The incidence of heart failure and cardiomyopathy increases over time in breast cancer patients exposed to anthracyclines and trastuzumab. Because patients are living longer because of cancer chemotherapy, their risk of dying of cardiovascular disease actually exceeds that of recurrent cancer in the long term,” she observed.
The study has three major limitations that prevent its findings being implemented in routine clinical practice at this time, Dr. Ky said. One is its relatively small size, even though it’s far bigger than any previous study. Another limitation is that this was an extremely low-cardiovascular-risk patient cohort: the baseline prevalence of diabetes was only 1.5%, fewer than 7% of patients had hypertension, and the baseline LVEF was 63%. That may be why no one developed a substantial decrement in LVEF or actual heart failure.
And since the incidence of cardiomyopathy following breast cancer therapy is known to climb over time, reaching a cumulative 12% at 6 years followup in trastuzumab-treated patients and 20% in those who receive both anthracyclines and trastuzumab (J Natl Cancer Inst. 2012 Sep 5;104(17):1293-305), the lack of extended followup time in PRADA is a significant shortcoming, she added.
The important questions raised by PRADA, Dr. Ky continued, include whether carvedilol or another beta blocker would have generated a positive result where metoprolol failed. Also, should the target population for prevention of cardiotoxicity be more narrowly focused on those at higher baseline cardiovascular risk? And bearing in mind that change in LVEF is a surrogate endpoint, what might be a more clinically meaningful and valid outcome measure? What’s the effect of carvedilol and other cardioprotective medications on cardiac biomarkers in breast cancer patients? And the most important questions of all, she said: What would be the effects of longer followup time and extended therapy?
“This study highlights for us in the field of cardio-oncology the critical need to develop a robust consensus definition of cardiotoxicity and a methodology to identify high cardiovascular risk patients,” she concluded.
PRADA was funded primarily by the University of Oslo and the Norwegian Cancer Society. Dr. Gulati reported having no financial conflicts of interest. Dr. Ky reported receiving a research grant from Pfizer and serving as a consultant to Bristol Myers Squibb.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point: Inroads are being made in the growing problem of breast cancer treatment-associated cardiomyopathy.
Major finding: The average 2.6% decline from baseline in breast cancer patients during adjuvant therapy with anthracyclines with or without trastuzumab was negated by concomitant candesartan but not by metoprolol.
Data source: The PRADA trial was a randomized, double-blind, placebo-controlled, 2 by 2 factorial design study involving 120 patients undergoing adjuvant therapy for early breast cancer.
Disclosures: The primary sponsors of the study were the University of Oslo and the Norwegian Cancer Society. Additional support was provided by Abbott Diagnostic and AstraZeneca. The presenter reported no financial conflicts of interest.
In angiography, intracoronary contrast damaged kidneys more than IV contrast
SAN DIEGO – Contrast agents administered through the coronary vessels for invasive angiography led to significantly more kidney damage than contrast agents administered intravenously for coronary computed tomography angiography, according to a randomized study.
In the Coronary Artery Disease-Management (CAD-Man) study, contrast-induced kidney injury was two to three times more likely after intracoronary than after intravenous contrast administration, explained study investigators Dr. Eva Schönenberger and Dr. Marc Dewey of Charité Medical University, Berlin.
Contrast agents used to detect and treat blockages in coronary arteries are known to damage the kidneys in 2%-20% of patients. In the United States, about 4 million doses of contrast are administered directly into the coronary vessels during invasive catheterization, and 40 million into superficial veins, said Dr. Dewey, Heisenberg Professor of Radiology at the German Research Foundation and vice chair of the department of radiology at Charité.
That makes contrast administration a significant clinical decision for physicians, he added, not just because of potential for harm, but also the potential for added costs.
CAD-Man included 326 patients with suspected coronary disease. Researchers randomized 161 patients to intracoronary contrast agent (ICA) for invasive coronary angiography and 165 patients to IV contrast agent for coronary computed tomography angiography (CTA). All patients received the same contrast agent.
Blood samples were taken at baseline before the procedure, and at two time points after: between 18 and 24 hours, and between 46 and 50 hours. Baseline creatinine levels were similar in the two groups. The researchers defined contrast-associated nephrotoxicity as an increase in creatinine of at least 0.5 mg/dL, or 25%.
At follow-up, 21 of 158 ICA patients (13%) and 9 of 160 CTA patients (6%) had contrast-associated nephropathy, a significant difference (P less than .05). In patients without coronary disease, 13% of ICA patients and 4% of CTA patients developed contrast-associated nephropathy, also a significant difference (P less than .05).
Catheter administration concentrates more contrast in the heart and above the kidneys than intravenous administration, Dr. Schönenberger explained at the meeting sponsored by the American Society of Nephrology. Thus, the increased kidney damage in invasive-angiography patients may be due to higher dosages of contrast in their kidneys.
Physicians “have to keep in mind that putting contrast agents directly into the coronaries might produce more of an increase of creatinine, and more acute kidney injury, than just giving it through an IV,” explained Dr. Schönenberger, a nephrologist in the department of anesthesiology and operative intensive care medicine at Charité.
Physicians should take this information into consideration when deciding how to administer contrast for patients suspected of having coronary artery disease, Dr. Dewey noted. “In addition to being noninvasive, cardiac CT may thus also have the advantage of reducing kidney risk.”
Cost should be a big concern as well. Dr. Dewey referred to published literature indicating that contrast-induced kidney injury can lead to “longer hospital and intensive care unit stays, [increased] dialysis, cost of adverse events, and higher mortality rates. The in-hospital cost was $10,000 per contrast-induced acute kidney injury, and the 1-year cost of treatment was more than $11,000.”
Because CAD-Man’s last patient was enrolled in mid-September, the data are still being analyzed, Dr. Schönenberger noted. Therefore, some confounders may be discovered that influenced the results.
For example, cardiologists may select their sicker patients for invasive procedures in order to be ready to insert stents, so there may not be as much flexibility in which approach to use.
Also unclear is the amount of contrast used for each patient in each arm of this study. Some physicians may have used more contrast for patients suspected of having disease that was harder to detect, although that part of the analysis remains under review, Dr. Dewey and Dr. Schönenberger said.
It remains unclear whether the nephrotoxicity found in the invasive angiography group was all due to the contrast, Dr. Schönenberger noted, or whether some of it might have been caused by small particles of hardened cholesterol spreading to blood vessels in the kidneys – a process known as atheroembolic renal disease. That, too, is under review.
The contrast agent used in the study, low-osmolar nonionic Xenetix 350, is used in 96 countries but is not approved by the U.S. Food and Drug Administration, Dr. Schönenberger said. However, it is very similar to those agents that are in use in the United States, she added.
The study was funded by the German Research Foundation through the Heisenberg Professorship Program. The researchers reported no financial disclosures.
SAN DIEGO – Contrast agents administered through the coronary vessels for invasive angiography led to significantly more kidney damage than contrast agents administered intravenously for coronary computed tomography angiography, according to a randomized study.
In the Coronary Artery Disease-Management (CAD-Man) study, contrast-induced kidney injury was two to three times more likely after intracoronary than after intravenous contrast administration, explained study investigators Dr. Eva Schönenberger and Dr. Marc Dewey of Charité Medical University, Berlin.
Contrast agents used to detect and treat blockages in coronary arteries are known to damage the kidneys in 2%-20% of patients. In the United States, about 4 million doses of contrast are administered directly into the coronary vessels during invasive catheterization, and 40 million into superficial veins, said Dr. Dewey, Heisenberg Professor of Radiology at the German Research Foundation and vice chair of the department of radiology at Charité.
That makes contrast administration a significant clinical decision for physicians, he added, not just because of potential for harm, but also the potential for added costs.
CAD-Man included 326 patients with suspected coronary disease. Researchers randomized 161 patients to intracoronary contrast agent (ICA) for invasive coronary angiography and 165 patients to IV contrast agent for coronary computed tomography angiography (CTA). All patients received the same contrast agent.
Blood samples were taken at baseline before the procedure, and at two time points after: between 18 and 24 hours, and between 46 and 50 hours. Baseline creatinine levels were similar in the two groups. The researchers defined contrast-associated nephrotoxicity as an increase in creatinine of at least 0.5 mg/dL, or 25%.
At follow-up, 21 of 158 ICA patients (13%) and 9 of 160 CTA patients (6%) had contrast-associated nephropathy, a significant difference (P less than .05). In patients without coronary disease, 13% of ICA patients and 4% of CTA patients developed contrast-associated nephropathy, also a significant difference (P less than .05).
Catheter administration concentrates more contrast in the heart and above the kidneys than intravenous administration, Dr. Schönenberger explained at the meeting sponsored by the American Society of Nephrology. Thus, the increased kidney damage in invasive-angiography patients may be due to higher dosages of contrast in their kidneys.
Physicians “have to keep in mind that putting contrast agents directly into the coronaries might produce more of an increase of creatinine, and more acute kidney injury, than just giving it through an IV,” explained Dr. Schönenberger, a nephrologist in the department of anesthesiology and operative intensive care medicine at Charité.
Physicians should take this information into consideration when deciding how to administer contrast for patients suspected of having coronary artery disease, Dr. Dewey noted. “In addition to being noninvasive, cardiac CT may thus also have the advantage of reducing kidney risk.”
Cost should be a big concern as well. Dr. Dewey referred to published literature indicating that contrast-induced kidney injury can lead to “longer hospital and intensive care unit stays, [increased] dialysis, cost of adverse events, and higher mortality rates. The in-hospital cost was $10,000 per contrast-induced acute kidney injury, and the 1-year cost of treatment was more than $11,000.”
Because CAD-Man’s last patient was enrolled in mid-September, the data are still being analyzed, Dr. Schönenberger noted. Therefore, some confounders may be discovered that influenced the results.
For example, cardiologists may select their sicker patients for invasive procedures in order to be ready to insert stents, so there may not be as much flexibility in which approach to use.
Also unclear is the amount of contrast used for each patient in each arm of this study. Some physicians may have used more contrast for patients suspected of having disease that was harder to detect, although that part of the analysis remains under review, Dr. Dewey and Dr. Schönenberger said.
It remains unclear whether the nephrotoxicity found in the invasive angiography group was all due to the contrast, Dr. Schönenberger noted, or whether some of it might have been caused by small particles of hardened cholesterol spreading to blood vessels in the kidneys – a process known as atheroembolic renal disease. That, too, is under review.
The contrast agent used in the study, low-osmolar nonionic Xenetix 350, is used in 96 countries but is not approved by the U.S. Food and Drug Administration, Dr. Schönenberger said. However, it is very similar to those agents that are in use in the United States, she added.
The study was funded by the German Research Foundation through the Heisenberg Professorship Program. The researchers reported no financial disclosures.
SAN DIEGO – Contrast agents administered through the coronary vessels for invasive angiography led to significantly more kidney damage than contrast agents administered intravenously for coronary computed tomography angiography, according to a randomized study.
In the Coronary Artery Disease-Management (CAD-Man) study, contrast-induced kidney injury was two to three times more likely after intracoronary than after intravenous contrast administration, explained study investigators Dr. Eva Schönenberger and Dr. Marc Dewey of Charité Medical University, Berlin.
Contrast agents used to detect and treat blockages in coronary arteries are known to damage the kidneys in 2%-20% of patients. In the United States, about 4 million doses of contrast are administered directly into the coronary vessels during invasive catheterization, and 40 million into superficial veins, said Dr. Dewey, Heisenberg Professor of Radiology at the German Research Foundation and vice chair of the department of radiology at Charité.
That makes contrast administration a significant clinical decision for physicians, he added, not just because of potential for harm, but also the potential for added costs.
CAD-Man included 326 patients with suspected coronary disease. Researchers randomized 161 patients to intracoronary contrast agent (ICA) for invasive coronary angiography and 165 patients to IV contrast agent for coronary computed tomography angiography (CTA). All patients received the same contrast agent.
Blood samples were taken at baseline before the procedure, and at two time points after: between 18 and 24 hours, and between 46 and 50 hours. Baseline creatinine levels were similar in the two groups. The researchers defined contrast-associated nephrotoxicity as an increase in creatinine of at least 0.5 mg/dL, or 25%.
At follow-up, 21 of 158 ICA patients (13%) and 9 of 160 CTA patients (6%) had contrast-associated nephropathy, a significant difference (P less than .05). In patients without coronary disease, 13% of ICA patients and 4% of CTA patients developed contrast-associated nephropathy, also a significant difference (P less than .05).
Catheter administration concentrates more contrast in the heart and above the kidneys than intravenous administration, Dr. Schönenberger explained at the meeting sponsored by the American Society of Nephrology. Thus, the increased kidney damage in invasive-angiography patients may be due to higher dosages of contrast in their kidneys.
Physicians “have to keep in mind that putting contrast agents directly into the coronaries might produce more of an increase of creatinine, and more acute kidney injury, than just giving it through an IV,” explained Dr. Schönenberger, a nephrologist in the department of anesthesiology and operative intensive care medicine at Charité.
Physicians should take this information into consideration when deciding how to administer contrast for patients suspected of having coronary artery disease, Dr. Dewey noted. “In addition to being noninvasive, cardiac CT may thus also have the advantage of reducing kidney risk.”
Cost should be a big concern as well. Dr. Dewey referred to published literature indicating that contrast-induced kidney injury can lead to “longer hospital and intensive care unit stays, [increased] dialysis, cost of adverse events, and higher mortality rates. The in-hospital cost was $10,000 per contrast-induced acute kidney injury, and the 1-year cost of treatment was more than $11,000.”
Because CAD-Man’s last patient was enrolled in mid-September, the data are still being analyzed, Dr. Schönenberger noted. Therefore, some confounders may be discovered that influenced the results.
For example, cardiologists may select their sicker patients for invasive procedures in order to be ready to insert stents, so there may not be as much flexibility in which approach to use.
Also unclear is the amount of contrast used for each patient in each arm of this study. Some physicians may have used more contrast for patients suspected of having disease that was harder to detect, although that part of the analysis remains under review, Dr. Dewey and Dr. Schönenberger said.
It remains unclear whether the nephrotoxicity found in the invasive angiography group was all due to the contrast, Dr. Schönenberger noted, or whether some of it might have been caused by small particles of hardened cholesterol spreading to blood vessels in the kidneys – a process known as atheroembolic renal disease. That, too, is under review.
The contrast agent used in the study, low-osmolar nonionic Xenetix 350, is used in 96 countries but is not approved by the U.S. Food and Drug Administration, Dr. Schönenberger said. However, it is very similar to those agents that are in use in the United States, she added.
The study was funded by the German Research Foundation through the Heisenberg Professorship Program. The researchers reported no financial disclosures.
AT KIDNEY WEEK 2015
Key clinical point: Patients undergoing angiography with intracoronary contrast agent instead of IV contrast agent may be at greater risk of kidney injury.
Major finding: Kidney injury was two to three times more likely after intracoronary than after intravenous contrast administration in patients undergoing angiography for suspected heart disease.
Data source: A randomized study of 326 patients with atypical angina pectoris who were scheduled for angiography.
Disclosures: The study was funded by the German Research Foundation through the Heisenberg Professorship Program. The researchers reported no financial disclosures.
AHA: SPRINT’s results upend hypertension targets
ORLANDO – Results from the SPRINT hypertension trial had been highly anticipated ever since the study stopped early in August and the sponsoring National Heart, Lung, and Blood Institute released the top-line positive result in September that treating systolic blood pressure to a target of less than 120 mm Hg led to statistically significant drops in a composite of cardiovascular endpoints as well as in all-cause death, compared with the standard target of less than 140 mm Hg.
When the much fuller report on the results finally came out in a special session at the American Heart Association scientific sessions as well as in a simultaneous publication (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939), the data left attendees buzzing and debating what the results will mean for revised hypertension guidelines and for clinical practice.
The most prominent reactions were accolades for the trial, starting with the independent discussants that the AHA invited to comment at the session, an outpouring of praise reminiscent of that showered on a hit movie:
“A major coup. Thank you, NHLBI,” declared Dr. Marc A. Pfeffer, professor of medicine at Harvard and a cardiologist at Brigham and Women’s Hospital in Boston.
“Thank you for this groundbreaking study,” said Dr. Clive Rosendorff, professor and cardiologist at Mount Sinai Hospital in New York.
“A remarkable trial. The most important blood pressure study in the last 40 years,” gushed Dr. Daniel W. Jones, professor of medicine at the University of Mississippi, Oxford, and director of clinical and population sciences at the Mississippi Center for Obesity Research, Jackson.
Following the huzzahs came a more substantive discussion among meeting attendees of what results from the 9,361-patient Systolic Blood Pressure Intervention Trial will mean for revised blood pressure goals in U.S. guidelines, what it might mean for defining who has hypertension, and how it might influence practice. Perhaps the most pressing issue for the AHA and American College of Cardiology panel that began work on a new revision of hypertension treatment guidelines earlier this year is how to reconcile the SPRINT results with finding from prior studies, especially the 2010 report of results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (N Engl J Med. 2010;362[17]:1575-85.).
ACCORD, at half the size of SPRINT with 4,733 patients, had a very similar design as SPRINT but included only patients with diabetes while SPRINT excluded patients with diabetes. ACCORD failed to show a significant difference in its primary composite outcome after an average of 4.7 years between patients randomized to a hypertension treatment target of less than 140 mm Hg or less than 120 mm Hg, the same goals as in SPRINT. ACCORD did show a statistically significant 41% relative risk reduction for stroke, also in contrast to SPRINT, which showed a much less robust and nonsignificant 11% relative risk reduction in stroke.
In his commentary on SPRINT, Dr. Jones offered several possible explanations for the divergent results, including a possible inherent difference in vascular physiology between patients with diabetes and those with normal glycemic control; the younger patients enrolled in ACCORD (patients averaged 62 years old in ACCORD and 68 years old in SPRINT, and 28% of patients in SPRINT were at least 75 years old); the use of hydrochlorothiazide as the predominant diuretic in ACCORD versus predominant use of chlorthalidone in SPRINT; and the multiple interventions simultaneously tested in ACCORD, which also randomized patients into two arms with respect to glycemic control and into two arms of different lipid-controlling treatment.
SPRINT’s results “need to be assessed in the context of ACCORD,” commented Dr. Salim Yusuf in an interview. “I think the real result is somewhere in between the results of SPRINT and ACCORD” in terms of the appropriate systolic blood pressure target. What we need is a balanced perspective that takes all the trials. SPRINT was a very good trial, but like all studies it should be interpreted in the context of all the other related studies, not in isolation,” said Dr. Yusuf, professor and director of the Population Health Research Institute of McMaster University in Hamilton, Ont.
“Understandably, when something like SPRINT comes out there is a lot of enthusiasm. The first reaction is always ‘Wow!’ For patients who meet SPRINT’s enrollment criteria I think we will treat to a target of less than 120 mm Hg. But the guideline writers need to discuss SPRINT and balance it,” he said.
Despite his regard for SPRINT, Dr. Yusuf cited several additional concerns he has about the trial:
• Its early stoppage (SPRINT had originally been designed to run 5-6 years, but it was halted after an average treatment duration of just over 3 years). “When you stop a trial early there is always an upward bias. The apparent treatment effect gets inflated,” he said.
• The increased rate of acute kidney injury among patients randomized to the more aggressive treatment arm, a 4.1% rate, compared with a 2.5% rate in the control patients randomized to treatment to a goal of systolic pressure less than 140 mm Hg, a statistically significant difference.
• The “highly selected, high-risk” patients enrolled into SPRINT. “You can’t extrapolate the results to the average patient,” Dr. Yusuf said.
Some of these concerns and cautions were shared by Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, although overall he called the SPRINT results “very exciting.”
“Superficially, SPRINT seems to say treat everyone to a blood pressure of less than 120 mm Hg, but that’s not the case. The patients in SPRINT were primarily very well established patients with hypertension. I’d be concerned about an elderly patient with cardiovascular disease and a blood pressure of 130 mm Hg. If you reduce that to less than 120 mm Hg the diastolic pressure may also fall and that’s important for coronary perfusion.” He also cited the absence so far of a subanalysis of what happened to patients with preexisting renal disease and the lack of data on the outcomes of patients whose systolic pressure fell to levels well below 120 mm Hg.
For others, however, the overall, statistically significant 27% reduction in overall mortality was a reassuring indicator of the safety of the aggressive treatment regimen used in SPRINT. “If there was a meaningful worsening of renal function that harmed patients, you would not see a reduction in all-cause mortality,” commented Dr. Gregg C. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.
“We have had so many trials that couldn’t dream of producing a reduction in all-cause mortality. Here we have a trial with a robust, clinically meaningful reduction in all-cause mortality that ultimately demonstrates the benefits outweigh the risks,” he said in an interview.
SPRINT “is a phenomenal breakthrough. It’s data we’ve been awaiting for 20-plus years, to now know that a lower blood pressure target is safe and absolutely essential, and where the benefits outweigh the risks,” Dr. Fonarow said. “Now implementation becomes critical. The SPRINT results are truly practice changing.”
SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.
On Twitter @mitchelzoler
ORLANDO – Results from the SPRINT hypertension trial had been highly anticipated ever since the study stopped early in August and the sponsoring National Heart, Lung, and Blood Institute released the top-line positive result in September that treating systolic blood pressure to a target of less than 120 mm Hg led to statistically significant drops in a composite of cardiovascular endpoints as well as in all-cause death, compared with the standard target of less than 140 mm Hg.
When the much fuller report on the results finally came out in a special session at the American Heart Association scientific sessions as well as in a simultaneous publication (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939), the data left attendees buzzing and debating what the results will mean for revised hypertension guidelines and for clinical practice.
The most prominent reactions were accolades for the trial, starting with the independent discussants that the AHA invited to comment at the session, an outpouring of praise reminiscent of that showered on a hit movie:
“A major coup. Thank you, NHLBI,” declared Dr. Marc A. Pfeffer, professor of medicine at Harvard and a cardiologist at Brigham and Women’s Hospital in Boston.
“Thank you for this groundbreaking study,” said Dr. Clive Rosendorff, professor and cardiologist at Mount Sinai Hospital in New York.
“A remarkable trial. The most important blood pressure study in the last 40 years,” gushed Dr. Daniel W. Jones, professor of medicine at the University of Mississippi, Oxford, and director of clinical and population sciences at the Mississippi Center for Obesity Research, Jackson.
Following the huzzahs came a more substantive discussion among meeting attendees of what results from the 9,361-patient Systolic Blood Pressure Intervention Trial will mean for revised blood pressure goals in U.S. guidelines, what it might mean for defining who has hypertension, and how it might influence practice. Perhaps the most pressing issue for the AHA and American College of Cardiology panel that began work on a new revision of hypertension treatment guidelines earlier this year is how to reconcile the SPRINT results with finding from prior studies, especially the 2010 report of results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (N Engl J Med. 2010;362[17]:1575-85.).
ACCORD, at half the size of SPRINT with 4,733 patients, had a very similar design as SPRINT but included only patients with diabetes while SPRINT excluded patients with diabetes. ACCORD failed to show a significant difference in its primary composite outcome after an average of 4.7 years between patients randomized to a hypertension treatment target of less than 140 mm Hg or less than 120 mm Hg, the same goals as in SPRINT. ACCORD did show a statistically significant 41% relative risk reduction for stroke, also in contrast to SPRINT, which showed a much less robust and nonsignificant 11% relative risk reduction in stroke.
In his commentary on SPRINT, Dr. Jones offered several possible explanations for the divergent results, including a possible inherent difference in vascular physiology between patients with diabetes and those with normal glycemic control; the younger patients enrolled in ACCORD (patients averaged 62 years old in ACCORD and 68 years old in SPRINT, and 28% of patients in SPRINT were at least 75 years old); the use of hydrochlorothiazide as the predominant diuretic in ACCORD versus predominant use of chlorthalidone in SPRINT; and the multiple interventions simultaneously tested in ACCORD, which also randomized patients into two arms with respect to glycemic control and into two arms of different lipid-controlling treatment.
SPRINT’s results “need to be assessed in the context of ACCORD,” commented Dr. Salim Yusuf in an interview. “I think the real result is somewhere in between the results of SPRINT and ACCORD” in terms of the appropriate systolic blood pressure target. What we need is a balanced perspective that takes all the trials. SPRINT was a very good trial, but like all studies it should be interpreted in the context of all the other related studies, not in isolation,” said Dr. Yusuf, professor and director of the Population Health Research Institute of McMaster University in Hamilton, Ont.
“Understandably, when something like SPRINT comes out there is a lot of enthusiasm. The first reaction is always ‘Wow!’ For patients who meet SPRINT’s enrollment criteria I think we will treat to a target of less than 120 mm Hg. But the guideline writers need to discuss SPRINT and balance it,” he said.
Despite his regard for SPRINT, Dr. Yusuf cited several additional concerns he has about the trial:
• Its early stoppage (SPRINT had originally been designed to run 5-6 years, but it was halted after an average treatment duration of just over 3 years). “When you stop a trial early there is always an upward bias. The apparent treatment effect gets inflated,” he said.
• The increased rate of acute kidney injury among patients randomized to the more aggressive treatment arm, a 4.1% rate, compared with a 2.5% rate in the control patients randomized to treatment to a goal of systolic pressure less than 140 mm Hg, a statistically significant difference.
• The “highly selected, high-risk” patients enrolled into SPRINT. “You can’t extrapolate the results to the average patient,” Dr. Yusuf said.
Some of these concerns and cautions were shared by Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, although overall he called the SPRINT results “very exciting.”
“Superficially, SPRINT seems to say treat everyone to a blood pressure of less than 120 mm Hg, but that’s not the case. The patients in SPRINT were primarily very well established patients with hypertension. I’d be concerned about an elderly patient with cardiovascular disease and a blood pressure of 130 mm Hg. If you reduce that to less than 120 mm Hg the diastolic pressure may also fall and that’s important for coronary perfusion.” He also cited the absence so far of a subanalysis of what happened to patients with preexisting renal disease and the lack of data on the outcomes of patients whose systolic pressure fell to levels well below 120 mm Hg.
For others, however, the overall, statistically significant 27% reduction in overall mortality was a reassuring indicator of the safety of the aggressive treatment regimen used in SPRINT. “If there was a meaningful worsening of renal function that harmed patients, you would not see a reduction in all-cause mortality,” commented Dr. Gregg C. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.
“We have had so many trials that couldn’t dream of producing a reduction in all-cause mortality. Here we have a trial with a robust, clinically meaningful reduction in all-cause mortality that ultimately demonstrates the benefits outweigh the risks,” he said in an interview.
SPRINT “is a phenomenal breakthrough. It’s data we’ve been awaiting for 20-plus years, to now know that a lower blood pressure target is safe and absolutely essential, and where the benefits outweigh the risks,” Dr. Fonarow said. “Now implementation becomes critical. The SPRINT results are truly practice changing.”
SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.
On Twitter @mitchelzoler
ORLANDO – Results from the SPRINT hypertension trial had been highly anticipated ever since the study stopped early in August and the sponsoring National Heart, Lung, and Blood Institute released the top-line positive result in September that treating systolic blood pressure to a target of less than 120 mm Hg led to statistically significant drops in a composite of cardiovascular endpoints as well as in all-cause death, compared with the standard target of less than 140 mm Hg.
When the much fuller report on the results finally came out in a special session at the American Heart Association scientific sessions as well as in a simultaneous publication (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939), the data left attendees buzzing and debating what the results will mean for revised hypertension guidelines and for clinical practice.
The most prominent reactions were accolades for the trial, starting with the independent discussants that the AHA invited to comment at the session, an outpouring of praise reminiscent of that showered on a hit movie:
“A major coup. Thank you, NHLBI,” declared Dr. Marc A. Pfeffer, professor of medicine at Harvard and a cardiologist at Brigham and Women’s Hospital in Boston.
“Thank you for this groundbreaking study,” said Dr. Clive Rosendorff, professor and cardiologist at Mount Sinai Hospital in New York.
“A remarkable trial. The most important blood pressure study in the last 40 years,” gushed Dr. Daniel W. Jones, professor of medicine at the University of Mississippi, Oxford, and director of clinical and population sciences at the Mississippi Center for Obesity Research, Jackson.
Following the huzzahs came a more substantive discussion among meeting attendees of what results from the 9,361-patient Systolic Blood Pressure Intervention Trial will mean for revised blood pressure goals in U.S. guidelines, what it might mean for defining who has hypertension, and how it might influence practice. Perhaps the most pressing issue for the AHA and American College of Cardiology panel that began work on a new revision of hypertension treatment guidelines earlier this year is how to reconcile the SPRINT results with finding from prior studies, especially the 2010 report of results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (N Engl J Med. 2010;362[17]:1575-85.).
ACCORD, at half the size of SPRINT with 4,733 patients, had a very similar design as SPRINT but included only patients with diabetes while SPRINT excluded patients with diabetes. ACCORD failed to show a significant difference in its primary composite outcome after an average of 4.7 years between patients randomized to a hypertension treatment target of less than 140 mm Hg or less than 120 mm Hg, the same goals as in SPRINT. ACCORD did show a statistically significant 41% relative risk reduction for stroke, also in contrast to SPRINT, which showed a much less robust and nonsignificant 11% relative risk reduction in stroke.
In his commentary on SPRINT, Dr. Jones offered several possible explanations for the divergent results, including a possible inherent difference in vascular physiology between patients with diabetes and those with normal glycemic control; the younger patients enrolled in ACCORD (patients averaged 62 years old in ACCORD and 68 years old in SPRINT, and 28% of patients in SPRINT were at least 75 years old); the use of hydrochlorothiazide as the predominant diuretic in ACCORD versus predominant use of chlorthalidone in SPRINT; and the multiple interventions simultaneously tested in ACCORD, which also randomized patients into two arms with respect to glycemic control and into two arms of different lipid-controlling treatment.
SPRINT’s results “need to be assessed in the context of ACCORD,” commented Dr. Salim Yusuf in an interview. “I think the real result is somewhere in between the results of SPRINT and ACCORD” in terms of the appropriate systolic blood pressure target. What we need is a balanced perspective that takes all the trials. SPRINT was a very good trial, but like all studies it should be interpreted in the context of all the other related studies, not in isolation,” said Dr. Yusuf, professor and director of the Population Health Research Institute of McMaster University in Hamilton, Ont.
“Understandably, when something like SPRINT comes out there is a lot of enthusiasm. The first reaction is always ‘Wow!’ For patients who meet SPRINT’s enrollment criteria I think we will treat to a target of less than 120 mm Hg. But the guideline writers need to discuss SPRINT and balance it,” he said.
Despite his regard for SPRINT, Dr. Yusuf cited several additional concerns he has about the trial:
• Its early stoppage (SPRINT had originally been designed to run 5-6 years, but it was halted after an average treatment duration of just over 3 years). “When you stop a trial early there is always an upward bias. The apparent treatment effect gets inflated,” he said.
• The increased rate of acute kidney injury among patients randomized to the more aggressive treatment arm, a 4.1% rate, compared with a 2.5% rate in the control patients randomized to treatment to a goal of systolic pressure less than 140 mm Hg, a statistically significant difference.
• The “highly selected, high-risk” patients enrolled into SPRINT. “You can’t extrapolate the results to the average patient,” Dr. Yusuf said.
Some of these concerns and cautions were shared by Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, although overall he called the SPRINT results “very exciting.”
“Superficially, SPRINT seems to say treat everyone to a blood pressure of less than 120 mm Hg, but that’s not the case. The patients in SPRINT were primarily very well established patients with hypertension. I’d be concerned about an elderly patient with cardiovascular disease and a blood pressure of 130 mm Hg. If you reduce that to less than 120 mm Hg the diastolic pressure may also fall and that’s important for coronary perfusion.” He also cited the absence so far of a subanalysis of what happened to patients with preexisting renal disease and the lack of data on the outcomes of patients whose systolic pressure fell to levels well below 120 mm Hg.
For others, however, the overall, statistically significant 27% reduction in overall mortality was a reassuring indicator of the safety of the aggressive treatment regimen used in SPRINT. “If there was a meaningful worsening of renal function that harmed patients, you would not see a reduction in all-cause mortality,” commented Dr. Gregg C. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.
“We have had so many trials that couldn’t dream of producing a reduction in all-cause mortality. Here we have a trial with a robust, clinically meaningful reduction in all-cause mortality that ultimately demonstrates the benefits outweigh the risks,” he said in an interview.
SPRINT “is a phenomenal breakthrough. It’s data we’ve been awaiting for 20-plus years, to now know that a lower blood pressure target is safe and absolutely essential, and where the benefits outweigh the risks,” Dr. Fonarow said. “Now implementation becomes critical. The SPRINT results are truly practice changing.”
SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: The first full report of results from the SPRINT trial of hypertension treatment targets generated lots of opinions on their implications.
Major finding: Combined cardiovascular events occurred in 5.2% of patients treated to a target systolic blood pressure of less than 120 mm Hg and 6.8% of patients treated to a target of less than 140 mm Hg.
Data source: The multicenter, randomized trial involved 9,361 patients.
Disclosures: SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.
Conservative management for AR safe at 10 years
Whether to operate on patients with severe aortic regurgitation (AR) before or after symptoms appear has been a point of controversy among cardiothoracic surgeons, but a recent study has found that patients who have early surgery may not fare any better for up to 10 years than those who opt for a more conservative “watchful waiting” course of care.
Investigators from Belgium reported results from an analysis of 160 patients in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1100-08). “In asymptomatic severe AR, delaying surgery until the onset of class I/IIa operative triggers is safe, supporting current guidelines,” said Dr. Christophe de Meester and colleagues at the Catholic University of Louvain and St. Luc University Clinic in Brussels.
The goal of the study was to evaluate long-term outcomes and incidence of cardiac complications in patients with severe AR who did not have any signs and symptoms that called for surgery, and who either had surgery early on or entered conservative management and eventually had an operation when signs and symptoms did appear.
The study found that close follow-up and monitoring of patients with severe AR was a cornerstone of successful conservative management. “We found that survival was similar between the two groups,” Dr. De Meester and coauthors said. “Better survival was nonetheless observed in conservatively managed patients with regular as opposed to no or a looser follow-up.”
The most recent European Society of Cardiology (ESC) guidelines and American Heart Association/American College of Cardiology guidelines state that symptomatic severe AR is a class I indication for surgery regardless of left ventricular (LV) systolic function.
However, Dr. De Meester and colleagues said, the timing of that surgery is not so clear-cut. Earlier studies have shown that surgery could be delayed for patients with minimal symptoms, but more recent evidence has suggested the opposite, according to the study. Two factors favor surgery before symptoms arise – poor aortic valve repair outcomes in patients with symptoms of heart failure and long-standing severe AR, which eventually leads to LV dysfunction.
Yet, the latest ESC guidelines have been “reluctant” to make a strong case for early surgery before symptoms of LV dysfunction appear, and the AHA/ACC guidelines call for surgery only when symptoms of LV dysfunction or LV dilatation develop, Dr. de Meester and his coauthors said.
In the past, the risks of aortic valve replacement were too high to consider early surgery, the study authors said. “However, with the advent of aortic valve repair, operative mortality and long-term outcomes have improved to such an extent that early surgery has become a plausible option for patients.”
But the risk of these patients developing symptoms for surgery was nonetheless low over 10 years, the study found: 7.4% for developing severe LV dilatation; 0.6% for becoming symptomatic; and 0.9% for developing LV dysfunction. Overall, the rate of adverse events in the study population was 9.9% at 10 years.
In the study, 69 patients were initially managed conservatively, 49 of whom were in the watchful waiting group that visited a cardiologist at least annually and another 20 considered an “irregular follow-up subgroup.” Among the watchful waiting group, 31 developed symptoms for surgery (only two declined surgery). Watchful waiting patients had five- and 10-year survival of 100% and 95%, respectively, compared with 90% and 79% among those who had irregular follow-up.
Overall, the conservatively managed group had outcomes better than or equal to the early surgery group. Ten-year cardiovascular survival was 96% in both groups, whereas event-free survival was 92% at 10 years in the conservatively managed group vs. 81% in the early surgery group.
The study was supported by the Belgium National Fund for Scientific Research. The authors had no conflicts to disclose.
The design of the Belgium study “challenges” existing treatment guidelines for asymptomatic chronic aortic insufficiency in two ways, Dr. Leora Balsam and Dr. Abe deAndra Jr., both of the New York University-Langone Medical Center, write in their commentary (J Thorac Cardiovasc Surg. 2015;150:1108-10): first, by making aortic valve repair the preferred surgical treatment in the study and, secondly, by offering surgery to both symptomatic and asymptomatic patients.
“In the era of evidence-based medicine,” Dr. Balsam and Dr. deAndra wrote, “there remains a need for research and innovation even in areas where guidelines exist.”
While many authors have described aortic valve repair as an alternative to aortic valve replacement for chronic severe aortic insufficiency, Dr. Balsam and Dr. deAndra explained that the term aortic valve repair “encompasses a wide array of techniques,” among them valve-sparing aortic root replacement, subcommissural annuloplasty and “myriad” leaf resection, plication, and reconstruction techniques. Because of mounting reports of excellent results with aortic valve repair techniques, growing ranks of cardiothoracic surgeons have advocated for repair as an early intervention for aortic valve problems. But the question remains: “Have we identified the optimal triggers for intervention for aortic insufficiency?” they asked. “The answer is probably no, and that newer technology and diagnostic studies will better discriminate between patients that can benefit from intervention and those that will not.”
Dr. Balsam and Dr. deAndra had no disclosures.
The design of the Belgium study “challenges” existing treatment guidelines for asymptomatic chronic aortic insufficiency in two ways, Dr. Leora Balsam and Dr. Abe deAndra Jr., both of the New York University-Langone Medical Center, write in their commentary (J Thorac Cardiovasc Surg. 2015;150:1108-10): first, by making aortic valve repair the preferred surgical treatment in the study and, secondly, by offering surgery to both symptomatic and asymptomatic patients.
“In the era of evidence-based medicine,” Dr. Balsam and Dr. deAndra wrote, “there remains a need for research and innovation even in areas where guidelines exist.”
While many authors have described aortic valve repair as an alternative to aortic valve replacement for chronic severe aortic insufficiency, Dr. Balsam and Dr. deAndra explained that the term aortic valve repair “encompasses a wide array of techniques,” among them valve-sparing aortic root replacement, subcommissural annuloplasty and “myriad” leaf resection, plication, and reconstruction techniques. Because of mounting reports of excellent results with aortic valve repair techniques, growing ranks of cardiothoracic surgeons have advocated for repair as an early intervention for aortic valve problems. But the question remains: “Have we identified the optimal triggers for intervention for aortic insufficiency?” they asked. “The answer is probably no, and that newer technology and diagnostic studies will better discriminate between patients that can benefit from intervention and those that will not.”
Dr. Balsam and Dr. deAndra had no disclosures.
The design of the Belgium study “challenges” existing treatment guidelines for asymptomatic chronic aortic insufficiency in two ways, Dr. Leora Balsam and Dr. Abe deAndra Jr., both of the New York University-Langone Medical Center, write in their commentary (J Thorac Cardiovasc Surg. 2015;150:1108-10): first, by making aortic valve repair the preferred surgical treatment in the study and, secondly, by offering surgery to both symptomatic and asymptomatic patients.
“In the era of evidence-based medicine,” Dr. Balsam and Dr. deAndra wrote, “there remains a need for research and innovation even in areas where guidelines exist.”
While many authors have described aortic valve repair as an alternative to aortic valve replacement for chronic severe aortic insufficiency, Dr. Balsam and Dr. deAndra explained that the term aortic valve repair “encompasses a wide array of techniques,” among them valve-sparing aortic root replacement, subcommissural annuloplasty and “myriad” leaf resection, plication, and reconstruction techniques. Because of mounting reports of excellent results with aortic valve repair techniques, growing ranks of cardiothoracic surgeons have advocated for repair as an early intervention for aortic valve problems. But the question remains: “Have we identified the optimal triggers for intervention for aortic insufficiency?” they asked. “The answer is probably no, and that newer technology and diagnostic studies will better discriminate between patients that can benefit from intervention and those that will not.”
Dr. Balsam and Dr. deAndra had no disclosures.
Whether to operate on patients with severe aortic regurgitation (AR) before or after symptoms appear has been a point of controversy among cardiothoracic surgeons, but a recent study has found that patients who have early surgery may not fare any better for up to 10 years than those who opt for a more conservative “watchful waiting” course of care.
Investigators from Belgium reported results from an analysis of 160 patients in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1100-08). “In asymptomatic severe AR, delaying surgery until the onset of class I/IIa operative triggers is safe, supporting current guidelines,” said Dr. Christophe de Meester and colleagues at the Catholic University of Louvain and St. Luc University Clinic in Brussels.
The goal of the study was to evaluate long-term outcomes and incidence of cardiac complications in patients with severe AR who did not have any signs and symptoms that called for surgery, and who either had surgery early on or entered conservative management and eventually had an operation when signs and symptoms did appear.
The study found that close follow-up and monitoring of patients with severe AR was a cornerstone of successful conservative management. “We found that survival was similar between the two groups,” Dr. De Meester and coauthors said. “Better survival was nonetheless observed in conservatively managed patients with regular as opposed to no or a looser follow-up.”
The most recent European Society of Cardiology (ESC) guidelines and American Heart Association/American College of Cardiology guidelines state that symptomatic severe AR is a class I indication for surgery regardless of left ventricular (LV) systolic function.
However, Dr. De Meester and colleagues said, the timing of that surgery is not so clear-cut. Earlier studies have shown that surgery could be delayed for patients with minimal symptoms, but more recent evidence has suggested the opposite, according to the study. Two factors favor surgery before symptoms arise – poor aortic valve repair outcomes in patients with symptoms of heart failure and long-standing severe AR, which eventually leads to LV dysfunction.
Yet, the latest ESC guidelines have been “reluctant” to make a strong case for early surgery before symptoms of LV dysfunction appear, and the AHA/ACC guidelines call for surgery only when symptoms of LV dysfunction or LV dilatation develop, Dr. de Meester and his coauthors said.
In the past, the risks of aortic valve replacement were too high to consider early surgery, the study authors said. “However, with the advent of aortic valve repair, operative mortality and long-term outcomes have improved to such an extent that early surgery has become a plausible option for patients.”
But the risk of these patients developing symptoms for surgery was nonetheless low over 10 years, the study found: 7.4% for developing severe LV dilatation; 0.6% for becoming symptomatic; and 0.9% for developing LV dysfunction. Overall, the rate of adverse events in the study population was 9.9% at 10 years.
In the study, 69 patients were initially managed conservatively, 49 of whom were in the watchful waiting group that visited a cardiologist at least annually and another 20 considered an “irregular follow-up subgroup.” Among the watchful waiting group, 31 developed symptoms for surgery (only two declined surgery). Watchful waiting patients had five- and 10-year survival of 100% and 95%, respectively, compared with 90% and 79% among those who had irregular follow-up.
Overall, the conservatively managed group had outcomes better than or equal to the early surgery group. Ten-year cardiovascular survival was 96% in both groups, whereas event-free survival was 92% at 10 years in the conservatively managed group vs. 81% in the early surgery group.
The study was supported by the Belgium National Fund for Scientific Research. The authors had no conflicts to disclose.
Whether to operate on patients with severe aortic regurgitation (AR) before or after symptoms appear has been a point of controversy among cardiothoracic surgeons, but a recent study has found that patients who have early surgery may not fare any better for up to 10 years than those who opt for a more conservative “watchful waiting” course of care.
Investigators from Belgium reported results from an analysis of 160 patients in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1100-08). “In asymptomatic severe AR, delaying surgery until the onset of class I/IIa operative triggers is safe, supporting current guidelines,” said Dr. Christophe de Meester and colleagues at the Catholic University of Louvain and St. Luc University Clinic in Brussels.
The goal of the study was to evaluate long-term outcomes and incidence of cardiac complications in patients with severe AR who did not have any signs and symptoms that called for surgery, and who either had surgery early on or entered conservative management and eventually had an operation when signs and symptoms did appear.
The study found that close follow-up and monitoring of patients with severe AR was a cornerstone of successful conservative management. “We found that survival was similar between the two groups,” Dr. De Meester and coauthors said. “Better survival was nonetheless observed in conservatively managed patients with regular as opposed to no or a looser follow-up.”
The most recent European Society of Cardiology (ESC) guidelines and American Heart Association/American College of Cardiology guidelines state that symptomatic severe AR is a class I indication for surgery regardless of left ventricular (LV) systolic function.
However, Dr. De Meester and colleagues said, the timing of that surgery is not so clear-cut. Earlier studies have shown that surgery could be delayed for patients with minimal symptoms, but more recent evidence has suggested the opposite, according to the study. Two factors favor surgery before symptoms arise – poor aortic valve repair outcomes in patients with symptoms of heart failure and long-standing severe AR, which eventually leads to LV dysfunction.
Yet, the latest ESC guidelines have been “reluctant” to make a strong case for early surgery before symptoms of LV dysfunction appear, and the AHA/ACC guidelines call for surgery only when symptoms of LV dysfunction or LV dilatation develop, Dr. de Meester and his coauthors said.
In the past, the risks of aortic valve replacement were too high to consider early surgery, the study authors said. “However, with the advent of aortic valve repair, operative mortality and long-term outcomes have improved to such an extent that early surgery has become a plausible option for patients.”
But the risk of these patients developing symptoms for surgery was nonetheless low over 10 years, the study found: 7.4% for developing severe LV dilatation; 0.6% for becoming symptomatic; and 0.9% for developing LV dysfunction. Overall, the rate of adverse events in the study population was 9.9% at 10 years.
In the study, 69 patients were initially managed conservatively, 49 of whom were in the watchful waiting group that visited a cardiologist at least annually and another 20 considered an “irregular follow-up subgroup.” Among the watchful waiting group, 31 developed symptoms for surgery (only two declined surgery). Watchful waiting patients had five- and 10-year survival of 100% and 95%, respectively, compared with 90% and 79% among those who had irregular follow-up.
Overall, the conservatively managed group had outcomes better than or equal to the early surgery group. Ten-year cardiovascular survival was 96% in both groups, whereas event-free survival was 92% at 10 years in the conservatively managed group vs. 81% in the early surgery group.
The study was supported by the Belgium National Fund for Scientific Research. The authors had no conflicts to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Delaying surgery until the onset of symptoms of aortic insufficiency is safe, in support of current clinical guidelines.
Major finding: Ten-year cardiovascular survival was equal among conservatively managed and early-surgery groups, but event free survival was 92% at 10 years in the conservatively managed group vs. 81% in the early surgery group.
Data source: Analysis of 160 consecutive asymptomatic patients with severe aortic regurgitation who were assigned to either conservative management or early surgery and followed up for a median of 7.2 years.
Disclosures: The Belgium National Fund of Scientific Research supported the study. The authors had no disclosures.
CHEST: Catheter-directed thrombolysis shows pulmonary embolism efficacy
MONTREAL – Catheter-directed thrombolysis surpassed systemic thrombolysis for minimizing in-hospital mortality of patients with an acute pulmonary embolism in a review of more than 1,500 U.S. patients.
The review also found evidence that U.S. pulmonary embolism (PE) patients increasingly undergo catheter-directed thrombolysis, with usage jumping by more than 50% from 2010 to 2012, although in 2012 U.S. clinicians performed catheter-directed thrombolysis on 160 patients with an acute pulmonary embolism (PE) who were included in a national U.S. registry of hospitalized patients, Dr. Amina Saqib said at the annual meeting of the American College of Chest Physicians.
Catheter-directed thrombolysis resulted in a 9% in-hospital mortality rate and a 10% combined rate of in-hospital mortality plus intracerebral hemorrhages, rates significantly below those tallied in propensity score–matched patients who underwent systemic thrombolysis of their acute PE. The matched group with systemic thrombolysis had a 17% in-hospital mortality rate and a 17% combined mortality plus intracerebral hemorrhage rate, said Dr. Saqib, a researcher at Staten Island (N.Y.) University Hospital.
“To the best of our knowledge, this is the first, large, nationwide, observational study that compared safety and efficacy outcomes between systemic thrombolysis and catheter-directed thrombolysis in acute PE,” Dr. Saqib said.
The U.S. data, collected during 2010-2012, also showed that, after adjustment for clinical and demographic variables, each acute PE treatment by catheter-directed thrombolysis cost an average $9,428 above the cost for systemic thrombolysis, she said.
“We need to more systematically identify the patients with an acute PE who could benefit from catheter-directed thrombolysis, especially patients with a massive PE,” commented Dr. Muthiah P. Muthiah, a critical-care medicine physician at the University of Tennessee Health Science Center in Memphis. “This may be something to offer to patients who have an absolute contraindication for systemic thrombolysis, such as recent surgery, but it is not available everywhere,” Dr. Muthiah said in an interview.
Dr. Saqib and her associates used data collected by the Federal National Inpatient Sample. Among U.S. patients hospitalized during 2010-2012 and entered into this database, they identified 1,169 adult acute PE patients who underwent systemic thrombolysis and 352 patients who received catheter-directed thrombolysis. The patients averaged about 58 years old and just under half were men.
The propensity score–adjusted analysis also showed no statistically significant difference between the two treatment approaches for the incidence of intracerebral hemorrhage, any hemorrhages requiring a transfusion, new-onset acute renal failure, or hospital length of stay. Among the patients treated by catheter-directed thrombolysis, all the intracerebral hemorrhages occurred during 2010; during 2011 and 2012 none of the patients treated this way had an intracerebral hemorrhage, Dr. Saqib noted.
Although the findings were consistent with results from prior analyses, the propensity-score adjustment used in the current study cannot fully account for all unmeasured confounding factors. The best way to compare catheter-directed thrombolysis and systemic thrombolysis for treating acute PE would be in a prospective, randomized study, Dr. Saqib said.
Dr. Saqib and Dr. Muthiah had no disclosures.
On Twitter @mitchelzoler
MONTREAL – Catheter-directed thrombolysis surpassed systemic thrombolysis for minimizing in-hospital mortality of patients with an acute pulmonary embolism in a review of more than 1,500 U.S. patients.
The review also found evidence that U.S. pulmonary embolism (PE) patients increasingly undergo catheter-directed thrombolysis, with usage jumping by more than 50% from 2010 to 2012, although in 2012 U.S. clinicians performed catheter-directed thrombolysis on 160 patients with an acute pulmonary embolism (PE) who were included in a national U.S. registry of hospitalized patients, Dr. Amina Saqib said at the annual meeting of the American College of Chest Physicians.
Catheter-directed thrombolysis resulted in a 9% in-hospital mortality rate and a 10% combined rate of in-hospital mortality plus intracerebral hemorrhages, rates significantly below those tallied in propensity score–matched patients who underwent systemic thrombolysis of their acute PE. The matched group with systemic thrombolysis had a 17% in-hospital mortality rate and a 17% combined mortality plus intracerebral hemorrhage rate, said Dr. Saqib, a researcher at Staten Island (N.Y.) University Hospital.
“To the best of our knowledge, this is the first, large, nationwide, observational study that compared safety and efficacy outcomes between systemic thrombolysis and catheter-directed thrombolysis in acute PE,” Dr. Saqib said.
The U.S. data, collected during 2010-2012, also showed that, after adjustment for clinical and demographic variables, each acute PE treatment by catheter-directed thrombolysis cost an average $9,428 above the cost for systemic thrombolysis, she said.
“We need to more systematically identify the patients with an acute PE who could benefit from catheter-directed thrombolysis, especially patients with a massive PE,” commented Dr. Muthiah P. Muthiah, a critical-care medicine physician at the University of Tennessee Health Science Center in Memphis. “This may be something to offer to patients who have an absolute contraindication for systemic thrombolysis, such as recent surgery, but it is not available everywhere,” Dr. Muthiah said in an interview.
Dr. Saqib and her associates used data collected by the Federal National Inpatient Sample. Among U.S. patients hospitalized during 2010-2012 and entered into this database, they identified 1,169 adult acute PE patients who underwent systemic thrombolysis and 352 patients who received catheter-directed thrombolysis. The patients averaged about 58 years old and just under half were men.
The propensity score–adjusted analysis also showed no statistically significant difference between the two treatment approaches for the incidence of intracerebral hemorrhage, any hemorrhages requiring a transfusion, new-onset acute renal failure, or hospital length of stay. Among the patients treated by catheter-directed thrombolysis, all the intracerebral hemorrhages occurred during 2010; during 2011 and 2012 none of the patients treated this way had an intracerebral hemorrhage, Dr. Saqib noted.
Although the findings were consistent with results from prior analyses, the propensity-score adjustment used in the current study cannot fully account for all unmeasured confounding factors. The best way to compare catheter-directed thrombolysis and systemic thrombolysis for treating acute PE would be in a prospective, randomized study, Dr. Saqib said.
Dr. Saqib and Dr. Muthiah had no disclosures.
On Twitter @mitchelzoler
MONTREAL – Catheter-directed thrombolysis surpassed systemic thrombolysis for minimizing in-hospital mortality of patients with an acute pulmonary embolism in a review of more than 1,500 U.S. patients.
The review also found evidence that U.S. pulmonary embolism (PE) patients increasingly undergo catheter-directed thrombolysis, with usage jumping by more than 50% from 2010 to 2012, although in 2012 U.S. clinicians performed catheter-directed thrombolysis on 160 patients with an acute pulmonary embolism (PE) who were included in a national U.S. registry of hospitalized patients, Dr. Amina Saqib said at the annual meeting of the American College of Chest Physicians.
Catheter-directed thrombolysis resulted in a 9% in-hospital mortality rate and a 10% combined rate of in-hospital mortality plus intracerebral hemorrhages, rates significantly below those tallied in propensity score–matched patients who underwent systemic thrombolysis of their acute PE. The matched group with systemic thrombolysis had a 17% in-hospital mortality rate and a 17% combined mortality plus intracerebral hemorrhage rate, said Dr. Saqib, a researcher at Staten Island (N.Y.) University Hospital.
“To the best of our knowledge, this is the first, large, nationwide, observational study that compared safety and efficacy outcomes between systemic thrombolysis and catheter-directed thrombolysis in acute PE,” Dr. Saqib said.
The U.S. data, collected during 2010-2012, also showed that, after adjustment for clinical and demographic variables, each acute PE treatment by catheter-directed thrombolysis cost an average $9,428 above the cost for systemic thrombolysis, she said.
“We need to more systematically identify the patients with an acute PE who could benefit from catheter-directed thrombolysis, especially patients with a massive PE,” commented Dr. Muthiah P. Muthiah, a critical-care medicine physician at the University of Tennessee Health Science Center in Memphis. “This may be something to offer to patients who have an absolute contraindication for systemic thrombolysis, such as recent surgery, but it is not available everywhere,” Dr. Muthiah said in an interview.
Dr. Saqib and her associates used data collected by the Federal National Inpatient Sample. Among U.S. patients hospitalized during 2010-2012 and entered into this database, they identified 1,169 adult acute PE patients who underwent systemic thrombolysis and 352 patients who received catheter-directed thrombolysis. The patients averaged about 58 years old and just under half were men.
The propensity score–adjusted analysis also showed no statistically significant difference between the two treatment approaches for the incidence of intracerebral hemorrhage, any hemorrhages requiring a transfusion, new-onset acute renal failure, or hospital length of stay. Among the patients treated by catheter-directed thrombolysis, all the intracerebral hemorrhages occurred during 2010; during 2011 and 2012 none of the patients treated this way had an intracerebral hemorrhage, Dr. Saqib noted.
Although the findings were consistent with results from prior analyses, the propensity-score adjustment used in the current study cannot fully account for all unmeasured confounding factors. The best way to compare catheter-directed thrombolysis and systemic thrombolysis for treating acute PE would be in a prospective, randomized study, Dr. Saqib said.
Dr. Saqib and Dr. Muthiah had no disclosures.
On Twitter @mitchelzoler
AT CHEST 2015
Key clinical point: Catheter-directed thrombolysis was linked to reduced mortality, compared with systemic thrombolysis in patients with an acute pulmonary embolism.
Major finding: In-hospital mortality in acute pulmonary embolism patients ran 10% with catheter-directed thrombolysis and 17% with systemic thrombolysis.
Data source: Review of 1,521 U.S. patients treated for acute pulmonary embolism during 2010-2012 in the National Inpatient Sample.
Disclosures: Dr. Saqib and Dr. Muthiah had no disclosures.
Does LVAD inhibit cardio protection?
Placement of a left ventricular assist device (LVAD) after a heart attack has been found to suppress certain cellular signaling pathways that protect coronary tissue, but at the same time LVAD placement seemed to help normalize other protective properties in areas of the heart closest to the infarcted region, investigators reported in a recent study.
The findings could have implications in determining the best method for unloading and other medical therapies in the aftermath of a heart attack, Dr. Keshava Rajagopal of the University of Texas, Houston, and associates reported in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1332-41).
To study the effect of LVAD on cardiac tissue, the investigators induced myocardial infarction in sheep and then placed the animals on LVAD support for 2 weeks. After 10 more weeks of observation, the investigators harvested and analyzed the myocardial specimens. The principal goal of the study was to investigate how heart attack and subsequent short-term mechanical support of the left ventricle can influence signaling controlled by the protein beta-arrestin.
They found that an infarction of myocardial tissue caused activation of the beta-arrestin protein that regulates cellular pathways that can benefit cardiac cells. At the same time, LVAD support inhibited beta-arrestin activation, specifically in regulating pathways of two cardioprotective proteins: Akt, also called protein kinase B (PKB), and, to a lesser extent, ERK-1 and -2.
They also found that MI resulted in regional activation of load-induced signaling of cardiac G protein-coupled receptor (GPCR) via G proteins.
“These studies demonstrate that small platform catheter-based LVAD support exerts suppressive effects on cardioprotective beta-arrestin–mediated signal transduction, while normalizing the signaling networks of G-alpha-q–coupled cardiac GPCRS in the MI-adjacent zone,” Dr. Rajagopal and colleagues said.
They acknowledged that further studies are needed to better understand the roles that specific GPCRs in beta-arrestin–regulated signaling play in left ventricle dysfunction after a heart attack and to help define the optimal timing for LVAD based on signaling and genetic markers along with standard LV functional endpoints.
The authors had no disclosures.
The University of Maryland investigators in this study have joined the ranks of other investigators who have begun to unravel the consequences of mechanical unloading at the cellular level as well as its effect on the heart’s ability to handle calcium after infarction, Dr. William Hiesinger and Dr. Pavan Atluri of the University of Pennsylvania wrote in their invited commentary (J Thorac Cardiovasc Surg. 2015;150:1342-3).
“More broadly, these investigations are building the foundation of what will likely be the best platform for an efficacious bridge to recovery: multimodal therapy utilizing the titration of mechanical myocardial unloading,” they said. Dr. Hiesinger and Dr. Atluri commented on the limitations of the University of Maryland study, namely its small sample size and narrow scope. “This is, however, reflective more of the amazing complexity of the biologic and mechanical interactions between the heart and VAD and the need for further investigations of this kind than the quality of the research,” they said.
Understanding the molecular basis and metabolic function cardiac dysfunction after a heart attack is in the “nascent stages,” and even less is known about the effect ventricular loading has on these pathways, Dr. Hiesinger and Dr. Atluri said. “This study offers a concrete platform for both specific treatment and further study,” they wrote.
The University of Maryland investigators in this study have joined the ranks of other investigators who have begun to unravel the consequences of mechanical unloading at the cellular level as well as its effect on the heart’s ability to handle calcium after infarction, Dr. William Hiesinger and Dr. Pavan Atluri of the University of Pennsylvania wrote in their invited commentary (J Thorac Cardiovasc Surg. 2015;150:1342-3).
“More broadly, these investigations are building the foundation of what will likely be the best platform for an efficacious bridge to recovery: multimodal therapy utilizing the titration of mechanical myocardial unloading,” they said. Dr. Hiesinger and Dr. Atluri commented on the limitations of the University of Maryland study, namely its small sample size and narrow scope. “This is, however, reflective more of the amazing complexity of the biologic and mechanical interactions between the heart and VAD and the need for further investigations of this kind than the quality of the research,” they said.
Understanding the molecular basis and metabolic function cardiac dysfunction after a heart attack is in the “nascent stages,” and even less is known about the effect ventricular loading has on these pathways, Dr. Hiesinger and Dr. Atluri said. “This study offers a concrete platform for both specific treatment and further study,” they wrote.
The University of Maryland investigators in this study have joined the ranks of other investigators who have begun to unravel the consequences of mechanical unloading at the cellular level as well as its effect on the heart’s ability to handle calcium after infarction, Dr. William Hiesinger and Dr. Pavan Atluri of the University of Pennsylvania wrote in their invited commentary (J Thorac Cardiovasc Surg. 2015;150:1342-3).
“More broadly, these investigations are building the foundation of what will likely be the best platform for an efficacious bridge to recovery: multimodal therapy utilizing the titration of mechanical myocardial unloading,” they said. Dr. Hiesinger and Dr. Atluri commented on the limitations of the University of Maryland study, namely its small sample size and narrow scope. “This is, however, reflective more of the amazing complexity of the biologic and mechanical interactions between the heart and VAD and the need for further investigations of this kind than the quality of the research,” they said.
Understanding the molecular basis and metabolic function cardiac dysfunction after a heart attack is in the “nascent stages,” and even less is known about the effect ventricular loading has on these pathways, Dr. Hiesinger and Dr. Atluri said. “This study offers a concrete platform for both specific treatment and further study,” they wrote.
Placement of a left ventricular assist device (LVAD) after a heart attack has been found to suppress certain cellular signaling pathways that protect coronary tissue, but at the same time LVAD placement seemed to help normalize other protective properties in areas of the heart closest to the infarcted region, investigators reported in a recent study.
The findings could have implications in determining the best method for unloading and other medical therapies in the aftermath of a heart attack, Dr. Keshava Rajagopal of the University of Texas, Houston, and associates reported in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1332-41).
To study the effect of LVAD on cardiac tissue, the investigators induced myocardial infarction in sheep and then placed the animals on LVAD support for 2 weeks. After 10 more weeks of observation, the investigators harvested and analyzed the myocardial specimens. The principal goal of the study was to investigate how heart attack and subsequent short-term mechanical support of the left ventricle can influence signaling controlled by the protein beta-arrestin.
They found that an infarction of myocardial tissue caused activation of the beta-arrestin protein that regulates cellular pathways that can benefit cardiac cells. At the same time, LVAD support inhibited beta-arrestin activation, specifically in regulating pathways of two cardioprotective proteins: Akt, also called protein kinase B (PKB), and, to a lesser extent, ERK-1 and -2.
They also found that MI resulted in regional activation of load-induced signaling of cardiac G protein-coupled receptor (GPCR) via G proteins.
“These studies demonstrate that small platform catheter-based LVAD support exerts suppressive effects on cardioprotective beta-arrestin–mediated signal transduction, while normalizing the signaling networks of G-alpha-q–coupled cardiac GPCRS in the MI-adjacent zone,” Dr. Rajagopal and colleagues said.
They acknowledged that further studies are needed to better understand the roles that specific GPCRs in beta-arrestin–regulated signaling play in left ventricle dysfunction after a heart attack and to help define the optimal timing for LVAD based on signaling and genetic markers along with standard LV functional endpoints.
The authors had no disclosures.
Placement of a left ventricular assist device (LVAD) after a heart attack has been found to suppress certain cellular signaling pathways that protect coronary tissue, but at the same time LVAD placement seemed to help normalize other protective properties in areas of the heart closest to the infarcted region, investigators reported in a recent study.
The findings could have implications in determining the best method for unloading and other medical therapies in the aftermath of a heart attack, Dr. Keshava Rajagopal of the University of Texas, Houston, and associates reported in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1332-41).
To study the effect of LVAD on cardiac tissue, the investigators induced myocardial infarction in sheep and then placed the animals on LVAD support for 2 weeks. After 10 more weeks of observation, the investigators harvested and analyzed the myocardial specimens. The principal goal of the study was to investigate how heart attack and subsequent short-term mechanical support of the left ventricle can influence signaling controlled by the protein beta-arrestin.
They found that an infarction of myocardial tissue caused activation of the beta-arrestin protein that regulates cellular pathways that can benefit cardiac cells. At the same time, LVAD support inhibited beta-arrestin activation, specifically in regulating pathways of two cardioprotective proteins: Akt, also called protein kinase B (PKB), and, to a lesser extent, ERK-1 and -2.
They also found that MI resulted in regional activation of load-induced signaling of cardiac G protein-coupled receptor (GPCR) via G proteins.
“These studies demonstrate that small platform catheter-based LVAD support exerts suppressive effects on cardioprotective beta-arrestin–mediated signal transduction, while normalizing the signaling networks of G-alpha-q–coupled cardiac GPCRS in the MI-adjacent zone,” Dr. Rajagopal and colleagues said.
They acknowledged that further studies are needed to better understand the roles that specific GPCRs in beta-arrestin–regulated signaling play in left ventricle dysfunction after a heart attack and to help define the optimal timing for LVAD based on signaling and genetic markers along with standard LV functional endpoints.
The authors had no disclosures.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Left ventricular assist device (LVAD) support inhibits pathologic responses to mechanical loading but also can inhibit adaptive responses after myocardial infarction.
Major finding: LVAD support inhibited cardioprotective beta-arrestin–mediated signaling, but net benefits of normalization of load-induced G protein-coupled receptor (GPCR) signaling were observed in the MI-adjacent zone.
Data source: Sheep were induced with myocardial infarction and then placed on LVAD support for 2 weeks and observed for a total of 12 weeks. Then myocardial specimens were harvested and analyzed.
Disclosures: The study authors had no relationships to disclose.
Hybrid revascularization shows promise, but there are concerns
A hybrid coronary revascularization procedure that combines off-pump left internal mammary artery (LIMA) grafting with percutaneous coronary intervention (PCI) showed good results at 1 year after surgery, but nonetheless showed a rate of adverse events that may raise questions about the procedure.
In a study published in the November issue of the Journal of Thoracic and Cardiovascular Surgery, a team of investigators from Aarhus University Hospital in Denmark reported high rates of graft patency and low rates of death and stroke with the procedure 1 year after a series of 100 operations (J Thorac Cardiovasc Surg. 2015;150:1181-6).
“The high left internal mammary artery graft patency rate and low risk of death and stroke at 1 year seem promising for the long-term outcome of this revascularization strategy,” said Dr. Ivy Susanne Modrau and colleagues.
The single-center study evaluated 1-year clinical and angiographic results of 100 consecutive trial patients with multivessel disease who had the hybrid procedure between October 2010 and February 2012. “The rationale of hybrid coronary revascularization is to achieve the survival benefits of the LIMA to LAD (left anterior descending artery) graft with reduced invasiveness to minimize postprocedural discomfort and morbidity, in particular the risk of stroke,” Dr. Modrau and colleagues said.
The study used the LIMA to LAD graft performed off-pump through a reversed J-hemisternotomy “We chose this technique because of its excellent exposure of the heart, technical ease, low risk of complicating chronic pain, and applicability in virtually all patients,” Dr. Modrau said. Eighty-nine patients had surgery prior to PCI and 11 had PCI prior to surgery.
The primary endpoint was rate of major adverse cardiac or cerebrovascular events (MACCE), the composite of all-cause death, stroke, myocardial infarction, and repeat revascularization by PCI or coronary artery bypass grafting at 1 year. Secondary endpoints included individual components and status of stent and graft patency on angiography.
Overall, 20 patients met the 1-year primary endpoint of MACCE. One patient died, one other had a stroke, and three had heart attacks. Sixteen patients had repeat revascularization procedures, eight performed during the index hospitalization. Graft patency was 98% after 1 year.
Dr. Modrau and coauthors noted the MACCE rate of 20% “was higher than expected,” and certainly higher than results in the SYNTAX study (17.8% in the PCI group and 12.4% in the coronary artery bypass grafting [CABG] group) (Euro. Intervention. 2015;10:e1-e6). One possible reason the Danish investigators cited for higher than expected MACCE rates was that they may be attributed to the learning curve involved with LIMA grafting and the use of early angiography possibly revealing “clinically silent LIMA graft dysfunction due to technical errors.”
The number of repeat revascularizations in the study was more in line with the SYNTAX study: 7% in the Aarhus University study and 6% in the SYNTAX CABG group. However, a meta-analysis of six studies with 1,190 patients reported 1-year repeat revascularization rates of 3.8% after a hybrid procedure and 1.4% after CABG (Am Heart J. 2014;167:585-92).
Ultimately, the safety and efficacy of the hybrid revascularization approach will require long-term follow-up data and head-to-head comparison with conventional CABG and PCI in clinical trials. “Meanwhile, LIMA patency, the cornerstone of surgical revascularization, may be used as a surrogate endpoint for long-term survival after HCR,” Dr. Modrau and coauthors said.
They reported having no disclosures.
Hybrid revascularization procedures are “still not ready for prime time,” Dr. Carlos Mestres of Cleveland Clinic Abu Dhabi, United Arab Emirates, said in his invited commentary (J Thorac Cardiovasc Surg. 2015;150:1028-9).
The study illuminates two key points of concern, Dr. Mestres said: the “unexpectedly high” 20% rate of major adverse cardiac or cerebrovascular events (MACCE); and the in-hospital revascularization rate that was significantly higher than the 1% after CABG that the authors reported in their own institution. That calls into question the reason the investigators would change their own department strategy away from conventional CABG, where they had optimal results, he said.
Dr. Mestres also said the Danish investigators’ conclusion that the study results seemed promising for long-term outcomes of the hybrid procedure “are to be carefully dissected.”
He commended the investigators for collecting angiographic data at 1 year, but said that 1 year of follow-up “is simply not enough” to credibly compare staged procedures with CABG.
Dr. Mestres had no disclosures.
Hybrid revascularization procedures are “still not ready for prime time,” Dr. Carlos Mestres of Cleveland Clinic Abu Dhabi, United Arab Emirates, said in his invited commentary (J Thorac Cardiovasc Surg. 2015;150:1028-9).
The study illuminates two key points of concern, Dr. Mestres said: the “unexpectedly high” 20% rate of major adverse cardiac or cerebrovascular events (MACCE); and the in-hospital revascularization rate that was significantly higher than the 1% after CABG that the authors reported in their own institution. That calls into question the reason the investigators would change their own department strategy away from conventional CABG, where they had optimal results, he said.
Dr. Mestres also said the Danish investigators’ conclusion that the study results seemed promising for long-term outcomes of the hybrid procedure “are to be carefully dissected.”
He commended the investigators for collecting angiographic data at 1 year, but said that 1 year of follow-up “is simply not enough” to credibly compare staged procedures with CABG.
Dr. Mestres had no disclosures.
Hybrid revascularization procedures are “still not ready for prime time,” Dr. Carlos Mestres of Cleveland Clinic Abu Dhabi, United Arab Emirates, said in his invited commentary (J Thorac Cardiovasc Surg. 2015;150:1028-9).
The study illuminates two key points of concern, Dr. Mestres said: the “unexpectedly high” 20% rate of major adverse cardiac or cerebrovascular events (MACCE); and the in-hospital revascularization rate that was significantly higher than the 1% after CABG that the authors reported in their own institution. That calls into question the reason the investigators would change their own department strategy away from conventional CABG, where they had optimal results, he said.
Dr. Mestres also said the Danish investigators’ conclusion that the study results seemed promising for long-term outcomes of the hybrid procedure “are to be carefully dissected.”
He commended the investigators for collecting angiographic data at 1 year, but said that 1 year of follow-up “is simply not enough” to credibly compare staged procedures with CABG.
Dr. Mestres had no disclosures.
A hybrid coronary revascularization procedure that combines off-pump left internal mammary artery (LIMA) grafting with percutaneous coronary intervention (PCI) showed good results at 1 year after surgery, but nonetheless showed a rate of adverse events that may raise questions about the procedure.
In a study published in the November issue of the Journal of Thoracic and Cardiovascular Surgery, a team of investigators from Aarhus University Hospital in Denmark reported high rates of graft patency and low rates of death and stroke with the procedure 1 year after a series of 100 operations (J Thorac Cardiovasc Surg. 2015;150:1181-6).
“The high left internal mammary artery graft patency rate and low risk of death and stroke at 1 year seem promising for the long-term outcome of this revascularization strategy,” said Dr. Ivy Susanne Modrau and colleagues.
The single-center study evaluated 1-year clinical and angiographic results of 100 consecutive trial patients with multivessel disease who had the hybrid procedure between October 2010 and February 2012. “The rationale of hybrid coronary revascularization is to achieve the survival benefits of the LIMA to LAD (left anterior descending artery) graft with reduced invasiveness to minimize postprocedural discomfort and morbidity, in particular the risk of stroke,” Dr. Modrau and colleagues said.
The study used the LIMA to LAD graft performed off-pump through a reversed J-hemisternotomy “We chose this technique because of its excellent exposure of the heart, technical ease, low risk of complicating chronic pain, and applicability in virtually all patients,” Dr. Modrau said. Eighty-nine patients had surgery prior to PCI and 11 had PCI prior to surgery.
The primary endpoint was rate of major adverse cardiac or cerebrovascular events (MACCE), the composite of all-cause death, stroke, myocardial infarction, and repeat revascularization by PCI or coronary artery bypass grafting at 1 year. Secondary endpoints included individual components and status of stent and graft patency on angiography.
Overall, 20 patients met the 1-year primary endpoint of MACCE. One patient died, one other had a stroke, and three had heart attacks. Sixteen patients had repeat revascularization procedures, eight performed during the index hospitalization. Graft patency was 98% after 1 year.
Dr. Modrau and coauthors noted the MACCE rate of 20% “was higher than expected,” and certainly higher than results in the SYNTAX study (17.8% in the PCI group and 12.4% in the coronary artery bypass grafting [CABG] group) (Euro. Intervention. 2015;10:e1-e6). One possible reason the Danish investigators cited for higher than expected MACCE rates was that they may be attributed to the learning curve involved with LIMA grafting and the use of early angiography possibly revealing “clinically silent LIMA graft dysfunction due to technical errors.”
The number of repeat revascularizations in the study was more in line with the SYNTAX study: 7% in the Aarhus University study and 6% in the SYNTAX CABG group. However, a meta-analysis of six studies with 1,190 patients reported 1-year repeat revascularization rates of 3.8% after a hybrid procedure and 1.4% after CABG (Am Heart J. 2014;167:585-92).
Ultimately, the safety and efficacy of the hybrid revascularization approach will require long-term follow-up data and head-to-head comparison with conventional CABG and PCI in clinical trials. “Meanwhile, LIMA patency, the cornerstone of surgical revascularization, may be used as a surrogate endpoint for long-term survival after HCR,” Dr. Modrau and coauthors said.
They reported having no disclosures.
A hybrid coronary revascularization procedure that combines off-pump left internal mammary artery (LIMA) grafting with percutaneous coronary intervention (PCI) showed good results at 1 year after surgery, but nonetheless showed a rate of adverse events that may raise questions about the procedure.
In a study published in the November issue of the Journal of Thoracic and Cardiovascular Surgery, a team of investigators from Aarhus University Hospital in Denmark reported high rates of graft patency and low rates of death and stroke with the procedure 1 year after a series of 100 operations (J Thorac Cardiovasc Surg. 2015;150:1181-6).
“The high left internal mammary artery graft patency rate and low risk of death and stroke at 1 year seem promising for the long-term outcome of this revascularization strategy,” said Dr. Ivy Susanne Modrau and colleagues.
The single-center study evaluated 1-year clinical and angiographic results of 100 consecutive trial patients with multivessel disease who had the hybrid procedure between October 2010 and February 2012. “The rationale of hybrid coronary revascularization is to achieve the survival benefits of the LIMA to LAD (left anterior descending artery) graft with reduced invasiveness to minimize postprocedural discomfort and morbidity, in particular the risk of stroke,” Dr. Modrau and colleagues said.
The study used the LIMA to LAD graft performed off-pump through a reversed J-hemisternotomy “We chose this technique because of its excellent exposure of the heart, technical ease, low risk of complicating chronic pain, and applicability in virtually all patients,” Dr. Modrau said. Eighty-nine patients had surgery prior to PCI and 11 had PCI prior to surgery.
The primary endpoint was rate of major adverse cardiac or cerebrovascular events (MACCE), the composite of all-cause death, stroke, myocardial infarction, and repeat revascularization by PCI or coronary artery bypass grafting at 1 year. Secondary endpoints included individual components and status of stent and graft patency on angiography.
Overall, 20 patients met the 1-year primary endpoint of MACCE. One patient died, one other had a stroke, and three had heart attacks. Sixteen patients had repeat revascularization procedures, eight performed during the index hospitalization. Graft patency was 98% after 1 year.
Dr. Modrau and coauthors noted the MACCE rate of 20% “was higher than expected,” and certainly higher than results in the SYNTAX study (17.8% in the PCI group and 12.4% in the coronary artery bypass grafting [CABG] group) (Euro. Intervention. 2015;10:e1-e6). One possible reason the Danish investigators cited for higher than expected MACCE rates was that they may be attributed to the learning curve involved with LIMA grafting and the use of early angiography possibly revealing “clinically silent LIMA graft dysfunction due to technical errors.”
The number of repeat revascularizations in the study was more in line with the SYNTAX study: 7% in the Aarhus University study and 6% in the SYNTAX CABG group. However, a meta-analysis of six studies with 1,190 patients reported 1-year repeat revascularization rates of 3.8% after a hybrid procedure and 1.4% after CABG (Am Heart J. 2014;167:585-92).
Ultimately, the safety and efficacy of the hybrid revascularization approach will require long-term follow-up data and head-to-head comparison with conventional CABG and PCI in clinical trials. “Meanwhile, LIMA patency, the cornerstone of surgical revascularization, may be used as a surrogate endpoint for long-term survival after HCR,” Dr. Modrau and coauthors said.
They reported having no disclosures.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point:High 1-year left internal mammary artery (LIMA) graft patency and low risk of death and stroke seem promising for long-term outcome after HCR.
Major finding: At 1 year, 98% of patients had patent LIMA grafts but the 20% rate of major adverse cardiac or cerebrovascular events was “higher than expected.”
Data source: Prospective single arm clinical feasibility study including 100 consecutive patients with multivessel disease undergoing staged hybrid coronary revascularization.
Disclosures: The study authors had no disclosures.
Stem cell benefits endure 3 years in infants
Infants with congenital heart disease, specifically left heart syndrome, who had cardiac stem-cell therapy after surgery showed improved cardiac and brain function after 3 years when compared with infants who had standard therapy, according to latest results from a clinical trial of progenitor cell infusion in infants.
The prospective, controlled study, published in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150[5]:1198-1208), involved 14 infants with hypoplastic left heart syndrome (HLHS). Dr. Suguru Tarui and colleagues at Okayama University Hospital in Japan infused seven infants with intracoronary cardiosphere-derived cells (CDCs) 1 month after they had two- or three-stage palliative surgery. Seven controls had standard care alone. The trial is known TICAP (Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology) (ClinicalTrials.gov ID: NCT01273857).
Infants born with HLHS are known to have poor prognoses. HLHS has been associated with the highest mortality of all congenital heart lesions (Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2015;18[1]:2-6).
The Okayama investigators conducted TICAP in 2011 and demonstrated the feasibility and safety of the intracoronary delivery of CDCs in infants with HLHS after staged procedures. The latest report looks at the secondary outcome of cardiac function through 36 months of follow-up, and is the first clinical trial to report on the mid-term results of cardiac progenitor therapy in congenital heart disease.
“CDC infusion could improve right ventricular function from 3 through 36 months of observation,” Dr. Tarui and colleagues said. “Patients treated by CDCs showed an increase in somatic growth and reduced heart failure status in mid-term follow-up.”
Upon entry into the study, all subjects were of similar age, body weight, and risk profiles. After 36 months, the CDC group showed no complications and significantly improved right ventricular injection fraction compared with controls. As a result, the CDC group had reduced brain natriuretic peptide levels, lower rates of unplanned catheterizations, and higher weight for age. No adverse events occurred in the CDC group, while two patients in the control group had complications (one developed heart failure, another developed enteropathy).
The investigators looked at predictors of cardiac functional efficacy in the CDC group and determined that younger age was associated with greater improvement of right ventricular ejection fraction, as measured on echocardiography. The lower weight-for-age Z score and reduced ejection fraction at the time of infusion may be predictors of cardiac function improvements at 3 years.
“This therapeutic strategy may merit somatic growth enhancement and reduce the incidence of heart failure,” Dr. Tarui and coauthors said.
They noted a number of limitations of their small clinical trial. The study was nonrandomized, and the cardiac interventions were not blinded, among others. “Larger phase II studies focusing on changes in cardiac function, myocardial fibrosis, and quality of life and clinical event rates are warranted to confirm these effects of CDC administration in patients with single ventricular physiology,” they said.
The government of Japan through its ministries of Health, Labor and Welfare, and Education, Culture Sports, Science and Technology provided funding for the study, as did the Research Foundation of Okayama University Hospital. The authors had no disclosures.
The benefits of stem cell treatments for cardiac function beyond the initial follow-up period have “remained an unanswered question,” Dr. Sunjay Kaushal of University of Maryland, Baltimore, said in his invited commentary (J Thorac Cardiovasc Surg. 2015;150[5]:1209-11). “The 3-year follow-up data from the TICAP trial, therefore, offers one of the first opportunities to examine the durability of the outcomes found in stem cell-treated patients,” Dr. Kaushal said.
While TICAP provides clues into independent predictors of success with stem cell treatments, the small study population of seven patients makes it difficult to confirm those predictors, he said. “Multivariate analysis of results from future trials with larger sample size will be needed to verify these preliminary findings,” he noted.
Nonetheless, the study adds to the emerging evidence that younger, sicker patients may respond better to stem cell infusion, a concept Dr. Kaushal termed “intriguing.”
“Meanwhile, the TICAP trial and its three-year follow-up should garner enthusiasm for stem cell therapy, and establish the basis for non-ischemic ventricular dysfunction in pediatric patients as an emerging indication for stem cell therapy,” he said.
The benefits of stem cell treatments for cardiac function beyond the initial follow-up period have “remained an unanswered question,” Dr. Sunjay Kaushal of University of Maryland, Baltimore, said in his invited commentary (J Thorac Cardiovasc Surg. 2015;150[5]:1209-11). “The 3-year follow-up data from the TICAP trial, therefore, offers one of the first opportunities to examine the durability of the outcomes found in stem cell-treated patients,” Dr. Kaushal said.
While TICAP provides clues into independent predictors of success with stem cell treatments, the small study population of seven patients makes it difficult to confirm those predictors, he said. “Multivariate analysis of results from future trials with larger sample size will be needed to verify these preliminary findings,” he noted.
Nonetheless, the study adds to the emerging evidence that younger, sicker patients may respond better to stem cell infusion, a concept Dr. Kaushal termed “intriguing.”
“Meanwhile, the TICAP trial and its three-year follow-up should garner enthusiasm for stem cell therapy, and establish the basis for non-ischemic ventricular dysfunction in pediatric patients as an emerging indication for stem cell therapy,” he said.
The benefits of stem cell treatments for cardiac function beyond the initial follow-up period have “remained an unanswered question,” Dr. Sunjay Kaushal of University of Maryland, Baltimore, said in his invited commentary (J Thorac Cardiovasc Surg. 2015;150[5]:1209-11). “The 3-year follow-up data from the TICAP trial, therefore, offers one of the first opportunities to examine the durability of the outcomes found in stem cell-treated patients,” Dr. Kaushal said.
While TICAP provides clues into independent predictors of success with stem cell treatments, the small study population of seven patients makes it difficult to confirm those predictors, he said. “Multivariate analysis of results from future trials with larger sample size will be needed to verify these preliminary findings,” he noted.
Nonetheless, the study adds to the emerging evidence that younger, sicker patients may respond better to stem cell infusion, a concept Dr. Kaushal termed “intriguing.”
“Meanwhile, the TICAP trial and its three-year follow-up should garner enthusiasm for stem cell therapy, and establish the basis for non-ischemic ventricular dysfunction in pediatric patients as an emerging indication for stem cell therapy,” he said.
Infants with congenital heart disease, specifically left heart syndrome, who had cardiac stem-cell therapy after surgery showed improved cardiac and brain function after 3 years when compared with infants who had standard therapy, according to latest results from a clinical trial of progenitor cell infusion in infants.
The prospective, controlled study, published in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150[5]:1198-1208), involved 14 infants with hypoplastic left heart syndrome (HLHS). Dr. Suguru Tarui and colleagues at Okayama University Hospital in Japan infused seven infants with intracoronary cardiosphere-derived cells (CDCs) 1 month after they had two- or three-stage palliative surgery. Seven controls had standard care alone. The trial is known TICAP (Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology) (ClinicalTrials.gov ID: NCT01273857).
Infants born with HLHS are known to have poor prognoses. HLHS has been associated with the highest mortality of all congenital heart lesions (Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2015;18[1]:2-6).
The Okayama investigators conducted TICAP in 2011 and demonstrated the feasibility and safety of the intracoronary delivery of CDCs in infants with HLHS after staged procedures. The latest report looks at the secondary outcome of cardiac function through 36 months of follow-up, and is the first clinical trial to report on the mid-term results of cardiac progenitor therapy in congenital heart disease.
“CDC infusion could improve right ventricular function from 3 through 36 months of observation,” Dr. Tarui and colleagues said. “Patients treated by CDCs showed an increase in somatic growth and reduced heart failure status in mid-term follow-up.”
Upon entry into the study, all subjects were of similar age, body weight, and risk profiles. After 36 months, the CDC group showed no complications and significantly improved right ventricular injection fraction compared with controls. As a result, the CDC group had reduced brain natriuretic peptide levels, lower rates of unplanned catheterizations, and higher weight for age. No adverse events occurred in the CDC group, while two patients in the control group had complications (one developed heart failure, another developed enteropathy).
The investigators looked at predictors of cardiac functional efficacy in the CDC group and determined that younger age was associated with greater improvement of right ventricular ejection fraction, as measured on echocardiography. The lower weight-for-age Z score and reduced ejection fraction at the time of infusion may be predictors of cardiac function improvements at 3 years.
“This therapeutic strategy may merit somatic growth enhancement and reduce the incidence of heart failure,” Dr. Tarui and coauthors said.
They noted a number of limitations of their small clinical trial. The study was nonrandomized, and the cardiac interventions were not blinded, among others. “Larger phase II studies focusing on changes in cardiac function, myocardial fibrosis, and quality of life and clinical event rates are warranted to confirm these effects of CDC administration in patients with single ventricular physiology,” they said.
The government of Japan through its ministries of Health, Labor and Welfare, and Education, Culture Sports, Science and Technology provided funding for the study, as did the Research Foundation of Okayama University Hospital. The authors had no disclosures.
Infants with congenital heart disease, specifically left heart syndrome, who had cardiac stem-cell therapy after surgery showed improved cardiac and brain function after 3 years when compared with infants who had standard therapy, according to latest results from a clinical trial of progenitor cell infusion in infants.
The prospective, controlled study, published in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150[5]:1198-1208), involved 14 infants with hypoplastic left heart syndrome (HLHS). Dr. Suguru Tarui and colleagues at Okayama University Hospital in Japan infused seven infants with intracoronary cardiosphere-derived cells (CDCs) 1 month after they had two- or three-stage palliative surgery. Seven controls had standard care alone. The trial is known TICAP (Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology) (ClinicalTrials.gov ID: NCT01273857).
Infants born with HLHS are known to have poor prognoses. HLHS has been associated with the highest mortality of all congenital heart lesions (Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2015;18[1]:2-6).
The Okayama investigators conducted TICAP in 2011 and demonstrated the feasibility and safety of the intracoronary delivery of CDCs in infants with HLHS after staged procedures. The latest report looks at the secondary outcome of cardiac function through 36 months of follow-up, and is the first clinical trial to report on the mid-term results of cardiac progenitor therapy in congenital heart disease.
“CDC infusion could improve right ventricular function from 3 through 36 months of observation,” Dr. Tarui and colleagues said. “Patients treated by CDCs showed an increase in somatic growth and reduced heart failure status in mid-term follow-up.”
Upon entry into the study, all subjects were of similar age, body weight, and risk profiles. After 36 months, the CDC group showed no complications and significantly improved right ventricular injection fraction compared with controls. As a result, the CDC group had reduced brain natriuretic peptide levels, lower rates of unplanned catheterizations, and higher weight for age. No adverse events occurred in the CDC group, while two patients in the control group had complications (one developed heart failure, another developed enteropathy).
The investigators looked at predictors of cardiac functional efficacy in the CDC group and determined that younger age was associated with greater improvement of right ventricular ejection fraction, as measured on echocardiography. The lower weight-for-age Z score and reduced ejection fraction at the time of infusion may be predictors of cardiac function improvements at 3 years.
“This therapeutic strategy may merit somatic growth enhancement and reduce the incidence of heart failure,” Dr. Tarui and coauthors said.
They noted a number of limitations of their small clinical trial. The study was nonrandomized, and the cardiac interventions were not blinded, among others. “Larger phase II studies focusing on changes in cardiac function, myocardial fibrosis, and quality of life and clinical event rates are warranted to confirm these effects of CDC administration in patients with single ventricular physiology,” they said.
The government of Japan through its ministries of Health, Labor and Welfare, and Education, Culture Sports, Science and Technology provided funding for the study, as did the Research Foundation of Okayama University Hospital. The authors had no disclosures.
FROM JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: This is the first clinical trial to report the midterm safety and efficacy of cardiac progenitor therapy in congenital heart disease.
Major finding: After 36 months, infants who received stem cells for congenital heart failure had better outcomes than did infants who had standard treatment.
Data source: Prospective clinical trial of 14 infants enrolled in the Transcoronary Infusion of Cardiac Progenitor Cells in Hypoplastic Left Heat Syndrome (TICAP) trial, divided evenly between treatment and control groups.
Disclosures: The government of Japan through its ministries of Health, Labor and Welfare, and Education, Culture Sports, Science and Technology provided funding for the study, as did the Research Foundation of Okayama University Hospital. The authors had no disclosures.
