Cleveland Clinic Journal of Medicine

A 54-year-old postmenopausal woman presents with a 3-day history of left lower quadrant pain. Abdominal and pelvic computed tomography confirm the diagnosis of acute diverticulitis, and a left ovarian cyst is incidentally noted. Her abdominal discomfort resolves with antibiotics.

Transvaginal ultrasonography confirms the presence of a 4.5-cm simple left ovarian cyst. The radiologist recommends follow-up ultrasonography in 3 months “if clinically indicated.” The patient feels well and is anxious about having additional testing. What do you recommend?

HOW USEFUL IS ULTRASONOGRAPHY FOR OVARIAN CYSTS?

Ovarian cysts are common and may affect up to 20% of women at some time during their life.¹ In a prospective study of almost 40,000 women enrolled in an ovarian cancer screening program, the prevalence of ovarian cysts was 15.3% in premenopausal women and 8.2% in postmenopausal women.²

Pelvic ultrasonography is the most effective way to evaluate incidentally noted cysts, and the transvaginal approach is preferred.³ The International Ovarian Tumor Analysis group has outlined morphologic features, referred to as “simple rules,” for predicting if a cyst is malignant or benign.⁴ In a prospective validation study, these simple rules were applied in 76% of cases, with a sensitivity of 95% and a specificity of 91%.⁴ However, it should be noted that these rules apply to examinations done by experienced gynecologic ultrasonographers, as accuracy of ultrasonography is both machine- and operator-dependent.

WHAT IS THE MALIGNANCY POTENTIAL OF A SIMPLE OVARIAN CYST?

A simple ovarian cyst is defined as an anechoic round or oval lesion, different from a unilocular cyst, which may contain septations, solid wall irregularities, or internal echoes.⁵ Overall, simple ovarian cysts have a very low likelihood of malignancy. In the large, multi-site Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, simple cysts were observed in 14% of postmenopausal women,6 but no cyst was associated with the development of ovarian cancer over 4 years of follow-up.

HOW OFTEN SHOULD IMAGING BE REPEATED?

In premenopausal women, most simple (thin-walled) ovarian cysts less than 5 cm in maximum diameter resolve in 2 to 3 menstrual cycles and do not require further intervention.³ Larger cysts (5–7 cm in diameter) should be followed with ultrasonography yearly. Cysts larger than 7 cm require advanced imaging or surgical intervention, and the patient should be referred to a gynecologist.³

In postmenopausal women, serum markers are combined with ultrasonography results to determine the risk of malignancy. Markers studied include cancer antigen 125 (CA-125), human epididymis protein 4, lactate dehydrogenase, alpha fetoprotein, and beta human chorionic gonadotropin (beta hCG).⁷

CA-125, the most studied marker, is elevated in more than 90% of advanced-stage ovarian cancers, but in only 50% of patients wth early-stage cancer.^1,8 However, CA-125 may be elevated in a variety of other settings, including benign gynecologic disorders (pelvic infection, fibroids, endometriosis, adenomyosis) and nongynecologic disorders (liver disease, pancreatitis, and diverticulitis). Thus, it is unreliable for distinguishing benign from malignant ovarian masses in premenopausal women.^1,3

Current guidelines recommend routine measurement of CA-125 in the initial evaluation of all postmenopausal women with an ovarian mass.^7,8

Using a cutoff of 30 IU/mL, CA-125 has a sensitivity of 81% and a specificity of 75% for ovarian malignancy. However, serial measurements may be more useful for assessing ovarian cancer risk, especially in the setting of rapidly rising values.^1,3

The Risk for Malignancy Index (RMI), which categorizes a cyst’s risk for malignancy, can be calculated based on the patient’s menopausal status, ultrasonographic characteristics (1 point each for multilocular cyst, solid area, metastasis, ascites, and bilateral lesions), and serum CA-125 level. The RMI has a sensitivity of 78% and a specificity of 87% for predicting ovarian cancer.8

Postmenopausal women with an asymptomatic small cyst (< 5 cm), a normal CA-125 level, and an RMI < 200 can be followed conservatively, with repeat ultrasonography in 4 to 6 months. At that time, if the cyst has not grown and the CA-125 level is normal, expectant management can continue, with reassessment in 4 to 6 months. If imaging remains unchanged and the CA-125 is persistently normal, the patient may be discharged from follow-up.⁸

If at any time during the evaluation the calculated RMI is greater than 200, there is an increased risk for malignancy, and the patient should be referred to a gynecologic oncologist for advanced imaging.

An algorithm from the Royal College of Obstetricians and Gynaecologists for managing ovarian cysts in postmenopausal women is available at www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg_34.pdf.⁸

The American College of Radiology (ACR) has created a “Choosing Wisely” guideline to clarify when repeat imaging for ovarian cysts is indicated, to reduce both patient anxiety and healthcare costs.⁹ These guidelines highlight the distress women may experience from repeat testing due to concerns about cancer.

The guidelines also note that testing is often done during varying times of the menstrual cycle, thereby detecting new cysts, as opposed to monitoring previously detected cysts. Repeat ultrasonography may lead to surgical interventions that are not evidence-based, such as cystectomy or oophorectomy, in patients without radiologic features of malignancy or associated pelvic pain. And while ultrasonography is less expensive than other imaging tests, unnecessary imaging can mean additional costs to the patient, such as copayments, and possibly large payments for patients without insurance.

The American College of Obstetricians and Gynecologists (ACOG) and the ACR guidelines recommend against unnecessary repeat imaging for ovarian cysts.^7,10 The ACOG Practice Bulletin on the Evaluation and Management of Adnexal Masses states, “Simple cysts up to 10 cm in diameter on transvaginal ultrasonography performed by experienced ultrasonographers are likely benign and may be safely monitored using repeat imaging without surgical intervention, even in postmenopausal patients.”⁷

The ideal frequency for repeat testing is yet to be determined. In postmenopausal women with a simple cyst smaller than 5 cm, ACOG guidelines recommend an interval of 4 to 6 months for initial repeat imaging. ACR guidelines recommend no follow-up imaging for simple cysts smaller than 5 cm detected by high-quality ultrasonography in asymptomatic women of reproductive age or for simple cysts smaller than 1 cm in postmenopausal women.¹⁰

THE CLINICAL BOTTOM LINE

Simple ovarian cysts can develop as part of the normal menstrual cycle, and although they are more common in premenopausal women, they have been detected in 1 out of 5 postmenopausal women.⁹ Simple ovarian cysts are typically not cancerous in women of any age. Therefore, most simple ovarian cysts in asymp­tomatic women either require no follow-up imaging or can be safely monitored with limited repeat ultrasonography for a defined length of time.

Our 54-year-old postmenopausal patient has a simple cyst smaller than 5 cm. Based on current guidelines, the CA-125 level should be measured, with subsequent calculation of the RMI. Assuming a normal CA-125 and RMI, she should be reassured that the risk of progression to malignancy is extremely low. Repeating ultrasonography 4 to 6 months after the initial imaging is warranted. At that time, if no change in cyst size or composition is detected, ultrasonography can be repeated at 1 year after initial detection. After that, assuming no changes of the cyst on repeat imaging, the patient does not require additional follow-up.

A 54-year-old postmenopausal woman presents with a 3-day history of left lower quadrant pain. Abdominal and pelvic computed tomography confirm the diagnosis of acute diverticulitis, and a left ovarian cyst is incidentally noted. Her abdominal discomfort resolves with antibiotics.

Transvaginal ultrasonography confirms the presence of a 4.5-cm simple left ovarian cyst. The radiologist recommends follow-up ultrasonography in 3 months “if clinically indicated.” The patient feels well and is anxious about having additional testing. What do you recommend?

HOW USEFUL IS ULTRASONOGRAPHY FOR OVARIAN CYSTS?

Ovarian cysts are common and may affect up to 20% of women at some time during their life.¹ In a prospective study of almost 40,000 women enrolled in an ovarian cancer screening program, the prevalence of ovarian cysts was 15.3% in premenopausal women and 8.2% in postmenopausal women.²

Pelvic ultrasonography is the most effective way to evaluate incidentally noted cysts, and the transvaginal approach is preferred.³ The International Ovarian Tumor Analysis group has outlined morphologic features, referred to as “simple rules,” for predicting if a cyst is malignant or benign.⁴ In a prospective validation study, these simple rules were applied in 76% of cases, with a sensitivity of 95% and a specificity of 91%.⁴ However, it should be noted that these rules apply to examinations done by experienced gynecologic ultrasonographers, as accuracy of ultrasonography is both machine- and operator-dependent.

WHAT IS THE MALIGNANCY POTENTIAL OF A SIMPLE OVARIAN CYST?

A simple ovarian cyst is defined as an anechoic round or oval lesion, different from a unilocular cyst, which may contain septations, solid wall irregularities, or internal echoes.⁵ Overall, simple ovarian cysts have a very low likelihood of malignancy. In the large, multi-site Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, simple cysts were observed in 14% of postmenopausal women,6 but no cyst was associated with the development of ovarian cancer over 4 years of follow-up.

HOW OFTEN SHOULD IMAGING BE REPEATED?

In premenopausal women, most simple (thin-walled) ovarian cysts less than 5 cm in maximum diameter resolve in 2 to 3 menstrual cycles and do not require further intervention.³ Larger cysts (5–7 cm in diameter) should be followed with ultrasonography yearly. Cysts larger than 7 cm require advanced imaging or surgical intervention, and the patient should be referred to a gynecologist.³

In postmenopausal women, serum markers are combined with ultrasonography results to determine the risk of malignancy. Markers studied include cancer antigen 125 (CA-125), human epididymis protein 4, lactate dehydrogenase, alpha fetoprotein, and beta human chorionic gonadotropin (beta hCG).⁷

CA-125, the most studied marker, is elevated in more than 90% of advanced-stage ovarian cancers, but in only 50% of patients wth early-stage cancer.^1,8 However, CA-125 may be elevated in a variety of other settings, including benign gynecologic disorders (pelvic infection, fibroids, endometriosis, adenomyosis) and nongynecologic disorders (liver disease, pancreatitis, and diverticulitis). Thus, it is unreliable for distinguishing benign from malignant ovarian masses in premenopausal women.^1,3

Current guidelines recommend routine measurement of CA-125 in the initial evaluation of all postmenopausal women with an ovarian mass.^7,8

Using a cutoff of 30 IU/mL, CA-125 has a sensitivity of 81% and a specificity of 75% for ovarian malignancy. However, serial measurements may be more useful for assessing ovarian cancer risk, especially in the setting of rapidly rising values.^1,3

The Risk for Malignancy Index (RMI), which categorizes a cyst’s risk for malignancy, can be calculated based on the patient’s menopausal status, ultrasonographic characteristics (1 point each for multilocular cyst, solid area, metastasis, ascites, and bilateral lesions), and serum CA-125 level. The RMI has a sensitivity of 78% and a specificity of 87% for predicting ovarian cancer.8

Postmenopausal women with an asymptomatic small cyst (< 5 cm), a normal CA-125 level, and an RMI < 200 can be followed conservatively, with repeat ultrasonography in 4 to 6 months. At that time, if the cyst has not grown and the CA-125 level is normal, expectant management can continue, with reassessment in 4 to 6 months. If imaging remains unchanged and the CA-125 is persistently normal, the patient may be discharged from follow-up.⁸

If at any time during the evaluation the calculated RMI is greater than 200, there is an increased risk for malignancy, and the patient should be referred to a gynecologic oncologist for advanced imaging.

An algorithm from the Royal College of Obstetricians and Gynaecologists for managing ovarian cysts in postmenopausal women is available at www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg_34.pdf.⁸

The American College of Radiology (ACR) has created a “Choosing Wisely” guideline to clarify when repeat imaging for ovarian cysts is indicated, to reduce both patient anxiety and healthcare costs.⁹ These guidelines highlight the distress women may experience from repeat testing due to concerns about cancer.

The guidelines also note that testing is often done during varying times of the menstrual cycle, thereby detecting new cysts, as opposed to monitoring previously detected cysts. Repeat ultrasonography may lead to surgical interventions that are not evidence-based, such as cystectomy or oophorectomy, in patients without radiologic features of malignancy or associated pelvic pain. And while ultrasonography is less expensive than other imaging tests, unnecessary imaging can mean additional costs to the patient, such as copayments, and possibly large payments for patients without insurance.

The American College of Obstetricians and Gynecologists (ACOG) and the ACR guidelines recommend against unnecessary repeat imaging for ovarian cysts.^7,10 The ACOG Practice Bulletin on the Evaluation and Management of Adnexal Masses states, “Simple cysts up to 10 cm in diameter on transvaginal ultrasonography performed by experienced ultrasonographers are likely benign and may be safely monitored using repeat imaging without surgical intervention, even in postmenopausal patients.”⁷

The ideal frequency for repeat testing is yet to be determined. In postmenopausal women with a simple cyst smaller than 5 cm, ACOG guidelines recommend an interval of 4 to 6 months for initial repeat imaging. ACR guidelines recommend no follow-up imaging for simple cysts smaller than 5 cm detected by high-quality ultrasonography in asymptomatic women of reproductive age or for simple cysts smaller than 1 cm in postmenopausal women.¹⁰

THE CLINICAL BOTTOM LINE

Simple ovarian cysts can develop as part of the normal menstrual cycle, and although they are more common in premenopausal women, they have been detected in 1 out of 5 postmenopausal women.⁹ Simple ovarian cysts are typically not cancerous in women of any age. Therefore, most simple ovarian cysts in asymp­tomatic women either require no follow-up imaging or can be safely monitored with limited repeat ultrasonography for a defined length of time.

Our 54-year-old postmenopausal patient has a simple cyst smaller than 5 cm. Based on current guidelines, the CA-125 level should be measured, with subsequent calculation of the RMI. Assuming a normal CA-125 and RMI, she should be reassured that the risk of progression to malignancy is extremely low. Repeating ultrasonography 4 to 6 months after the initial imaging is warranted. At that time, if no change in cyst size or composition is detected, ultrasonography can be repeated at 1 year after initial detection. After that, assuming no changes of the cyst on repeat imaging, the patient does not require additional follow-up.

A 54-year-old postmenopausal woman presents with a 3-day history of left lower quadrant pain. Abdominal and pelvic computed tomography confirm the diagnosis of acute diverticulitis, and a left ovarian cyst is incidentally noted. Her abdominal discomfort resolves with antibiotics.

Transvaginal ultrasonography confirms the presence of a 4.5-cm simple left ovarian cyst. The radiologist recommends follow-up ultrasonography in 3 months “if clinically indicated.” The patient feels well and is anxious about having additional testing. What do you recommend?

HOW USEFUL IS ULTRASONOGRAPHY FOR OVARIAN CYSTS?

Ovarian cysts are common and may affect up to 20% of women at some time during their life.¹ In a prospective study of almost 40,000 women enrolled in an ovarian cancer screening program, the prevalence of ovarian cysts was 15.3% in premenopausal women and 8.2% in postmenopausal women.²

Pelvic ultrasonography is the most effective way to evaluate incidentally noted cysts, and the transvaginal approach is preferred.³ The International Ovarian Tumor Analysis group has outlined morphologic features, referred to as “simple rules,” for predicting if a cyst is malignant or benign.⁴ In a prospective validation study, these simple rules were applied in 76% of cases, with a sensitivity of 95% and a specificity of 91%.⁴ However, it should be noted that these rules apply to examinations done by experienced gynecologic ultrasonographers, as accuracy of ultrasonography is both machine- and operator-dependent.

WHAT IS THE MALIGNANCY POTENTIAL OF A SIMPLE OVARIAN CYST?

A simple ovarian cyst is defined as an anechoic round or oval lesion, different from a unilocular cyst, which may contain septations, solid wall irregularities, or internal echoes.⁵ Overall, simple ovarian cysts have a very low likelihood of malignancy. In the large, multi-site Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, simple cysts were observed in 14% of postmenopausal women,6 but no cyst was associated with the development of ovarian cancer over 4 years of follow-up.

HOW OFTEN SHOULD IMAGING BE REPEATED?

In premenopausal women, most simple (thin-walled) ovarian cysts less than 5 cm in maximum diameter resolve in 2 to 3 menstrual cycles and do not require further intervention.³ Larger cysts (5–7 cm in diameter) should be followed with ultrasonography yearly. Cysts larger than 7 cm require advanced imaging or surgical intervention, and the patient should be referred to a gynecologist.³

In postmenopausal women, serum markers are combined with ultrasonography results to determine the risk of malignancy. Markers studied include cancer antigen 125 (CA-125), human epididymis protein 4, lactate dehydrogenase, alpha fetoprotein, and beta human chorionic gonadotropin (beta hCG).⁷

CA-125, the most studied marker, is elevated in more than 90% of advanced-stage ovarian cancers, but in only 50% of patients wth early-stage cancer.^1,8 However, CA-125 may be elevated in a variety of other settings, including benign gynecologic disorders (pelvic infection, fibroids, endometriosis, adenomyosis) and nongynecologic disorders (liver disease, pancreatitis, and diverticulitis). Thus, it is unreliable for distinguishing benign from malignant ovarian masses in premenopausal women.^1,3

Current guidelines recommend routine measurement of CA-125 in the initial evaluation of all postmenopausal women with an ovarian mass.^7,8

Using a cutoff of 30 IU/mL, CA-125 has a sensitivity of 81% and a specificity of 75% for ovarian malignancy. However, serial measurements may be more useful for assessing ovarian cancer risk, especially in the setting of rapidly rising values.^1,3

The Risk for Malignancy Index (RMI), which categorizes a cyst’s risk for malignancy, can be calculated based on the patient’s menopausal status, ultrasonographic characteristics (1 point each for multilocular cyst, solid area, metastasis, ascites, and bilateral lesions), and serum CA-125 level. The RMI has a sensitivity of 78% and a specificity of 87% for predicting ovarian cancer.8

Postmenopausal women with an asymptomatic small cyst (< 5 cm), a normal CA-125 level, and an RMI < 200 can be followed conservatively, with repeat ultrasonography in 4 to 6 months. At that time, if the cyst has not grown and the CA-125 level is normal, expectant management can continue, with reassessment in 4 to 6 months. If imaging remains unchanged and the CA-125 is persistently normal, the patient may be discharged from follow-up.⁸

If at any time during the evaluation the calculated RMI is greater than 200, there is an increased risk for malignancy, and the patient should be referred to a gynecologic oncologist for advanced imaging.

An algorithm from the Royal College of Obstetricians and Gynaecologists for managing ovarian cysts in postmenopausal women is available at www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg_34.pdf.⁸

The American College of Radiology (ACR) has created a “Choosing Wisely” guideline to clarify when repeat imaging for ovarian cysts is indicated, to reduce both patient anxiety and healthcare costs.⁹ These guidelines highlight the distress women may experience from repeat testing due to concerns about cancer.

The guidelines also note that testing is often done during varying times of the menstrual cycle, thereby detecting new cysts, as opposed to monitoring previously detected cysts. Repeat ultrasonography may lead to surgical interventions that are not evidence-based, such as cystectomy or oophorectomy, in patients without radiologic features of malignancy or associated pelvic pain. And while ultrasonography is less expensive than other imaging tests, unnecessary imaging can mean additional costs to the patient, such as copayments, and possibly large payments for patients without insurance.

The American College of Obstetricians and Gynecologists (ACOG) and the ACR guidelines recommend against unnecessary repeat imaging for ovarian cysts.^7,10 The ACOG Practice Bulletin on the Evaluation and Management of Adnexal Masses states, “Simple cysts up to 10 cm in diameter on transvaginal ultrasonography performed by experienced ultrasonographers are likely benign and may be safely monitored using repeat imaging without surgical intervention, even in postmenopausal patients.”⁷

The ideal frequency for repeat testing is yet to be determined. In postmenopausal women with a simple cyst smaller than 5 cm, ACOG guidelines recommend an interval of 4 to 6 months for initial repeat imaging. ACR guidelines recommend no follow-up imaging for simple cysts smaller than 5 cm detected by high-quality ultrasonography in asymptomatic women of reproductive age or for simple cysts smaller than 1 cm in postmenopausal women.¹⁰

THE CLINICAL BOTTOM LINE

Simple ovarian cysts can develop as part of the normal menstrual cycle, and although they are more common in premenopausal women, they have been detected in 1 out of 5 postmenopausal women.⁹ Simple ovarian cysts are typically not cancerous in women of any age. Therefore, most simple ovarian cysts in asymp­tomatic women either require no follow-up imaging or can be safely monitored with limited repeat ultrasonography for a defined length of time.

Our 54-year-old postmenopausal patient has a simple cyst smaller than 5 cm. Based on current guidelines, the CA-125 level should be measured, with subsequent calculation of the RMI. Assuming a normal CA-125 and RMI, she should be reassured that the risk of progression to malignancy is extremely low. Repeating ultrasonography 4 to 6 months after the initial imaging is warranted. At that time, if no change in cyst size or composition is detected, ultrasonography can be repeated at 1 year after initial detection. After that, assuming no changes of the cyst on repeat imaging, the patient does not require additional follow-up.

In 2017, the American College of Cardiology (ACC), American Heart Association (AHA), and 9 other professional associations published a new guideline on high blood pressure in adults.¹ Their document addresses a range of topics relevant to preventing, diagnosing, and managing hypertension. It incorporates evidence from randomized controlled trials, including the Systolic Blood Pressure Intervention Trial (SPRINT),² systematic reviews, and expert opinion.

The new guidelines contain many noteworthy changes, some of which are generating intense debate and discussion. Here, we provide our opinions to help practicing clinicians broaden their perspective and make informed decisions about management.

ACC AND AHA ARE NOW RESPONSIBLE FOR HYPERTENSION GUIDELINES

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC), organized by the National Heart, Lung, and Blood Institute, began issuing hypertension guidelines in 1977. Based on observational and clinical trial data, succeeding JNC reports recommended ever-lower blood pressure goals, with emphasis shifting to treatment of systolic hypertension.

The last official JNC report—JNC 7—was published in 2003.³ In 2013, the Institute transferred the responsibility for cardiovascular prevention guidelines to the ACC and AHA.⁴

A report from the panel members appointed to JNC 8 was published independently in 2014.⁵ It focused on a few key questions and used evidence limited to randomized controlled trials. In this report, the panel relaxed the goals for many subgroups, leading to criticism from many professional societies and from some members of the panel writing group.⁶

WHAT'S NEW IN THE 2017 GUIDELINES?

The new ACC/AHA guidelines contain a number of changes from previous documents that have been the topic of debate.

New definition and classification of hypertension

Strong recommendation, based on moderate-quality evidence­.

Our opinion. While this new classification is intended to promote closer monitoring and earlier intervention to lower cardiovascular event rates, creating a new level of disease may lead to more pharmacologic treatment for those with lower risk, without emphasis on lifestyle modifications.

Emphasis on measurement technique and out-of-office measurements

Strong recommendation, based on expert opinion, for accurate measurement of blood pressure in the office, high-quality evidence from systematic review for out-of-office measurement.

Appropriate management of hypertension entails accurate blood pressure measurement. While office-based measurement remains the most commonly used method, this “snapshot” may not reflect a patient’s true baseline blood pressure.

Out-of-office measurements. Based on the results of a systematic review commissioned by the guideline committee, out-of-office measurements are now recommended to confirm the diagnosis of hypertension and to assess response to therapy.

Ambulatory blood pressure monitoring should be strongly considered as the preferred method for out-of-office monitoring; home blood pressure monitoring can be done if ambulatory monitoring is not feasible. Ambulatory monitoring provides additional information on nighttime blood pressure, including the dipping status (normal defined as a nighttime blood pressure decrease of 10% to 20%). Ambulatory monitoring predicts long-term cardiovascular outcomes independent of office blood pressure, and elevated nighttime pressure and non-dipping have been shown to be independently associated with increased cardiovascular mortality rates.^8,9 Unfortunately, despite evidence supporting its use, ambulatory blood pressure monitoring is not widely available for a variety of reasons, including high cost (roughly $2,000–$4,000) and minimal reimbursement.

Out-of-office measurements can also detect white coat hypertension and masked hypertension. White coat hypertension is defined as blood pressure that is elevated in the office but normal in an out-of-office setting, and masked hypertension is blood pressure that is normal in the office and elevated in an out-of-office setting. Currently, pharmacologic therapy is not recommended to treat white coat hypertension, and treatment for masked hypertension should be the same as for sustained hypertension.

While the guidelines do not comment specifically on manual office measurement vs automated office measurements using devices that take multiple measurements with the patient alone in the room to reduce the white coat effect, they acknowledge “increasing evidence” favoring the use of automated office measurement.

Proper technique for measuring blood pressure is appropriately emphasized; correct patient positioning, allowing a period of rest, and using the appropriate cuff size are all important. Unfortunately, many busy clinical practices may not follow correct technique when measuring blood pressure in the office, leading to misdiagnosis and unnecessary pharmacologic therapy that may result in adverse events.

Of note, the SPRINT trial, which informed many of the new guideline recommendations, followed a strict protocol of blood pressure measurement with an automated device, checking sitting blood pressure 3 times at 1-minute intervals, with the patient alone in the room and without an observer present at many of the sites.¹⁰

Most guidelines^11,12 agree on an average of at least 135/85 mm Hg as the threshold for diagnosing hypertension by home monitoring, or an average daytime pressure of at least 135/85 mm Hg by ambulatory monitoring, corresponding with office-based blood pressure of 140/90 mm Hg.­ However, the new guidelines recommend a lower threshold of 130/80 mm Hg for both home monitoring and average daytime ambulatory monitoring, corresponding with an office blood pressure of 130/80 mm Hg. They do not specify whether the office-based measurement is manual or automated.

Our opinion. Since office-based measurement will likely remain the principal method for managing hypertension due to constraints with ambulatory or home monitoring, the use of automated devices for office measurement should be strongly considered. Studies have shown that, compared with routine office measurements, automated measurements more closely approximate those obtained by ambulatory and home blood pressure monitoring.¹³

Risk-based approach to hypertension management

The algorithm for hypertension management now incorporates objective assessment of cardiovascular risk. Specifically, it calls for estimation of the 10-year risk of atherosclerotic cardiovascular disease, defined as coronary heart disease death, nonfatal myocardial infarction, or fatal or nonfatal stroke.

The information required to estimate risk includes age, sex, race, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, use of blood pressure-lowering medication, diabetes status, and smoking status. The guideline recommends an easy-to-use online risk calculator (http://tools.acc.org/ASCVD-Risk-Estimator).

A 10-year risk of 10% or more is designated as the cutoff between high risk and low risk. However, this is not based on trial evidence, and the risk calculator has not been verified in prospective trials to show that its use reduces cardiovascular events. The SPRINT trial,² which was a study of blood pressure-lowering in high-risk patients, used a 10-year risk of 15% or more based on the Framingham risk score to delineate high risk.

Additionally, the 10-year risk calculator is valid only in patients ages 40 through 79, and some studies indicate that it may overestimate risk in older adults.^14,15 This overestimation may lead to patients being started on pharmacologic therapy when it may not truly be indicated. The risk calculator controversy has been discussed in a previous issue of this journal.¹⁶

Blood pressure goals

Strong recommendation for known cardiovascular disease or atherosclerotic cardiovascular disease risk 10% or greater, weak recommendation for risk less than 10%, based on moderate-quality evidence for systolic blood pressure, expert opinion for diastolic.

The guidelines recommend a blood pressure goal of less than 130/80 mm Hg for all patients, including the elderly and patients with chronic kidney disease or diabetes.

The SPRINT trial,² which showed better cardiovascular outcomes in the intensive treatment group (aiming for systolic pressure < 120 mm Hg) compared with a standard treatment group (aiming for systolic pressure < 140 mm Hg), excluded participants with diabetes and severe chronic kidney disease (estimated glomerular filtration rate < 20 mL/min/m² and proteinuria > 1 g/day), and those who were in nursing homes or had dementia.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial showed that intensive blood pressure control did not have cardiovascular benefits compared with standard therapy.¹⁷ However, many now believe that the study may have been underpowered due to its design, and a meta-analysis of the results from SPRINT and ACCORD suggested that findings from both trials were consistent, favoring intensive blood pressure control in a high-risk population.¹⁸

While the totality of evidence favors a lower achieved blood pressure for many patients, this lower goal may be difficult to achieve in many, particularly those with vascular stiffness, which is common in the elderly. These patients also tend to have low diastolic pressure, and lowering diastolic pressure below 60 mm Hg in those with documented coronary artery disease could increase the risk of adverse cardiovascular outcomes.^19,20 The guidelines do not address the potential issues with lowering diastolic blood pressure.

Our opinion. While a “universal” blood pressure goal may simplify decision-making, we believe it is important to individualize goals, taking into account patient characteristics, lifestyle factors, medication side effects, patient preferences, cost issues, and adherence to therapy.

The goal blood pressure should also consider the method of measurement. Systolic blood pressure readings have been reported to be 5 to 10 mm Hg lower with automated office measurement than with routine office measurement.²¹

It is also not clear that the magnitude of absolute benefit from pursuing more intensive blood pressure control with antihypertensive therapy in patients with high cardiovascular risk (as in SPRINT) would translate to similar benefits in a lower-risk population. Thus, we believe that in patients with lower cardiovascular risk, a goal blood pressure of less than 140/90 mm Hg (if routine office measurement is done) and less than 135/85 mm Hg (if automated office measurement is done) would be reasonable.

We also believe that it is reasonable to relax these goals in the very elderly (age ≥ 80), especially those who are frail and at risk of falls, with low diastolic pressures. In these patients, we recommend individualizing blood pressure goals that can be achieved without significant side effects from antihypertensive therapy.

Nonpharmacologic therapy

Strong recommendation, based on high-quality evidence from randomized controlled trials

Nonpharmacologic therapy and lifestyle modification are appropriately emphasized in the new guidelines. Most of the lifestyle changes that are recommended are in concordance with prior JNC 7 recommendations.³

Recognizing the roles of sodium and potassium in the pathogenesis of hypertension, the guidelines emphasize a diet that is higher in potassium, the DASH (Dietary Approaches to Stop Hypertension) diet, and a low-sodium diet. The recommended optimal goal of sodium intake of less than 1,500 mg/day may be difficult to achieve with a Western diet, and there is debate about the potential adverse effects of a very-low sodium diet.²² The general recommendation for sodium intake of less than 2,300 mg/day is supported in the literature, and it is unclear if further reduction has additional beneficial effects on blood pressure.²³

The guidelines recommend a 3- to 6-month reassessment of patients who are prescribed risk-factor modification, but are unclear about initiation of pharmacologic therapy or other steps if these low-risk patients have not responded to lifestyle modifications alone at the time of reassessment.

Pharmacologic therapy

Strong recommendation, based on high-quality evidence from randomized controlled trials for systolic blood pressure, expert opinion for diastolic blood pressure for those with atherosclerotic cardiovascular disease risk 10% or greater, and limited data for those with risk less than 10%.

Pharmacologic therapy is recommended in patients with stage 1 hypertension and pre-existing cardiovascular disease or 10-year risk of atherosclerotic cardiovascular disease of 10% or more, and in those with stage 2 hypertension even if their 10-year risk is less than 10%.

In the absence of compelling indications, the primary drugs recommended for initial therapy are:

• Thiazide or thiazide-type diuretics (preferably chlorthalidone)
• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin II receptor blockers (ARBs)
• Calcium channel blockers (CCBs).

In black adults, thiazide diuretics or CCBs are recommended for initial therapy. Beta-blockers are not recommended as first-line agents in the absence of a compelling indication, although meta-analyses that suggested beta-blockers are less effective than other classes of agents included trials that used beta-blockers in doses now considered suboptimal. ACE inhibitors or ARBs are recommended as initial therapy in proteinuric patients with chronic kidney disease or diabetes. Combining an ACE inhibitor and an ARB or renin inhibitor is potentially harmful and is not recommended. The guidelines provide a helpful table describing important characteristics and available dosage forms of the commonly used antihypertensive agents.

These recommendations are concordant with the JNC 8 panel recommendations,⁵ and differ from JNC 7, which recommended thiazide-type diuretics as first-line therapy.³ The European guidelines recommend that all major classes of antihypertensive agents, including beta-blockers, are suitable for initiation of therapy.²⁴ The UK National Institute for Clinical Excellence guidelines adopt an age-based approach to deciding initial therapy—with ACE inhibitors or ARBs favored in those below the age of 55 and CCBs in those who are 55 and older.²⁵

Starting with a single antihypertensive agent is recommended for stage 1 hypertension with increased cardiovascular risk, and starting with 2 agents (either separately or in fixed-dose combination) is recommended for stage 2 hypertension. The guidelines emphasize a team-based approach to improve hypertension care, using adjunctive interventions such as telehealth strategies and leveraging electronic medical records to guide quality improvement initiatives.

Our opinion. We agree with Bakris and Sorrentino^₂₆ that general patient profiles should be considered to decide on efficient pharmacologic management in clinical practice—thiazide diuretics would be best in those who are volume-expanded; ACE inhibitors, ARBs, or CCBs in those who are obese or have metabolic syndrome; and beta-blockers or nondihydropyridine CCBs in those who are hyperadrenergic. More patients will likely be classified as having resistant hypertension based on the blood pressure goal of less than 130/80 mm Hg, which may require greater use of mineralocorticoid receptor antagonists such as spironolactone.

STRENGTHS AND LIMITATIONS

The new guidelines stress correct technique of blood pressure measurement, out-of-office and self-monitoring of blood pressure, and lifestyle modifications. In addition, they comprehensively review topics relevant to hypertension management of practical use for healthcare providers, including resistant hypertension, secondary hypertension, hypertensive crises, and special populations. The guidelines also incorporate multiple lines of evidence rather than just randomized controlled trials (which may not be available for every scenario).

There will be ongoing debate and discussion about the new definition and classification of hypertension, and the “conversion” of previously healthy adults to a new disease category. The blood pressure goals will also be debated: Should the goal for a young patient be applied to an elderly patient? The pathophysiology of the disease process should be considered rather than a one-size-fits-all approach. For example, older patients with stiff arteries and low diastolic blood pressure will have more difficulty achieving a lower systolic pressure, are more likely to experience medication side effects, and may have adherence issues due to polypharmacy.

A clinical trial, with strict adherence to protocols and rigorous follow-up procedures, is different from real-world clinical practice. Busy clinical practices with time and space constraints may forgo the steps needed for accurate blood pressure measurement in the office and may not reinforce lifestyle modifications, instead opting for more pharmacologic therapy to achieve a blood pressure goal that may become mandated by healthcare payment models without consideration for clinical judgment and individual patient characteristics.

The ACC/AHA guidelines have not been universally endorsed. The American College of Physicians and the American Academy of Family Physicians released their own guidelines for older adults earlier in 2017, echoing the recommendations from the panel appointed to JNC 8.²⁷ Contrasting recommendations can unfortunately lead to confusion among healthcare providers and patients and can undermine confidence and trust in the healthcare system.

In the background of ongoing debate, where battle lines have been drawn by key stakeholders with regard to their contrasting positions, it is even more important for the practicing clinician who is in the front lines of hypertension management to be knowledgeable about the pros and cons of different recommendations as they apply to individual patients, and to be able to clearly communicate this with patients when deciding on a treatment plan.

FINAL THOUGHTS

• Accurate measurement of blood pressure in the office is imperative—position the patient properly, use an appropriately sized  cuff, and allow for a period of rest. Consider using automated office measurement to minimize potential white coat effect.
• Out-of-office blood pressure monitoring is recommended to confirm the diagnosis of hypertension and for monitoring response to therapy. Ambulatory monitoring is preferred, but home blood pressure monitoring can be done if ambulatory monitoring is unavailable or unfeasible.
• Nonpharmacologic therapy should be emphasized for everyone, regardless of blood pressure level.
• Guidelines should be used as a framework for management. Individualize decisions about blood pressure goals and pharmacologic therapy based on patient characteristics and clinical judgment.

In 2017, the American College of Cardiology (ACC), American Heart Association (AHA), and 9 other professional associations published a new guideline on high blood pressure in adults.¹ Their document addresses a range of topics relevant to preventing, diagnosing, and managing hypertension. It incorporates evidence from randomized controlled trials, including the Systolic Blood Pressure Intervention Trial (SPRINT),² systematic reviews, and expert opinion.

The new guidelines contain many noteworthy changes, some of which are generating intense debate and discussion. Here, we provide our opinions to help practicing clinicians broaden their perspective and make informed decisions about management.

ACC AND AHA ARE NOW RESPONSIBLE FOR HYPERTENSION GUIDELINES

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC), organized by the National Heart, Lung, and Blood Institute, began issuing hypertension guidelines in 1977. Based on observational and clinical trial data, succeeding JNC reports recommended ever-lower blood pressure goals, with emphasis shifting to treatment of systolic hypertension.

The last official JNC report—JNC 7—was published in 2003.³ In 2013, the Institute transferred the responsibility for cardiovascular prevention guidelines to the ACC and AHA.⁴

A report from the panel members appointed to JNC 8 was published independently in 2014.⁵ It focused on a few key questions and used evidence limited to randomized controlled trials. In this report, the panel relaxed the goals for many subgroups, leading to criticism from many professional societies and from some members of the panel writing group.⁶

WHAT'S NEW IN THE 2017 GUIDELINES?

The new ACC/AHA guidelines contain a number of changes from previous documents that have been the topic of debate.

New definition and classification of hypertension

Strong recommendation, based on moderate-quality evidence­.

Our opinion. While this new classification is intended to promote closer monitoring and earlier intervention to lower cardiovascular event rates, creating a new level of disease may lead to more pharmacologic treatment for those with lower risk, without emphasis on lifestyle modifications.

Emphasis on measurement technique and out-of-office measurements

Strong recommendation, based on expert opinion, for accurate measurement of blood pressure in the office, high-quality evidence from systematic review for out-of-office measurement.

Appropriate management of hypertension entails accurate blood pressure measurement. While office-based measurement remains the most commonly used method, this “snapshot” may not reflect a patient’s true baseline blood pressure.

Out-of-office measurements. Based on the results of a systematic review commissioned by the guideline committee, out-of-office measurements are now recommended to confirm the diagnosis of hypertension and to assess response to therapy.

Ambulatory blood pressure monitoring should be strongly considered as the preferred method for out-of-office monitoring; home blood pressure monitoring can be done if ambulatory monitoring is not feasible. Ambulatory monitoring provides additional information on nighttime blood pressure, including the dipping status (normal defined as a nighttime blood pressure decrease of 10% to 20%). Ambulatory monitoring predicts long-term cardiovascular outcomes independent of office blood pressure, and elevated nighttime pressure and non-dipping have been shown to be independently associated with increased cardiovascular mortality rates.^8,9 Unfortunately, despite evidence supporting its use, ambulatory blood pressure monitoring is not widely available for a variety of reasons, including high cost (roughly $2,000–$4,000) and minimal reimbursement.

Out-of-office measurements can also detect white coat hypertension and masked hypertension. White coat hypertension is defined as blood pressure that is elevated in the office but normal in an out-of-office setting, and masked hypertension is blood pressure that is normal in the office and elevated in an out-of-office setting. Currently, pharmacologic therapy is not recommended to treat white coat hypertension, and treatment for masked hypertension should be the same as for sustained hypertension.

While the guidelines do not comment specifically on manual office measurement vs automated office measurements using devices that take multiple measurements with the patient alone in the room to reduce the white coat effect, they acknowledge “increasing evidence” favoring the use of automated office measurement.

Proper technique for measuring blood pressure is appropriately emphasized; correct patient positioning, allowing a period of rest, and using the appropriate cuff size are all important. Unfortunately, many busy clinical practices may not follow correct technique when measuring blood pressure in the office, leading to misdiagnosis and unnecessary pharmacologic therapy that may result in adverse events.

Of note, the SPRINT trial, which informed many of the new guideline recommendations, followed a strict protocol of blood pressure measurement with an automated device, checking sitting blood pressure 3 times at 1-minute intervals, with the patient alone in the room and without an observer present at many of the sites.¹⁰

Most guidelines^11,12 agree on an average of at least 135/85 mm Hg as the threshold for diagnosing hypertension by home monitoring, or an average daytime pressure of at least 135/85 mm Hg by ambulatory monitoring, corresponding with office-based blood pressure of 140/90 mm Hg.­ However, the new guidelines recommend a lower threshold of 130/80 mm Hg for both home monitoring and average daytime ambulatory monitoring, corresponding with an office blood pressure of 130/80 mm Hg. They do not specify whether the office-based measurement is manual or automated.

Our opinion. Since office-based measurement will likely remain the principal method for managing hypertension due to constraints with ambulatory or home monitoring, the use of automated devices for office measurement should be strongly considered. Studies have shown that, compared with routine office measurements, automated measurements more closely approximate those obtained by ambulatory and home blood pressure monitoring.¹³

Risk-based approach to hypertension management

The algorithm for hypertension management now incorporates objective assessment of cardiovascular risk. Specifically, it calls for estimation of the 10-year risk of atherosclerotic cardiovascular disease, defined as coronary heart disease death, nonfatal myocardial infarction, or fatal or nonfatal stroke.

The information required to estimate risk includes age, sex, race, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, use of blood pressure-lowering medication, diabetes status, and smoking status. The guideline recommends an easy-to-use online risk calculator (http://tools.acc.org/ASCVD-Risk-Estimator).

A 10-year risk of 10% or more is designated as the cutoff between high risk and low risk. However, this is not based on trial evidence, and the risk calculator has not been verified in prospective trials to show that its use reduces cardiovascular events. The SPRINT trial,² which was a study of blood pressure-lowering in high-risk patients, used a 10-year risk of 15% or more based on the Framingham risk score to delineate high risk.

Additionally, the 10-year risk calculator is valid only in patients ages 40 through 79, and some studies indicate that it may overestimate risk in older adults.^14,15 This overestimation may lead to patients being started on pharmacologic therapy when it may not truly be indicated. The risk calculator controversy has been discussed in a previous issue of this journal.¹⁶

Blood pressure goals

Strong recommendation for known cardiovascular disease or atherosclerotic cardiovascular disease risk 10% or greater, weak recommendation for risk less than 10%, based on moderate-quality evidence for systolic blood pressure, expert opinion for diastolic.

The guidelines recommend a blood pressure goal of less than 130/80 mm Hg for all patients, including the elderly and patients with chronic kidney disease or diabetes.

The SPRINT trial,² which showed better cardiovascular outcomes in the intensive treatment group (aiming for systolic pressure < 120 mm Hg) compared with a standard treatment group (aiming for systolic pressure < 140 mm Hg), excluded participants with diabetes and severe chronic kidney disease (estimated glomerular filtration rate < 20 mL/min/m² and proteinuria > 1 g/day), and those who were in nursing homes or had dementia.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial showed that intensive blood pressure control did not have cardiovascular benefits compared with standard therapy.¹⁷ However, many now believe that the study may have been underpowered due to its design, and a meta-analysis of the results from SPRINT and ACCORD suggested that findings from both trials were consistent, favoring intensive blood pressure control in a high-risk population.¹⁸

While the totality of evidence favors a lower achieved blood pressure for many patients, this lower goal may be difficult to achieve in many, particularly those with vascular stiffness, which is common in the elderly. These patients also tend to have low diastolic pressure, and lowering diastolic pressure below 60 mm Hg in those with documented coronary artery disease could increase the risk of adverse cardiovascular outcomes.^19,20 The guidelines do not address the potential issues with lowering diastolic blood pressure.

Our opinion. While a “universal” blood pressure goal may simplify decision-making, we believe it is important to individualize goals, taking into account patient characteristics, lifestyle factors, medication side effects, patient preferences, cost issues, and adherence to therapy.

The goal blood pressure should also consider the method of measurement. Systolic blood pressure readings have been reported to be 5 to 10 mm Hg lower with automated office measurement than with routine office measurement.²¹

It is also not clear that the magnitude of absolute benefit from pursuing more intensive blood pressure control with antihypertensive therapy in patients with high cardiovascular risk (as in SPRINT) would translate to similar benefits in a lower-risk population. Thus, we believe that in patients with lower cardiovascular risk, a goal blood pressure of less than 140/90 mm Hg (if routine office measurement is done) and less than 135/85 mm Hg (if automated office measurement is done) would be reasonable.

We also believe that it is reasonable to relax these goals in the very elderly (age ≥ 80), especially those who are frail and at risk of falls, with low diastolic pressures. In these patients, we recommend individualizing blood pressure goals that can be achieved without significant side effects from antihypertensive therapy.

Nonpharmacologic therapy

Strong recommendation, based on high-quality evidence from randomized controlled trials

Nonpharmacologic therapy and lifestyle modification are appropriately emphasized in the new guidelines. Most of the lifestyle changes that are recommended are in concordance with prior JNC 7 recommendations.³

Recognizing the roles of sodium and potassium in the pathogenesis of hypertension, the guidelines emphasize a diet that is higher in potassium, the DASH (Dietary Approaches to Stop Hypertension) diet, and a low-sodium diet. The recommended optimal goal of sodium intake of less than 1,500 mg/day may be difficult to achieve with a Western diet, and there is debate about the potential adverse effects of a very-low sodium diet.²² The general recommendation for sodium intake of less than 2,300 mg/day is supported in the literature, and it is unclear if further reduction has additional beneficial effects on blood pressure.²³

The guidelines recommend a 3- to 6-month reassessment of patients who are prescribed risk-factor modification, but are unclear about initiation of pharmacologic therapy or other steps if these low-risk patients have not responded to lifestyle modifications alone at the time of reassessment.

Pharmacologic therapy

Strong recommendation, based on high-quality evidence from randomized controlled trials for systolic blood pressure, expert opinion for diastolic blood pressure for those with atherosclerotic cardiovascular disease risk 10% or greater, and limited data for those with risk less than 10%.

Pharmacologic therapy is recommended in patients with stage 1 hypertension and pre-existing cardiovascular disease or 10-year risk of atherosclerotic cardiovascular disease of 10% or more, and in those with stage 2 hypertension even if their 10-year risk is less than 10%.

In the absence of compelling indications, the primary drugs recommended for initial therapy are:

• Thiazide or thiazide-type diuretics (preferably chlorthalidone)
• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin II receptor blockers (ARBs)
• Calcium channel blockers (CCBs).

In black adults, thiazide diuretics or CCBs are recommended for initial therapy. Beta-blockers are not recommended as first-line agents in the absence of a compelling indication, although meta-analyses that suggested beta-blockers are less effective than other classes of agents included trials that used beta-blockers in doses now considered suboptimal. ACE inhibitors or ARBs are recommended as initial therapy in proteinuric patients with chronic kidney disease or diabetes. Combining an ACE inhibitor and an ARB or renin inhibitor is potentially harmful and is not recommended. The guidelines provide a helpful table describing important characteristics and available dosage forms of the commonly used antihypertensive agents.

These recommendations are concordant with the JNC 8 panel recommendations,⁵ and differ from JNC 7, which recommended thiazide-type diuretics as first-line therapy.³ The European guidelines recommend that all major classes of antihypertensive agents, including beta-blockers, are suitable for initiation of therapy.²⁴ The UK National Institute for Clinical Excellence guidelines adopt an age-based approach to deciding initial therapy—with ACE inhibitors or ARBs favored in those below the age of 55 and CCBs in those who are 55 and older.²⁵

Starting with a single antihypertensive agent is recommended for stage 1 hypertension with increased cardiovascular risk, and starting with 2 agents (either separately or in fixed-dose combination) is recommended for stage 2 hypertension. The guidelines emphasize a team-based approach to improve hypertension care, using adjunctive interventions such as telehealth strategies and leveraging electronic medical records to guide quality improvement initiatives.

Our opinion. We agree with Bakris and Sorrentino^₂₆ that general patient profiles should be considered to decide on efficient pharmacologic management in clinical practice—thiazide diuretics would be best in those who are volume-expanded; ACE inhibitors, ARBs, or CCBs in those who are obese or have metabolic syndrome; and beta-blockers or nondihydropyridine CCBs in those who are hyperadrenergic. More patients will likely be classified as having resistant hypertension based on the blood pressure goal of less than 130/80 mm Hg, which may require greater use of mineralocorticoid receptor antagonists such as spironolactone.

STRENGTHS AND LIMITATIONS

The new guidelines stress correct technique of blood pressure measurement, out-of-office and self-monitoring of blood pressure, and lifestyle modifications. In addition, they comprehensively review topics relevant to hypertension management of practical use for healthcare providers, including resistant hypertension, secondary hypertension, hypertensive crises, and special populations. The guidelines also incorporate multiple lines of evidence rather than just randomized controlled trials (which may not be available for every scenario).

There will be ongoing debate and discussion about the new definition and classification of hypertension, and the “conversion” of previously healthy adults to a new disease category. The blood pressure goals will also be debated: Should the goal for a young patient be applied to an elderly patient? The pathophysiology of the disease process should be considered rather than a one-size-fits-all approach. For example, older patients with stiff arteries and low diastolic blood pressure will have more difficulty achieving a lower systolic pressure, are more likely to experience medication side effects, and may have adherence issues due to polypharmacy.

A clinical trial, with strict adherence to protocols and rigorous follow-up procedures, is different from real-world clinical practice. Busy clinical practices with time and space constraints may forgo the steps needed for accurate blood pressure measurement in the office and may not reinforce lifestyle modifications, instead opting for more pharmacologic therapy to achieve a blood pressure goal that may become mandated by healthcare payment models without consideration for clinical judgment and individual patient characteristics.

The ACC/AHA guidelines have not been universally endorsed. The American College of Physicians and the American Academy of Family Physicians released their own guidelines for older adults earlier in 2017, echoing the recommendations from the panel appointed to JNC 8.²⁷ Contrasting recommendations can unfortunately lead to confusion among healthcare providers and patients and can undermine confidence and trust in the healthcare system.

In the background of ongoing debate, where battle lines have been drawn by key stakeholders with regard to their contrasting positions, it is even more important for the practicing clinician who is in the front lines of hypertension management to be knowledgeable about the pros and cons of different recommendations as they apply to individual patients, and to be able to clearly communicate this with patients when deciding on a treatment plan.

FINAL THOUGHTS

• Accurate measurement of blood pressure in the office is imperative—position the patient properly, use an appropriately sized  cuff, and allow for a period of rest. Consider using automated office measurement to minimize potential white coat effect.
• Out-of-office blood pressure monitoring is recommended to confirm the diagnosis of hypertension and for monitoring response to therapy. Ambulatory monitoring is preferred, but home blood pressure monitoring can be done if ambulatory monitoring is unavailable or unfeasible.
• Nonpharmacologic therapy should be emphasized for everyone, regardless of blood pressure level.
• Guidelines should be used as a framework for management. Individualize decisions about blood pressure goals and pharmacologic therapy based on patient characteristics and clinical judgment.

In 2017, the American College of Cardiology (ACC), American Heart Association (AHA), and 9 other professional associations published a new guideline on high blood pressure in adults.¹ Their document addresses a range of topics relevant to preventing, diagnosing, and managing hypertension. It incorporates evidence from randomized controlled trials, including the Systolic Blood Pressure Intervention Trial (SPRINT),² systematic reviews, and expert opinion.

The new guidelines contain many noteworthy changes, some of which are generating intense debate and discussion. Here, we provide our opinions to help practicing clinicians broaden their perspective and make informed decisions about management.

ACC AND AHA ARE NOW RESPONSIBLE FOR HYPERTENSION GUIDELINES

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC), organized by the National Heart, Lung, and Blood Institute, began issuing hypertension guidelines in 1977. Based on observational and clinical trial data, succeeding JNC reports recommended ever-lower blood pressure goals, with emphasis shifting to treatment of systolic hypertension.

The last official JNC report—JNC 7—was published in 2003.³ In 2013, the Institute transferred the responsibility for cardiovascular prevention guidelines to the ACC and AHA.⁴

A report from the panel members appointed to JNC 8 was published independently in 2014.⁵ It focused on a few key questions and used evidence limited to randomized controlled trials. In this report, the panel relaxed the goals for many subgroups, leading to criticism from many professional societies and from some members of the panel writing group.⁶

WHAT'S NEW IN THE 2017 GUIDELINES?

The new ACC/AHA guidelines contain a number of changes from previous documents that have been the topic of debate.

New definition and classification of hypertension

Strong recommendation, based on moderate-quality evidence­.

Our opinion. While this new classification is intended to promote closer monitoring and earlier intervention to lower cardiovascular event rates, creating a new level of disease may lead to more pharmacologic treatment for those with lower risk, without emphasis on lifestyle modifications.

Emphasis on measurement technique and out-of-office measurements

Strong recommendation, based on expert opinion, for accurate measurement of blood pressure in the office, high-quality evidence from systematic review for out-of-office measurement.

Appropriate management of hypertension entails accurate blood pressure measurement. While office-based measurement remains the most commonly used method, this “snapshot” may not reflect a patient’s true baseline blood pressure.

Out-of-office measurements. Based on the results of a systematic review commissioned by the guideline committee, out-of-office measurements are now recommended to confirm the diagnosis of hypertension and to assess response to therapy.

Ambulatory blood pressure monitoring should be strongly considered as the preferred method for out-of-office monitoring; home blood pressure monitoring can be done if ambulatory monitoring is not feasible. Ambulatory monitoring provides additional information on nighttime blood pressure, including the dipping status (normal defined as a nighttime blood pressure decrease of 10% to 20%). Ambulatory monitoring predicts long-term cardiovascular outcomes independent of office blood pressure, and elevated nighttime pressure and non-dipping have been shown to be independently associated with increased cardiovascular mortality rates.^8,9 Unfortunately, despite evidence supporting its use, ambulatory blood pressure monitoring is not widely available for a variety of reasons, including high cost (roughly $2,000–$4,000) and minimal reimbursement.

Out-of-office measurements can also detect white coat hypertension and masked hypertension. White coat hypertension is defined as blood pressure that is elevated in the office but normal in an out-of-office setting, and masked hypertension is blood pressure that is normal in the office and elevated in an out-of-office setting. Currently, pharmacologic therapy is not recommended to treat white coat hypertension, and treatment for masked hypertension should be the same as for sustained hypertension.

While the guidelines do not comment specifically on manual office measurement vs automated office measurements using devices that take multiple measurements with the patient alone in the room to reduce the white coat effect, they acknowledge “increasing evidence” favoring the use of automated office measurement.

Proper technique for measuring blood pressure is appropriately emphasized; correct patient positioning, allowing a period of rest, and using the appropriate cuff size are all important. Unfortunately, many busy clinical practices may not follow correct technique when measuring blood pressure in the office, leading to misdiagnosis and unnecessary pharmacologic therapy that may result in adverse events.

Of note, the SPRINT trial, which informed many of the new guideline recommendations, followed a strict protocol of blood pressure measurement with an automated device, checking sitting blood pressure 3 times at 1-minute intervals, with the patient alone in the room and without an observer present at many of the sites.¹⁰

Most guidelines^11,12 agree on an average of at least 135/85 mm Hg as the threshold for diagnosing hypertension by home monitoring, or an average daytime pressure of at least 135/85 mm Hg by ambulatory monitoring, corresponding with office-based blood pressure of 140/90 mm Hg.­ However, the new guidelines recommend a lower threshold of 130/80 mm Hg for both home monitoring and average daytime ambulatory monitoring, corresponding with an office blood pressure of 130/80 mm Hg. They do not specify whether the office-based measurement is manual or automated.

Our opinion. Since office-based measurement will likely remain the principal method for managing hypertension due to constraints with ambulatory or home monitoring, the use of automated devices for office measurement should be strongly considered. Studies have shown that, compared with routine office measurements, automated measurements more closely approximate those obtained by ambulatory and home blood pressure monitoring.¹³

Risk-based approach to hypertension management

The algorithm for hypertension management now incorporates objective assessment of cardiovascular risk. Specifically, it calls for estimation of the 10-year risk of atherosclerotic cardiovascular disease, defined as coronary heart disease death, nonfatal myocardial infarction, or fatal or nonfatal stroke.

The information required to estimate risk includes age, sex, race, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, use of blood pressure-lowering medication, diabetes status, and smoking status. The guideline recommends an easy-to-use online risk calculator (http://tools.acc.org/ASCVD-Risk-Estimator).

A 10-year risk of 10% or more is designated as the cutoff between high risk and low risk. However, this is not based on trial evidence, and the risk calculator has not been verified in prospective trials to show that its use reduces cardiovascular events. The SPRINT trial,² which was a study of blood pressure-lowering in high-risk patients, used a 10-year risk of 15% or more based on the Framingham risk score to delineate high risk.

Additionally, the 10-year risk calculator is valid only in patients ages 40 through 79, and some studies indicate that it may overestimate risk in older adults.^14,15 This overestimation may lead to patients being started on pharmacologic therapy when it may not truly be indicated. The risk calculator controversy has been discussed in a previous issue of this journal.¹⁶

Blood pressure goals

Strong recommendation for known cardiovascular disease or atherosclerotic cardiovascular disease risk 10% or greater, weak recommendation for risk less than 10%, based on moderate-quality evidence for systolic blood pressure, expert opinion for diastolic.

The guidelines recommend a blood pressure goal of less than 130/80 mm Hg for all patients, including the elderly and patients with chronic kidney disease or diabetes.

The SPRINT trial,² which showed better cardiovascular outcomes in the intensive treatment group (aiming for systolic pressure < 120 mm Hg) compared with a standard treatment group (aiming for systolic pressure < 140 mm Hg), excluded participants with diabetes and severe chronic kidney disease (estimated glomerular filtration rate < 20 mL/min/m² and proteinuria > 1 g/day), and those who were in nursing homes or had dementia.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial showed that intensive blood pressure control did not have cardiovascular benefits compared with standard therapy.¹⁷ However, many now believe that the study may have been underpowered due to its design, and a meta-analysis of the results from SPRINT and ACCORD suggested that findings from both trials were consistent, favoring intensive blood pressure control in a high-risk population.¹⁸

While the totality of evidence favors a lower achieved blood pressure for many patients, this lower goal may be difficult to achieve in many, particularly those with vascular stiffness, which is common in the elderly. These patients also tend to have low diastolic pressure, and lowering diastolic pressure below 60 mm Hg in those with documented coronary artery disease could increase the risk of adverse cardiovascular outcomes.^19,20 The guidelines do not address the potential issues with lowering diastolic blood pressure.

Our opinion. While a “universal” blood pressure goal may simplify decision-making, we believe it is important to individualize goals, taking into account patient characteristics, lifestyle factors, medication side effects, patient preferences, cost issues, and adherence to therapy.

The goal blood pressure should also consider the method of measurement. Systolic blood pressure readings have been reported to be 5 to 10 mm Hg lower with automated office measurement than with routine office measurement.²¹

It is also not clear that the magnitude of absolute benefit from pursuing more intensive blood pressure control with antihypertensive therapy in patients with high cardiovascular risk (as in SPRINT) would translate to similar benefits in a lower-risk population. Thus, we believe that in patients with lower cardiovascular risk, a goal blood pressure of less than 140/90 mm Hg (if routine office measurement is done) and less than 135/85 mm Hg (if automated office measurement is done) would be reasonable.

We also believe that it is reasonable to relax these goals in the very elderly (age ≥ 80), especially those who are frail and at risk of falls, with low diastolic pressures. In these patients, we recommend individualizing blood pressure goals that can be achieved without significant side effects from antihypertensive therapy.

Nonpharmacologic therapy

Strong recommendation, based on high-quality evidence from randomized controlled trials

Nonpharmacologic therapy and lifestyle modification are appropriately emphasized in the new guidelines. Most of the lifestyle changes that are recommended are in concordance with prior JNC 7 recommendations.³

Recognizing the roles of sodium and potassium in the pathogenesis of hypertension, the guidelines emphasize a diet that is higher in potassium, the DASH (Dietary Approaches to Stop Hypertension) diet, and a low-sodium diet. The recommended optimal goal of sodium intake of less than 1,500 mg/day may be difficult to achieve with a Western diet, and there is debate about the potential adverse effects of a very-low sodium diet.²² The general recommendation for sodium intake of less than 2,300 mg/day is supported in the literature, and it is unclear if further reduction has additional beneficial effects on blood pressure.²³

The guidelines recommend a 3- to 6-month reassessment of patients who are prescribed risk-factor modification, but are unclear about initiation of pharmacologic therapy or other steps if these low-risk patients have not responded to lifestyle modifications alone at the time of reassessment.

Pharmacologic therapy

Strong recommendation, based on high-quality evidence from randomized controlled trials for systolic blood pressure, expert opinion for diastolic blood pressure for those with atherosclerotic cardiovascular disease risk 10% or greater, and limited data for those with risk less than 10%.

Pharmacologic therapy is recommended in patients with stage 1 hypertension and pre-existing cardiovascular disease or 10-year risk of atherosclerotic cardiovascular disease of 10% or more, and in those with stage 2 hypertension even if their 10-year risk is less than 10%.

In the absence of compelling indications, the primary drugs recommended for initial therapy are:

• Thiazide or thiazide-type diuretics (preferably chlorthalidone)
• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin II receptor blockers (ARBs)
• Calcium channel blockers (CCBs).

In black adults, thiazide diuretics or CCBs are recommended for initial therapy. Beta-blockers are not recommended as first-line agents in the absence of a compelling indication, although meta-analyses that suggested beta-blockers are less effective than other classes of agents included trials that used beta-blockers in doses now considered suboptimal. ACE inhibitors or ARBs are recommended as initial therapy in proteinuric patients with chronic kidney disease or diabetes. Combining an ACE inhibitor and an ARB or renin inhibitor is potentially harmful and is not recommended. The guidelines provide a helpful table describing important characteristics and available dosage forms of the commonly used antihypertensive agents.

These recommendations are concordant with the JNC 8 panel recommendations,⁵ and differ from JNC 7, which recommended thiazide-type diuretics as first-line therapy.³ The European guidelines recommend that all major classes of antihypertensive agents, including beta-blockers, are suitable for initiation of therapy.²⁴ The UK National Institute for Clinical Excellence guidelines adopt an age-based approach to deciding initial therapy—with ACE inhibitors or ARBs favored in those below the age of 55 and CCBs in those who are 55 and older.²⁵

Starting with a single antihypertensive agent is recommended for stage 1 hypertension with increased cardiovascular risk, and starting with 2 agents (either separately or in fixed-dose combination) is recommended for stage 2 hypertension. The guidelines emphasize a team-based approach to improve hypertension care, using adjunctive interventions such as telehealth strategies and leveraging electronic medical records to guide quality improvement initiatives.

Our opinion. We agree with Bakris and Sorrentino^₂₆ that general patient profiles should be considered to decide on efficient pharmacologic management in clinical practice—thiazide diuretics would be best in those who are volume-expanded; ACE inhibitors, ARBs, or CCBs in those who are obese or have metabolic syndrome; and beta-blockers or nondihydropyridine CCBs in those who are hyperadrenergic. More patients will likely be classified as having resistant hypertension based on the blood pressure goal of less than 130/80 mm Hg, which may require greater use of mineralocorticoid receptor antagonists such as spironolactone.

STRENGTHS AND LIMITATIONS

The new guidelines stress correct technique of blood pressure measurement, out-of-office and self-monitoring of blood pressure, and lifestyle modifications. In addition, they comprehensively review topics relevant to hypertension management of practical use for healthcare providers, including resistant hypertension, secondary hypertension, hypertensive crises, and special populations. The guidelines also incorporate multiple lines of evidence rather than just randomized controlled trials (which may not be available for every scenario).

There will be ongoing debate and discussion about the new definition and classification of hypertension, and the “conversion” of previously healthy adults to a new disease category. The blood pressure goals will also be debated: Should the goal for a young patient be applied to an elderly patient? The pathophysiology of the disease process should be considered rather than a one-size-fits-all approach. For example, older patients with stiff arteries and low diastolic blood pressure will have more difficulty achieving a lower systolic pressure, are more likely to experience medication side effects, and may have adherence issues due to polypharmacy.

A clinical trial, with strict adherence to protocols and rigorous follow-up procedures, is different from real-world clinical practice. Busy clinical practices with time and space constraints may forgo the steps needed for accurate blood pressure measurement in the office and may not reinforce lifestyle modifications, instead opting for more pharmacologic therapy to achieve a blood pressure goal that may become mandated by healthcare payment models without consideration for clinical judgment and individual patient characteristics.

The ACC/AHA guidelines have not been universally endorsed. The American College of Physicians and the American Academy of Family Physicians released their own guidelines for older adults earlier in 2017, echoing the recommendations from the panel appointed to JNC 8.²⁷ Contrasting recommendations can unfortunately lead to confusion among healthcare providers and patients and can undermine confidence and trust in the healthcare system.

In the background of ongoing debate, where battle lines have been drawn by key stakeholders with regard to their contrasting positions, it is even more important for the practicing clinician who is in the front lines of hypertension management to be knowledgeable about the pros and cons of different recommendations as they apply to individual patients, and to be able to clearly communicate this with patients when deciding on a treatment plan.

FINAL THOUGHTS

• Accurate measurement of blood pressure in the office is imperative—position the patient properly, use an appropriately sized  cuff, and allow for a period of rest. Consider using automated office measurement to minimize potential white coat effect.
• Out-of-office blood pressure monitoring is recommended to confirm the diagnosis of hypertension and for monitoring response to therapy. Ambulatory monitoring is preferred, but home blood pressure monitoring can be done if ambulatory monitoring is unavailable or unfeasible.
• Nonpharmacologic therapy should be emphasized for everyone, regardless of blood pressure level.
• Guidelines should be used as a framework for management. Individualize decisions about blood pressure goals and pharmacologic therapy based on patient characteristics and clinical judgment.

Bicuspid aortic valve is the most common congenital cardiac abnormality in humans and is a significant risk factor for premature aortic valve dysfunction due to accelerated leaflet deterioration and calcification from altered hemodynamics. From 20% to 50% of patients with bicuspid aortic valve need aortic valve replacement during their lifetime, mostly for aortic stenosis.^1,2

See related article

While 0.5% to 2% of the general population are born with a bicuspid aortic valve, more than 40% of patients (mainly younger patients) who undergo surgical or transcatheter intervention for aortic valve disease in some cohorts have this abnormality, suggesting that its true prevalence may be underreported.³

In the past decade, transcatheter aortic valve replacement (TAVR) has cemented its place as an option for patients with severe tricuspid aortic stenosis who cannot undergo surgery because their surgical risk is intermediate or high.⁴ However, most of the studies of balloon-expandable and self-expanding TAVR devices have excluded patients with bicuspid aortic valve.

BICUSPID AORTIC VALVE POSES CHALLENGES FOR TAVR

As TAVR is explored in younger and lower-risk populations, in which the prevalence of bicuspid aortic valve is presumably higher, the discussion of feasibility, safety, and efficacy of TAVR in patients with bicuspid aortic valve is both important and timely.

Bicuspid aortic valve is commonly categorized according to the Sievers classification,⁵ which describes 3 main morphologic types (designated types 0, 1, and 2) according to the number of raphes connecting the leaflets. Unique anatomic features of bicuspid aortic valve render the TAVR procedure challenging in these patients and merit consideration. These include, but are not limited to:

• Asymmetric calcification of the valve leaflets and calcified raphes. This results in asymmetric and incomplete expansion of the prosthesis, leading to incomplete sealing and paravalvular leak.
• A larger and more elliptically shaped aortic annulus, leading to challenges with proper sizing and apposition of the prosthesis
• Concomitant aortopathy, posing a higher risk of aortic rupture, dissection, paravalvular leak, and other complications during implantation.

Thus, compared with patients with tricuspid degenerative aortic stenosis, patients undergoing TAVR who have bicuspid aortic valve have a higher short-term risk of death and a higher risk of residual aortic regurgitation, and are more likely to need implantation of a second valve.

PARAVALVULAR LEAK

Paravalvular leak, arguably an independent marker of higher morbidity and mortality risk after TAVR, is more common in patients with bicuspid aortic valve undergoing TAVR than in those with tricuspid aortic valve. Earlier studies reported rates of moderate or severe paravalvular leak between 16% and 32%.^6,7

The newer-generation balloon-expandable Sapien 3 valve (Edwards Lifesciences, Irvine, CA) is associated with a lower incidence of moderate or severe paravalvular leak than earlier devices, mainly attributable to its outer skirt, which allows more complete sealing.⁸ There are also reports of successful treatment of bicuspid aortic valve stenosis using the Lotus device (Boston Scientific, Marlborough, MA).⁹ This device features adaptive sealing along with retrievability and repositioning ability, which may facilitate optimal positioning and prevent paravalvular leak.

Sizing of the prosthesis in patients with bicuspid aortic valve stenosis remains a challenge: some experts advocate the usual practice of measuring the perimeter and area at the level of the annulus, while others advocate measuring at the level of the commissures, 4 to 8 mm above the annulus. Balloon valvuloplasty may be a useful sizing tool, though it carries the hazards of severe aortic regurgitation and periprocedural stroke.

Angiography of the ascending aorta during balloon valvuloplasty can help verify whether an adequate seal is achievable and aid in selecting an appropriately sized prosthesis. Liu et al¹⁰ performed sequential balloon aortic valvuloplasty before TAVR with a self-expanding valve in 12 patients. Of these, 11 (91.7%) received a smaller device than they would have with multidetector computed tomography-guided annulus measurement.

Given that a larger valve may increase the risk of annular rupture, implantation of a smaller valve is always reasonable in bicuspid aortic valve as long as it achieves appropriate sealing with no paravalvular leak.

THE NEED FOR A PACEMAKER

After undergoing TAVR, more patients who have a bicuspid aortic valve need a permanent pacemaker than those who have a tricuspid aortic valve. This group appears to be more vulnerable to conduction abnormalities after TAVR, and rates of new pacemaker implantation as high as 25% have been reported with the newer-generation devices. Perlman et al⁸ observed that even when the Sapien 3 valve was implanted high in the left ventricular outflow tract, nearly 10% of patients needed a new pacemaker.

This is an important issue, as most patients with bicuspid aortic valve with severe aortic stenosis are relatively young and may endure deleterious effects from long-term pacing.

LONG-TERM OUTCOMES

The data on long-term outcomes of patients with bicuspid aortic valve who undergo TAVR are limited, and the available studies were small, with relatively short-term follow-up. However, Yoon et al compared TAVR outcomes between bicuspid and tricuspid aortic stenosis patients using propensity-score matching and demonstrated comparable all-cause mortality rates at 2 years (17.2% vs 19.4%, P = .28).⁶

Given the relatively long life expectancy of patients with bicuspid aortic valve undergoing TAVR, who tend to be younger than those with tricuspid aortic valve stenosis, longer-term data are needed to draw meaningful conclusions about the durability of transcatheter valves in this population. The bicuspid aortic valve is asymmetric, so that during TAVR the stent may not expand completely, and this in theory may result in more strain on the prosthesis and accelerate its structural deterioration.

In a recent meta-analysis, Reddy et al¹¹ analyzed 13 observational studies in 758 patients with severe bicuspid aortic valve stenosis undergoing TAVR with older and newer devices. The mean Society of Thoracic Surgeons Predicted Risk of Mortality score, which predicts the risk of death within 30 days, was 5.0%, but the actual rate was 3.7% (95% confidence interval [CI] 2.1%–5.6%). A high procedural success rate of 95% (95% CI 90.2%–98.5%] was also noted, but the rates of new permanent pacemaker implantation (17.9%, 95% CI 14.2%–22%) and severe perivalvular leak (12.2%, 95% CI 3.1%–24.8%) were somewhat elevated.¹¹

NOT FOR ALL, BUT AN EMERGING, VIABLE OPTION

As implanted prostheses and TAVR techniques undergo continuous improvement and as the experience of operators and institutions advances, procedural outcomes will likely improve.

The available data suggest that TAVR with the newer devices, when performed by experienced hands, is a viable option across most of the risk spectrum in patients with severe tricuspid aortic stenosis, including low-risk patients,¹² and selectively in patients with bicuspid aortic valve stenosis. However, for patients with bicuspid aortic valve with severe aortic stenosis and associated aortopathy, surgery remains the standard of care.

More study is needed to identify patients with bicuspid aortic valve who can be safely and effectively treated with TAVR.

Bicuspid aortic valve is the most common congenital cardiac abnormality in humans and is a significant risk factor for premature aortic valve dysfunction due to accelerated leaflet deterioration and calcification from altered hemodynamics. From 20% to 50% of patients with bicuspid aortic valve need aortic valve replacement during their lifetime, mostly for aortic stenosis.^1,2

See related article

While 0.5% to 2% of the general population are born with a bicuspid aortic valve, more than 40% of patients (mainly younger patients) who undergo surgical or transcatheter intervention for aortic valve disease in some cohorts have this abnormality, suggesting that its true prevalence may be underreported.³

In the past decade, transcatheter aortic valve replacement (TAVR) has cemented its place as an option for patients with severe tricuspid aortic stenosis who cannot undergo surgery because their surgical risk is intermediate or high.⁴ However, most of the studies of balloon-expandable and self-expanding TAVR devices have excluded patients with bicuspid aortic valve.

BICUSPID AORTIC VALVE POSES CHALLENGES FOR TAVR

As TAVR is explored in younger and lower-risk populations, in which the prevalence of bicuspid aortic valve is presumably higher, the discussion of feasibility, safety, and efficacy of TAVR in patients with bicuspid aortic valve is both important and timely.

Bicuspid aortic valve is commonly categorized according to the Sievers classification,⁵ which describes 3 main morphologic types (designated types 0, 1, and 2) according to the number of raphes connecting the leaflets. Unique anatomic features of bicuspid aortic valve render the TAVR procedure challenging in these patients and merit consideration. These include, but are not limited to:

• Asymmetric calcification of the valve leaflets and calcified raphes. This results in asymmetric and incomplete expansion of the prosthesis, leading to incomplete sealing and paravalvular leak.
• A larger and more elliptically shaped aortic annulus, leading to challenges with proper sizing and apposition of the prosthesis
• Concomitant aortopathy, posing a higher risk of aortic rupture, dissection, paravalvular leak, and other complications during implantation.

Thus, compared with patients with tricuspid degenerative aortic stenosis, patients undergoing TAVR who have bicuspid aortic valve have a higher short-term risk of death and a higher risk of residual aortic regurgitation, and are more likely to need implantation of a second valve.

PARAVALVULAR LEAK

Paravalvular leak, arguably an independent marker of higher morbidity and mortality risk after TAVR, is more common in patients with bicuspid aortic valve undergoing TAVR than in those with tricuspid aortic valve. Earlier studies reported rates of moderate or severe paravalvular leak between 16% and 32%.^6,7

The newer-generation balloon-expandable Sapien 3 valve (Edwards Lifesciences, Irvine, CA) is associated with a lower incidence of moderate or severe paravalvular leak than earlier devices, mainly attributable to its outer skirt, which allows more complete sealing.⁸ There are also reports of successful treatment of bicuspid aortic valve stenosis using the Lotus device (Boston Scientific, Marlborough, MA).⁹ This device features adaptive sealing along with retrievability and repositioning ability, which may facilitate optimal positioning and prevent paravalvular leak.

Sizing of the prosthesis in patients with bicuspid aortic valve stenosis remains a challenge: some experts advocate the usual practice of measuring the perimeter and area at the level of the annulus, while others advocate measuring at the level of the commissures, 4 to 8 mm above the annulus. Balloon valvuloplasty may be a useful sizing tool, though it carries the hazards of severe aortic regurgitation and periprocedural stroke.

Angiography of the ascending aorta during balloon valvuloplasty can help verify whether an adequate seal is achievable and aid in selecting an appropriately sized prosthesis. Liu et al¹⁰ performed sequential balloon aortic valvuloplasty before TAVR with a self-expanding valve in 12 patients. Of these, 11 (91.7%) received a smaller device than they would have with multidetector computed tomography-guided annulus measurement.

Given that a larger valve may increase the risk of annular rupture, implantation of a smaller valve is always reasonable in bicuspid aortic valve as long as it achieves appropriate sealing with no paravalvular leak.

THE NEED FOR A PACEMAKER

After undergoing TAVR, more patients who have a bicuspid aortic valve need a permanent pacemaker than those who have a tricuspid aortic valve. This group appears to be more vulnerable to conduction abnormalities after TAVR, and rates of new pacemaker implantation as high as 25% have been reported with the newer-generation devices. Perlman et al⁸ observed that even when the Sapien 3 valve was implanted high in the left ventricular outflow tract, nearly 10% of patients needed a new pacemaker.

This is an important issue, as most patients with bicuspid aortic valve with severe aortic stenosis are relatively young and may endure deleterious effects from long-term pacing.

LONG-TERM OUTCOMES

The data on long-term outcomes of patients with bicuspid aortic valve who undergo TAVR are limited, and the available studies were small, with relatively short-term follow-up. However, Yoon et al compared TAVR outcomes between bicuspid and tricuspid aortic stenosis patients using propensity-score matching and demonstrated comparable all-cause mortality rates at 2 years (17.2% vs 19.4%, P = .28).⁶

Given the relatively long life expectancy of patients with bicuspid aortic valve undergoing TAVR, who tend to be younger than those with tricuspid aortic valve stenosis, longer-term data are needed to draw meaningful conclusions about the durability of transcatheter valves in this population. The bicuspid aortic valve is asymmetric, so that during TAVR the stent may not expand completely, and this in theory may result in more strain on the prosthesis and accelerate its structural deterioration.

In a recent meta-analysis, Reddy et al¹¹ analyzed 13 observational studies in 758 patients with severe bicuspid aortic valve stenosis undergoing TAVR with older and newer devices. The mean Society of Thoracic Surgeons Predicted Risk of Mortality score, which predicts the risk of death within 30 days, was 5.0%, but the actual rate was 3.7% (95% confidence interval [CI] 2.1%–5.6%). A high procedural success rate of 95% (95% CI 90.2%–98.5%] was also noted, but the rates of new permanent pacemaker implantation (17.9%, 95% CI 14.2%–22%) and severe perivalvular leak (12.2%, 95% CI 3.1%–24.8%) were somewhat elevated.¹¹

NOT FOR ALL, BUT AN EMERGING, VIABLE OPTION

As implanted prostheses and TAVR techniques undergo continuous improvement and as the experience of operators and institutions advances, procedural outcomes will likely improve.

The available data suggest that TAVR with the newer devices, when performed by experienced hands, is a viable option across most of the risk spectrum in patients with severe tricuspid aortic stenosis, including low-risk patients,¹² and selectively in patients with bicuspid aortic valve stenosis. However, for patients with bicuspid aortic valve with severe aortic stenosis and associated aortopathy, surgery remains the standard of care.

More study is needed to identify patients with bicuspid aortic valve who can be safely and effectively treated with TAVR.

Bicuspid aortic valve is the most common congenital cardiac abnormality in humans and is a significant risk factor for premature aortic valve dysfunction due to accelerated leaflet deterioration and calcification from altered hemodynamics. From 20% to 50% of patients with bicuspid aortic valve need aortic valve replacement during their lifetime, mostly for aortic stenosis.^1,2

See related article

While 0.5% to 2% of the general population are born with a bicuspid aortic valve, more than 40% of patients (mainly younger patients) who undergo surgical or transcatheter intervention for aortic valve disease in some cohorts have this abnormality, suggesting that its true prevalence may be underreported.³

In the past decade, transcatheter aortic valve replacement (TAVR) has cemented its place as an option for patients with severe tricuspid aortic stenosis who cannot undergo surgery because their surgical risk is intermediate or high.⁴ However, most of the studies of balloon-expandable and self-expanding TAVR devices have excluded patients with bicuspid aortic valve.

BICUSPID AORTIC VALVE POSES CHALLENGES FOR TAVR

As TAVR is explored in younger and lower-risk populations, in which the prevalence of bicuspid aortic valve is presumably higher, the discussion of feasibility, safety, and efficacy of TAVR in patients with bicuspid aortic valve is both important and timely.

Bicuspid aortic valve is commonly categorized according to the Sievers classification,⁵ which describes 3 main morphologic types (designated types 0, 1, and 2) according to the number of raphes connecting the leaflets. Unique anatomic features of bicuspid aortic valve render the TAVR procedure challenging in these patients and merit consideration. These include, but are not limited to:

• Asymmetric calcification of the valve leaflets and calcified raphes. This results in asymmetric and incomplete expansion of the prosthesis, leading to incomplete sealing and paravalvular leak.
• A larger and more elliptically shaped aortic annulus, leading to challenges with proper sizing and apposition of the prosthesis
• Concomitant aortopathy, posing a higher risk of aortic rupture, dissection, paravalvular leak, and other complications during implantation.

Thus, compared with patients with tricuspid degenerative aortic stenosis, patients undergoing TAVR who have bicuspid aortic valve have a higher short-term risk of death and a higher risk of residual aortic regurgitation, and are more likely to need implantation of a second valve.

PARAVALVULAR LEAK

Paravalvular leak, arguably an independent marker of higher morbidity and mortality risk after TAVR, is more common in patients with bicuspid aortic valve undergoing TAVR than in those with tricuspid aortic valve. Earlier studies reported rates of moderate or severe paravalvular leak between 16% and 32%.^6,7

The newer-generation balloon-expandable Sapien 3 valve (Edwards Lifesciences, Irvine, CA) is associated with a lower incidence of moderate or severe paravalvular leak than earlier devices, mainly attributable to its outer skirt, which allows more complete sealing.⁸ There are also reports of successful treatment of bicuspid aortic valve stenosis using the Lotus device (Boston Scientific, Marlborough, MA).⁹ This device features adaptive sealing along with retrievability and repositioning ability, which may facilitate optimal positioning and prevent paravalvular leak.

Sizing of the prosthesis in patients with bicuspid aortic valve stenosis remains a challenge: some experts advocate the usual practice of measuring the perimeter and area at the level of the annulus, while others advocate measuring at the level of the commissures, 4 to 8 mm above the annulus. Balloon valvuloplasty may be a useful sizing tool, though it carries the hazards of severe aortic regurgitation and periprocedural stroke.

Angiography of the ascending aorta during balloon valvuloplasty can help verify whether an adequate seal is achievable and aid in selecting an appropriately sized prosthesis. Liu et al¹⁰ performed sequential balloon aortic valvuloplasty before TAVR with a self-expanding valve in 12 patients. Of these, 11 (91.7%) received a smaller device than they would have with multidetector computed tomography-guided annulus measurement.

Given that a larger valve may increase the risk of annular rupture, implantation of a smaller valve is always reasonable in bicuspid aortic valve as long as it achieves appropriate sealing with no paravalvular leak.

THE NEED FOR A PACEMAKER

After undergoing TAVR, more patients who have a bicuspid aortic valve need a permanent pacemaker than those who have a tricuspid aortic valve. This group appears to be more vulnerable to conduction abnormalities after TAVR, and rates of new pacemaker implantation as high as 25% have been reported with the newer-generation devices. Perlman et al⁸ observed that even when the Sapien 3 valve was implanted high in the left ventricular outflow tract, nearly 10% of patients needed a new pacemaker.

This is an important issue, as most patients with bicuspid aortic valve with severe aortic stenosis are relatively young and may endure deleterious effects from long-term pacing.

LONG-TERM OUTCOMES

The data on long-term outcomes of patients with bicuspid aortic valve who undergo TAVR are limited, and the available studies were small, with relatively short-term follow-up. However, Yoon et al compared TAVR outcomes between bicuspid and tricuspid aortic stenosis patients using propensity-score matching and demonstrated comparable all-cause mortality rates at 2 years (17.2% vs 19.4%, P = .28).⁶

Given the relatively long life expectancy of patients with bicuspid aortic valve undergoing TAVR, who tend to be younger than those with tricuspid aortic valve stenosis, longer-term data are needed to draw meaningful conclusions about the durability of transcatheter valves in this population. The bicuspid aortic valve is asymmetric, so that during TAVR the stent may not expand completely, and this in theory may result in more strain on the prosthesis and accelerate its structural deterioration.

In a recent meta-analysis, Reddy et al¹¹ analyzed 13 observational studies in 758 patients with severe bicuspid aortic valve stenosis undergoing TAVR with older and newer devices. The mean Society of Thoracic Surgeons Predicted Risk of Mortality score, which predicts the risk of death within 30 days, was 5.0%, but the actual rate was 3.7% (95% confidence interval [CI] 2.1%–5.6%). A high procedural success rate of 95% (95% CI 90.2%–98.5%] was also noted, but the rates of new permanent pacemaker implantation (17.9%, 95% CI 14.2%–22%) and severe perivalvular leak (12.2%, 95% CI 3.1%–24.8%) were somewhat elevated.¹¹

NOT FOR ALL, BUT AN EMERGING, VIABLE OPTION

As implanted prostheses and TAVR techniques undergo continuous improvement and as the experience of operators and institutions advances, procedural outcomes will likely improve.

The available data suggest that TAVR with the newer devices, when performed by experienced hands, is a viable option across most of the risk spectrum in patients with severe tricuspid aortic stenosis, including low-risk patients,¹² and selectively in patients with bicuspid aortic valve stenosis. However, for patients with bicuspid aortic valve with severe aortic stenosis and associated aortopathy, surgery remains the standard of care.

More study is needed to identify patients with bicuspid aortic valve who can be safely and effectively treated with TAVR.

To the Editor: We read with interest the article by Young et al on hypertrophic cardiomyop­athy (HCM)¹ and would like to raise a few important points.

HCM has a complex phenotypic expression and doesn’t necessarily involve left ventricular outflow obstruction. Midventricular obstruction is a unique subtype of HCM, with increased risk of left ventricular apical aneurysm (LVAA) formation. We reported that 25% of HCM patients with midventricular obstruction progress to LVAA compared with 0.3% of patients with other HCM subtypes.² Magnetic resonance imaging plays a pivotal role in assessing midventricular obstruction, owing to asymmetric geometry of the left ventricle and the shortcomings of echocardiography in assessing the apical aneurysm.²

Anticoagulation remains one of the cornerstones in treating midventricular obstruction with LVAA. We performed a systematic review and found a high prevalence of atrial arrhythmia, apical thrombus, and stroke, which necessitated anticoagulation in one-fifth of patients.²

Ventricular arrhythmias are prevalent in midventricular obstruction with LVAA, mainly from increased fibrosis formation at the apical rim.³ In our review, 25.7% of patients with midventricular obstruction with LVAA and an implantable cardioverter-defibrillator (ICD) experienced appropriate shocks.² Our finding was in line with those of Rowin et al,³ who showed appropriate ICD shocks in one-third of HCM patients with apical aneurysm. Apical aneurysm is currently considered an independent risk factor for sudden cardiac death in HCM, with an increased rate of sudden death of up to 5% every year.^3,4

It is imperative to distinguish midventricular obstruction with LVAA as a unique disease imposing a higher risk of thromboembolism, ventricular arrhythmia, and progression to end-stage heart failure.³ We suggest that those patients be evaluated early in the course of disease for anticoagulation, ICD implantation, and early surgical intervention.²

To the Editor: We read with interest the article by Young et al on hypertrophic cardiomyop­athy (HCM)¹ and would like to raise a few important points.

HCM has a complex phenotypic expression and doesn’t necessarily involve left ventricular outflow obstruction. Midventricular obstruction is a unique subtype of HCM, with increased risk of left ventricular apical aneurysm (LVAA) formation. We reported that 25% of HCM patients with midventricular obstruction progress to LVAA compared with 0.3% of patients with other HCM subtypes.² Magnetic resonance imaging plays a pivotal role in assessing midventricular obstruction, owing to asymmetric geometry of the left ventricle and the shortcomings of echocardiography in assessing the apical aneurysm.²

Anticoagulation remains one of the cornerstones in treating midventricular obstruction with LVAA. We performed a systematic review and found a high prevalence of atrial arrhythmia, apical thrombus, and stroke, which necessitated anticoagulation in one-fifth of patients.²

Ventricular arrhythmias are prevalent in midventricular obstruction with LVAA, mainly from increased fibrosis formation at the apical rim.³ In our review, 25.7% of patients with midventricular obstruction with LVAA and an implantable cardioverter-defibrillator (ICD) experienced appropriate shocks.² Our finding was in line with those of Rowin et al,³ who showed appropriate ICD shocks in one-third of HCM patients with apical aneurysm. Apical aneurysm is currently considered an independent risk factor for sudden cardiac death in HCM, with an increased rate of sudden death of up to 5% every year.^3,4

It is imperative to distinguish midventricular obstruction with LVAA as a unique disease imposing a higher risk of thromboembolism, ventricular arrhythmia, and progression to end-stage heart failure.³ We suggest that those patients be evaluated early in the course of disease for anticoagulation, ICD implantation, and early surgical intervention.²

To the Editor: We read with interest the article by Young et al on hypertrophic cardiomyop­athy (HCM)¹ and would like to raise a few important points.

HCM has a complex phenotypic expression and doesn’t necessarily involve left ventricular outflow obstruction. Midventricular obstruction is a unique subtype of HCM, with increased risk of left ventricular apical aneurysm (LVAA) formation. We reported that 25% of HCM patients with midventricular obstruction progress to LVAA compared with 0.3% of patients with other HCM subtypes.² Magnetic resonance imaging plays a pivotal role in assessing midventricular obstruction, owing to asymmetric geometry of the left ventricle and the shortcomings of echocardiography in assessing the apical aneurysm.²

Anticoagulation remains one of the cornerstones in treating midventricular obstruction with LVAA. We performed a systematic review and found a high prevalence of atrial arrhythmia, apical thrombus, and stroke, which necessitated anticoagulation in one-fifth of patients.²

Ventricular arrhythmias are prevalent in midventricular obstruction with LVAA, mainly from increased fibrosis formation at the apical rim.³ In our review, 25.7% of patients with midventricular obstruction with LVAA and an implantable cardioverter-defibrillator (ICD) experienced appropriate shocks.² Our finding was in line with those of Rowin et al,³ who showed appropriate ICD shocks in one-third of HCM patients with apical aneurysm. Apical aneurysm is currently considered an independent risk factor for sudden cardiac death in HCM, with an increased rate of sudden death of up to 5% every year.^3,4

It is imperative to distinguish midventricular obstruction with LVAA as a unique disease imposing a higher risk of thromboembolism, ventricular arrhythmia, and progression to end-stage heart failure.³ We suggest that those patients be evaluated early in the course of disease for anticoagulation, ICD implantation, and early surgical intervention.²

To the Editor: I read with interest the case of a 67-year-old woman with bilateral hand numbness, published in the March 2018 issue of the Journal, and I would like to suggest 2 important corrections to this article.¹

The authors present a case of hypocalcemia secondary to postsurgical hypoparathyroidism but describe it as due to primary hypoparathyroidism. The patient had undergone thyroidectomy 10 years earlier and since then had hypocalcemia, secondary to postsurgical hypoparathyroidism, that was treated with calcium and vitamin D, until she stopped taking these agents. Postsurgical hypothyroidism is the most common cause of acquired or secondary hypoparathyroidism and is not primary hypoparathyroidism. I strongly feel that this requires an update or correction to the article. This patient may have associated malabsorption, as the authors alluded to, as the cause of her “normal” serum parathyroid hormone level.

The patient also had hypomagnesemia, which the authors state could have been due to furosemide use and “uncontrolled” diabetes mellitus. Diabetes doesn’t need to be uncontrolled to cause hypomagnesemia. Hypomagnesemia is common in patients with type 2 diabetes mellitus, with a prevalence of 14% to 48% in patients with diabetes compared with 2.5% to 15% in the general population.² It is often multifactorial and may be secondary to one or more of the following factors: poor dietary intake, autonomic dysfunction, altered insulin resistance, glomerular hyperfiltration, osmotic diuresis (uncontrolled diabetes), recurrent metabolic acidosis, hypophosphatemia, hypokalemia, and therapy with drugs such as metformin and sulfonylureas.

Patients with type 2 diabetes and hypo­magnesemia often enter a vicious cycle in which hypomagnesemia worsens insulin resistance and insulin resistance, by reducing the activity of renal magnesium channel transient receptor potential melastatin (TRPM) type 6, perpetuates hypomagnesemia.³

To the Editor: I read with interest the case of a 67-year-old woman with bilateral hand numbness, published in the March 2018 issue of the Journal, and I would like to suggest 2 important corrections to this article.¹

The authors present a case of hypocalcemia secondary to postsurgical hypoparathyroidism but describe it as due to primary hypoparathyroidism. The patient had undergone thyroidectomy 10 years earlier and since then had hypocalcemia, secondary to postsurgical hypoparathyroidism, that was treated with calcium and vitamin D, until she stopped taking these agents. Postsurgical hypothyroidism is the most common cause of acquired or secondary hypoparathyroidism and is not primary hypoparathyroidism. I strongly feel that this requires an update or correction to the article. This patient may have associated malabsorption, as the authors alluded to, as the cause of her “normal” serum parathyroid hormone level.

The patient also had hypomagnesemia, which the authors state could have been due to furosemide use and “uncontrolled” diabetes mellitus. Diabetes doesn’t need to be uncontrolled to cause hypomagnesemia. Hypomagnesemia is common in patients with type 2 diabetes mellitus, with a prevalence of 14% to 48% in patients with diabetes compared with 2.5% to 15% in the general population.² It is often multifactorial and may be secondary to one or more of the following factors: poor dietary intake, autonomic dysfunction, altered insulin resistance, glomerular hyperfiltration, osmotic diuresis (uncontrolled diabetes), recurrent metabolic acidosis, hypophosphatemia, hypokalemia, and therapy with drugs such as metformin and sulfonylureas.

Patients with type 2 diabetes and hypo­magnesemia often enter a vicious cycle in which hypomagnesemia worsens insulin resistance and insulin resistance, by reducing the activity of renal magnesium channel transient receptor potential melastatin (TRPM) type 6, perpetuates hypomagnesemia.³

To the Editor: I read with interest the case of a 67-year-old woman with bilateral hand numbness, published in the March 2018 issue of the Journal, and I would like to suggest 2 important corrections to this article.¹

The authors present a case of hypocalcemia secondary to postsurgical hypoparathyroidism but describe it as due to primary hypoparathyroidism. The patient had undergone thyroidectomy 10 years earlier and since then had hypocalcemia, secondary to postsurgical hypoparathyroidism, that was treated with calcium and vitamin D, until she stopped taking these agents. Postsurgical hypothyroidism is the most common cause of acquired or secondary hypoparathyroidism and is not primary hypoparathyroidism. I strongly feel that this requires an update or correction to the article. This patient may have associated malabsorption, as the authors alluded to, as the cause of her “normal” serum parathyroid hormone level.

The patient also had hypomagnesemia, which the authors state could have been due to furosemide use and “uncontrolled” diabetes mellitus. Diabetes doesn’t need to be uncontrolled to cause hypomagnesemia. Hypomagnesemia is common in patients with type 2 diabetes mellitus, with a prevalence of 14% to 48% in patients with diabetes compared with 2.5% to 15% in the general population.² It is often multifactorial and may be secondary to one or more of the following factors: poor dietary intake, autonomic dysfunction, altered insulin resistance, glomerular hyperfiltration, osmotic diuresis (uncontrolled diabetes), recurrent metabolic acidosis, hypophosphatemia, hypokalemia, and therapy with drugs such as metformin and sulfonylureas.

Patients with type 2 diabetes and hypo­magnesemia often enter a vicious cycle in which hypomagnesemia worsens insulin resistance and insulin resistance, by reducing the activity of renal magnesium channel transient receptor potential melastatin (TRPM) type 6, perpetuates hypomagnesemia.³

In Reply: We thank Dr. Parmar and appreciate his important comments.

Regarding the difference between primary and secondary hypoparathyroidism, the definition varies among investigators. Some define primary hypoparathyroidism as a condition characterized by primary absence or deficiency of parathyroid hormone (PTH), which results in hypocalcemia and which can be congenital or acquired, including postsurgical hypoparathyroidism.^1–4 In principle, this is similar to the classification of disorders affecting other endocrine glands as primary and secondary. For example, primary hypothyroidism refers to a state of low thyroid hormones resulting from impairment or loss of function of the thyroid gland itself, such as in Hashimoto thyroiditis, radioactive iodine therapy, or thyroidectomy, among others.⁵ We adopted this definition in our article. In contrast, secondary hypoparathyroidism is characterized by low PTH secretion in response to certain conditions that cause hypercalcemia. Non-PTH-mediated hypercalcemia is a more common term used to describe this state of secondary hypoparathyroidism.

Other investigators restrict the term “primary hypoparathyroidism” to nonacquired (congenital or hereditary) etiologies, while applying the term “secondary hypoparathyroidism” to acquired etiologies.⁶

Concerning the association between diabetes mellitus and hypomagnesemia, we agree that diabetes does not need to be uncontrolled to cause hypomagnesemia. However, the patient described in our article presented with severe hypomagnesemia (serum level 0.6 mg/dL), which is not commonly associated with diabetes. Most cases of hypomagnesemia in patients with type 2 diabetes mellitus are mild and asymptomatic, whereas severe manifestations including seizures, cardiac arrhythmias, and acute tetany are rarely encountered in clinical practice.⁷ Furthermore, numerous studies have shown a negative correlation between serum magnesium level and glycemic control.^7–11 A recent study reported that plasma triglyceride and glucose levels are the main determinants of the plasma magnesium concentration in patients with type 2 diabetes.¹²

Our patient’s diabetes was uncontrolled, as evidenced by her hemoglobin A_1c level of 9.7% and her random serum glucose level of 224 mg/dL. Therefore, it is more likely that “uncontrolled diabetes mellitus” (in addition to diuretic use) was the cause of her symptomatic severe hypomagnesemia rather than controlled diabetes mellitus.

In Reply: We thank Dr. Parmar and appreciate his important comments.

Regarding the difference between primary and secondary hypoparathyroidism, the definition varies among investigators. Some define primary hypoparathyroidism as a condition characterized by primary absence or deficiency of parathyroid hormone (PTH), which results in hypocalcemia and which can be congenital or acquired, including postsurgical hypoparathyroidism.^1–4 In principle, this is similar to the classification of disorders affecting other endocrine glands as primary and secondary. For example, primary hypothyroidism refers to a state of low thyroid hormones resulting from impairment or loss of function of the thyroid gland itself, such as in Hashimoto thyroiditis, radioactive iodine therapy, or thyroidectomy, among others.⁵ We adopted this definition in our article. In contrast, secondary hypoparathyroidism is characterized by low PTH secretion in response to certain conditions that cause hypercalcemia. Non-PTH-mediated hypercalcemia is a more common term used to describe this state of secondary hypoparathyroidism.

Other investigators restrict the term “primary hypoparathyroidism” to nonacquired (congenital or hereditary) etiologies, while applying the term “secondary hypoparathyroidism” to acquired etiologies.⁶

Concerning the association between diabetes mellitus and hypomagnesemia, we agree that diabetes does not need to be uncontrolled to cause hypomagnesemia. However, the patient described in our article presented with severe hypomagnesemia (serum level 0.6 mg/dL), which is not commonly associated with diabetes. Most cases of hypomagnesemia in patients with type 2 diabetes mellitus are mild and asymptomatic, whereas severe manifestations including seizures, cardiac arrhythmias, and acute tetany are rarely encountered in clinical practice.⁷ Furthermore, numerous studies have shown a negative correlation between serum magnesium level and glycemic control.^7–11 A recent study reported that plasma triglyceride and glucose levels are the main determinants of the plasma magnesium concentration in patients with type 2 diabetes.¹²

Our patient’s diabetes was uncontrolled, as evidenced by her hemoglobin A_1c level of 9.7% and her random serum glucose level of 224 mg/dL. Therefore, it is more likely that “uncontrolled diabetes mellitus” (in addition to diuretic use) was the cause of her symptomatic severe hypomagnesemia rather than controlled diabetes mellitus.

In Reply: We thank Dr. Parmar and appreciate his important comments.

Regarding the difference between primary and secondary hypoparathyroidism, the definition varies among investigators. Some define primary hypoparathyroidism as a condition characterized by primary absence or deficiency of parathyroid hormone (PTH), which results in hypocalcemia and which can be congenital or acquired, including postsurgical hypoparathyroidism.^1–4 In principle, this is similar to the classification of disorders affecting other endocrine glands as primary and secondary. For example, primary hypothyroidism refers to a state of low thyroid hormones resulting from impairment or loss of function of the thyroid gland itself, such as in Hashimoto thyroiditis, radioactive iodine therapy, or thyroidectomy, among others.⁵ We adopted this definition in our article. In contrast, secondary hypoparathyroidism is characterized by low PTH secretion in response to certain conditions that cause hypercalcemia. Non-PTH-mediated hypercalcemia is a more common term used to describe this state of secondary hypoparathyroidism.

Other investigators restrict the term “primary hypoparathyroidism” to nonacquired (congenital or hereditary) etiologies, while applying the term “secondary hypoparathyroidism” to acquired etiologies.⁶

Concerning the association between diabetes mellitus and hypomagnesemia, we agree that diabetes does not need to be uncontrolled to cause hypomagnesemia. However, the patient described in our article presented with severe hypomagnesemia (serum level 0.6 mg/dL), which is not commonly associated with diabetes. Most cases of hypomagnesemia in patients with type 2 diabetes mellitus are mild and asymptomatic, whereas severe manifestations including seizures, cardiac arrhythmias, and acute tetany are rarely encountered in clinical practice.⁷ Furthermore, numerous studies have shown a negative correlation between serum magnesium level and glycemic control.^7–11 A recent study reported that plasma triglyceride and glucose levels are the main determinants of the plasma magnesium concentration in patients with type 2 diabetes.¹²

Our patient’s diabetes was uncontrolled, as evidenced by her hemoglobin A_1c level of 9.7% and her random serum glucose level of 224 mg/dL. Therefore, it is more likely that “uncontrolled diabetes mellitus” (in addition to diuretic use) was the cause of her symptomatic severe hypomagnesemia rather than controlled diabetes mellitus.

In the article by Agganis B, Lee D, Sepe T (Liver enzymes: No trivial elevations, even if asymptomatic. Cleve Clin J Med 2018; 85(8):612–617, doi:10.3949/ccjm.85a.17103), an error occurred on page 613, in the second paragraph in the section about alcohol intake. The words ALT and AST were reversed. The paragraph should read as follows:

The exact pathogenesis of alcoholic hepatitis is incompletely understood, but alcohol is primarily metabolized by the liver, and damage likely occurs during metabolism of the ingested alcohol. AST elevations tend to be higher than ALT elevations; the reason is ascribed to hepatic deficiency of pyridoxal 5´-phosphate, a cofactor of the enzymatic activity of ALT, which leads to a lesser increase in ALT than in AST.

We thank Avinash Alexander, MD, Texas Tech University Health Sciences Center, for calling this to our attention. The correction has been made online.

In the article by Agganis B, Lee D, Sepe T (Liver enzymes: No trivial elevations, even if asymptomatic. Cleve Clin J Med 2018; 85(8):612–617, doi:10.3949/ccjm.85a.17103), an error occurred on page 613, in the second paragraph in the section about alcohol intake. The words ALT and AST were reversed. The paragraph should read as follows:

The exact pathogenesis of alcoholic hepatitis is incompletely understood, but alcohol is primarily metabolized by the liver, and damage likely occurs during metabolism of the ingested alcohol. AST elevations tend to be higher than ALT elevations; the reason is ascribed to hepatic deficiency of pyridoxal 5´-phosphate, a cofactor of the enzymatic activity of ALT, which leads to a lesser increase in ALT than in AST.

We thank Avinash Alexander, MD, Texas Tech University Health Sciences Center, for calling this to our attention. The correction has been made online.

In the article by Agganis B, Lee D, Sepe T (Liver enzymes: No trivial elevations, even if asymptomatic. Cleve Clin J Med 2018; 85(8):612–617, doi:10.3949/ccjm.85a.17103), an error occurred on page 613, in the second paragraph in the section about alcohol intake. The words ALT and AST were reversed. The paragraph should read as follows:

The exact pathogenesis of alcoholic hepatitis is incompletely understood, but alcohol is primarily metabolized by the liver, and damage likely occurs during metabolism of the ingested alcohol. AST elevations tend to be higher than ALT elevations; the reason is ascribed to hepatic deficiency of pyridoxal 5´-phosphate, a cofactor of the enzymatic activity of ALT, which leads to a lesser increase in ALT than in AST.

We thank Avinash Alexander, MD, Texas Tech University Health Sciences Center, for calling this to our attention. The correction has been made online.

Obesity is a major health problem in the United States. The facts are well known:

• Its prevalence has almost tripled since the early 1960s¹
• More than 35% of US adults are obese (body mass index [BMI] ≥ 30 kg/m²)²
• It increases the risk of comorbid conditions including type 2 diabetes mellitus, heart disease, hypertension, obstructive sleep apnea, certain cancers, asthma, and osteoarthritis^3,4
• It decreases life expectancy⁵
• Medical costs are up to 6 times higher per patient.⁶

Moreover, obesity is often not appropriately managed, owing to a variety of factors. In this article, we describe use of shared medical appointments as a strategy to improve the efficiency and effectiveness of treating patients with obesity.

Big benefits from small changes in weight

As little as 3% to 5% weight loss is associated with significant clinical benefits, such as improved glycemic control, reduced blood pressure, and reduced cholesterol levels.^7,8 However, many patients are unable to reach this modest goal using current approaches to obesity management.

This failure is partially related to the complexity and chronic nature of obesity, which requires continued medical management from a multidisciplinary team. We believe this is an area of care that can be appropriately addressed through shared medical appointments.

CURRENT APPROACHES

Interventions for obesity have increased along with the prevalence of the disease. Hundreds of diets, exercise plans, natural products, and behavioral interventions are marketed, all claiming to be successful. More-intense treatment options include antiobesity medications, intra-abdominal weight loss devices, and bariatric surgery. Despite the availability of treatments, rates of obesity have not declined.

Counseling is important, but underused

Lifestyle modifications that encompass nutrition, physical activity, and behavioral interventions are the mainstay of obesity treatment.

Intensive interventions work better than less-intensive ones. In large clinical trials in overweight patients with diabetes, those who received intensive lifestyle interventions lost 3 to 5 kg more (3% to 8% of body weight) than those who received brief diet and nutrition counseling, as is often performed in a physician’s office.^9–12 The US Preventive Services Task Force recommends that patients whose BMI is 30 kg/m² or higher be offered intensive lifestyle intervention consisting of at least 12 sessions in 1 year.¹³

But fewer than half of primary care practitioners consistently provide specific guidance on diet, exercise, or weight control to patients with obesity, including those with a weight-related comorbidity.¹⁴ The rate has decreased since the 1990s despite the increase in obesity.¹⁵

One reason for the underuse is that many primary care practitioners do not have the training or time to deliver the recommended high-intensity obesity treatment.¹⁴ Plus, evidence does not clearly show a weight loss benefit from low-intensity interventions. Even when patients lose weight, most regain it, and only 20% are able to maintain their weight loss 1 year after treatment ends.¹⁶

Drugs and surgery also underused

Antiobesity medications and bariatric surgery are effective when added to lifestyle interventions, but they are also underused.

Bariatric surgery provides the greatest and most durable weight loss—15% to 30% of body weight—along with improvement in comorbidities such as type 2 diabetes, and its benefits are sustained for at least 10 years.¹⁷ However, fewer than 1% of eligible patients undergo bariatric surgery because of its limited availability, invasive nature, potential complications, limited insurance coverage, and high cost.¹⁷

The story is similar for antiobesity drugs. They are useful adjuncts to lifestyle interventions, providing an additional 3% to 7% weight loss,¹⁸ but fewer than 2% of eligible patients receive them.¹⁹ This may be attributed to their modest effectiveness, weight regain after discontinuation, potential adverse effects, and expense due to lack of insurance coverage.

ARE SHARED MEDICAL APPOINTMEMNTS AN ANSWER?

Although treatments have shown some effectiveness at producing weight loss, none has had a widespread impact on obesity. Lifestyle interventions, drugs, and bariatric surgery continue to be underused. Current treatment models are not providing patients with the intensive interventions needed.

Providers often find themselves offering repetitive advice to patients with obesity regarding nutrition and exercise, while simultaneously trying to manage obesity-related comorbidities, all in a 20-minute appointment. Too often, a patient returns home with prescriptions for hypertension or diabetes but no clear plan for weight management.

What can a shared medical appointment do?

A shared medical appointment is a group medical visit in which several patients with a similar clinical diagnosis, such as obesity, see a multidisciplinary team of healthcare providers. Typically, 5 to 10 patients have consultations with providers during a 60- to 90-minute appointment.²⁰

Part of the session is dedicated to education on the patients’ common medical condition with the goal of improving their self-management, but most of the time is spent addressing individual patient concerns.

Each patient takes a turn consulting with a provider, as in a traditional medical appointment, but in a group setting. This allows others in the group to observe and learn from their peers’ experiences. During this consultation, the patient’s concerns are addressed, medications are managed, necessary tests are ordered, and a treatment plan is made.

Patients can continue to receive follow-up care through shared medical appointments at predetermined times, instead of traditional individual medical appointments.

Shared medical appointments could improve patient access, clinical outcomes, and patient and provider satisfaction and decrease costs.^20,21 Since being introduced in the 1990s, their use has dramatically increased. For example, in the first 2 years of conducting shared medical appointments at Cleveland Clinic (2002–2004), there were just 385 shared medical appointments,²¹ but in 2017 there were approximately 12,300. They are used in a variety of medical and surgical specialties, and have been studied most for treating diabetes.^22–24

Increased face time and access

Individual patient follow-up visits typically last 15 to 20 minutes, limiting the provider to seeing a maximum of 6 patients in 90 minutes. In that same time in the setting of a shared appointment, a multidisciplinary team can see up to 10 patients, and the patients receive up to 90 minutes of time with multiple providers.

Additionally, shared medical appointments can improve patient access to timely appointments. In a busy bariatric surgery practice, implementing shared medical appointments reduced patients’ wait time for an appointment by more than half.²⁵ This is particularly important for patients with obesity, who usually require 12 to 26 appointments per year.

Improved patient outcomes

Use of shared medical appointments has improved clinical outcomes compared with traditional care. Patients with type 2 diabetes who attend shared medical appointments are more likely to reach target hemoglobin A_1c and blood pressure levels.^22­­−24 These benefits may be attributed to increased access to care, improved self-management skills, more frequent visits, peer support of the group, and the synergistic knowledge of multiple providers on the shared medical appointment team.

Although some trials reported patient retention rates of 75% to 90% in shared medical appointments, many trials did not report their rates. It is likely that some patients declined randomization to avoid shared medical appointments, which could have led to potential attrition and selection biases.²³

Increased patient and provider satisfaction

Both patients and providers report high satisfaction with shared medical appointments.^22,26 Although patients may initially hesitate to participate, their opinions significantly improve after attending 1 session.²⁶ From 85% to 90% of patients who attend a shared medical appointment schedule their next follow-up appointment as a shared appointment as well.^21,25

In comparative studies, patients who attended shared medical appointments had satisfaction rates equal to or higher than rates in patients who participated in usual care,²² noting better access to care and more sensitivity to their needs.²⁷ Providers report greater satisfaction from working more directly with a team of providers, clearing up a backlogged schedule, and adding variety to their practice.^21,24

Decreased costs

Data on the cost-effectiveness of shared medical appointments are mixed; however, some studies have shown that they are associated with a decrease in hospital admissions and emergency department visits.²² It seems reasonable to assume that, in an appropriate patient population, shared medical appointments can be cost-effective owing to increased provider productivity, but more research is needed to verify this.

CHALLENGES TO STARTING SHARED APPOINTMENTS FOR OBESITY

Despite their potential to provide comprehensive care to patients, shared medical appointments have limitations. These need to be addressed before implementing a shared medical appointment program.

Adequate resources and staff training

To be successful, a shared medical appointment program needs to have intensive physical and staffing resources. You need a space large enough to accommodate the group and access to the necessary equipment (eg, projector, whiteboard) for educational sessions. Larger or armless chairs may better accommodate patients with obesity. Facilitators need training in how to lead the group sessions, including time management and handling conflicts between patients. Schedulers and clinical intake staff need training in answering patient questions regarding these appointments.

Maintaining patient attendance

The benefits of provider efficiency rest on having an adequate number of patients attend the shared appointments.²¹ Patient cancellations and no-shows decrease both the efficiency and cost-effectiveness of this model, and they detract from the peer support and group learning that occurs in the group dynamic. To help minimize patient dropout, a discussion of patient expectations should take place prior to enrollment in shared medical appointments. This should include information on the concept of shared appointments, frequency and duration of appointments, and realistic weight loss goals.

Logistical challenges

A shared medical appointment requires a longer patient time slot and is usually less flexible than an individual appointment. Not all patients can take the time for a prescheduled 60- to 90-minute appointment. However, reduced waiting-room time and increased face time with a provider offset some of these challenges.

Recruiting patients

A shared medical appointment is a novel experience for some, and concerns about it may make it a challenge to recruit patients. Patients might worry that the presence of the group will compromise the patient-doctor relationship. Other concerns include potential irrelevance of other patients’ medical issues and reluctance to participate because of body image and the stigma of obesity.

One solution is to select patients from your existing practice so that the individual patient-provider relationship is established before introducing the concept of shared appointments. You will need to explain how shared appointments work, discuss their pros and cons, stress your expectations about attendance and confidentiality, and address any concerns of the patient. It is also important to emphasize that nearly all patients find shared medical appointments useful.

Once a group is established, it may be a challenge to keep a constant group membership to promote positive group dynamics. In practice, patients may drop out or be added, and facilitators need to be able to integrate new members into the group. It is important to emphasize to the group that obesity is chronic and that patients at all stages and levels of treatment can contribute to group learning.

Despite the advantages of shared medical appointments, some patients may not find them useful, even after attending several sessions. These patients should be offered individual follow-up visits. Also, shared appointments may not be suitable for patients who cannot speak English very well, are hearing-impaired, have significant cognitive impairment, or have acute medical issues.

Maintaining confidentiality of personal and health information in a shared medical appointment is an important concern for patients but can be appropriately managed. In a survey of patients attending pulmonary hypertension shared medical appointments, 24% had concerns about confidentiality before participating, but after a few sessions, this rate was cut in half.²⁸

Patients have reported initially withholding some information, but over time, they usually become more comfortable with the group and disclose more helpful information.²⁹ Strategies to ensure confidentiality include having patients sign a confidentiality agreement at each appointment, providing specific instruction on what characterizes confidentiality breaches, and allowing patients the opportunity to schedule individual appointments as needed.

Ensuring insurance coverage

A shared medical appointment should be billed as an individual medical appointment for level of care, rather than time spent with the provider. This ensures that insurance coverage and copayments are the same as for individual medical appointments.

Lack of insurance coverage is a major barrier to obesity treatment in general. The US Centers for Medicare and Medicaid Services reimburses intensive behavioral obesity treatment delivered by a primary care practitioner, but limits it to 1 year of treatment and requires patients to meet weight loss goals. Some individual and employer-based healthcare plans do not cover dietitian visits, weight management programs, or antiobesity prescriptions.

EVIDENCE OF EFFECTIVENESS IN OBESITY

Few studies have investigated the use of shared medical appointments in obesity treatment. In the pediatric population, these programs significantly decreased BMI and some other anthropometric measurements,^30–32 but they did not consistently involve a prescribing provider. This means they did not manage medications or comorbidities as would be expected in a shared medical appointment.

In adults, reported effects have been encouraging, although the studies are not particularly robust. In a 2-year observational study of a single physician conducting biweekly weight management shared medical appointments, participants lost 1% of their baseline weight, while those continuing with usual care gained 0.8%, a statistically significant difference.³³ However, participation rates were low, with patients attending an average of only 3 shared medical appointments during the study.

In a meta-analysis of 13 randomized controlled trials of shared medical appointments for patients with type 2 diabetes, only 3 studies reported weight outcomes.²³ These results indicated a trend toward weight loss among patients attending shared appointments, but they were not statistically significant.

Positive results also were reported by the Veterans Administration’s MOVE! (Managing Overweight/obesity for Veterans Everywhere) program.³⁴ Participants in shared medical appointments reported that they felt empowered to make positive lifestyle changes, gained knowledge about obesity, were held accountable by their peers, and appreciated the individualized care they received from the multidisciplinary healthcare teams.

A systematic review involving 336 participants in group-based obesity interventions found group treatment produced more robust weight loss than individual treatment.³⁵ However, shared medical appointments are different from weight loss groups in that they combine an educational session and a medical appointment in a peer-group setting, which requires a provider with prescribing privileges to be present. Thus, shared medical appointments can manage medications as well as weight-related comorbidities such as diabetes, hypertension, polycystic ovarian syndrome, and hyperlipidemia.

One more point is that continued attendance at shared medical appointments, even after successful weight loss, may help to maintain the weight loss, which has otherwise been found to be extremely challenging using traditional medical approaches.

WHO SHOULD BE ON THE TEAM?

Because obesity is multifactorial, it requires a comprehensive treatment approach that can be difficult to deliver given the limited time of an individual appointment. In a shared appointment, providers across multiple specialties can meet with patients at the same time to coordinate approaches to obesity treatment.

A multidisciplinary team for shared medical appointments for obesity needs a physician or a nurse practitioner—or ideally, both— who specializes in obesity to facilitate the session. Other key providers include a registered dietitian, an exercise physiologist, a behavioral health specialist, a sleep specialist, and a social worker to participate as needed in the educational component of the appointment or act as outside consultants.

WHAT ARE REALISTIC TARGETS?

• Nutrition
• Physical activity
• Appetite control
• Sleep
• Stress and mood disorders.

Nutrition

A calorie deficit of 500 to 750 calories per day is recommended for weight loss.^7,8 Although there is no consensus on the best nutritional content of a diet, adherence to a diet is a significant predictor of weight loss.³⁶ One reason diets fail to bring about weight loss is that patients tend to underestimate their caloric intake by almost 50%.³⁷ Thus, they may benefit from a structured and supervised diet plan.

A dietitian can help patients develop an individualized diet plan that will promote adherence, which includes specific information on food choices, portion sizes, and timing of meals.

Physical activity

At least 150 minutes of physical activity per week is recommended for weight loss, and 200 to 300 minutes per week is recommended for long-term weight maintenance.^7,8

An exercise physiologist can help patients design a personalized exercise plan to help achieve these goals. This plan should take into account the patient’s cardiac status, activity level, degree of mobility, and lifestyle.

Most patients are not able to achieve the recommended physical activity goals initially, and activity levels need to be gradually increased over a period of weeks to months. Patients who were previously inactive or have evidence of cardiovascular, renal, or metabolic disease may require a cardiopulmonary assessment, including an electrocardiogram and cardiac stress test, before starting an exercise program.

It is very difficult for patients to lose weight without appetite control. Weight loss that results from diet and exercise is often accompanied by a change in weight-regulating hormones (eg, leptin, ghrelin, peptide YY, and cholecystokinin) that promote weight regain.³⁸ Thus, multiple compensatory mechanisms promote weight regain through increases in appetite and decreases in energy expenditure, resisting weight loss efforts.

Antiobesity drugs can help mitigate these adaptive weight-promoting responses through several mechanisms. They are indicated for use with lifestyle interventions for patients with a BMI of at least 30 mg/kg² or a BMI of at least 27 kg/m² with an obesity-related comorbidity.

These drugs promote an additional 3% to 7% weight loss when added to lifestyle interventions.¹⁸ But their effects are limited without appropriate lifestyle interventions.

Sleep

Adequate sleep is an often-overlooked component of obesity treatment. Inadequate sleep is associated with weight gain and an appetite-inducing hormone profile.³⁹ Just 2 days of sleep deprivation in healthy normal-weight adult men was associated with a 70% increase in the ghrelin-to-leptin ratio, which showed a linear relationship with self-reported increased hunger.³⁹ Sleep disorders, especially obstructive sleep apnea, are common in patients with obesity but are often underdiagnosed and undertreated.⁴⁰

Healthy sleep habits and sleep quality should be addressed in shared medical appointments for obesity, as patients may be unaware of the impact that sleep may be having on their obesity treatment. The STOP-BANG questionnaire (­snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference, and male sex) is a simple and reliable tool to screen for obstructive sleep apnea.⁴¹ Patients with symptoms of a sleep disorder should be referred to a sleep specialist for diagnosis and management.

Stress management and mood disorders

Stress and psychiatric disorders are underappreciated contributors to obesity. All patients receiving obesity treatment need to be screened for mood disorders and suicidal ideation.⁸

Chronic stress promotes weight gain through activation of the hypothalamic-pituitary-adrenocortical axis, whereby increased cortisol levels enhance appetite and accumulation of visceral fat.⁴² In addition, obesity is associated with a 25% increased risk of mood disorders, although the mechanism and direction of this association are unclear.⁴³ Weight gain as a side effect of antidepressant or other psychiatric medications is another important consideration.

Management of stress and psychiatric disorders through goal-setting, self-monitoring, and patient education is vital to help patients fully participate in lifestyle changes and maximize weight loss. Patients participating in shared medical appointments usually benefit from consultations with psychiatrists or psychologists to manage psychiatric comorbidities and assist with adherence to behavior modification. 


IN FAVOR OF SHARED MEDICAL APPOINTMENTS FOR OBESITY

Shared medical appointments can be an effective method of addressing the challenges of treating patients with obesity, using a multidisciplinary approach that combines nutrition, physical activity, appetite suppression, sleep improvement, and stress management. In addition, shared appointments allow practitioners to treat the primary problem of excess weight, rather than just its comorbidities, recognizing that obesity is a chronic disease that requires long-term, individualized treatment. Satisfaction rates are high for both patients and providers. Overall, education is essential to implementing and maintaining a successful shared medical appointment program.