Hypertension and Hypertrophic Cardiomyopathy

Abstract

Across the age spectrum of HCM, HTN is a common, comorbid condition in approximately half of all HCM patients. HCM and hypertensive cardiomyopathy lead to similar structural abnormalities in the myocardium, but these are generally more pronounced in HCM. A composite of clinical variables may be used to differentiate these conditions. The appropriate treatment of HTN in HCM is not well defined, and recommendations for use of drugs with blood pressure-lowering effects have focused largely on the potential for exacerbating left ventricular outflow obstruction by reducing preload or afterload, rather than clinical endpoints used in outcome studies of HTN treatments.

Questions

Multiple-Choice Questions

• 1. A 58-year-old man is referred for evaluation of mild dyspnea on exertion and abnormal EKG, which shows left ventricular hypertrophy with repolarization abnormality. His family history is negative for hypertrophic cardiomyopathy (HCM) or sudden death. He has a history of hypertension (HTN) for 10 years, treated with lisinopril with good control. Transthoracic echocardiogram shows left ventricular ejection fraction 60%, septal wall thickness 15 mm, and posterior wall thickness 13 mm, with mild mitral regurgitation. There is grade 1 diastolic dysfunction but no systolic anterior motion of the mitral valve or dynamic left ventricular outflow obstruction.

• Which of the following tests would be most useful to differentiate HCM from hypertensive heart disease?

  • A. Genetic testing for sarcomeric protein mutation.

  • B. Cardiac magnetic resonance imaging.

  • C. 48-hour Holter monitor

  • D. Stress echocardiogram.

• Answer: The correct answer is B. HCM is typically diagnosed when there is left ventricular hypertrophy >14 mm in any region that is not secondary to another condition. This patient has a history of HTN of long duration but controlled with single drug. The finding of left ventricular hypertrophy may be due to HTN or HCM, and mild dyspnea on exertion may be related to left ventricular diastolic dysfunction. Cardiac MRI has been shown to identify left ventricular hypertrophy that is increased in degree compared with echocardiography owing to its better spatial resolution, particularly in the anterolateral wall. In addition, cardiac MRI may identify other findings suggesting of HCM, such as late gadolinium enhancement (myocardial fibrosis ) and abnormal mitral valve anatomy. Genetic testing (answer A) is incorrect because the yield for genetic testing is low (approximately 50%) in patients diagnosed with HCM without a family history of HCM. Although Holter monitoring (answer C) may be helpful for risk stratification in patients with diagnosis of HCM, the results are not diagnostic for HCM. A stress echocardiogram (answer C) similarly does not provide diagnostic information for HCM over resting transthoracic echocardiogram but may help to identify causes of symptoms in HCM such as provocable, dynamic left ventricular outflow obstruction.

• 2. A 45-year-old woman with HTN for 5 years present for evaluation of dyspnea on exertion. She has been treated with amlodipine 5 mg daily and hydrochlorothiazide 25 mg daily, but her blood pressure has remained elevated (systolic BP range 15–160 mm Hg on home measurements). She has had gradual worsening of dyspnea on exertion for 1 year, now with dyspnea walking up two flights of stairs. She has no history of angina or syncope. Family history is notable for HTN in both parents. Electrocardiogram shows sinus rhythm, left ventricular hypertrophy with repolarization abnormality. Transthoracic echocardiogram shows left ventricular ejection fraction 65%, septal wall thickness 18 mm, and posterior wall thickness 14 mm; mild chordal systolic anterior motion with resting left ventricular outflow tract velocity 1.5 m/sec; left atrial enlargement (area = 26 cm²); and grade 1 diastolic dysfunction.

• What diagnostic test would be most useful to further manage her condition?

  • A. 24-hour urine collection for metanephrines and VMA

  • B. Abdominal CT scan with contrast.

  • C. Stress echocardiogram.

  • D. Serum and urine protein electrophoresis and plasma free light chain measurement.

• Answer: The correct answer is C. Although this patient has HTN that has not been adequately controlled, her degree of left ventricular hypertrophy and its asymmetry suggest possible HCM rather than hypertensive heart disease. She has NYHA 3 symptoms but only mild diastolic dysfunction by echocardiography. Stress echocardiography with exercise would provide information regarding her exercise capacity, blood pressure response, and outflow tract gradient at peak exercise. Approximately 30–40% of HCM patients have no significant outflow tract obstruction (<30 mm Hg) at rest but a provoked gradient (>50 mm Hg) at peak exercise. These patients are considered to have obstructive HCM, and medical therapy for outflow tract obstruction may improve her symptoms. Answers A and B are incorrect because this patient does not have refractory HTN (she is not on maximal doses of three antihypertensive drugs). Answer D is incorrect because she has no other clinical findings suggestive of an infiltrative cardiomyopathy such as AL amyloidosis.

• 3. A 36-year-old woman is referred for evaluation of a systolic murmur. She has a history of HTN for the past 5 years, which has been treated with amlodipine 10 mg daily, lisinopril 40 mg daily, and chlorthalidone 25 mg daily. She has no cardiac symptoms and exercises by walking 30 minutes 3–4 days a week. Her father died suddenly at age 65 of a “massive heart attack.”

• On physical exam, blood pressure is 145/92 mm Hg, and heart rate is 78 bpm. There is a 2/6 systolic ejection murmur at the right upper sternal border without radiation. The murmur does not change from squat to stand position. There is a systolic abdominal bruit in epigastric area. There is no brachial-femoral artery pulse delay by palpation, and peripheral pulses are intact and symmetric in both feet. Basic metabolic panel shows potassium concentration 4.8 meq/L and serum creatinine 1.3 mg/dl. EKG shows sinus rhythm, left ventricular hypertrophy with repolarization abnormality. Transthoracic echocardiogram shows LVEF 60%, concentric left ventricular hypertrophy with septal and posterior wall thicknesses 15 mm, no outflow tract gradient, and normal aortic and mitral valves.

• What test would be most appropriate to manage her condition?

  • A. Cardiac MRI.

  • B. Urine metanephrines and VMA.

  • C. Serum aldosterone level.

  • D. Duplex renal ultrasound.

• Answer: The correct answer is D. This patient has had early-onset HTN which has required three drugs at maximum doses for treatment, and her blood pressure remains elevated. Her physical exam revealed a soft systolic ejection murmur but an abdominal bruit. Echocardiogram showed concentric left ventricular hypertrophy likely related to refractory hypertension. In a patient with early-onset, refractory HTN, evaluation for secondary causes of HTN is appropriate. The presence of an abdominal bruit suggests possible renal artery disease, specifically fibromuscular dysplasia, as a cause of HTN. Although a pheochromocytoma or hyperaldosteronism are other causes of refractory HTN, these causes are less likely than renal artery disease. Cardiac MRI (answer B) would not provide information about possible causes of HTN and would not change the clinical assessment that concentric left ventricular hypertrophy is due to refractory HTN.

• 4. A 57-year-old woman is referred for evaluation of heart murmur. She has a 15-year history of hypertension treated with atenolol initially, and losartan was added 3 years ago for additional blood pressure lowering. Her blood pressure has been well controlled. She walks her dogs for an hour most days and has not had angina, dyspnea, or light-headedness. Her family history is notable for coronary artery disease and bypass surgery in her father and atrial fibrillation in her mother.

• On physical exam, her blood pressure is 130/78 mm Hg and heart rate 64 bpm. There is 2/6 systolic ejection murmur at the left lower sternal border which increases to 3/6 intensity from squat to stand position. Peripheral pulses are normal and symmetric in all extremities. EKG shows sinus rhythm and left ventricular hypertrophy. Transthoracic echocardiogram shows left ventricular ejection fraction 62%, septal wall thickness 17 mm and posterior wall thickness 12 mm and maximum wall thickness in mid-septum 19 mm, elongated anterior mitral valve leaflet with systolic anterior motion and resting left ventricular outflow tract gradient 20 mm Hg, and mild mitral regurgitation.

• What diagnostic testing would be most appropriate to manage her condition?

  • A. Cardiac MRI.

  • B. 24 hour Holter monitor

  • C. Stress echocardiogram.

  • D. Exercise treadmill test.

  • E. A and C.

  • F. B and D.

• Answer: The correct answer is F. The findings on her physical exam and transthoracic echocardiogram are consistent with hypertrophic cardiomyopathy. Although she does have a history of HTN for many years, her blood pressure has been well controlled, and the asymmetric hypertrophy is not consistent with hypertension as the cause. In this patient with probable hypertrophic cardiomyopathy, assessment of her risk for sudden cardiac death is appropriate. She does not have a family history of sudden death nor a personal history of syncope or extreme hypertrophy (maximum wall thickness > 30 mm) on echocardiography. She has not had ambulatory ECG (answer B) or exercise testing to assess her blood pressure response (answer D), so both these tests are recommended. In contrast, cardiac MRI (answer A) is not recommended routinely for sudden death risk assessment in HCM. Although stress echocardiography (answer C) may provide additional information about possible provoked left ventricular outflow obstruction during exercise, this finding would not likely change her treatment because she is currently asymptomatic and already prescribed a beta-blocker for HTN.

• 5. A 61-year-old man with obstructive hypertrophic cardiomyopathy returns for annual follow-up. He has a history of hypertension and has been treated with metoprolol succinate 200 mg daily. One year ago, he had mild dyspnea during moderate intensity exercise (30 min of walking on a treadmill 4 days a week). At that time, transthoracic echocardiogram showed left ventricular ejection fraction 65%; asymmetric septal hypertrophy with sigmoid septum and maximum wall thickness 19 mm; systolic anterior motion of the mitral valve with resting outflow tract velocity 2 m/sec which increased to 3.5 m/sec during Valsalva maneuver; and mild, posteriorly directed mitral regurgitation. Metoprolol was increased at that time from 100 mg daily to 200 mg daily. His dyspnea has improved, and he has not had any chest discomfort or pre-syncope with the same exercise regimen.

• On physical examination, his blood pressure is 148/92 mm Hg, and heart rate is 54 bpm and regular. His cardiac exam is notable for a regular rate and rhythm, normal heart sounds, and 2/6 systolic ejection murmur at the left lower sternal border which increases in intensity from squat to stand position. EKG shows sinus bradycardia 52 bpm, left ventricular hypertrophy with repolarization abnormality, QRS duration 100 msec, and QTc duration 445 msec.

• What is the best management for his condition?

  • A. Addition of verapamil sustained release 180 mg daily.

  • B. Addition of losartan 25 mg daily.

  • C. Addition of disopyramide 100 mg three times daily.

  • D. Surgical myectomy.

• Answer: The correct answer is B. This patient has obstructive hypertrophic cardiomyopathy and hypertension. He has excellent functional status, which improved with higher dosage of metoprolol a year ago. His hypertension is not effectively treated with high dose beta-blocker, and his resting heart rate precludes higher dosage. Losartan is an antihypertensive drug which has been found to be safe and tolerated in patients with obstructive HCM (inherit clinical trial). Verapamil (answer A) is incorrect because this medication may result in worsening bradycardia or other conduction abnormalities in patients treated with beta-blocker. Disopyramide (answer C) does not have blood pressure-lowering effect and is not indicated in this patient without HCM-related symptoms on beta-blocker. Surgical myectomy (answer D) is not indicated because this patient does not have HCM-related symptoms refractory to medical therapy.

• 6. A 73-year-old woman with obstructive hypertrophic cardiomyopathy, hypertension, coronary artery disease status post-previous percutaneous coronary stent in right coronary artery, and chronic stage 2 kidney disease is admitted for severe shortness of breath and near syncope. She has had refractory hypertension. Despite adherence to her medical regimen including metoprolol tartrate 100 mg twice a day, losartan 50 mg daily, and furosemide 40 mg daily, her blood pressure has remained elevated. She reports that her blood pressure “spiked” last night to 220/100 mm Hg, and she took her husband’s clonidine 0.1 mg tablet because she was scared of having a stroke.

• She awoke this morning with severe shortness of breath and called 911. Upon arrival to the emergency department, her blood pressure is 216/108 mm Hg, heart rate is 96 bpm and regular, and oxygen saturation 85% on high flow oxygen mask. Physical exam is notable for coarse breath sounds bilaterally with scattered expiratory wheezing and rapid, regular heart rhythm with a 3/6 systolic ejection murmur at the left lower sternal border. Stat EKG shows sinus tachycardia 104 bpm and left ventricular hypertrophy with 1 mm anterolateral ST depression. Chest radiograph shows cardiomegaly and pulmonary edema. Serum chemistries are notable for potassium concentration 3.5 mEq/l, blood urea nitrogen 42 mg/dl, and creatinine 2.0 mg/dl.

• What intravenous treatment do you recommend?

  • A. Nitroprusside.

  • B. Nitroglycerin.

  • C. Esmolol.

  • D. Diltiazem.

• Answer: The correct answer is C. This patient with HCM and HTN has a hypertensive emergency associated with pulmonary edema. Treatment of her severely elevated blood pressure in a controlled manner without worsening left ventricular outflow tract obstruction should be the acute care objective. Esmolol is an intravenous, selective, beta-blocking drug with very short half-life (9 min) that is indicated for the treatment of postoperative HTN. In this case, esmolol may ameliorate both the patient’s elevated blood pressure and dynamic outflow tract obstruction with a lower risk of hypotension. Options A, B, and D are incorrect because these drugs may exacerbate left ventricular outflow obstruction by acutely reducing afterload (nitroprusside and diltiazem) or preload (nitroglycerin) and precipitate acute hypotension.

• 7. Which of these abnormalities differentiates hypertrophic cardiomyopathy from hypertensive heart disease?

  • A. Cardiomyocyte hypertrophy.

  • B. Increased extracellular volume and collagen.

  • C. Arteriolar mural thickening.

  • D. Asymmetric hypertrophy.

• Answer: The correct answer is D. Asymmetric septal hypertrophy, defined as septal/posterior wall thickness ratio > 1.3, is present in most patients with HCM but found in 10% or less of patients with hypertensive heart disease. The posterior left ventricular wall is the least commonly affected in HCM but may develop mild hypertrophy in the presence of concomitant HTN. Options A, B, and C are incorrect because all of these structural changes are found in both HCM and hypertensive heart disease.

• 8. A 68-year-old woman with nonobstructive hypertrophic cardiomyopathy is seen in outpatient clinic for pre-syncope. She has a history of hypertension treated with metoprolol succinate 200 mg daily and chlorthalidone 25 mg daily and paroxysmal atrial fibrillation, treated with amiodarone and apixaban. She reports that she has had several episodes of near syncope in the past 2 months, often when getting out of her car or when arising from bed or when walking in warmer temperatures. These are not associated with palpitations and resolve after lying supine for 5 minutes. She walks about 20 min for exercise every day without angina or dyspnea.

• Her physical examination shows supine blood pressure 96/58 mm Hg and heart rate 56 bpm and standing blood pressure 100/66 mm Hg and heart rate 72 bpm. Jugular venous pressure is not elevated. There is a regular rate and rhythm, normal heart sounds, and 2/6 systolic ejection murmur at the left lower sternal border, increasing in intensity from squat to stand position. Electrocardiogram shows sinus bradycardia, rate 54 bpm, and left ventricular hypertrophy with QTc 510 ms. Transthoracic echocardiogram shows left ventricular ejection fraction 75%; left ventricular end-diastolic dimension 4.8 cm and end-systolic diameter 2.3 cm; severe, asymmetric hypertrophy with maximum septal wall thickness 26 mm; no systolic anterior motion of the mitral valve but mid-cavitary outflow tract velocity 3 m/sec.

• What is the appropriate management of this patient?

  • A. 30 day loop monitor

  • B. Stress echocardiogram.

  • C. Reduce metoprolol to 100 mg daily.

  • D. Discontinue chlorthalidone.

  • E. Discontinue amiodarone.

• Answer: The correct answer is D. This patient with HCM has severe left ventricular hypertrophy with a small left ventricular volume and mid-cavitary obstruction. She has orthostatic light-headedness. Her blood pressure is well controlled on metoprolol and chlorthalidone. However, diuretic therapy may reduce her intravascular volume, increase dynamic mid-ventricular obstruction, and exacerbate her symptoms. If her blood pressure is abnormally high after discontinuing chlorthalidone, another medication such as an angiotensin receptor blocker may be better tolerated. Answer A is incorrect because her history is not consistent with an arrhythmic cause. Answer B is incorrect because this test is likely to confirm the previous echo results and shows greater degree of mid-cavitary obstruction during exercise. Answer C is incorrect because beta-blocker therapy is beneficial for her dynamic mid-ventricular obstruction, as well as her hypertension. Answer E is incorrect because amiodarone is not likely contributing to her symptoms.

• 9. A 54-year-old man with obstructive hypertrophic cardiomyopathy and hypertension presents for annual office visit. He has been treated with atenolol 100 mg daily and losartan 100 mg daily. He does not exercise regularly but is able to do his activities of daily living, including work as an automobile mechanic and yardwork, without any angina, dyspnea, or light-headedness. His home blood pressure measurements have been elevated in the last month (systolic blood pressure range 144–160 mm Hg) and heart rates 50–60 bpm. Transthoracic echocardiogram 1 year ago showed normal left ventricular ejection fraction 63%, asymmetric septal hypertrophy (2.2 cm) with systolic anterior motion of the mitral valve, and resting left ventricular outflow tract gradient 45 mm Hg which increased to 68 mm Hg during Valsalva maneuver. Basic metabolic panel shows potassium 3.7 mg/dl and serum creatinine 1.0 mg/dl.

• What is the appropriate management of this patient?

  • A. Begin disopyramide 100 mg three times a day.

  • B. Begin hydrochlorothiazide 25 mg daily.

  • C. Begin amlodipine 5 mg daily.

  • D. Begin spironolactone 25 mg daily.

  • E. Begin lisinopril 10 mg daily.

• Answer: The correct answer is D. In patients with refractory hypertension, spironolactone has been shown to reduce blood pressure more effectively than other agents. Spironolactone ≤50 mg daily has little natriuretic effect and therefore may not reduce preload or worsen left ventricular outflow tract obstruction as might other diuretics. Option A is incorrect because disopyramide does not have blood pressure-lowering effect. Dihydropyridine calcium channel blockers, such as amlodipine (option C), should be avoided in patients with obstructive HCM due to potential for worsening obstruction. Option D is incorrect because although the combination of an ACE inhibitor (lisinopril) with an angiotensin receptor blocker (losartan) is associated with greater blood pressure lowering than either agent alone, the combination has not been found to reduce clinical endpoints (death, stroke or myocardial infarction) and has been associated with greater decline in renal function and more hypotensive episodes.

• 10. A 58-year-old woman with a history of obstructive hypertrophic cardiomyopathy and hypertension presents for worsening dyspnea with exertion. Fifteen years ago, she had successful surgical myectomy for severe, dynamic left ventricular outflow obstruction. Postoperatively, she developed a left bundle branch block, and transthoracic echocardiography showed left ventricular ejection fraction 55%, maximum wall thickness 18 mm in mid-septum without systolic anterior motion of the mitral valve, resting left ventricular outflow velocity 1.9 m/sec, and mild mitral regurgitation. Her medical regimen is metoprolol succinate 50 mg daily and atorvastatin.

• Over the past 6 months, she has had worsening dyspnea with normal activities such as housework and gardening. She has not had angina, orthopnea, or edema. No palpitations or pre-syncope. She has noticed that her blood pressure has been elevated on multiple home measurements.

• Her physical exam shows blood pressure 154/96 mm Hg, heart rate 82 bpm, and oxygen saturation 95% on room air. Her lungs are clear. Jugular venous pressure is approximately 10 cm H20. There is a regular rate and rhythm and normal heart sounds, with a 2/6 holosystolic murmur at the apex. Extremities are warm without edema. EKG shows sinus rhythm and left bundle branch block, QRS duration 152 ms. Echocardiogram shows left ventricular ejection fraction 40% with dyssynchronous septal motion, no outflow tract gradient, moderate mitral regurgitation, and left atrial enlargement.

• What is the appropriate treatment?

  • A. Begin lisinopril 10 mg daily.

  • B. Increase metoprolol succinate to 200 mg daily.

  • C. Begin spironolactone 25 mg daily.

  • D. Begin furosemide 40 mg daily.

  • E. Refer for biventricular pacemaker.

• Answer: The correct answer is A. This patient with hypertrophic cardiomyopathy has had successful surgical myectomy but now has developed left ventricular systolic dysfunction, possibly related to chronic left bundle branch block or “end-stage” HCM. In this patient with systolic dysfunction and hypertension, lisinopril is a guideline-directed medication. Increasing metoprolol to 200 mg daily (answer B) because the patient is currently on low dosage and a drastic increase in dosage may exacerbate her heart failure symptoms. Beta-blocker therapy should be titrated gradually over several weeks. This patient’s ejection fraction is above 35%, so spironolactone (answer C) is not correct. Furosemide (answer D) may improve symptoms of heart failure, but does not offer survival benefit. Biventricular pacemaker (answer E) is not indicated for patients with left ventricular ejection fraction greater than 35%.