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Medical Therapy: From Beta-Blockers to Disopyramide

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Abstract

Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease with a significant clinical variation requiring individualized treatment unique for each patient. Many patients can be managed conservatively with few or even no medications. The history, physical examination, and baseline echocardiogram usually determine the need for, type of, and titration of medications. Obstructive and nonobstructive patients are treated differently. Medications should be carefully titrated to manage each patient’s unique pathophysiology, particularly when there is LV outflow obstruction. Septal reduction therapy should generally only be considered once a patient has failed maximal medical treatment. Atrial fibrillation occurs in 25% of HCM patients and often is marked by a worsening of symptoms; it should be managed with rate control, attempts to maintain sinus rhythm and anticoagulation. This chapter also discusses the management of apical hypertrophic cardiomyopathy, hypertrophic cardiomyopathy associated with mid-ventricular obstruction, transformation into LV systolic dysfunction, and takotsubo cardiomyopathy in patients with HCM.

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Authors and Affiliations

  1. Department of Internal Medicine – Cardiology, St Luke’s Hospital, Chesterfield, MO, USA

    Keith Mankowitz

  2. Leon Charney Division of Cardiology, New York University Langone Medical Center, New York City, NY, USA

    Mark V. Sherrid

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  1. Keith Mankowitz
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Editor information

Editors and Affiliations

  1. Westchester Medical Center, Valhalla, NY, USA

    Srihari S. Naidu

Questions

Questions

Hypertrophic Cardiomyopathy Medications: Questions and Answers

  1. 1.

    What medications can prevent adverse remodeling, especially worsening left ventricular hypertrophy in patients with hypertrophic cardiomyopathy?

    1. A.

      Beta blockers.

    2. B.

      Amiodarone.

    3. C.

      Calcium channel blockers.

    4. D.

      Disopyramide.

    5. E.

      Spironolactone.

    6. F.

      No medication prevents adverse remodeling.

  • Answer: F

  • No medication has been shown to prevent worsening/progression of left ventricular hypertrophy or the development of symptoms.

  1. 2.

    What is the best management strategy for patients with left ventricular outflow tract gradients that are above 50 mm?

    1. A.

      Beta blockers

    2. B.

      Myectomy

    3. C.

      Calcium channel blockers

    4. D.

      Disopyramide

    5. E.

      Alcohol septal ablation

    6. F.

      Symptoms guided

  • Answer: F

  • Treatment should be guided by symptoms and not by the echocardiogram or cardiac catheterization results especially the severity of the left ventricular outflow tract gradient. Asymptomatic patients do not need any treatment, although patients with severe gradients should be objectively followed. Symptomatic patients should always be started on medical management prior to considering septal reduction therapy. Beta blockers are the initial first-line medication unless they are contraindicated.

  1. 3.

    When is it appropriate to refer patients for septal reduction therapy such as myectomy or alcohol septal ablation?

    1. A.

      Left ventricular outflow tract gradient above 50 mm

    2. B.

      Anatomy suitable for myectomy or alcohol septal ablation

    3. C.

      Symptoms refractory to medical treatment

    4. D.

      Expertise of the institution

    5. E.

      Need all of the above

  • Answer: E

  • Patients who have symptoms related to hypertrophic obstructive cardiomyopathy such as shortness of breath, chest pain, or exertional syncope related to the outflow tract obstruction should always be treated with medications prior to considering invasive treatment such as myectomy or alcohol septal ablation. Anatomy must be suitable for one or the other procedure, and peak gradients should be at least 50 mm Hg. Septal reduction therapy should only be performed at institutions that have performed over 50 procedures or by operators who have performed more than 20.

  1. 4.

    What is the first-line drug to prescribe patients with symptomatic hypertrophic obstructive cardiomyopathy, and how should these drugs be titrated?

    1. A.

      Beta blockers

    2. B.

      Amiodarone

    3. C.

      Calcium channel blockers

    4. D.

      Disopyramide

    5. E.

      Spironolactone

  • Answer: A

  • Beta blockers should always be started prior to other medications as they have an excellent track record in treating patients with dilated cardiomyopathy and coronary artery disease. The lowest effective dose should be used and should be guided according to the patient’s clinical response. Each patient will require a different dose based on the blood pressure, pulse rate, and the patient’s tolerance of beta blockers. The left ventricular outflow tract gradient on the echocardiogram or cardiac catheterization should not be used to determine the ineffectiveness of medications, but instead one should rely on the clinical response of the patient and treat them according to how they feel.

  1. 5.

    What is the role of calcium channel blockers in the treatment of hypertrophic obstructive cardiomyopathy?

    1. A.

      Improve diastolic dysfunction.

    2. B.

      Reduce left ventricular outflow tract gradient.

    3. C.

      Treat angina.

    4. D.

      Improve survival.

    5. E.

      Reduce left ventricular hypertrophy.

  • Answer: C

  • Non-dihydropyridine calcium channel blocker such as verapamil and diltiazem are useful medications to treat patients with hypertrophic obstructive cardiomyopathy if patients fail beta blockers. Verapamil and diltiazem should generally not be combined with a beta blocker in elderly patients as the combination can cause significant bradycardia and/or hypotension and do not appear to be more effective than using the drug without a beta blocker. Calcium channel blockers should be avoided in patients with volume overload manifested by jugular venous distention, significant shortness of breath, and edema as they can aggravate congestive heart failure and cause hypotension and possibly death. Calcium channel blockers do not improve diastolic dysfunction and should never be given to patients who are volume overloaded. Calcium channel blockers in high doses should be avoided in patients with significant resting left ventricular outflow tract obstruction with gradients above 50 mm as they can worsen left ventricular outflow tract obstruction due to their vasodilator properties and cause hypotension. Calcium channel blockers are useful medications for treating chest pain and shortness of breath in patients with nonobstructive forms of hypertrophic cardiomyopathy.

  1. 6.

    Which is the best medication to reduce the left ventricular outflow tract obstruction in symptomatic patients with hypertrophic obstructive cardiomyopathy?

    1. A.

      Beta blockers

    2. B.

      Amiodarone

    3. C.

      Non-dihydropyridine calcium channel blockers

    4. D.

      Disopyramide

    5. E.

      Spironolactone

  • Answer: D

  • Disopyramide is the most useful medication to treat patients whose symptoms are related to significant left ventricular outflow tract obstruction, as it lowers both the resting and provocable left ventricular outflow tract gradient. Disopyramide should be used in combination with a beta blocker to provide AV delay should atrial fibrillation occur, due to their anticholinergic effects.

  1. 7.

    How should hypertrophic cardiomyopathy patients with frank congestive heart failure and fluid retention be treated?

    1. A.

      Beta blockers

    2. B.

      Diuretics

    3. C.

      Calcium channel blockers

    4. D.

      Disopyramide

    5. E.

      Myectomy

  • Answer: B

  • Patients with hypertrophic cardiomyopathy may have significant diastolic dysfunction causing fluid retention. The best medications for fluid retention are diuretics. Diuretics should be used cautiously in patients with hypertrophic obstructive cardiomyopathy to avoid causing hypotension and worsening of the left ventricular outflow tract gradient. The lowest effective dose of the diuretic should be used to achieve euvolemia. Mild diuretics such as thiazides should be tried first, moving to loop diuretics such as furosemide for more significant volume overload. Right heart catheterization may be needed to confirm the degree of fluid overload and guide choice of diuretic.

  1. 8.

    How should patients with hypertrophic cardiomyopathy and angina be treated?

    1. A.

      Beta blockers

    2. B.

      Amiodarone

    3. C.

      Ranexa (ranolazine)

    4. D.

      Disopyramide

    5. E.

      Plavix

  • Answer: A

  • One should always rule out coronary artery disease as a cause for chest pain and angina in patients with hypertrophic cardiomyopathy. Calcium channel blockers and beta blockers are the first-line drugs for treating patients with angina due to hypertrophic cardiomyopathy. In patients with obstruction at rest or after exercise, an effort should be made to decrease LVOT gradient with medication, with beta blocker and disopyramide being the most effective combination. In nonobstructive hypertrophic cardiomyopathy patients who fail to respond to beta blockers or calcium channel blockers, a trial of low-dose nitrates such as a nitroglycerin patch may be useful.

  1. 9.

    When is an anticoagulant indicated for hypertrophic cardiomyopathy patients who develop atrial fibrillation?

    1. A.

      CHADS score above 2

    2. B.

      CHA2DS2-Vasc above 2

    3. C.

      History of stroke

    4. D.

      Significant left atrial enlargement

    5. E.

      Presence of atrial fibrillation or atrial flutter

  • Answer: E

  • The CHADS and CHAD2DS2-Vasc scores are not applicable in HCM patients with Afib. Patients with hypertrophic cardiomyopathy and atrial fibrillation/flutter are at high risk of embolic stroke and should be started on warfarin, a direct thrombin inhibitor or a novel oral anticoagulant (NOAC).

  1. 10.

    If a symptomatic obstructive patient has dry mouth or constipation after beginning oral disopyramide. What would be the best therapeutic strategy?

    1. A.

      Decrease the dose till side effects abate.

    2. B.

      Administer with pyridostigmine sustained release to relieve vagolytic side effects, and continue a therapeutic dose of disopyramide.

    3. C.

      Stop disopyramide.

    4. D.

      Add 500 ccs of electrolyte-repleted oral fluids daily.

  • Answer: B

  • Pyridostigmine sustained release through its cholinesterase inhibition restores vagal tone. Lowering the dose or stopping disopyramide completely might preclude disopyramide benefit for this patient.

  1. 11.

    A symptomatic obstructive HCM patient has been started on disopyramide 500mg/day in divided doses. ECG 3 days after beginning therapy shows that the QTc has increased from 455 msec to 490 msec. What is the most appropriate response?

    1. A.

      Continue therapy and observe for symptom relief. Everyone responds this way.

    2. B.

      Administer an ampule of calcium gluconate.

    3. C.

      Hold one dose of disopyramide, and repeat the ECG, and restart disopyramide at lower dose.

    4. D.

      Transfer to an ICU bed for close monitoring.

  • Answer: A

  • Disopyramide predictably prolongs the QTc. However, as with some other agents like amiodarone that widen QTc, pro-arrhythmic complications do not appear to occur. It is recommended to avoid co-administering other drugs that prolong the QTc like macrolides, quinolones, and certain SSRIs. Also it is advisable to avoid hypokalemia. If a patient on disopyramide must be given one of the abovementioned antibiotics, one should hold the disopyramide till the course of medication is completed.

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Mankowitz, K., Sherrid, M.V. (2019). Medical Therapy: From Beta-Blockers to Disopyramide. In: Naidu, S. (eds) Hypertrophic Cardiomyopathy. Springer, Cham. https://doi.org/10.1007/978-3-319-92423-6_15

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  • DOI: https://doi.org/10.1007/978-3-319-92423-6_15

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