Hypertrophic cardiomyopathy medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]Cafer Zorkun, M.D. , Caitlin J. Harrigan ; Martin S. Maron, M.D.; Barry J. Maron, M.D.; Lakshmi Gopalakrishnan, M.B.B.S. [3]

Overview

The medical management of the patient with hypertrophic cardiomyopathy involves minimizing diastolic dysfunction, reducing left ventricular outflow tract obstruction, optimizing heart failure management, maintaining normal sinus rhythm, rate control and anticoagulation in the presence of atrial fibrillation, and implantation of an automatic implantable cardiac defibrillator in those patients who survive sudden cardiac death.

One of the fundamental goals of treatment is to relieve disabling dyspnea and improve exercise tolerance. It should be noted that the majority of patients do not have outflow tract obstruction, and therefore would not benefit from surgery. Medical therapy is, therefore, a mainstay of treatment. Given the limited number of patients with the condition, there are few randomized trials comparing strategies/agents in the management of HCM.

In all patients with hypertrophic cardiomyopathy risk stratification is essential to attempt to ascertain which patients are at risk for sudden cardiac death. In those patients deemed to be at high risk the benefits and infrequent complications of defibrillator therapy are discussed; devices have been implanted in as many as 15% of patients at HOCM centers. Treatment symptoms of obstructive HOCM is directed towards decreasing the left ventricular outflow tract gradient and symptoms of dyspnea, chest pain and syncope.

Initiation of Medical Therapy

Medical therapy is usually first initiated when signs and symptoms of exercise intolerance develop.

Diuretics

Treatment with diuretics (a mainstay of CHF treatment) will exacerbate symptoms in hypertrophic cardiomyopathy by decreasing ventricular volume and increasing outflow resistance.

Simple Supportive Measures

Avoid volume depletion

  • These patients should avoid volume depletion and dehydration which reduces Left ventricular volume and thereby exacerbates left ventricular outflow tract obstruction.

Avoid strenuous Activity

  • Strenuous activity has been associated with sudden cardiac death in these patients and for this reason these patients are counseled to avoid engaging in competitive sports.

Screening Relatives

  • This autosomal dominant disease has a high degree of penetrance and first degree relatives should be screened.

Contraindicated medications

Idiopathic hypertrophic subaortic stenosis is considered an absolute contraindication to the use of the following medications:

Pharmacotherapy

Medical therapy is successful in the majority of patients. The first medication that is routinely used is beta-blockade (metoprolol, atenolol, bisoprolol, propranolol).[1][2][3] If symptoms and gradient persist disopyramide may be added to the beta-blocker.[2] Alternately a calcium channel blocker such as verapamil may be substituted for beta-blockade. It should be stressed that most patient's symptoms may be managed medically without needing to resort to inteventions such as surgical septal myectomy, alcohol septal ablation or pacing. Severe symptoms in non-obstructive HCM may actually be more difficult to treat because there is no obvious target (obstruction) to treat. Medical therapy with verapamil, beta-blockade may improve symptoms. Diuretics should be avoided, as they reduce the intravascular volume of blood, decreasing the amount of blood available to distend the left ventricular outflow tract, leading to an increase in the obstruction to the outflow of blood in the left ventricle. [4]

As a summary:

  • The asymptomatic patient without risk factors for SCD (sudden cardiac death[) does not require therapy, even in the presence of NSVT. The symptomatic patient can be treated with negative inotropes such as calcium channel blockers and/or beta-blockers. Atrial fibrillation should be treated aggressively. Some use Disopyramide to maintain NSR (normal sinus rhythm) because of its negative inotropic effects. Amiodarone is the best medicine to maintain NSR and has been associated with symptomatic improvement in patients with HCM.

2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy (DO NOT EDIT)[5]

Pharmacologic Management in Symptomatic Patients (DO NOT EDIT)[5]

Class I
"1. Beta-blocking drugs are recommended for the treatment of symptoms (angina or dyspnea) in adult patients with obstructive or non-obstructive HCM but should be used with caution in patients with sinus bradycardia or severe conduction disease.[6][7][8][1][9][10][11][12][13][14][15][16][17] (Level of Evidence: B)"
"2. If low doses of beta-blocking drugs are ineffective for controlling symptoms (angina or dyspnea) in patients with HCM, it is useful to titrate the dose to a resting heart rate of less than 60 to 65 bpm (up to generally accepted and recommended maximum doses of these drugs).[6][7][8][10][11][12][13][14][15][16][17] (Level of Evidence: B)"
"3. Verapamil therapy (starting in low doses and titrating up to 480 mg/d) is recommended for the treatment of symptoms (angina or dyspnea) in patients with obstructive or non-obstructive HCM who do not respond to beta-blocking drugs or who have side effects or contraindications to beta-blocking drugs. However, verapamil should be used with caution in patients with high gradients, advanced heart failure, or sinus bradycardia.[7][8][1][18][19][20][21][22] (Level of Evidence: B)"
"4. Intravenous phenylephrine (or another pure vasoconstricting agent) is recommended for the treatment of acute hypotension in patients with obstructive HCM who do not respond to fluid administration.[8][23][24][25] (Level of Evidence: B)"
Class IIa
"1. It is reasonable to combine disopyramide with a beta-blocking drug or verapamil in the treatment of symptoms (angina or dyspnea) in patients with obstructive HCM who do not respond to beta-blocking drugs or verapamil alone.[7][8][1][26][27][28][29] (Level of Evidence: B)"
"2. It is reasonable to add oral diuretics in patients with non-obstructive HCM when dyspnea persists despite the use of beta blockers or verapamil or their combination.[3][9] (Level of Evidence: C)"
Class IIb
"1. Beta-blocking drugs might be useful in the treatment of symptoms (angina or dyspnea) in children or adolescents with HCM, but patients treated with these drugs should be monitored for side effects, including depression, fatigue, or impaired scholastic performance. (Level of Evidence: C)"
"2. It may be reasonable to add oral diuretics with caution to patients with obstructive HCM when congestive symptoms persist despite the use of beta-blockers or verapamil or their combination.[7][8][1](Level of Evidence: C)"
"3. The usefulness of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in the treatment of symptoms (angina or dyspnea) in patients with HCM with preserved systolic function is not well established, and these drugs should be used cautiously (if at all) in patients with resting or provocable LVOT obstruction. (Level of Evidence: C)"
"4. In patients with HCM who do not tolerate verapamil or in whom verapamil is contraindicated, diltiazem may be considered. (Level of Evidence: C)"
Class III (Harm)
"1. Nifedipine or other dihydropyridine calcium channel-blocking drugs are potentially harmful for treatment of symptoms (angina or dyspnea) in patients with HCM who have resting or provocable LVOT obstruction. (Level of Evidence: C)"
"2. Verapamil is potentially harmful in patients with obstructive HCM in the setting of systemic hypotension or severe dyspnea at rest. (Level of Evidence: C)"
"3. Digitalis is potentially harmful in the treatment of dyspnea in patients with HCM and in the absence of AF[6][7][8][30][31][32]. (Level of Evidence: B)"
"4. The use of disopyramide alone without beta blockers or verapamil is potentially harmful in the treatment of symptoms (angina or dyspnea) in patients with HCM with AF because disopyramide may enhance atrioventricular conduction and increase the ventricular rate during episodes of AF.[7][33][9][34][35][36][37][38][39] (Level of Evidence: B)"
"5. Dopamine, dobutamine, norepinephrine, and other intravenous positive inotropic drugs are potentially harmful for the treatment of acute hypotension in patients with obstructive HCM.[6][23][24][25][40][41][42][43] (Level of Evidence: B)"

Management of Atrial Fibrillation in HCM (DO NOT EDIT)[44]

Class I
"1. Anticoagulation with vitamin K antagonists (ie, warfarin, to an international normalized ratio of 2.0 to 3.0) is indicated in patients with paroxysmal, persistent, or chronic AF and HCM.[44][45][46] (Anticoagulation with direct thrombin inhibitors [ie, dabigatran] may represent another option to reduce the risk of thromboembolic events, but data for patients with HCM are not available.).[47] (Level of Evidence: C)"
"2. Ventricular rate control in patients with HCM with AF is indicated for rapid ventricular rates and can require high doses of beta antagonists and nondihydropyridine calcium channel blockers.[44][46] (Level of Evidence: C)"
Class IIa
"1. Disopyramide (with ventricular rate-controlling agents) and amiodarone are reasonable antiarrhythmic agents for AF in patients with HCM.[44][48] (Level of Evidence: B)"
"2. Radiofrequency ablation for AF can be beneficial in patients with HCM who have refractory symptoms or who are unable to take antiarrhythmic drugs.[49][50][51][52][53] (Level of Evidence: B)"
"3. Maze procedure with closure of left atrial appendage is reasonable in patients with HCM with a history of AF, either during septal myectomy or as an isolated procedure in selected patients. (Level of Evidence: C)"
Class IIb
"1. Sotalol, dofetilide, and dronedarone might be considered alternative antiarrhythmic agents in patients with HCM, especially in those with an ICD, but clinical experience is limited. (Level of Evidence: C)"

Sources

Asymptomatic Patients

2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy (DO NOT EDIT)[5]

Asymptomatic Patients (DO NOT EDIT) [5]

Class I
"1. For patients with HCM, it is recommended that comorbidities that may contribute to cardiovascular disease (e.g., hypertension, diabetes, hyperlipidemia, obesity) be treated in compliance with relevant existing guidelines.[55] (Level of Evidence: C) "
Class IIa
"1. Low-intensity aerobic exercise is reasonable as part of a healthy lifestyle for patients with HCM.[56][7] (Level of Evidence: C) "
Class IIb
"1. The usefulness of beta blockade and calcium channel blockers to alter clinical outcome is not well established for the management of asymptomatic patients with HCM with or without obstruction.[7] (Level of Evidence: C) "
Class III (Harm)
"1. Septal reduction therapy should not be performed for asymptomatic adult and pediatric patients with HCM with normal effort tolerance regardless of the severity of obstruction.[1][7] (Level of Evidence: C) "
"2. In patients with HCM with resting or provocable outflow tract obstruction, regardless of symptom status, pure vasodilators and high-dose diuretics are potentially harmful.[1][6] (Level of Evidence: C) "

Patients With LV Systolic Dysfunction

Patients With LV Systolic Dysfunction (DO NOT EDIT)[5]

Class I
"1. Patients with non-obstructive HCM who develop systolic dysfunction with an EF less than or equal to 50% should be treated according to evidence-based medical therapy for adults with other forms of heart failure with reduced EF, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, and other indicated drugs[57][58]. (Level of Evidence: B) "
"2. Other concomitant causes of systolic dysfunction (such as CAD) should be considered as potential contributors to systolic dysfunction in patients with HCM. (Level of Evidence: C) "
Class IIb
"1. ICD therapy may be considered in adult patients with advanced (as defined by NYHA functional class III or IV heart failure) non-obstructive HCM, on maximal medical therapy, and EF less than or equal to 50%, who do not otherwise have an indication for an ICD[57]. (Level of Evidence: C) "
"2. For patients with HCM who develop systolic dysfunction, it may be reasonable to reassess the use of negative inotropic agents previously indicated, for example, verapamil, diltiazem, or disopyramide, and to consider discontinuing those therapies. (Level of Evidence: C) "

Sources

2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy [54][5]

Pregnancy

Overview

Women with hypertrophic cardiomyopathy should be managed by a skilled cardiovascular specialist and a high-risk obstetrician during pregnancy. Any activity, drug or circumstance that increases left ventricular outflow obstruction, reduced left ventricular filling, or increases left ventricular afterload should be avoided.

Natural History, Complications And Prognosis In The Hypertrophic Cardiomyopathy Patient During Pregnancy

Among HCM patients who chronically have mild symptoms, pregnancy is generally well tolerated [59][60]. Although pregnancy causes vasodilation which should exacerbate the outflow gradient, pregnancy also causes fluid retention and an increase in plasma volume which increases preload and offsets the reduction in afterload. In a series of 100 HCM patients, only one of 28 asymptomatic patients developed NYHA Class III or IV heart failure. Among 12 previously symptomatic patients, 5 patients developed NYHA Class III or IV heart failure. It is notable that two sudden deaths occurred in this series of 100 patients. One of the two patients had a resting gradient of 115 mm Hg. The other patient had a markedly positive family history with 8 family members sustaining any early death, 5 of which were sudden death [60].

Avoid Activities That Increase Left Ventricular Outflow Tract Obstruction

The following activities increase left ventricular outflow tract obstruction and should be avoided:

  • Epidural Anesthesia Should Be Avoided due to the potential for venous pooling.
  • Bleeding should be minimized. Blood should be crossed and typed in case a transfusion is needed for bleeding, which can exacerbate outflow obstruction.
  • Nausea and vomiting
  • Dehydration
  • Hypovolemia (i.e., use diuretics with caution)
  • Medications that reduce preload and left ventricular filling such as nitrates

Avoid Activities That Increase Afterload

The following activities increase left ventricular afterload should be avoided:

  • Intense isometric exercise

Beta Blockade and Calcium Channel Blockade

Although both beta blockers and verapamil may improve symptoms in the mother, the dosing should be limited to minimize the risk of fetal bradycardia, growth retardation and hypoglycemia. There is more experience with the use beta blockers during pregnancy.

Home Delivery Should Be Avoided

Home delivery without IV access is not preferred.

Vaginal Delivery Versus C-Section

Vaginal delivery is usually successful.

2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy (DO NOT EDIT)[5]

Pregnancy/Delivery (DO NOT EDIT)[5]

Class I
"1. In women with HCM who are asymptomatic or whose symptoms are controlled with beta-blocking drugs, the drugs should be continued during pregnancy, but increased surveillance for fetal bradycardia or other complications is warranted[61][62][63][64]. (Level of Evidence: C) "
"2. For patients (mother or father) with HCM, genetic counseling is indicated before planned conception. (Level of Evidence: C) "
"3. In women with HCM and resting or provocable LVOT obstruction greater than or equal to 50 mm Hg and/or cardiac symptoms not controlled by medical therapy alone, pregnancy is associated with increased risk, and these patients should be referred to a high-risk obstetrician. (Level of Evidence: C) "
"4. The diagnosis of HCM among asymptomatic women is not considered a contraindication for pregnancy, but patients should be carefully evaluated in regard to the risk of pregnancy. (Level of Evidence: C) "
Class IIa
"1. For women with HCM whose symptoms are controlled (mild to moderate), pregnancy is reasonable, but expert maternal/fetal medical specialist care, including cardiovascular and prenatal monitoring, is advised. (Level of Evidence: C) "
Class III (Harm)
"1. For women with advanced heart failure symptoms and HCM, pregnancy is associated with excess morbidity/mortality. (Level of Evidence: C) "

References

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