INTRODUCTION — Hypertrophic cardiomyopathy (HCM) is a genetically determined heart muscle disease most often caused by mutations (which can be identified in 30 to 50 percent of patients) in one of several sarcomere genes which encode components of the contractile apparatus. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".)
HCM is characterized by left ventricular hypertrophy (LVH) of various morphologies, with a wide array of clinical manifestations and hemodynamic abnormalities (figure 1). Depending in part upon the site and extent of cardiac hypertrophy, HCM patients can develop one or more of the following abnormalities:
●LV outflow obstruction. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction".)
●Diastolic dysfunction.
●Myocardial ischemia.
●Mitral regurgitation.
These structural and functional abnormalities can produce a variety of symptoms, including:
●Fatigue
●Dyspnea
●Chest pain
●Palpitations
●Presyncope or syncope
In broad terms, the symptoms related to HCM can be categorized as those related to heart failure (HF), chest pain, or arrhythmias.
The medical management of non-HF symptoms in patients with HCM will be reviewed here. The pharmacologic treatment of patients with HCM who have HF symptoms, as well as discussion of other issues such as the clinical manifestations and diagnosis, natural history, management of arrhythmias, and nonpharmacologic treatment of this disorder, are presented separately.
●(See "Hypertrophic cardiomyopathy: Medical therapy for heart failure".)
●(See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".)
●(See "Hypertrophic cardiomyopathy: Natural history and prognosis".)
●(See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation".)
●(See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".)
PATHOPHYSIOLOGY — Symptoms, including those of HF and chest pain, are due to the combination of diastolic dysfunction, LV outflow tract obstruction, mitral regurgitation, and "small vessel" ischemia due to microvascular dysfunction [1]. A detailed discussion of the pathophysiology of HCM is presented separately, but will be briefly reviewed here. A detailed discussion of the typical clinical manifestations of HCM is also presented separately. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction" and "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".)
TREATMENT SCENARIOS
Asymptomatic patients — For nearly all patients with HCM (with or without LV outflow tract [LVOT] obstruction) who remain asymptomatic, close clinical observation and follow-up is the preferred approach. Given the absence of data demonstrating a clinical benefit with drug therapy in altering natural history in asymptomatic patients, patients should be engaged in a shared decision-making discussion to help resolve decisions about initiating medical therapy. Studies of pharmacologic therapy in HCM have largely been limited to symptomatic patients. In asymptomatic populations, prophylactic treatment does not appear to alter the natural history of HCM, and routine pharmacologic therapy of asymptomatic patients has not been supported by major professional societies [2].
Chest pain — Chest discomfort is a common symptom in patients with HCM, which can be due to several causes:
●Chest fullness and pressure is often associated with HF and increased filling pressures.
●Angina may be due to increased myocardial oxygen demand or impaired microvascular function.
●Anginal-like chest pain may occur unrelated to exercise or relief with rest.
●Patients may have coincident coronary artery disease.
In patients with angina or coronary disease risk factors, coronary heart disease (CHD) should be excluded [3]. In most patients without obstructive CHD, the pharmacologic management of chest discomfort is similar to that of HF in patients with HCM. Beta blockers and verapamil are the first-line agents. In patients without LVOT obstruction, verapamil is often the most efficacious at improving chest pain. Alternatively, beta blockers can be tried initially in patients with isolated chest pain and LVOT obstruction. Isolated refractory chest pain is uncommon, but may be troublesome and requires aggressive use of high dose nondihydropyridine calcium blocker therapy or, alternatively, beta blockers. In some patients with high LVOT gradients, lower or abolishing obstruction with medical therapy, including disopyramide, may also improve limiting chest pain symptoms.
For patients with significant obstruction and persistent chest pain despite medical therapy, nonpharmacologic therapies may be beneficial. These treatments are discussed in detail separately. (See "Hypertrophic cardiomyopathy: Nonpharmacologic treatment of left ventricular outflow tract obstruction".)
Ranolazine — Ranolazine has been considered a novel drug therapy option for some patients with HCM who have symptoms refractory to conventional medical therapy. Clinical trial data have not supported its efficacy in HCM, and for this reason, ranolazine is not used in the management of most HCM patients. However, although data have not demonstrated efficacy for ranolazine in improving functional capacity, expert HCM opinion would support considering ranolazine as an additional therapeutic agent for treatment of atypical chest pain in patients with HCM, as this is often challenging to improve with only atrioventricular (AV) nodal blocking agents.
●In the RESTYLE-HCM study, a randomized, double-blind study comparing five months of therapy with either ranolazine (1000 mg twice daily) or placebo in 80 patients with HCM, maximal LV wall thickness ≥15 mm, no LVOT obstruction, reduced peak oxygen consumption, and symptoms of HF or angina, there was no significant difference in the primary outcome of improvement in functional capacity as measured by peak oxygen consumption on cardiopulmonary exercise testing [4].
●The LIBERTY-HCM trial, which was evaluating eleclazine (similar in mechanism of action to ranolazine) in symptomatic patients with HCM, was stopped prematurely, and future manufacturing and development of the drug was discontinued by the manufacturer [5].
Arrhythmias — A variety of symptoms may be associated with supraventricular and ventricular arrhythmias in patients with HCM, including palpitations, lightheadedness, syncope, and exacerbations of HF and chest pain. The management of arrhythmias in patients with HCM is presented in detail separately, but highlights will be reviewed here. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation" and "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".)
Rate and rhythm control — Patients with symptomatic HCM can be intolerant of tachyarrhythmias. Both rapid heart rates and the loss of "atrial kick" impair LV filling, which has an even greater clinical impact in patients with diastolic dysfunction. Thus, aggressive rate control and, if necessary, rhythm control is particularly important in these patients. The management of arrhythmias in HCM, including the role of anticoagulation, is discussed separately. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation".)
Thromboembolism prophylaxis — Patients with HCM and atrial fibrillation have an increased risk of thromboembolism, regardless of CHA2DS2-VASc score, which is not applicable in this population as patients with HCM have been excluded from all trials of thromboembolism prophylaxis. The discussion of thromboembolism prophylaxis in patients with HCM and atrial fibrillation is presented separately. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation", section on 'For symptomatic AF'.)
Another subset of patients with HCM who have an increased risk of thromboembolism are those patients with an LV apical aneurysm. For patients with HCM and an LV apical aneurysm, we suggest long-term oral anticoagulation, rather than aspirin or no anticoagulation, to reduce the risk of thromboembolism. Typically we use warfarin for thromboembolic prophylaxis, with a target international normalized ratio of 2.0 to 3.0; use of a direct oral anticoagulant (eg, dabigatran, rivaroxaban, apixaban, etc) may be an option, although there are no data evaluating the efficacy of agents other than warfarin in this population.
Among a cohort of 93 patients with HCM and LV apical aneurysm followed for an average of 4.4 years, five patients (5.4 percent) experienced a nonfatal thromboembolic event, with all patients being in sinus rhythm at the time of the thromboembolism [6]. Conversely, no embolic events occurred in the 13 patients (14.8 percent) on long-term oral anticoagulation who had a thrombus identified within the apical aneurysm. There was no relationship between aneurysm size and risk for thromboembolic events.
Perioperative management during noncardiac surgery — For the majority of low and intermediate risk noncardiac surgeries in patients with HCM, particularly those procedures associated with minimal fluid shifts, the majority of patients with HCM are at low risk for perioperative cardiovascular complications. However, close monitoring of intraoperative hemodynamics, particularly during induction, hemorrhage, and other perioperative stressors, is critical. (See "Anesthesia for patients with hypertrophic cardiomyopathy undergoing noncardiac surgery".)
Limited data are available on perioperative risk of noncardiac surgery in patients with HCM. In a small series, adverse cardiac events included HF, myocardial ischemia, arrhythmias, and hypotension [7,8]. The duration and magnitude (major versus minor) of the surgical procedure were predictors of adverse cardiac outcomes [8].
Perioperative hemodynamic fluctuations (such as may accompany induction of anesthesia, hemorrhage, and other perioperative stressors) may be poorly tolerated by patients with HCM [9,10]:
●Conditions that reduce LV volumes (and thereby may increase outflow obstruction) include reduction in blood volume, decrease in systemic vascular resistance, and increased venous capacitance.
●In the setting of impaired LV diastolic filling, reduced filling pressures may lead to a fall in stroke volume.
●Increases in contractility may worsen outflow obstruction and may provoke ischemia.
●Tachycardia may further impair diastolic filling.
In HCM patients undergoing noncardiac surgery associated with a high likelihood of substantial fluid shifts, invasive monitoring of arterial blood pressure and LV filling pressure has been advocated [9]. However, pulmonary capillary wedge pressure measurements should be interpreted with caution in the presence of diastolic dysfunction since relatively high filling pressures may be required to maintain adequate stroke volume while excessive fluid administration may cause pulmonary edema.
The role of transesophageal echocardiography to help guide intraoperative management is not well established and should be considered on an individual patient basis. [9]. (See "Transesophageal echocardiography in the evaluation of the left ventricle".)
The following maneuvers may help preserve LV stroke volume in the perioperative period [9]:
●Preservation of LV volumes/preload via careful hydration and avoidance of high airway pressures with mechanical ventilation (smaller tidal volumes with higher respiratory rates are favored).
●Treatment of hypotension with volume and augmentation of afterload via administration of alpha-1 agonists (eg, phenylephrine).
●Limiting contractility, tachycardia, and oxygen demand. This can be achieved by avoidance of beta adrenergic agonists and by administration of beta blockers (eg, esmolol or metoprolol). Additionally, patients who are taking AV nodal blocking medications preoperatively should be continued on these medications perioperatively.
●Avoidance of vasodilators (eg, nitroglycerin or nitroprusside) since they decrease preload and systemic vascular resistance.
●Maintenance of sinus rhythm. Atrial fibrillation is frequently poorly tolerated if adequate rate control cannot be achieved with pharmacologic therapy, and may require cardioversion.
Acute hemodynamic collapse in the setting of LVOT obstruction — In patients with significant hemodynamic instability in the setting of LVOT obstruction, the following management regimen should be considered:
●Increase preload with elevation of the legs and administration of intravenous fluids; in addition, anemia, if present, should be corrected.
●Intravenous phenylephrine to increase blood pressure. Phenylephrine can be given in a solution that contains 10 mg (1 mL of 1 percent phenylephrine) of phenylephrine in 500 mL of dextrose in water. This solution is administered at a rate of 5 to 9 mL/minute (or 100 to 180 drops/minute if there are 20 drops/mL). It provides phenylephrine at a rate of 100 to 180 mcg/minute. When the blood pressure is stabilized, the rate may be reduced to 2 to 3 mL/minute (40 to 60 drops/minute).
●Avoidance of inotropes, which may further worsen LVOT obstruction.
●Intravenous administration of a beta blocker (propranolol, metoprolol, or esmolol are commonly available intravenous agents).
●Administration of intravenous disopyramide 50 mg over one to five minutes. (Intravenous disopyramide is not available in United States.)
●In select situations, semi-emergent septal reduction therapy (either surgical septal myectomy or alcohol septal ablation) for relief of obstruction can be considered in order to potentially mitigate hemodynamic collapse.
●Less severe cases can be managed with oral fluids and administration of an oral beta blocker.
HCM during pregnancy and delivery — Reproductive and genetic counseling should be offered to all HCM patients considering pregnancy [2]. While patients with HCM should generally be followed by an obstetrician experienced with high-risk patients, pregnancy is generally tolerated well in most patients with HCM [11,12]. This includes patients with HCM and LVOT obstruction who, prior to pregnancy, have no symptoms or only mild and stable symptoms. Most pregnant women with HCM increase cardiac output adequately in response to the enhanced physiologic demands of pregnancy. Fluid retention with a subsequent increase in plasma volume appears to offset the characteristic vasodilation that occurs in the setting. Normal vaginal delivery is the preferred delivery option. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".)
Among a series of 100 women with HCM who had a total of 199 births, the following findings were noted [12]:
●Among the 40 patients evaluated in close proximity to pregnancy, only one of 28 previously asymptomatic patients progressed to New York Heart Association (NYHA) class III or IV during pregnancy. By comparison, such progression occurred in 5 of 12 previously symptomatic patients.
●One patient had atrial fibrillation and one had syncope; in both cases, the problem was not new, having occurred repeatedly prior to pregnancy.
●Two deaths occurred, both sudden and both in patients at particularly high risk. One patient had massive LV hypertrophy and a resting outflow gradient of 115 mmHg. The other patient had a family history of eight deaths in young patients, five of which were sudden.
In a different cohort of 60 pregnant women with HCM (mean age 30.4 years, 42 percent with LVOT obstruction) from the prospective worldwide Registry of Pregnancy and Cardiac disease, there were no maternal deaths, but 14 patients (23 percent) experienced HF and/or arrhythmic complications, with three women (5 percent) experiencing loss of the fetus [13].
Beta blockers and verapamil can be used as necessary to alleviate symptoms, but the doses should be kept as low as possible to avoid fetal bradycardia, hypoglycemia, and growth retardation. Beta blockers are preferred since there is greater experience with these agents in pregnant women.
Patients with HCM, in particular those with LVOT obstruction, are particularly susceptible to changes in preload, afterload, contractility, and heart rate, which can occur at the time of labor and delivery. General or epidural anesthesia is reasonable along with close hemodynamic monitoring by an anesthesiologist experienced in both cardiology and obstetrics. It is important to avoid a significant decrease in venous return which may be associated with spinal anesthesia, which is not carefully titrated. The approach to analgesia and anesthesia for either vaginal or cesarean delivery in patients with HCM is discussed in detail separately. (See "Anesthesia for labor and delivery in high-risk heart disease: Specific lesions", section on 'Hypertrophic cardiomyopathy (HCM)'.)
Endocarditis prophylaxis — Patients with HCM and a resting or provoked LVOT gradient may be at increased risk for developing endocarditis, particularly those patients with concomitant mitral valve abnormalities. However, revisions to guidelines for endocarditis prophylaxis state that patients with HCM no longer require routine prophylaxis [14]. Some expert opinion amongst those who manage large numbers of patients with HCM continues to favor antimicrobial bacterial endocarditis prophylaxis before dental procedures, particularly for patients with LVOT obstruction and significant mitral valve abnormalities/regurgitation [15]. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiomyopathy".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Hypertrophic cardiomyopathy in adults (The Basics)")
●Beyond the Basics topic (see "Patient education: Hypertrophic cardiomyopathy (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●For most patients with hypertrophic cardiomyopathy (HCM), with or without left ventricular outflow tract (LVOT) obstruction who remain asymptomatic, close clinical observation and follow-up is the preferred approach. Given the absence of data demonstrating a clinical benefit with drug therapy in altering natural history in asymptomatic patients, patients should be engaged in a shared decision-making discussion to help resolve decisions about initiating medical therapy. (See 'Asymptomatic patients' above.)
●In patients with angina or coronary disease risk factors, coronary heart disease (CHD) should be excluded. In most patients without obstructive CHD, the pharmacologic management of chest discomfort is similar to that of HF in patients with HCM. Beta blockers and verapamil are the first-line agents. In patients without LVOT obstruction, verapamil is often the most efficacious at improving chest pain. (See 'Chest pain' above.)
●Patients with HCM and atrial fibrillation have an increased risk of thromboembolism, regardless of CHA2DS2-VASc score, which is not applicable in this population, as patients with HCM have been excluded from all trials of thromboembolism prophylaxis. For patients with HCM and atrial fibrillation, we recommend chronic oral anticoagulation (Grade 1A), with either warfarin or a direct oral anticoagulant chosen as the initial agent. (See 'Thromboembolism prophylaxis' above and "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation", section on 'For symptomatic AF'.)
●For the subset of patients with HCM and an LV apical aneurysm, we suggest long-term oral anticoagulation, rather than aspirin or no anticoagulation, to reduce the risk of thromboembolism (Grade 2C). (See 'Thromboembolism prophylaxis' above.)
●For the majority of low and intermediate risk noncardiac surgeries in patients with HCM, particularly those procedures associated with minimal fluid shifts, most patients with HCM are at low risk for perioperative cardiovascular complications. In patients with HCM who are undergoing noncardiac surgery, close monitoring of intraoperative hemodynamics, particularly during induction, hemorrhage, and other perioperative stressors, is critical. Invasive monitoring of arterial blood pressure and LV filling pressure has been advocated in higher-risk surgical procedures. Transesophageal echocardiography may help guide intraoperative management. (See 'Perioperative management during noncardiac surgery' above.)
●Patients with HCM and a resting or provoked LVOT gradient may be at increased risk for developing endocarditis. However, revisions to guidelines for endocarditis prophylaxis state that patients with HCM no longer require routine prophylaxis. Expert opinion amongst those who manage large numbers of patients with HCM continues to favor antimicrobial bacterial endocarditis prophylaxis before dental procedures, particularly for patients with LVOT obstruction and significant mitral valve abnormalities/regurgitation. (See 'Endocarditis prophylaxis' above.)
