INTRODUCTION — Hypertrophic cardiomyopathy (HCM) is a genetically determined heart muscle disease most often (60 to 70 percent) caused by mutations 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 pharmacologic treatment of patients with HCM and HF symptoms will be reviewed here. The medical management of non-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 management for non-heart failure symptoms".)
●(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, left ventricular outflow tract (LVOT) 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".)
The most important factor contributing to LVOT obstruction is anterior displacement of the mitral valve during systole, which is referred to as systolic anterior motion (SAM). SAM is caused by high velocity of systolic blood flow through the LVOT, which pulls (or drags) the mitral valve leaflet toward the ventricular septum, resulting in SAM-septal contact and direct impedance of blood flow out of the heart. SAM can also contribute to mitral regurgitation (MR); thus, therapies that relieve SAM and LVOT obstruction can also reduce MR.
LVOT obstruction is a highly visible feature of HCM and the most important mechanism responsible for limiting HF symptoms in this disease. HCM patients without LVOT obstruction can also develop symptoms often due to other factors, including diastolic dysfunction, and microvascular dysfunction. Among these abnormalities, diastolic dysfunction appears to be the most important [1-3]. (See "Treatment and prognosis of heart failure with preserved ejection fraction".)
OVERVIEW OF HF THERAPY IN HCM — There have been no large randomized trials of pharmacologic therapies in HCM. As a result, treatment strategies are based upon observational data and clinical experience [4]. An empiric approach is usually required, since it is not possible to predict which drug will work best for a given patient (algorithm 1).
Asymptomatic patients — We do not routinely use prophylactic drug therapy prior to the onset of symptoms, because there is no evidence that pharmacologic therapy alters the natural history of asymptomatic patients. (See 'Prophylactic therapy for asymptomatic patients' below.)
Approach to symptomatic patients with LVOT obstruction — Negative inotropic agents, including beta blockers and nondihydropyridine calcium channel blockers (most commonly verapamil), are the most widely used initial therapies [5]. A beta blocker is usually tried first (algorithm 1), with the drug initiated at a low dose that is titrated until symptoms are relieved or side effects occur [6]. If this does not provide symptom improvement, monotherapy with a nondihydropyridine calcium channel blocker is sometimes attempted, or combination therapy with two drugs is pursued.
Our approach to the treatment of symptomatic patients with HCM and LVOT obstruction is as follows:
●For patients who have significant symptoms of HF and LVOT obstruction, we recommend initial monotherapy with a negative inotropic agent. Because of the known safety profile and lower likelihood of peripheral vasodilation, we suggest using a beta blocker (rather than a nondihydropyridine calcium channel blocker) as the initial choice [1,3,7,8]. If the patient has contraindications to a beta blocker (eg, reactive airway disease) or is unable to tolerate a beta blocker due to side effects, we switch to monotherapy with a nondihydropyridine calcium channel blocker. Nondihydropyridine calcium channel blockers should not be used in patients with HCM and LVOT obstruction who have severe dyspnea, volume overload, or hypotension at rest. There is no role for monotherapy with disopyramide. (See 'Initial therapy' below.)
●For patients who have significant symptoms of HF and LVOT obstruction despite monotherapy with a beta blocker or calcium channel blocker, we suggest combination therapy with the initial agent and a negative inotropic agent. Options for combination therapy include:
•Beta blocker and disopyramide
•Nondihydropyridine calcium channel blocker and disopyramide
•Beta blocker and nondihydropyridine calcium channel blocker
UpToDate experts prefer a beta blocker and disopyramide as the most efficacious dual therapy for treating HF symptoms due to LVOT obstruction. The combination of a nondihydropyridine calcium channel blocker and a beta blocker is frequently limited by symptomatic bradycardia. (See 'Nondihydropyridine calcium channel blockers' below.)
●There is generally no role for using three negative inotropic drugs (beta blockers, nondihydropyridine calcium channel blocker, and disopyramide) simultaneously. For patients who have persistent symptoms of HF and LVOT obstruction despite combination therapy with maximally tolerated doses of two medications, we recommend evaluation for invasive septal reduction therapy. (See "Hypertrophic cardiomyopathy: Nonpharmacologic treatment of left ventricular outflow tract obstruction".)
Nonpharmacologic therapies include surgical myectomy and alcohol septal ablation. These therapies are only appropriate for patients with both symptoms and severe resting or provoked LVOT obstruction (eg, LVOT gradient ≥50 mmHg). Exercise echocardiography may be required to unmask important exertion/stress-related LVOT obstruction and/or mitral regurgitation, which should be considered in patients with refractory symptoms. (See "Hypertrophic cardiomyopathy: Nonpharmacologic treatment of left ventricular outflow tract obstruction".)
Approach to symptomatic patients without LVOT obstruction — The approach to medical therapy for symptomatic patients with HCM but without LVOT obstruction varies depending upon the patients LV ejection fraction (LVEF).
●For patients without LVOT obstruction with LVEF ≥50 percent, we suggest the following approach:
•Initial monotherapy with either a beta blocker or a nondihydropyridine calcium channel blocker. If the patient has minimal response to the maximal tolerated dose of the initial agent, it is reasonable to switch to the other category of drugs to see if there is a response.
•Diuretics, as needed, for patients with volume overload.
•If limiting symptoms persist in spite with optimal medical therapy, the patient should be re-evaluated for any evidence of LVOT obstruction. In the absence of LVOT obstruction with ongoing limiting symptoms, the patient should be referred for evaluation for heart transplantation.
●For patients without LVOT obstruction with LVEF <50 percent, the approach to the treatment of HF is similar to the approach for patients without HCM who have HF with reduced EF. This approach, which includes beta blockers, ACE-inhibitors, aldosterone antagonists, diuretics (for volume overload), and potentially cardiac resynchronization therapy, is discussed in greater detail separately. (See "Overview of the management of heart failure with reduced ejection fraction in adults".)
Mechanisms of action — Among the commonly used medications for treatment of symptomatic patients with HCM (beta blockers, nondihydropyridine calcium channel blockers, and disopyramide), a variety of potential mechanisms are felt to contribute to the beneficial effects. Possible mechanisms of benefit of these drugs include:
●All three agents are negative inotropes, which reduce LVOT obstruction [9].
●Beta blockers and nondihydropyridine calcium channel blockers slow the heart rate and prolong diastole, allowing increased ventricular filling [1]. Among the nondihydropyridine calcium channel blockers, verapamil is used most commonly, but diltiazem can be considered in those who are intolerant of verapamil.
●Beta blockers may reduce anginal symptoms by decreasing myocardial oxygen demand [10,11].
●Nondihydropyridine calcium channel blockers may reduce anginal symptoms by improving microvascular function and, therefore, myocardial perfusion [12-14].
Avoidance of volume depletion — In patients with HCM and LVOT obstruction, volume depletion tends to decrease stroke volume and worsen the LVOT gradient. This can lead to hypotension, lightheadedness, and syncope.
Medications to avoid or use cautiously in patients with LVOT obstruction — In patients with significant LVOT obstruction, hemodynamics can be compromised by the following medications:
●Vasodilators – Vasodilators, such as dihydropyridine calcium channel blockers (eg, nifedipine, amlodipine), nitroglycerin, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers, can produce a fall in peripheral resistance with an increase in LVOT obstruction and filling pressures, thereby resulting in hypotension and/or worsening HF symptoms.
●Diuretics – By reducing preload, diuretics can result in less LV filling, a smaller LV chamber, and therefore greater LVOT obstruction. As such, diuretics should rarely if ever be used in patients with LVOT obstruction. However, cautious use of diuretics may be attempted only in patients with nonobstructed HCM who have persistent HF and evidence of volume overload. (See 'Approach to symptomatic patients with LVOT obstruction' above.)
MEDICAL THERAPY FOR HF IN HCM WITH LVOT OBSTRUCTION — Patients with HCM may present with one or more of several symptoms, including:
●Fatigue
●Dyspnea
●Chest pain
●Palpitations
●Presyncope or syncope
Fatigue and dyspnea are typically considered together to be a manifestation of HF. Symptoms of HF are among the most common clinical manifestations of HCM. Most patients with HCM have normal or hyperdynamic LV systolic function, in which case one or more of the following contribute to HF symptoms: left ventricular outflow tract (LVOT) obstruction, diastolic dysfunction, and mitral regurgitation.
The treatment of HF in patients with HCM differs significantly depending upon the presence of absence of LVOT obstruction.
Initial therapy — For patients with HCM and LVOT obstruction who have symptoms of HF, we recommend initial monotherapy with a negative inotropic agent, with the following approach to choosing an agent:
●For most patients, we suggest starting a beta blocker as the initial choice because of the known safety profile and lower likelihood of peripheral vasodilation compared with nondihydropyridine calcium channel blocker.
●If the patient has contraindications to a beta blocker (eg, reactive airway disease) or is unable to tolerate a beta blocker due to side effects, we switch to monotherapy with a nondihydropyridine calcium channel blocker, usually verapamil. Extended-release verapamil can be initiated at 120 or 180 mg daily and increased to a total of 480 mg daily. If extended-release diltiazem is chosen rather than verapamil, the typical starting dose is 120 or 180 mg daily, which can be increased to a total of 480 mg daily.
●There is no role for monotherapy with disopyramide.
Drug therapy in symptomatic patients with HCM and LVOT obstruction is usually initiated at a low dose, with a strategy for the drug to be titrated to higher doses as heart rate and blood pressure tolerate until clinical improvement is observed or side effects occur.
Beta blockers — Beta blockers were among the first drugs used for the treatment of symptomatic HCM. The potential benefits of beta blockers were first described in the 1960s, and a number of subsequent, predominantly nonrandomized, studies have noted beneficial hemodynamic effects [10,11,15-18]. In one small, randomized crossover trial which compared nadolol with verapamil and placebo in 18 patients with mild or moderately symptomatic HCM, neither drug improved measured exercise capacity compared with placebo, but 13 patients reported fewer symptoms with drug treatment (eight with verapamil and five with nadolol). [18]. Because the patients were only mildly or moderately symptomatic at baseline, the lack of improvement in exercise capacity cannot be extrapolated to patients with more severe disease.
The majority of evidence supporting beta blocker use in HCM is derived from its benefit in blunting increases in gradient with provocation, such as with exercise. In a cohort study of 27 patients without resting LVOT obstruction but an exercise-provoked LVOT gradient of 30 mmHg or greater, treatment with nadolol or bisoprolol for one year resulted in significantly lower post-exercise LVOT gradients (36 mmHg versus 87 mmHg at baseline) [19]. While the findings of a reduction in LVOT obstruction are encouraging, additional studies are needed to confirm these results and investigate whether this reduction in provoked LVOT obstruction results in improved outcomes.
Society guidelines have advocated for the use of beta blockers as first-line therapy [8,20]. In the absence of large randomized trials, the use of beta blockers is based upon an understanding of the pathophysiology of HCM, the characteristics of these drugs, and extensive clinical experience. Potential mechanisms of benefit include (see "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction", section on 'Pathophysiology and evolution of LVOT obstruction'):
●Reduced heart rates at rest and exercise, permitting improved LV filling, which reduces LVOT obstruction.
●Negative inotropy, which can also alleviate LVOT obstruction.
●Reduced myocardial oxygen consumption, which may improve chest pain.
In addition, beta blockers do not have the potential risks associated with vasodilators, which may be harmful in patients with significant outflow obstruction. Thus, many experts prefer beta blockers over verapamil in HCM patients with obstruction. (See 'Medications to avoid or use cautiously in patients with LVOT obstruction' above.)
Nondihydropyridine calcium channel blockers — As with beta blockers, most of the data supporting the use of nondihydropyridine calcium channel blockers come from nonrandomized studies [12,21,22]. The potential benefit of verapamil can be illustrated by the following observations:
●In a series of 227 patients, 59 percent remained on verapamil at two years because their perceived quality of life was improved compared with their previous therapy (usually a beta blocker) [22].
●In a series of 15 patients with HCM and severe HF symptoms despite treatment with beta blockers, intravenous verapamil reduced the resting LVOT gradient in six (40 percent) [21]. Chronic oral verapamil was given to 11 of these patients for six months, nine of whom experienced an improvement in symptoms. Despite symptomatic improvement, only five had a reduction in the LVOT gradient, supporting the possible significance of additional pathophysiologic mechanisms, such as diastolic dysfunction or ischemia.
●Among 55 patients treated with oral verapamil (360 to 640 mg/day) for one to four weeks, 35 (64 percent) reported an improvement in symptoms [12]. Symptomatic improvement correlated with improvements in diastolic filling. This benefit persisted for one to two years and was reversed when therapy was discontinued.
Verapamil is tolerated well in most patients. However, it may be associated with a variety of side effects including sinus arrest, atrioventricular (AV) block, and pulmonary edema in patients with markedly elevated pulmonary venous pressures [22,23]. In contrast to beta blockers, verapamil has more significant vasodilatory properties, which may cause hypotension in patients with LVOT obstruction. For this reason, verapamil should not be used in patients with HCM and LVOT obstruction who have severe dyspnea, volume overload, or hypotension at rest. (See 'Medications to avoid or use cautiously in patients with LVOT obstruction' above.)
The potential mechanisms of benefit are similar to beta blockers, with some differences (see 'Initial therapy' above):
●Reduced heart rates at rest and exercise, permitting improved LV filling, which reduces LVOT obstruction
●Negative inotropy, which can also alleviate LVOT obstruction
●Improved cardiac microvascular function, which may alleviate chest pain
Experience with other calcium channel blockers in obstructive HCM is limited. Diltiazem may improve LV diastolic function, although the benefit may be less than with verapamil [22,24]. Nifedipine and other dihydropyridine calcium channel blockers should be avoided in patients with resting or provoked LVOT obstruction because of their potent peripheral vasodilator properties. (See 'Medications to avoid or use cautiously in patients with LVOT obstruction' above.)
Combination therapy for ongoing symptoms — For patients with HCM who have persistent symptoms of HF and LVOT obstruction despite monotherapy with a beta blocker or nondihydropyridine calcium channel blocker, we suggest combination therapy with the initial agent and a negative inotropic agent. Options for combination therapy include:
•Beta blocker and disopyramide
•Nondihydropyridine calcium channel blocker and disopyramide
•Beta blocker and nondihydropyridine calcium channel blocker
UpToDate experts prefer a beta blocker and disopyramide as the most efficacious dual therapy for treating HF symptoms due to LVOT obstruction and with this approach lower dosing of AV nodal agent is feasible. When using a nondihydropyridine calcium channel blocker and beta blocker together, this approach is frequently limited by symptomatic bradycardia.
Disopyramide — Disopyramide, an antiarrhythmic drug with negative inotropic properties, is the only drug that has been shown to lower resting LVOT gradients in HCM [25-27]. However, given the potential for side effects from disopyramide, it is generally reserved as a second-line agent as part of combination therapy, and is not indicated for the treatment of HF symptoms in patients without LVOT obstruction. For patients at higher risk of QTc prolongation or side effects, including elderly patients, those with prolonged QTc at baseline, conduction disease on an electrocardiogram (ECG), those taking other QTc prolonging drugs and patients prone to electrolyte abnormalities, disopyramide is typically started in a monitored hospital setting. Among patients not considered at high risk for adverse effects, UpToDate experts initiate disopyramide in the outpatient setting, with follow up ECGs at one week, two months and then every six months.
The potential efficacy of disopyramide in patients with HCM and LVOT obstruction has been evaluated in several studies:
●A randomized, double-blind crossover study compared the effects of disopyramide (150 mg four times daily), propranolol (40 mg four times daily), and placebo, each given for a period of four days, the subaortic pressure gradient decreased from 61 mmHg with placebo to 5 mmHg with disopyramide and 30 mmHg with propranolol [26]. Disopyramide also increased the exercise duration, while propranolol produced no significant change.
●In a multicenter cohort assessing the efficacy and safety of disopyramide (mean dose 432 mg/day), 118 patients with HCM and LVOT obstruction (mean age 47 years, most also receiving a beta blocker) were compared with 373 patients with HCM and LVOT obstruction not treated with disopyramide, with an average follow-up of three years [27]. After a mean follow-up of 3.1 years, 78 patients (66 percent) were maintained on disopyramide without the need for major nonpharmacologic interventions (surgical myectomy, alcohol ablation, or pacing), while the remaining 40 patients (34 percent) required invasive intervention. The mean outflow gradient at rest fell from 75 to 40 mmHg, and New York Heart Association (NYHA) functional class significantly improved from 2.3 to 1.7 (table 1). When the patients treated with disopyramide were compared with those not treated with this agent, there was a trend toward lower rates of mortality (1.4 versus 2.6 percent per year) and sudden death (1.0 versus 1.8 percent per year).
●In a prospective single-center cohort of 737 patients with HCM, including 299 patients with LVOT obstruction and symptoms despite therapy with a beta blocker or verapamil, disopyramide (mean dose 501 mg/day) was added as a second medical therapy in 221 patients, with adequate symptom control or improvement to avoid invasive septal reduction therapy in 141 patients (64 percent) [28]. The addition of disopyramide also significantly lowered the resting LVOT gradient (from mean 61 mmHg to 10 mmHg), with no adverse impact on survival compared with patients not receiving disopyramide.
These observations seem to allay concerns about proarrhythmia in patients with HCM, although patients receiving diuretics or other antiarrhythmics may be at risk [29]. With initiation of disopyramide, the dosing of the accompanying AV nodal blocking agent can be reduced.
Limitations to treatment with disopyramide — Although disopyramide is a more potent negative inotrope than either beta blockers or calcium channel blockers, there are important limitations to the use of disopyramide in patients with HCM and symptomatic LVOT obstruction, which preclude its use as monotherapy and can limit its use in combination therapy:
●Disopyramide can accelerate AV nodal conduction, resulting in an increased ventricular rate if atrial fibrillation or flutter develops. Thus, patients treated with disopyramide should also be treated with a beta blocker [1].
●Like other class IA antiarrhythmic drugs (table 2), disopyramide can prolong the QT interval, possibly leading to torsades de pointes. Disopyramide has traditionally been started in the hospital setting to monitor for prolongation of the QTc and arrhythmias. However, outpatient initiation of disopyramide appears to be safe in low-risk patients who are closely monitored. Among a cohort of 168 patients started on disopyramide 300 mg (100 mg three times daily), the QTc increased by an average of 19 milliseconds, and none of the patients experienced a cardiac event (including death, cardiac arrest, or syncope) over three month follow-up [30].
Patients treated with disopyramide should have a baseline 12-lead ECG and periodic ECGs during follow-up (eg, every 6 to 12 months). Disopyramide should not be used if the baseline QTc is prolonged and it should be discontinued if the QTc prolongs by 25 percent or more. (See "Major side effects of class I antiarrhythmic drugs" and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".)
●Disopyramide should not be given to patients concurrently treated with amiodarone, sotalol, or other class I antiarrhythmic drugs because of concern about proarrhythmia [8,27].
●Disopyramide can have significant anticholinergic side effects and should not be given to patients with symptoms of prostatic hypertrophy or open-angle glaucoma [8,27]. Among a cohort of 168 patients with HCM who took disopyramide for an average of 447 days, 38 patients (23 percent) developed side effects, including 30 patients (18 percent) with anticholinergic effects, leading to discontinuation of the drug in 18 of 38 patients (47 percent) [30]. The addition of pyridostigmine may help to mitigate the anticholinergic side effects related to disopyramide.
In addition, the benefit of disopyramide is limited to patients with LVOT obstruction either at rest or with provocation, and there is no role for its use in patients with HCM without LVOT obstruction.
Therapy in patients with midcavity obstruction — Midventricular (ie, midcavity) obstruction (in the absence of subaortic obstruction) is a morphologic variant of HCM, which arises from different anatomic and hemodynamic circumstances [31,32]. Perhaps the most common HCM morphology associated with midcavitary obstruction occurs due to the apposition of septum and lateral wall in the context of a small, hyperdynamic cavity. In these patients the intracavitary "gradient" does not usually produce clinically significant symptoms, although beta blockers appear to be the most reasonable therapy in patients with symptoms. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction", section on 'Midcavity obstructive HCM'.)
Another cause of midcavitary obstruction is anomalous insertion of the anterolateral papillary muscle directly into the anterior leaflet of the mitral valve (in the absence of chordae tendineae), with anterior leaflet and papillary muscle together contacting ventricular septum at midsystole to produce midcavitary obstruction [33,34]. In patients with limiting symptoms due to anomalous papillary muscle obstruction, AV nodal blocking agents (ie, beta blockers and nondihydropyridine calcium channel blockers) should be the initial treatment option. Patients with advanced symptoms refractory to drug therapy should be evaluated for invasive septal reduction therapy, specifically surgical myectomy rather than alcohol septal ablation, since only surgery can address the morphologic abnormality of midcavitary obstruction.
Refractory symptoms with LVOT obstruction — Patients with HCM, LVOT gradient of ≥50 mmHg at rest or with provocation, and advanced and limiting HF symptoms that are refractory to medical therapy should undergo septal reduction therapy. The nonpharmacologic treatment of HCM with LVOT obstruction is discussed in detail separately. (See "Hypertrophic cardiomyopathy: Nonpharmacologic treatment of left ventricular outflow tract obstruction".)
MEDICAL THERAPY FOR HF IN HCM WITHOUT LVOT OBSTRUCTION — For patients with HCM with HF symptoms but who do not have LVOT obstruction, the approach to therapy varies depending upon the patients' LVEF. Patients with an LVEF ≥50 percent are typically treated with beta blocker or nondihydropyridine calcium channel blocker monotherapy, with or without diuretics, while patients with an LVEF <50 percent are usually treated similarly to patients with HF and reduced LVEF who do not have HCM.
HF without LVOT obstruction with LVEF ≥50 percent — For patients without LVOT obstruction with an LVEF ≥50 percent, options for medical therapy are more limited, and there is no role for invasive septal reduction therapy. We suggest the following approach to medical therapy in such patients:
•Initial monotherapy with either a beta blocker or a nondihydropyridine calcium channel blocker. If the patient has minimal response to the maximal tolerated dose of the initial agent, it is reasonable to switch to the other category of drugs to see if there is a response.
•Diuretics, as needed, for patients with volume overload.
•If limiting symptoms persist in spite of optimal medical therapy, the patient should be re-evaluated for any evidence of LVOT obstruction. In the absence of LVOT obstruction and with ongoing, severe (ie, limiting) symptoms, the patient should be referred for specialty evaluation for consideration of advanced HF therapies, including potentially heart transplantation.
Losartan, an angiotensin receptor blocker, has also been investigated as a potential disease-modifying agent in patients with HCM. In a randomized trial of 133 patients with HCM who had minimal or no symptoms (94 percent NYHA class 1 or 2) and no resting LVOT obstruction (mean LVOT gradient 8 mmHg), in which patients were randomized to losartan 100 mg daily or placebo (in addition to standard HCM therapy), there was no significant difference in LV systolic function, left atrial volume, or exercise capacity at 12-month follow-up [35]. While apparently safe in patients without LVOT obstruction, losartan had no impact of HCM disease-progression and should not be routinely used in the treatment of HCM, although it could be considered as an antihypertensive agent in nonobstructive HCM.
HF without LVOT obstruction with LVEF <50 percent — Up to 5 percent of patients with HCM will progress to an end-stage phase of the disease that is characterized by LV dilation and thinning and systolic dysfunction with LVEF <50 percent. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'HCM with LV systolic dysfunction (ejection fraction <50 percent)'.)
End-stage HCM has a distinct pathophysiology, and management strategies are significantly different compared with HCM patients with the typical phenotype of hyperdynamic systolic function. Evidence regarding the optimal approach to such patients is limited, but most experts treat these patients according to the standard approach to patients with HF due to systolic dysfunction (eg, beta blockers, ACE-inhibitors, diuretics, etc) [8,36]. In addition, many of these patients become candidates for heart transplantation [3,8,36,37]. The approach to the treatment of HF due to systolic dysfunction, as well as the consideration of candidacy for heart transplantation, are discussed in detail separately. (See "Heart transplantation in adults: Indications and contraindications" and "Overview of the management of heart failure with reduced ejection fraction in adults".)
PROPHYLACTIC THERAPY FOR ASYMPTOMATIC PATIENTS — For nearly all patients with 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. 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 [8].
Some asymptomatic patients have clinical or morphologic features that may put them at an increased risk for the future development of HF (eg, substantial resting LVOT obstruction; gradient ≥75 mmHg) [1,8]. Some experts recommend offering asymptomatic patients treatment with low-dose beta blockers, based on the theoretical benefit that beta blockers will mitigate greater increases in gradient during routine daily activities. However, there is no evidence that beta blockers provide any protective benefit from developing life-threatening arrhythmias; therefore, for patients considered high-risk for sudden cardiac death based on the conventional risk factors, implantable cardioverter-defibrillator ICD therapy for primary prevention of sudden death should be considered, following an extended discussion with the patient regarding the potential benefits and burdens of this approach. The issue of ICD use for the prevention of sudden cardiac death is discussed in detail separately. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".)
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, we do not routinely use prophylactic drug therapy prior to the onset of symptoms, because there is no evidence that pharmacologic therapy alters the natural history of asymptomatic patients. (See 'Prophylactic therapy for asymptomatic patients' above.)
●Vasodilators and diuretics should be used with caution or avoided in patients with significant LVOT obstruction, given the possibility of worsening LVOT obstruction and symptoms. (See 'Medications to avoid or use cautiously in patients with LVOT obstruction' above.)
●For patients who have symptoms of heart failure (HF) and LVOT obstruction, we recommend initial monotherapy with a negative inotropic agent (either a beta blocker or a nondihydropyridine calcium channel blocker) (Grade 1B). Because of the known safety profile and lower likelihood of peripheral vasodilation, we suggest using a beta blocker as the initial choice (Grade 2C). If the patient has contraindications to a beta blocker (eg, reactive airway disease), monotherapy with a nondihydropyridine calcium channel blocker can be considered or, in the appropriate patient, proceeding directly to combination therapy with an atrioventricular nodal blocking agent and disopyramide. UpToDate experts generally prefer a beta blocker and disopyramide as the most efficacious dual therapy for treating HF symptoms due to LVOT obstruction. Decision to pursue dual therapy with disopyramide should take into consideration patient overall clinical profile and desires, including discussion regarding potential for side effects as well as limited long-term efficacy. (See 'Initial therapy' above and 'Combination therapy for ongoing symptoms' above.)
●For patients who have persistent symptoms of HF and LVOT obstruction despite optimal medical therapy, we suggest combination therapy with the initial agent and a negative inotropic agent as the next step, rather than proceeding directly to invasive septal reduction therapy (Grade 2C). However, patients with HCM, LVOT gradient of ≥50 mmHg at rest or with provocation, and advanced and limiting HF symptoms that are refractory to medical therapy should undergo septal reduction therapy. (See 'Refractory symptoms with LVOT obstruction' above and "Hypertrophic cardiomyopathy: Nonpharmacologic treatment of left ventricular outflow tract obstruction".)
●For patients without LVOT obstruction with LV ejection fraction (LVEF) ≥50 percent, options for medical therapy are more limited, and there is no role for invasive septal reduction therapy. We suggest initial monotherapy with either a beta blocker or a nondihydropyridine calcium channel blocker, along with diuretics (as needed) for volume overload (Grade 2C). (See 'HF without LVOT obstruction with LVEF ≥50 percent' above.)
●The end-stage phase of HCM is characterized by LV dilation and thinning and systolic dysfunction with LVEF <50 percent without LVOT obstruction. Evidence regarding the optimal approach to such patients is limited, but most experts treat these patients according to the standard approach to patients with HF due to systolic dysfunction. (See 'HF without LVOT obstruction with LVEF <50 percent' above and "Overview of the management of heart failure with reduced ejection fraction in adults".)
