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Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction

Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction
Literature review current through: Jan 2024.
This topic last updated: Sep 13, 2023.

INTRODUCTION — Hypertrophic cardiomyopathy (HCM) is a genetically determined disease that commonly results in obstruction of the left ventricular outflow tract (LVOT), which can produce chest discomfort, dyspnea, fatigue, and syncope.

This topic discusses the management of patients with HCM and symptoms attributable to LVOT obstruction.

The approach to patients who have other symptoms of HCM (ie, not attributable to LVOT obstruction) is discussed separately. (See "Hypertrophic cardiomyopathy: Management of patients without outflow tract obstruction".)

The pathophysiology, clinical manifestations, diagnosis, and management of other clinical sequelae of HCM are covered elsewhere.

(See "Hypertrophic cardiomyopathy: Natural history and prognosis".)

(See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".)

(See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".)

(See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation".)

OTHER CAUSES OF SYMPTOMS — In patients with obstructive HCM, obstruction is the most likely cause of symptoms, but it is important to evaluate for the presence of other conditions that may contribute to the overall burden of symptoms. These conditions include:

Ischemia Epicardial coronary artery disease (CAD) or microvascular ischemia may cause severe exertional symptoms, hypotension, or arrhythmias in patients with HCM. Patients with HCM who have symptoms or signs suggestive of CAD based should undergo further evaluation with stress testing, coronary computed tomographic angiography, or coronary catheterization.

Atrial fibrillation or other supraventricular tachycardias – In patients with obstructive HCM, atrial fibrillation (AF) or other supraventricular tachycardias may contribute to the overall burden of symptoms. The clinical manifestations, evaluation, and management of supraventricular arrhythmias in patients with HCM are discussed elsewhere. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation".)

Diastolic dysfunction – Impaired LV relaxation is common in patients with HCM and can be a cause of symptoms. In patients with HCM, noninvasive measures of diastolic function are generally considered unreliable.

Ventricular arrhythmias – In patients with obstructive HCM, ventricular arrhythmias are a rare cause of exertional symptoms. However, patients with HCM are at increased risk of ventricular arrhythmias, and patients with syncope, palpitations, or other signs of malignant arrhythmias should be evaluated for the presence of these rhythms (eg, ambulatory electrocardiogram [ECG] monitoring) and should be evaluated for implantable cardioverter-defibrillator placement. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".)

Valve disease – Patients with obstructive HCM may develop primary mitral or aortic valve disease, which could contribute to or be the main driver of exercise-limiting symptoms. In patients with obstructive HCM who have severe mitral regurgitation (MR; at rest or with provocation) and who have a centrally or anteriorly directed MR jet, this should raise concern for the presence of intrinsic mitral valve disease. In such patients, additional evaluation is typically required and may include further characterization of the mechanism and severity of MR with transesophageal echocardiography (TEE). In addition, for patients with obstructive HCM in whom the severity of coexistent aortic stenosis is uncertain, TEE or invasive measurement of the aortic valve gradient may be required.

Further details on the evaluation of mitral and aortic valve disease can be found separately. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation", section on 'Diagnosis and evaluation' and "Clinical manifestations and diagnosis of aortic stenosis in adults", section on 'Diagnosis and evaluation'.)

Noncardiac causes of severe symptoms If the assessment for a cardiac cause of exertional symptoms is inconclusive and not judged to be due to LVOT obstruction, an evaluation for noncardiac causes of dyspnea and chest pain (eg, primary lung disease, obesity, anemia) is indicated.

DETERMINING THE SEVERITY OF OBSTRUCTION — The identification of LVOT obstruction and assessment of its severity are characterized as follows:

Echocardiography – In patients with HCM who were recently diagnosed with HCM or who have a change in symptoms, echocardiography should be performed to assess for the severity of LVOT obstruction and for other causes of symptoms. Echocardiographic evidence of an LVOT gradient ≥30 mmHg at rest or with exertion that is caused by systolic anterior motion of the mitral valve defines the presence of obstructive HCM. However, limiting symptoms attributable to LVOT obstruction typically occur when the LVOT gradient is ≥50 mmHg at rest or with provocation. In patients with HCM who have symptoms that may be due to obstruction and an LVOT gradient <50 mmHg at rest, exercise echocardiography (or other provocative maneuvers) should be performed to assess for a provocable gradient. The technical aspects of LVOT gradient measurement are discussed separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'LVOT obstruction'.)

Symptom evaluation – Therapy for obstructive HCM is determined by the presence of symptoms attributable to the LVOT gradient. The patient’s symptoms are typically elicited and classified using the New York Heart Association heart failure (HF) classification (table 1).

Invasive hemodynamic assessment – In patients whose echocardiographic LVOT gradient measurement may be inaccurate due to poor image quality, inability to separate intracavitary Doppler signals from mitral valve signals, or other technical aspects of measurement and in whom an accurate LVOT gradient would change management, invasive measurement of the LVOT gradient with left heart catheterization is indicated. Additional indications and the left heart catheterization procedure are described separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Cardiac catheterization'.)

Role of formal exercise testing – The severity of symptoms can be difficult to assess in patients with HCM who have adapted to their limitations over long periods of time. Our contributors have different approaches to exercise testing. One contributor obtains an exercise test in all patients with HCM at the time of diagnosis, with a change in symptoms, or if the burden of symptoms are unclear after a detailed evaluation (eg, conflicting data), while another contributor only tests select patients in whom the burden of symptoms is unclear [1]. In patients who will undergo testing, we use objective exercise testing with a cardiopulmonary exercise test (CPET) to aid in clarifying the patient's cardiac limitations, though testing with a standard exercise treadmill protocol is also reasonable. CPET should only be performed at facilities with a highly reliable exercise laboratory. There are no HCM-specific cutoffs for exercise tolerance measured by a CPET; normal values for CPET for sex and age can be found separately. (See "Cardiopulmonary exercise testing in cardiovascular disease" and "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Common exercise protocols'.)

GENERAL MEASURES

Counseling regarding hydration — In patients with symptoms attributable to LVOT obstruction, lower LV end-diastolic volume and lower afterload can worsen symptoms; both conditions lead to higher LVOT velocity that promotes obstruction. Thus, health care providers should counsel patients to maintain hydration during activities (eg, exercise, outdoor pursuits) or illnesses (eg, diarrhea, fever) that may lead to dehydration and to avoid treatments that decrease preload or afterload.

Therapies to avoid — Common treatments that cause peripheral vasodilation, intravascular volume depletion, or increasing myocardial contractility that may increase LVOT obstruction include:

Nifedipine and amlodipine

Nitroglycerin

Arterial vasodilators, such as angiotensin converting enzyme inhibitors and angiotensin II receptor blockers

Digoxin

Furosemide and other diuretics, except in rare circumstances and in small doses

These general measures are based on the pathophysiology of obstruction and our experience; there are no high-quality studies that assess the efficacy of these measures.

APPROACH TO THERAPY

Asymptomatic patients — Patients with obstructive HCM who do not have symptoms (ie, New York Heart Association [NYHA] class I HF (table 1)) do not require medical therapy or septal reduction therapy. Thus, asymptomatic patients with HCM can typically continue with clinical observation and periodic echocardiography to detect changes in symptoms or changes in cardiac structure and function that may warrant therapy.

Initial medical therapy for symptomatic patients — For patients with HCM who have symptoms that limit quality of life (eg, dyspnea, fatigue, syncope, or chest discomfort) attributable to LVOT obstruction, medical therapy is the first step in management (algorithm 1).

Initial therapy (beta blocker) — For most patients, we suggest initial therapy with a beta blocker rather than a calcium channel blocker or other agents (eg, disopyramide, myosin inhibitors). We typically treat with a nonvasodilating beta blocker (eg, nadolol, metoprolol succinate) and increase the dose, as tolerated, until symptoms are improved or resolved (algorithm 1). A typical starting dose of metoprolol succinate is 25 mg daily.

Refractoriness or intolerance to beta blockers — If the patient has contraindications to a beta blocker (eg, reactive airway disease), is unable to tolerate a beta blocker due to side effects, or if beta blocker therapy is not effective, we suggest treatment with extended-release verapamil (our usual choice) or extended-release diltiazem rather than other agents or septal reduction therapy (algorithm 1). 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, the typical starting dose is 120 or 180 mg daily, which can be increased to a total of 480 mg daily.

Verapamil is well-tolerated in most patients. However, it may be associated with a variety of side effects including sinus arrest, atrioventricular (AV) block, and pulmonary edema [2,3]. 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 volume overload or hypotension.

This approach to initial medical therapy is consistent with professional guidelines [1].

Rationale and evidence – For the initial treatment of patients with obstructive HCM, beta blockers and calcium channel blockers are effective and safer than other medical therapies or septal reduction therapy. However, this approach is based on our experience and the results of retrospective studies; there are no trials that directly compare beta blockers or calcium channel blockers with other therapies or with each other.

We prefer beta blockers as the initial choice of therapy based on our experience, the favorable safety profile of beta blockers, and the lower likelihood of peripheral vasodilation compared with nondihydropyridine calcium channel blockers [1]. Small studies have noted the beneficial effects of beta blockers [4,5], while a small, randomized crossover trial noted an improvement in symptoms without a change in exercise performance [6]. The majority of evidence supporting beta blocker use in patients with HCM is derived from its favorable effect on mitigating the magnitude of the LVOT gradient with exercise, which was demonstrated in small studies [7].

The use of nondihydropyridine calcium channel blockers to treat obstructive HCM is based on experience, the likely mechanism of action, and small studies from over 20 years ago [2,8,9]. In patients with obstructive HCM, nondihydropyridine calcium channel blockers may reduce obstruction and myocardial oxygen consumption via their effect on reducing heart rate and inotropy as well as via improved cardiac microvascular function. Experience with other calcium channel blockers in obstructive HCM is limited.

Therapies for refractory symptoms — For patients with obstructive HCM and severe symptoms that impact quality of life despite initial monotherapy with a beta blocker or nondihydropyridine calcium channel blocker, the options for management include either septal reduction therapy (ie, alcohol septal ablation, surgical myectomy) or additional medical therapy with more potent negative inotropic agents (ie, disopyramide combination therapy, myosin inhibitor combination therapy) (algorithm 1). The choice of medical therapy or septal reduction therapy for HCM is individualized based on the preferences of each patient after being fully informed of the strengths and limitations of each management option.

Additional medical therapy — In patients who elect to undergo additional medical therapy, the choice of therapy is individualized and includes disopyramide combination therapy (eg, disopyramide with a beta blocker or calcium channel blocker) or myosin inhibitor combination therapy (eg, mavacamten with a beta blocker or calcium channel blocker). In general, there is greater clinical experience with disopyramide, but there are more rigorous studies of myosin inhibitors (eg, mavacamten) [10,11]. Myosin inhibitors require frequent echocardiographic monitoring of LV ejection fraction (LVEF) to ensure that systolic function does not decrease to unacceptably low values, while disopyramide requires occasional ECG monitoring to ensure that the QTc interval has not increased to unsafe values. Thus, the choice of agent is typically based on the experience of the treating center, the side effect profiles of each agent, drug interactions, the availability of insurance coverage for myosin inhibitors, and the patient's characteristics and preferences.

Professional guidelines support the use of disopyramide for refractory symptoms but have not addressed the use of mavacamten [1]. There are no trials that directly compare the two agents.

The details of each agent are discussed below. (See 'Disopyramide' below and 'Myosin inhibitors' below.)

Disopyramide — Disopyramide is an agent with negative inotropic effects and class I antiarrhythmic effects. Disopyramide is typically used to treat patients who have severe symptoms despite monotherapy with either a beta blocker or calcium channel blocker.

Cautions – There are important limitations to the use of disopyramide in patients with HCM and symptomatic LVOT obstruction that preclude its use as monotherapy and can limit its use in combination therapy:

Concomitant use with an atrioventricular nodal blockerDisopyramide 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 or a nondihydropyridine calcium channel blocker [12].

QTc prolongation – Similar to other class IA antiarrhythmic drugs (table 2), disopyramide can prolong the QT interval, which can lead to ventricular fibrillation (ie, torsades de pointes). Among a cohort of 168 patients started on disopyramide 300 mg (100 mg three times daily), the QTc increased by an average of 19 ms, and none of the patients experienced a cardiac event (including death, cardiac arrest, or syncope) over three months of follow-up [13].

Proarrhythmic effectsDisopyramide should not be given to patients concurrently treated with amiodarone, sotalol, or other class I antiarrhythmic drugs because of concern about proarrhythmia [14,15].

Anticholinergic effectsDisopyramide can have anticholinergic side effects and should not be given to patients with symptoms of prostatic hypertrophy or open-angle glaucoma [14,15]. 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 patients (10 percent) [13]. The addition of pyridostigmine may help to mitigate the anticholinergic side effects related to disopyramide.

Starting therapy with disopyramide – Depending on the risk of QTc prolongation, disopyramide is either started in the inpatient or outpatient setting. The risk factors for significant QTc prolongation include older age, preexisting QTc prolongation, conduction system disease on an ECG, use of other QTc-prolonging drugs, and electrolyte abnormalities.

Hospital-based initiation In patients who will undergo inpatient initiation of disopyramide, the patient is placed on telemetry and four doses are given. If the QTc remains <520 ms or 550 ms in the presence of a baseline wide QRS, the patient is discharged and then undergoes ECG monitoring one week later, two months thereafter, and every six months [16].

Outpatient initiation – Among patients who do not have risk factors for adverse effects (see above), UpToDate experts initiate disopyramide in the outpatient setting and obtain ECGs at one week, two months, and then every six months. The initial dose is extended-release disopyramide 100 mg twice daily; short-acting disopyramide is given as 150 mg three times daily. If symptoms remain and side effects are absent or tolerable, the dose is then increased to a maximum of extended-release disopyramide 600 mg twice daily.

Patients treated with disopyramide should have a baseline 12-lead ECG and periodic ECGs during follow-up (eg, every six 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 to more than 520 ms. (See "Major side effects of class I antiarrhythmic drugs" and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".)

Management of concomitant beta blocker or calcium channel blocker therapy Disopyramide should only be used in combination with a beta blocker or a nondihydropyridine calcium channel blocker; it can accelerate AV nodal conduction, which may allow for rapid conduction of AF [12]. Either a nonvasodilating beta blocker or a nondihydropyridine calcium channel blocker can be used. When disopyramide is initiated, the dose of any accompanying AV nodal blocking agent can be reduced to a dose no lower than metoprolol 25 mg daily or its equivalent.

Long-term management – In our experience, symptoms improve in approximately two-thirds of patients who start disopyramide, while the remainder receive little or no effect. Among those who respond to treatment, the duration of the effect is variable and may last months or years.

Evidence – The aggregate studies of disopyramide in patients with obstructive HCM suggest that disopyramide reduces exertional symptoms, delays the need for septal reduction therapy, and reduces the LVOT gradient. There is no clear effect on mortality. The observational studies include:

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 [14]. 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), while the remaining 40 patients (34 percent) required invasive intervention. The mean LVOT gradient at rest decreased from 75 to 40 mmHg, and NYHA functional class significantly improved from 2.3 to 1.7. 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 299 patients with HCM and LVOT obstruction who had symptoms despite therapy with a beta blocker or verapamil, disopyramide (mean dose 501 mg/day) was added as a second medical therapy [17]. In this group, symptom control improved in 64 percent of patients. 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.

Myosin inhibitors — Myosin inhibitors act by inhibiting the cardiac myosin ATPase enzyme, which limits the formation of myosin-actin crossbridges and decreases myocardial contractility [18]. In patients with obstructive HCM, lower contractility mitigates early systolic ejection velocity, which decreases or eliminates contact between the mitral valve and ventricular septum. Myosin inhibitors may improve diastolic function [19]. The end effect is a reduction in the LVOT gradient and symptom burden.

Cautions – Myosin inhibitors have important on-target effects, side effects, and drug interactions that may limit their use in selective obstructive HCM:

Effect on ejection fraction Mavacamten reduces LVEF by 4 percent, on average, but, in some patients, systolic dysfunction may decrease significantly. Notably, reduction in systolic function is reversible after discontinuation of the drug. Mavacamten is only appropriate for use in patients with an LVEF ≥55 percent who do not have NYHA class IV HF symptoms. Mavacamten can only be given to patients who agree to participate in a monitoring program.

Pregnancy and lactation Myosin inhibitors are teratogenic in animal models and cannot be used in patients who intend to become pregnant, during pregnancy, or in patients who are breastfeeding. Females of child-bearing age should have a pregnancy test before starting therapy with a myosin inhibitor and must use appropriate contraception during therapy.

Pharmacologic interactions Mavacamten should not be taken by patients who take certain drugs that inhibit or induce the CYP450 system.

Atrial fibrillation – Myosin inhibitors should be used with caution in HCM patients with a history of AF. AF is often not well tolerated in patients with HCM, and the reduction in systolic function with mavacamten may potentiate HF symptoms in some patients with HCM who develop AF. However, there is no evidence that mavacamten increases the risk for developing AF in patients with HCM [10].

Pretreatment management – Before therapy with a myosin inhibitor is started, we take the following steps:

Screen for contraindications – We review the patient's medical history and obtain an ECG and echocardiogram to evaluate for any contraindications to therapy (see above).

Assess for barriers to monitoring – In addition, we confirm that the patient can follow up with the frequent schedule of echocardiograms and other testing (eg, liver function tests) required for monitoring.

Discontinue disopyramide – If the patient is taking disopyramide therapy, it is discontinued seven days before initiating mavacamten to avoid treatment with two agents with strong negative inotropic effects.

Initiation and maintenance of therapy Mavacamten is a direct myosin inhibitor that decreases myocardial contractility and therefore requires frequent monitoring of symptom severity, ECGs, and echocardiograms. During the course of therapy, the dose of mavacamten may be stopped, decreased, or maintained depending on the patient’s symptoms and the results of monitoring. The requirements for monitoring and response to changes in cardiac function are described in a US Food and Drug Administration-mandated regulatory guideline [20].

Evidence – The efficacy and safety of mavacamten was established in trials that included patients resistant to monotherapy with a beta blocker or calcium channel blocker; there are no studies that compare the effect of mavacamten with other medical therapies or septal reduction therapy. The trials of mavacamten demonstrate that, on average, patients taking mavacamten had improved functional capacity as measured by peak VO2max, improved symptom burden by NYHA class and Kansas City Cardiomyopathy Questionnaire, and a reduction in the LVOT gradient compared with the group of patients taking placebo [10,11]. The trials include:

In a trial of patients with HCM and an LVOT gradient ≥50 mm, assignment to mavacamten was more likely to improve NYHA class by at least 1 level (59 versus 15 percent in placebo) and to improve LVOT gradient with Valsalva (difference in difference -70 mmHg; 95% CI -90 to -51) [21].

In a trial of 112 patients with obstructive HCM who were maximally treated with medical therapy and who were referred for septal reduction therapy, patients were randomly assigned to receive therapy with mavacamten or to receive placebo for 16 weeks prior to septal reduction therapy [11]. After 16 weeks, patients in the mavacamten group were less likely to meet criteria for septal reduction therapy or to have undergone septal reduction therapy compared with those who received placebo (77 versus 18 percent in the mavacamten group; difference 59 percent, 95% CI 44-74 percent). More patients treated with mavacamten had improvement in symptoms of ≥1 NYHA class (63 versus 21 percent) and lower LVOT gradient with Valsalva at 16 weeks (28 versus 78 mmHg). Notably, two patients in each group underwent septal reduction therapy; thus, events primarily consisted of patients who met criteria for septal reduction therapy. The limitations of this study include the relatively short follow-up period and the use of surrogate outcomes.

Among those treated with mavacamten after the initial randomized phase of the trial, including patients in the placebo group, there was further reduction in the fraction of patients who underwent or met criteria for septal reduction therapy [22]. After 56 weeks of follow-up, 11 percent of patients treated with mavacamten had significant LV systolic dysfunction and one death was associated with mavacamten-induced LV systolic dysfunction.

In the EXPLORER-HCM trial of 251 patients with obstructive HCM (LVEF >55 percent and LVOT gradient ≥50 mmHg) and NYHA class II or III HF symptoms despite monotherapy with a beta blocker or calcium channel blocker, patients were randomly assigned to mavacamten or placebo for 30 weeks [10]. A clinical evaluation, ECG, and echocardiography were scheduled every two to four weeks throughout the study.

After 30 weeks of observation, five patients discontinued their assigned therapy (three in the mavacamten group and two in the placebo group). The improvement in oxygen consumption measured by cardiopulmonary exercise test was higher in the mavacamten group than in the placebo group (1.4 versus -0.1 mL/kg/min), and the fraction of patients with improvement in both oxygen consumption of ≥3.0 mL/kg/min and NYHA class ≥1 was greater in the mavacamten group (20 versus 8 percent; difference 12.5 percent, 95% CI 4-21 percent). Adverse effects that included AF, syncope, sudden death, and HF were similar between the two groups. At the end of the study, LVEF was 4 percent lower in the mavacamten group.

Septal reduction therapy — In patients who elect to proceed with septal reduction therapy, the choices for therapy are surgical myectomy or alcohol septal ablation. The decision of which septal reduction therapy to use is individualized to the patient. (See 'Choosing between therapies' below.)

In addition to the patient-specific factors, and given the potential for complications, septal reduction therapy should be performed at centers that can reliably perform these procedures with a low risk of morbidity and mortality. (See 'Evidence and rationale' below.)

This approach to septal reduction therapy is consistent with the American Heart Association/American College of Cardiology (AHA/ACC) guidelines on the management of HCM [1].

Choosing between therapies — The primary features of the two septal reduction therapies include:

Benefits and risks of surgical myectomy – During surgical myectomy, a sternotomy is performed, and the patient is placed on cardiopulmonary bypass. Following this, an aortotomy is performed and the proximal septum is approached through the aortic valve. Approximately 3 to 10 g of ventricular septal muscle are excised in order to widen the LVOT area [23-30]. The procedure usually involves extension of the myectomy to the base of the papillary muscles and may include mitral valve repair [31-34]. Before the end of the surgery, TEE imaging and provocation with dobutamine or isoproterenol are often used to determine whether additional myectomy is necessary [35-37].

Surgical myectomy typically results in reduction of symptoms by one or more NYHA class in approximately 95 percent of patients who undergo the procedure. The risks of surgical myectomy include the morbidity associated with cardiac surgery (eg, time in hospital, recovery), a perioperative mortality risk of approximately 1 percent, and permanent pacemaker placement of approximately 3 to 5 percent. If additional surgeries are performed (eg, mitral valve apparatus surgery), the risk of perioperative mortality is higher. The high clinical benefit and low procedural risk of myectomy is derived from experienced high-volume HCM centers, and, therefore, similar outcomes are not generalizable to the overall population of patients with HCM.

Septal myectomy is the treatment of choice in patients who require mitral valve repair, surgery for morphologic abnormalities contributing to obstruction (eg, correction of anomalous papillary muscle insertion into the mitral valve), extreme septal hypertrophy, or other cardiac surgery (eg, coronary artery bypass grafting, severe aortic stenosis). Patients who undergo surgical myectomy typically require only one procedure, though surgical myectomy is more invasive and has a longer recovery time compared with alcohol septal ablation. Further details are described elsewhere in this topic. (See 'Evidence and rationale' below.)

Benefits and risks of alcohol septal ablation – Alcohol septal ablation is performed as part of a cardiac catheterization in which the first or second septal perforator coronary artery branch are accessed and a minimal volume of ethanol injected to create a controlled and localized myocardial infarction in the area of the basal septum where systolic anterior motion-septal contact is occurring. The use of myocardial contrast echocardiography and low-volume ethanol injection may reduce the rate of complications associated with alcohol septal ablation [38-40]. It may take a few months for the remodeling from the infarct to be complete and the LVOT area widened to reduce or eliminate septal anterior motion-septal contact (figure 1 and waveform 1 and image 1) [38,41-44].

Alcohol septal ablation results in reduction of one or more NYHA class in approximately 90 percent of patients who undergo the procedure. The risks of alcohol septal ablation include a mortality risk of approximately 1 percent, a 10 percent risk of permanent pacemaker placement, and a 10 percent chance for the need for a repeat procedure due to suboptimal gradient reduction after the initial procedure. In patients who are not candidates for surgical myectomy or in patients who do not want to undergo cardiac surgery, alcohol septal ablation is the treatment of choice. Alcohol septal ablation is less invasive than surgical myectomy and its efficacy in reducing symptoms is similar to surgical myectomy (90 versus 96 percent have a reduction in symptoms with alcohol septal ablation and surgical myectomy, respectively). (See 'Evidence and rationale' below.)

Evidence and rationale — The evidence to support septal reduction therapy includes studies that describe symptom improvement in the majority of patients who undergo these therapies. The available studies describe a relatively low mortality with either procedure and both are associated with a risk of conduction injury requiring permanent pacemaker placement (higher for alcohol septal ablation compared with surgery). There are no direct comparisons of septal reduction therapy with continued medical therapy, nor randomized trials that compare the efficacy and safety of septal alcohol ablation with surgical myectomy. In addition, the available studies are likely influenced by patient selection, referral bias, and overrepresentation of the results of high-volume centers.

Efficacy – Surgical myectomy and septal ablation are associated with a high success rate for symptom reduction:

In a cohort of patients who underwent surgical myectomy or alcohol septal ablation, an improvement in HF symptoms to NYHA class I or II occurred in 96 and 90 percent, respectively [45].

In a cohort of patients who underwent alcohol septal ablation at a single center, functional status improved after alcohol septal ablation from a mean NYHA class of 2.9 to 1.6 [46].

Perioperative mortality The perioperative mortality of surgical myectomy and alcohol septal ablation is approximately 1 percent or lower among procedures performed at high-volume centers.

In a cohort of 1275 patients with HCM (mean age 58 years, median follow-up 5.7 years) who underwent alcohol septal ablation at one of seven European sites between 1996 and 2015, 30-day mortality was 1 percent [46].

In a series of 298 consecutive patients undergoing isolated septal myectomy at Mayo Clinic between 2011 and 2014, 30-day mortality was zero, with 99 percent survival at six years [47].

In patients with obstructive HCM who undergo surgical myectomy and other adjunctive procedure, the risk of perioperative mortality increases:

-In patients with HCM who underwent septal myectomy and mitral valve surgery, 30-day mortality was approximately 5 percent, which is higher than that for patients with septal myectomy alone (adjusted odds ratio 4.7; 95% CI, 1.6-13.6) [48].

-At a single center, the 30-day mortality rate was 3.4 percent (three deaths) in a sample of 89 patients who had septal myectomy and a concomitant surgical procedure, while mortality among 249 patients who underwent myectomy alone was 0.8 percent [49].

Medium- and long-term mortality – In most cohort studies, the medium- and long-term mortality is similar for patients undergoing either alcohol septal ablation or surgical myectomy [50,51]. As examples:

Among patients from a single cohort who were followed long-term, four-year mortality was similar for patients undergoing septal myectomy or alcohol septal ablation (2.9 versus 2 percent, respectively) [45].

In a 2015 systematic review and meta-analysis of 4804 patients from 27 nonrandomized studies with long-term follow-up, mortality after surgical myectomy was 1.4 percent per year and after alcohol septal ablation was 1.5 percent per year [52].

Studies that compared survival of patients who had septal reduction therapy with the general population showed similar survival for both surgical myectomy and alcohol septal ablation [45,53].

Specific complications The rate of common complications associated with surgical myectomy and alcohol septal ablation includes:

Heart block – Complete heart block requiring a permanent pacemaker occurs in approximately 3 to 5 percent of patients undergoing surgical myectomy and 10 percent of patients undergoing alcohol septal ablation [23,49,54-57]. In contrast to septal myectomy, injury to the right bundle branch is much more common with alcohol ablation (54 versus 6 percent in one report) [58,59], which is likely the result of the dependence of the right bundle branch and the left anterior fascicle on sepal branches, which are the targets of alcohol septal ablation [55,56,58].

Ventricular septal defect – Excessive removal of muscle or alcohol ablation can cause a ventricular septal defect (VSD) [23,60]. The rate of VSDs is approximately 2 percent for surgical myectomy. A VSD after alcohol septal ablation is unusual.

Coronary artery injury – Among patients undergoing alcohol septal ablation, coronary artery injury (eg, left anterior descending artery dissection) occurs in approximately 2 percent) [61].

Aortic regurgitation – Very rarely, traction on the aortic valve to improve visualization of and access to the interventricular septum may cause aortic regurgitation during surgical myectomy. In most cases, the degree of aortic regurgitation after myectomy is minimal [62].

Sudden cardiac death – While reentrant ventricular tachyarrhythmias may be caused by the myocardial scar resulting from alcohol septal ablation, the totality of data suggest that the risk of sudden cardiac death is not clearly increased [52,53,63-68].

Role of center-specific procedural outcomes – Regardless of which invasive septal reduction therapy is chosen, the procedure should be performed in a center that has high-quality results. This recommendation is consistent with the 2020 AHA/ACC HCM guidelines, which include several metrics for assessing the quality of septal myectomy and alcohol septal ablation [1]:

30-day mortality ≤1 percent

30-day rates of tamponade, left anterior descending coronary artery dissection, infection, and major bleeding ≤1 percent

Repeat procedure rate ≤3 percent for surgical myectomy and ≤10 percent for alcohol septal ablation

Improvement in NYHA class ≥1 class in more than 90 percent of patients

These quality metrics are associated with procedural volumes. A study of 11,248 patients who underwent either surgical myectomy (57 percent) or alcohol septal ablation over a nine year period found that median surgical myectomy case volume was 1.0 cases and alcohol septal ablation case volume was 0.7 cases [69]. For increasing surgical myectomy volume by center (tertiles), there was a lower risk of in-hospital death (16, 10, and 4 percent), need for permanent pacemaker (10, 14, and 9 percent), and bleeding complications (3, 4, and 2 percent). For increasing alcohol septal ablation volume by center, there was a lower risk of in-hospital death (2, 0.8, and 0.6 percent).

Repeat septal reduction — The majority of patients who undergo an invasive septal reduction therapy report fewer symptoms following the procedure [45]. However, patients who do not respond to the first attempt of septal reduction therapy may be candidates for a second attempt at invasive septal reduction therapy. In the case of alcohol septal ablation, appropriately cautious use of low-volume alcohol injection may result in an insufficient septal infarction that requires a repeat procedure (approximately 10 percent), while patients who undergo surgical myectomy are less likely to require a repeat procedure (<2 percent) [52].

Timing after initial alcohol septal ablation For patients who undergo initial alcohol septal ablation, the benefit of the procedure can be delayed. This was illustrated in a series of 47 patients with a mean baseline LVOT gradient of 98 mmHg who underwent alcohol septal ablation [70]. All patients were followed with serial echocardiograms at three days, three months, and one year after the procedure. Among 22 patients who had no significant reduction in the LVOT gradient three days after the procedure, 16 had a significant improvement at three months.

Timing after initial surgical myectomy – In general, patients who undergo surgical myectomy have improvement in symptoms between two to three months after surgery.

Type of repeat procedure – The choice of surgical septal myectomy or alcohol septal ablation for the second procedure depends on the individual circumstances of why the first procedure failed and the risks and benefits of a repeat procedure. In general, the second procedure (typically surgical myectomy after alcohol septal ablation) carries a higher risk of mortality, pacemaker placement, and VSD.

There are few studies describing the effects of repeated septal reduction therapy. In one retrospective single-center cohort of 375 patients who underwent alcohol septal ablation, 20 patients (5 percent) subsequently underwent surgical septal myectomy for refractory symptoms of LVOT obstruction [71]. Following the second procedure, patients experienced a significant improvement in functional status, exercise time, and LVOT obstruction; twelve percent (2 of 17 patients) required a permanent pacemaker following the surgery.

In patients who fail to respond to septal myectomy and continue to have severe symptoms of obstruction or who progress to end-stage HCM (eg, NYHA class IV HF symptoms refractory to medical therapy), cardiac transplantation may be an option. (See "Heart transplantation in adults: Indications and contraindications".)

THERAPIES OF LIMITED BENEFIT — Therapies with limited or no clinical benefit include:

Combination of a beta blocker and calcium channel blocker – We do not recommend simultaneous therapy with a beta blocker and a calcium channel blocker due to the risk of symptomatic bradycardia.

Transcatheter mitral valve repair – For patients with HCM and refractory HF symptoms related to LVOT obstruction and who are not candidates for a septal reduction therapy, percutaneous mitral valve end-to-end repair may be reasonable to eliminate systolic anterior motion-septal contact and improve symptoms by reducing the LVOT gradient, but septal reduction therapy is the preferred approach to treatment of symptoms caused by obstruction. (See 'Septal reduction therapy' above.)

Isolated mitral valve replacement Mitral valve surgery without concomitant septal myectomy should not be performed as a treatment for LVOT obstruction. In most cases, LVOT obstruction can be relieved with septal myectomy alone, which we consider a more definitive surgery [1,15,72-76]. If the patient has outflow obstruction and mitral valve disease, septal myectomy with mitral valvuloplasty, repair, or replacement is typically preferred to mitral valve surgery alone. While isolated mitral valve replacement will relieve outflow obstruction, surgical myectomy is our preferred approach.

Dual-chamber pacing We do not routinely place a dual-chamber pacemaker to treat obstructive HCM [1]. The available evidence suggests an unclear benefit in symptom improvement except in a small subgroup of patients with obstructive HCM >65 years old [77,78]. The American Heart Association/American College of Cardiology guidelines for the treatment of HCM suggest that dual-chamber pacing is reasonable to consider in patients with symptoms of obstructive HCM who have another indication for insertion of a pacemaker or implantable cardioverter-defibrillator.

Off-pump septal myectomy – Minimally invasive surgical myectomy is a technique designed to reduce septal obstruction and address some of the challenges of typical surgical myectomy, including limited exposure of the septum through the narrow transaortic approach and assessing the immediate effects of myectomy while the heart is unloaded. Data on this approach include a single-center experience [79]. In patients with HCM and typical subaortic outflow tract obstruction who underwent off-pump septal myectomy via a minithoracotomy with a novel device, procedural success (reduction in LVOT gradient and absence of moderate or worse mitral regurgitation) occurred in 42 of 46 patients. The complications included one postoperative death, one ventricular septal defect, and one LV apical tear.

SPECIAL CIRCUMSTANCES

Midcavitary obstruction — Midventricular (ie, midcavity) obstruction in the absence of subaortic obstruction is a morphologic variant of HCM that arises from different anatomic and hemodynamic circumstances [80]. Perhaps the most common HCM morphology associated with midcavitary obstruction occurs due to the apposition of the septum and lateral wall in the context of a small hyperdynamic cavity (figure 2). In these patients the intracavitary "gradient" does not usually produce clinically significant symptoms.

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), which results in the contact between the anterior leaflet and papillary muscle during midsystole.

In patients with midcavitary obstruction who experience limiting symptoms, AV nodal blocking agents (ie, beta blockers and nondihydropyridine calcium channel blockers) are typically the initial treatment option. In patients with advanced symptoms refractory to drug therapy, septal myectomy with or without anomalous papillary muscle surgery is an option for therapy [79].

Apical hypertrophy — Rarely, patients with HCM have extensive hypertrophy of the apex and mid-LV that results in decreased LV end-diastolic volume index (<50 mL/m2) and low stroke volume index (<30 mL/m2). This can lead to HF in some patients due to low cardiac output. In patients who are refractory to medical therapy, transapical myectomy is a surgical procedure in which an excision is made in the apex to allow for resection of apical myocardium to increase LV chamber size and decrease LV end-diastolic pressure [1]. However, this procedure is technically difficult to perform (eg, close proximity of the mitral valve chords) and expertise is confined to a small number of centers worldwide. In some patients who are candidates for transapical myectomy, subaortic outflow obstruction may also be present due to typical mitral valve-ventricular septal contact, requiring traditional myectomy via a transaortic approach to relieve subaortic obstruction.

Perioperative management during noncardiac surgery — The approach to perioperative management depends on the risk of surgery and the presence or severity of LVOT obstruction. The approach to patients with HCM who will undergo a procedure or surgery is discussed elsewhere.(See "Anesthesia for patients with hypertrophic cardiomyopathy undergoing noncardiac surgery".)

Acute shock — In patients with HCM and LVOT obstruction who have shock with hypotension or low cardiac output, the approach to management is focused on minimizing the effect of LVOT obstruction. The management of all patients with HCM requires consultation with an HCM specialist, and we obtain urgent echocardiography to assess the severity of LVOT obstruction, severity of any valve disease, and estimate cardiac filling pressures. The specific management (eg, volume, pressors) is individualized to the patient.

Therapy to minimize outflow obstruction – The severity of LVOT obstruction and its contribution to the overall severity of shock are determined on a case-by-case basis and influence the choice of therapy, if any, for LVOT obstruction. Therapies used to reduce LVOT obstruction in patients with shock include:

Increase preload – Increasing preload minimizes LVOT obstruction by increasing the LVOT diameter. Measures that may increase preload include elevation of the legs and administration of intravenous fluids or blood, as appropriate; in addition, anemia, if present, should be corrected.

Increase afterload – Pressors can be used to increase afterload, which decreases the velocity of flow in the LVOT and subsequently, reduces the risk of LVOT obstruction. We use pressors with no or minimal beta-1 receptor agonist activity (eg, phenylephrine).

Administration of negative inotropes – Negative inotropes decrease the velocity of flow in the LVOT, which decreases the propensity for LVOT obstruction. Options for therapy include intravenous administration of a beta blocker (propranolol, metoprolol, or esmolol are commonly available intravenous agents) or intravenous disopyramide 50 mg over one to five minutes (intravenous disopyramide is not available in United States).

Mechanical circulatory support – In patients with severe shock and obstruction, venoarterial extracorporeal membrane oxygenation can be used to support the patient until definitive therapy occurs.

Septal reduction therapy – In select situations, urgent surgical septal myectomy or alcohol septal ablation may be used for relief of obstruction [81,82].

Therapies to avoid – Positive inotropic agents increase LVOT flow velocity, which increases the risk of LVOT obstruction. Agents such as dobutamine and other beta-1 agonists (eg, epinephrine, dopamine) should be avoided.

This approach is based on our experience and the pathophysiology of disease.

Pregnancy

Prepregnancy counseling – Reproductive and genetic counseling should be offered to all patients with HCM considering pregnancy [1].

Management prior to parturition – 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 [83,84]. This includes patients with HCM and LVOT obstruction who, prior to pregnancy, have no symptoms or only mild and stable symptoms. Most pregnant patients 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 during pregnancy.

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 patients.

The data in this population are limited:

Among a series of 100 patients with HCM who had a total of 199 births, the following findings were noted [84]:

-Among the 40 patients evaluated in close proximity to pregnancy, only one of 28 previously asymptomatic patients progressed to New York Heart Association class III or IV during pregnancy. By comparison, such progression occurred in 5 of 12 previously symptomatic patients.

-One patient had AF 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 patients 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 patients (5 percent) experiencing loss of the fetus [85].

Anesthesia during delivery – 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 inadequately titrated spinal anesthesia. 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)'.)

Mode of delivery – Normal vaginal delivery is the preferred delivery option. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".)

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

Other causes of symptoms – In patients with obstructive hypertrophic cardiomyopathy (HCM), obstruction is the most likely cause of symptoms, but it is important to evaluate for the presence of other conditions that may contribute to the overall burden of symptoms, which include: (See 'Other causes of symptoms' above.)

Ischemia

Atrial fibrillation (AF) or other supraventricular tachycardias

Ventricular arrhythmias

Valve disease

Noncardiac causes of severe symptoms

Determining the severity of symptoms – The identification of left ventricular outflow tract (LVOT) obstruction and assessment of its severity are characterized as follows (see 'Determining the severity of obstruction' above):

Echocardiography – Echocardiographic evidence of an LVOT gradient ≥30 mmHg at rest or with exertion that is caused by systolic anterior motion of the mitral valve defines the presence of obstructive HCM. In patients with HCM with an LVOT gradient <30 mmHg at rest, exercise echocardiography (or other provocative maneuvers) should be performed to assess for a provocable gradient. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'LVOT obstruction'.)

Symptom evaluation – The patient's symptoms are typically elicited and classified using the New York Heart Association (NYHA) heart failure (HF) classification (table 1).

Invasive hemodynamic assessment – In patients whose echocardiographic LVOT gradient measurement may be inaccurate due to poor image quality, inability to separate intracavitary Doppler signals from mitral valve signals, or other technical aspects of measurement, and in whom an accurate LVOT gradient would change management, invasive measurement of the LVOT gradient with left heart catheterization is indicated. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Cardiac catheterization'.)

Role of formal exercise testing – In select patients in whom the burden of symptoms is unclear after detailed history taking (eg, conflicting data), we use objective exercise testing with a cardiopulmonary exercise test (CPET) to aid in clarifying the patient’s cardiac limitations. (See "Cardiopulmonary exercise testing in cardiovascular disease" and "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Common exercise protocols'.)

General measures for patients with obstruction – In patients with symptoms attributable to LVOT obstruction, health care providers should counsel patients to maintain hydration during activities (eg, exercise, outdoor pursuits) or illnesses (eg, diarrhea, fever) that may lead to dehydration and to avoid treatments that decrease preload or afterload.

Common treatments that may worsen LVOT obstruction include:

Nifedipine and amlodipine

Nitroglycerin

Arterial vasodilators, such as angiotensin converting enzyme inhibitors and angiotensin II receptor blockers

Digoxin

Furosemide and other diuretics, except in rare circumstances and in small doses

Approach to therapy

Asymptomatic patients – In patients with obstructive HCM who do not have symptoms (ie, NYHA class I HF (table 1)), routine medical therapy and septal reduction therapy are not indicated. (See 'Asymptomatic patients' above.)

Initial medical therapy for symptomatic patients – For patients with HCM who have symptoms that limit quality of life (eg, dyspnea, fatigue, syncope, or chest discomfort) attributable to LVOT obstruction, medical therapy is the first step in management (algorithm 1). (See 'Initial medical therapy for symptomatic patients' above.)

-Initial therapy (beta blocker) – For most patients, we suggest initial therapy with a beta blocker rather than a calcium channel blocker or other agents (eg, disopyramide, myosin inhibitors) (Grade 2C).

-Refractoriness or intolerance to beta blockers – If the patient has contraindications to a beta blocker (eg, reactive airway disease), is unable to tolerate a beta blocker due to side effects, or beta blocker therapy is not effective, we suggest therapy with extended-release verapamil (our usual choice) or extended-release diltiazem rather than other agents or septal reduction therapy (Grade 2C).

Therapies for refractory symptoms For patients with obstructive HCM with severe symptoms that limit quality of life despite initial monotherapy with a beta blocker or nondihydropyridine calcium channel blocker, the options for management include additional medical therapy or septal reduction therapy; the approach is individualized (algorithm 1). (See 'Therapies for refractory symptoms' above.)

-Additional medical therapy – The options for medical therapy include disopyramide combination therapy (eg, disopyramide with a beta blocker or calcium channel blocker) or myosin inhibitor therapy. (See 'Additional medical therapy' above.)

-Septal reduction therapy – The options for septal reduction therapy are surgical myectomy or alcohol septal ablation. (See 'Choosing between therapies' above.)

Therapies of limited benefit – Therapies with limited or no clinical benefit include (see 'Therapies of limited benefit' above):

-Combination of a beta blocker and calcium channel blocker

-Transcatheter mitral valve repair

-Isolated mitral valve replacement

-Dual-chamber pacing

Special populations – Patients with HCM who have less common LV morphology or clinical scenarios where LVOT obstruction may require differential management include (see 'Special circumstances' above):

Midcavitary obstruction (see 'Midcavitary obstruction' above)

Apical obstruction (see 'Apical hypertrophy' above)

Perioperative management (see 'Perioperative management during noncardiac surgery' above)

Acute shock (see 'Acute shock' above)

Pregnancy (see 'Pregnancy' above)

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Topic 4920 Version 43.0

References

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