Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. This disorder is caused by a mutations in genes encoding cardiac sarcomere protein, resulting in variety of phenotypical expression and clinical course. HCM is the most common cause of sudden death in young people.
Although HCM was written about and known as idiopathic hypertrophic subaortic stenosis (IHSS) or asymmetrical septal hypertrophy (ASH) decades ago, these terms were replaced by hypertrophic cardiomyopathy because the segmental hypertrophy can occur in any segment of the ventricle, not just the septum. Furthermore, this entity can present without subaortic obstruction to flow yet still carry the same ominous risk of arrhythmogenic sudden death and many of its clinical symptoms.
HCM can be separated into obstructive and nonobstructive types. Obstructive HCM is due to midsystolic obstruction of flow through the left ventricular outflow tract as a result of a Bernoulli effect–induced systolic anterior mitral valve movement toward the septum.
The significance of this obstruction, however, is highly controversial. Some investigators and experts believe the obstruction has less to do with the overall hemodynamic and pathophysiologic manifestations of this entity than it does with the inappropriate segmental hypertrophy, which, with its increased myocardial oxygen consumption and substrate for fatal ventricular arrhythmias, has much more significance in the overall clinical picture of this entity and in the treatment and prognosis of HCM.
Since the initial descriptions of hypertrophic cardiomyopathy (HCM), the feature that has attracted the greatest attention is the dynamic pressure gradient across the LV outflow tract. The pressure gradient appears to be related to further narrowing of an already small outflow tract (already narrowed by the marked asymmetrical septal hypertrophy and possibly by an abnormal location of the mitral valve) by the systolic anterior motion of the mitral valve against the hypertrophied septum.
Three explanations for the systolic anterior motion of the mitral valve have been offered, as follows: (1) the mitral valve is pulled against the septum by contraction of the papillary muscles, which occurs because of the valve's abnormal location and septal hypertrophy altering the orientation of the papillary muscles; (2) the mitral valve is pushed against the septum because of its abnormal position in the outflow tract; (3) the mitral valve is drawn toward the septum because of the lower pressure that occurs as blood is ejected at high velocity through a narrowed outflow tract (Venturi effect).
Most patients with HCM have abnormal diastolic function (whether or not a pressure gradient is present), which impairs ventricular filling and increases filling pressure, despite a normal or small ventricular cavity. These patients have abnormal calcium kinetics and subendocardial ischemia, which are related to the profound hypertrophy and myopathic process.
Data link abnormal myocardial calcium kinetics to the cause of the inappropriate myocardial hypertrophy and specific features of hypertrophic cardiomyopathy (HCM), particularly in patients with diastolic functional abnormalities. Abnormal myocardial calcium kinetics and abnormal calcium fluxes from an increase in the number of calcium channels result in an increase in intracellular calcium concentration, which, in turn, may produce hypertrophy and cellular disarray.
Familial HCM occurs as an autosomal dominant Mendelian-inherited disease in approximately 50% of cases. Some, if not all, of the sporadic forms of the disease may be caused by spontaneous mutations.
At least 6 different genes on at least 4 chromosomes are associated with HCM, with more than 50 different mutations discovered thus far. Familial HCM is a genetically heterogenous disease in that it can be caused by genetic defects at more than 1 locus.
In 1989, Seidman and collaborators first reported the genetic basis for HCM. They reported the existence of a disease gene located on the long arm of chromosome 14. Subsequently, they found this to be the gene encoding for beta cardiac myosin heavy chain.
Wide variation exists in the phenotypic expression of a given mutation of a given gene, with variability in clinical symptoms and the degree of hypertrophy expressed. Phenotypic variability is related to the differences in genotype, with specific mutations associated with particular symptoms, the degree of hypertrophy, and the prognosis.[1]
Other possible causes of HCM include the following:
Hypertrophic cardiomyopathy (HCM) is reported in 0.5% of the outpatient population referred for echocardiography.[2] The overall prevalence of HCM is low and has been estimated to occur in 0.05-0.2% of the population.[3] Morphologic evidence of disease is found by echocardiography in approximately 25% of first-degree relatives of patients with HCM. Genetic testing still is in the early stages of research development but can be used to identify asymptomatic family members with the same mutation as the proband (index case).
HCM is slightly more common in males than in females. However, the genetic inheritance pattern is autosomal dominant, without sex predilection. Modifying genetic, hormonal, and environmental factors may lead to a higher likelihood of identification in males, increased symptomatology, or higher degrees of LV outflow obstruction, with more prominent findings upon physical examination.
HCM usually presents at a younger age in females. Females tend to be more symptomatic and are more likely to be disabled by their symptoms than males.
In general, HCM has a bimodal peak of occurrence. The most common presentation is in the third decade of life, but it may present in persons of any age, from newborns to elderly individuals.
In children, inherited cases are found in an age range from newborn (ie, stillborn babies) to adult. The peak incidence is in these cases is in the second decade of life.
In adults, the peak incidence is in the third decade of life, with the vast majority of cases occurring in the age range between the third and sixth decades of life.
Reported annual mortality rates in patients with hypertrophic cardiomyopathy (HCM) have ranged from less than 1% to 3-6%, and studies suggest that they have significantly improved over the past 40 years.[4]
A study by Elliott et al reported that published sudden death rates over the previous 10 years were lower than were previously published figures (median 1.0% (range 0.1–1.7) v 2.0% (0–3.5)). Nevertheless, HCM still carries a high risk for mortality and morbidity.[5]
One series of 46 patients with midventricular obstruction was found to have an increased risk of apical aneurysm formation, symptoms, and HCM-related death compared with those who did not have midventricular obstruction; the increased risk of symptoms and death was similar to that seen in patients with LV outflow obstruction.[6]
Most patients with HCM are asymptomatic. Unfortunately, the first clinical manifestation of the disease in such individuals may be sudden death, likely from ventricular tachycardia or fibrillation. Younger patients, particularly children, have a much higher mortality rate. Children have a much greater degree of ventricular hypertrophy and are much more symptomatic early on in the disease course, most likely because more malignant genotypes are present earlier in life.
The more benign mutations do not elicit a clinical or echocardiographic phenotype or symptoms in the pediatric population. Death often is sudden, unexpected, and typically is associated with sports or vigorous exertion. Early diagnosis is of prime importance in order to prescribe an appropriate level of safe activity.[1, 7, 8]
Screening of first-degree relatives is useful to identify additional affected family members prior to the onset of significant symptoms or sudden death.
Patients can have a myriad of arrhythmias, including atrial fibrillation, atrial flutter, ventricular ectopy, ventricular tachycardia, and ventricular fibrillation. These patients are among the highest-risk group for ventricular fibrillation and pose difficult therapeutic decisions for risk reduction.
Patients have a high likelihood of recurrent heart failure resulting from mitral regurgitation and profound diastolic dysfunction. HCM is a progressive condition that worsens over time, as does the gradient across the LV outflow tract if left untreated. Systolic function usually is well preserved until the late stages of the disease. Angina is rare in children but common in adults. Syncope and presyncope are common and may identify individuals at high risk for sudden death.
Complications of HCM may include the following:
Family members should learn cardiopulmonary resuscitation. In addition, refer the patient and family for psychosocial counseling. Refer children of patients with hypertrophic cardiomyopathy (HCM), especially those in the pediatric age range, for urgent echocardiography and genetic testing if an echocardiogram does not yet reveal overt disease.
Impose activity restrictions that include total abstinence from highly competitive athletic activities and very strenuous physical exertion, such as lifting heavy objects, lifting weights, and shoveling snow.
For patient education information, see the Heart Health Center, as well as Palpitations.
Symptoms of hypertrophic cardiomyopathy (HCM) can include dyspnea, syncope and presyncope, angina, palpitations, orthopnea, paroxysmal nocturnal dyspnea, congestive heart failure, dizziness, and sudden cardiac death.
Sudden cardiac death is the most devastating presenting manifestation of HCM. It has the highest incidence in preadolescent and adolescent children and is particularly related to extreme exertion. The risk of sudden death in children is as high as 6% per year.
In more than 80% of cases, the arrhythmia that causes sudden death is ventricular fibrillation. Many of these cases degenerate into ventricular fibrillation from rapid atrial arrhythmias, such as fibrillation, supraventricular tachycardia, or Wolff-Parkinson-White syndrome, while others result from ventricular tachycardia and low cardiac output hemodynamic collapse.
This is the most common presenting symptom, occurring in as many as 90% of symptomatic patients. Dyspnea largely is a consequence of elevated LV diastolic filling pressures (and transmission of those elevated pressures back into the pulmonary circulation). The elevated LV filling pressures principally are caused by impaired diastolic compliance as a result of marked hypertrophy of the ventricle.
Syncope is a very common symptom, resulting from inadequate cardiac output upon exertion or from cardiac arrhythmia. It occurs more commonly in children and young adults with small LV chamber size and evidence of ventricular tachycardia upon ambulatory monitoring.
Alternatively, syncope may be caused by arrhythmias, either tachycardias or bradycardias. Some patients with HCM have abnormalities in sinus node function, leading to sick sinus syndrome with alternating tachyarrhythmias and bradyarrhythmias or severe bradyarrhythmias.
Syncope and presyncope identify patients at high risk of sudden death and warrant an urgent workup and aggressive treatment.
Presyncope includes "graying-out" spells that occur in the erect posture and can be relieved by immediately lying down. They occur quite commonly and identify patients at high risk for sudden death. These symptoms are exacerbated by vagal stimulation. Presyncope also may occur with nonsustained atrial or ventricular tachyarrhythmias.
Typical symptoms of angina are quite common in patients with HCM and may occur in the absence of detectable coronary atherosclerosis. Impaired diastolic relaxation and markedly increased myocardial oxygen consumption are caused by ventricular hypertrophy that results in subendocardial ischemia, particularly during exertion.
Palpitations are common. These result from arrhythmias, such as premature atrial and ventricular beats, sinus pauses, atrial fibrillation, atrial flutter, supraventricular tachycardia, and ventricular tachycardia.
These are early signs of congestive heart failure and, while relatively uncommon, are observed in patients with severe HCM. They result from impaired diastolic function and elevated LV filling pressure. Orthopnea and paroxysmal nocturnal dyspnea result from pulmonary venous congestion.
This is relatively uncommon but is observed in patients with severe HCM. It may occur as a result of a combination of impaired diastolic function and subendocardial ischemia. Systolic function in these patients almost always is well preserved.
Dizziness is common in patients with HCM with elevated pressure gradients across the LV outflow tract. It is worsened by exertion and may be exacerbated by hypovolemia following high levels of exertion or increased insensible fluid loss (eg, during extreme heat).
Dizziness also may occur as a result of maneuvers, such as rapid standing or Valsalva during defecation, or certain medications, such as diuretics, nitroglycerin, and vasodilating antihypertensive agents, that decrease preload and afterload and increase the pressure gradient across the LV outflow tract.
Dizziness also may be secondary to arrhythmia-related hypotension and decreased cerebral perfusion. Nonsustained arrhythmias often cause symptoms of dizziness, lightheadedness, and presyncope, whereas sustained arrhythmias are more likely to lead to syncope, collapse, and/or sudden cardiac death.
Double apical impulse results from a forceful left atrial contraction against a highly noncompliant left ventricle. This occurs quite commonly in adults. Triple apical impulse results from a late systolic bulge that occurs when the heart is almost empty and is performing near-isometric contraction. This is a highly characteristic finding of hypertrophic cardiomyopathy (HCM); however, it occurs less frequently than does the double apical impulse.
First heart sound is normal. Second heart sound usually is normally split, but in some patients with severe outflow gradients, it is paradoxically split.
An S3 gallop is common in children, but it does not have the same ominous significance as in patients with valvular aortic stenosis. When it occurs in adults, it signifies decompensated congestive heart failure. A fourth heart sound, an S4, frequently is heard and results from atrial systole against a highly noncompliant left ventricle.
Jugular venous pulse reveals a prominent a wave caused by diminished right ventricular compliance secondary to massive hypertrophy of the ventricular septum.
Double carotid arterial pulse is common. The carotid pulse rises quickly because of the increased velocity of blood through the LV outflow tract and into the aorta. The carotid pulse then declines in midsystole as the gradient develops. This is followed by a secondary rise in carotid pulsation during late systole.
Apical precordial impulse frequently is displaced laterally and usually is abnormally forceful and enlarged.
Systolic ejection murmur typically is a systolic ejection crescendo-decrescendo murmur, which is best heard between the apex and left sternal border and radiates to the suprasternal notch but not to the carotid arteries or neck. The murmur and the gradient across the LV outflow tract diminish with any increase in preload (eg, Mueller maneuver, squatting) or increase in afterload (eg, handgrip). The murmur and the gradient increase with any decrease in preload (eg, Valsalva maneuver, nitrate administration, diuretic administration, standing) or with any decrease in afterload (eg, vasodilator administration).
Holosystolic murmur at the apex and axilla of mitral regurgitation is heard in patients with systolic anterior motion of the mitral valve and significant LV outflow gradients. Diastolic decrescendo murmur of aortic regurgitation is heard in 10% of patients, although mild aortic regurgitation can be detected by Doppler echocardiography in 33% of patients.
Approach to hypertrophic cardiomyopathy (HCM) starts with a comprehensive history and physical examination. Multiple tests are used not only in the evaluation of patients with possible HCM but also to determine the diagnosis of HCM, severity of left ventricular (LV) outflow tract gradient, degree of mitral regurgitation, types of arrhythmias, LV function, and prognosis.
First-line laboratory tests are similar in adults and children.[9] Routine laboratory studies may aid in the evaluation of the etiology and/or exacerbating factors underlying the left ventricular (LV) dysfunction.
Additional laboratory tests can be performed after a specialist evaluation, as needed.
When considering a diagnosis of hypertrophic cardiomyopathy (HCM), all patients should undergo complete transthoracic echocardiography (TTE) with two dimensional (2D), color Doppler, spectral Doppler, and tissue Doppler. TTE aids in evaluation of the cardiac morphology, systolic and diastolic function, presence and severity of left ventricular outflow tract (LVOT) gradient, and the degree of mitral regurgitation.
LVH is evaluated primarily in the parasternal short-axis plane during diastole at the level of mitral valve and papillary muscles. Parasternal long-axis and apical 2- and 4- chamber views are also utilized with short-axis images of LVH.
Unexplained LV wall thickness of ≥15 mm anywhere within the LV confirms the diagnosis of HCM. LV wall thickness ≥13 mm in the presence of a family history of HCM may also be considered diagnostic of HCM. The most common location of LVH is the basal anterior septum. About 10% of patients have LV wall thickening involving one or two LV segments.
SAM of the mitral valve is positioned in the LVOT. When there is contact between the mitral valve and septum, LVOT obstruction will develop. The greater the duration of the mitral-septum contact, the higher the LVOT obstruction.
LVOT obstruction gradient can be measured noninvasively using echocardiography continuous-wave Doppler. The best views to determine the LVOT gradient is the apical long-axis window. SAM and mitral regurgitation are often present together, and it can be difficult to distinguish LVOT signal from mitral regurgitation.
Outflow gradient varies from day to day. It is influenced by myocardial contractility and loading conditions such as dehydration, alcohol, etc. If patients do not have an LVOT gradient at rest, then provoking the gradient is important for patient management. Exercise (stress) echocardiography using the standard Bruce protocol is the preferred method because it represents daily activities. A pharmacologic approach using amyl nitrite, dobutamine, or isoproterenol and the Valsalva maneuver are alternative approaches to provoke the LVOT gradient. However, note that the pharmacologic and nonpharmacologic approaches do not represent true LVOT gradient during daily activities.
Ambulatory electrocardiographic (ECG) monitoring should be performed all patients with hypertrophic cardiomyopathy (HCM) for risk assessment of not only ventricular arrhythmias but also for sudden cardiac death. It should be also be performed in patients with palpitations to assess for atrial fibrillation / atrial flutter. Ambulatory ECG monitoring is performed for 24-48 hours.
Routine use of extended ambulatory monitoring for longer than 48 hours to detect ventricular arrhythmia for risk stratification is not determined.
Cardiac magnetic resonance imaging (CMRI) provides far more information compared to echocardiography. CMRI should be performed when a diagnosis of hypertrophic cardiomyopathy (HCM) is not certain after echocardiography.
CMRI can be performed to risk stratify, detect left ventricular hypertrophy that is unrecognized or not well seen on echocardiography, consider septal reduction therapy in those whose mitral valve and papillary muscle anatomy is not well defined by echocardiography, or to determine septal ablation versus surgical myectomy. CMRI also aids in determining the ischemia burden in HCM, which has been associated with morphologic markers of disease severity, fibrosis, arrhythmia, and functional capacity.[10]
Contrast-enhanced CMRI uses intravenous injection of gadolinium for hyperenhancement (late gadolinium enhancement). This hyperenhancement represents myocardial fibrosis. CMRI also provides the following information:
Electrocardiography (ECG) should be performed on all patients with possible hypertrophic cardiomyopathy (HCM), although ECG is not specific for HCM.
The ECG is normal in 10% of cases of HCM; thus, it typically abnormal with the most common ECG abnormality being repolarization changes. Other common ECG abnormalities are as follows:
Although not required for the diagnosis of hypertrophic cardiomyopathy (HCM), a diagnostic cardiac catheterization is useful to determine the degree of outflow obstruction, cardiac hemodynamics, the diastolic characteristics of the left ventricle and LV anatomy, and, of particular importance, the coronary anatomy. Cardiac catheterization is also reserved for situations when invasive modalities of therapy, such as a pacemaker or surgery, are being considered.
Therapeutic cardiac catheterization interventions, utilized in well selected cases of hypertrophic cardiomyopathy, include transcatheter septal alcohol ablation to relieve the LV outflow obstruction by intentional infarction of a portion of the interventricular septum.
Cardiac catheterization frequently reveals diminished diastolic LV compliance and, in cases of obstructive hypertrophic cardiomyopathy, a systolic intracavitary pressure gradient within the body of the left ventricle, related to subaortic systolic anterior motion of the mitral valve abutting the markedly hypertrophied septum. The subaortic pressure gradient may be quite labile and may vary between 0 and 175 mm Hg in the same patient under different conditions.
The arterial pressure tracing found on cardiac catheterization may demonstrate a "spike and dome" configuration similar to the carotid pulse recording. As a consequence of diminished left ventricular compliance, the mean left atrial pressure and, particularly, the a wave, in the left atrial pressure pulse and left ventricular end-diastolic pressures are usually elevated.
Artifactual outflow gradients may occur if the left ventricular catheter becomes entrapped in the trabeculae of a markedly hypertrophied left ventricle.
Cardiac output may be depressed in patients with long-standing severe gradients, but in the majority of patients, it is normal. Occasionally, cardiac output is elevated in patients with markedly hyperdynamic LV systolic function.
Hemodynamic abnormality in hypertrophic cardiomyopathy (HCM) is not limited to the left side of the heart. Approximately one fourth of patients demonstrate pulmonary hypertension. It is usually mild, but in some cases, it can be moderate to severe, due (at least in part) to elevated mean left atrial pressures resulting from diminished LV compliance. A pressure gradient in the right ventricular outflow tract occurs in approximately 15% of patients who have obstruction to LV outflow and appears to result from markedly hypertrophied right ventricular tissue. Right atrial and right ventricular end-diastolic pressures may be slightly elevated.
A feature characteristic of HCM is the variability and lability of the LV outflow gradient. A patient may demonstrate a large gradient on one occasion and have none at another time. In some patients without a resting gradient, it may be temporarily provoked.
Three basic mechanisms involved in the production of dynamic gradients include increased contractility, decreased preload, and decreased afterload. In many patients with HCM, the gradient is midventricular and may be intensified by increased contractility, which exerts a direct muscular sphincter action.
The stimuli that provoke or intensify LV outflow tract gradients in HCM generally improve myocardial performance in normal subjects and in patients with most other forms of heart disease. Conversely, reductions in contractility or increases in preload or afterload, which increased LV dimensions, reduce or abolish the LV outflow gradient.
One of the most potent stimuli for enhancing the LV outflow gradient is postextrasystolic potentiation, which may occur after a spontaneous premature contraction or be induced by mechanical stimulation with a catheter. The resultant increase in contractility in the beat after the extrasystole is so marked that it produces an increase in the outflow gradient. A characteristic change often occurs in the directly recorded arterial pressure tracing, which, in addition to displacing a more marked spike and dome configuration, exhibits a pulse pressure that fails to increase as expected or actually decreases (the so-called Brockenbrough-Braunwald phenomenon).
This is one of the more reliable signs of dynamic obstruction of the LV outflow tract. In some patients, the postextrasystolic murmur is attenuated despite an increase in the outflow gradient, apparently because, in this setting, the murmur mirrors to a greater degree changes in the severity of mitral regurgitation than changes in the outflow tract gradient.
Left ventriculography typically shows a hypertrophied ventricle and the presence of an outflow gradient. The anterior leaflet of the mitral valve moves anteriorly during systole and encroaches on the outflow tract. Associated with this motion is mitral regurgitation, which is a constant finding in patients with gradients. The LV cavity is often small, and systolic ejection is typically vigorous, resulting in virtual obliteration of the ventricular cavity at end systole. In patients with apical involvement, the extensive hypertrophy may convey a spade-like configuration to the left ventricular angiogram.
In patients older than age 45 years, obstructive coronary artery disease may be present, although the symptoms of ischemic pain are indistinguishable from those of patients with normal coronary angiograms and HCM. The left anterior descending and septal perforator coronary arteries may demonstrate phasic narrowing and associated abnormalities of flow during systole
A diagnostic electrophysiology study (EPS) uses programmed electrical stimulation to identify conduction abnormalities, sinus node dysfunction (SND), and the potential for inducible arrhythmias. In hypertrophic cardiomyopathy (HCM), syncope and presyncope are due to arrhythmia, left ventricular outflow tract (LVOT) obstruction, or inappropriate vasodilatation with adequate cardiac output. EPSs rarely discover the mechanism of sudden death, and they are not indicated for decision making on implantable cardioverter-defibrillator (ICD) therapy for primary prevention of sudden death.
Exercise stress testing should be performed on patients with known or suspected hypertrophic cardiomyopathy (HCM) for risk stratification and evaluation of the left ventricular outflow tract (LVOT) gradient. It is preferred over pharmacologic stress testing. Exercise stress testing provides information on functional capacity, exercise-induced ischemia, arrhythmia, and obstruction.
Echocardiographic images should be utilized with stress testing.
Exercise stress testing should be performed prior to the institution of therapy. Follow-up exercise testing may be helpful to assess treatment. Important findings during exercise testing include the following:
Evaluation usually can be conducted on an outpatient basis. Inpatient studies and surgical treatment also may be necessary. Medical and surgical therapy are used to reduce ventricular contractility or increase ventricular volume, increase ventricular compliance and outflow tract dimensions, and, in the case of obstructive hypertrophic cardiomyopathy (HCM), reduce the pressure gradient across the LV outflow tract. Paramount to any therapy is reduction in the risk of sudden death by identification of these patients early on and effective medical and/or surgical implantation of an automatic defibrillator.[11]
Medications include beta blockers, calcium channel blockers, and, rarely, diltiazem, amiodarone, and disopyramide.[12] Antitussives may be administered as needed to avoid coughing.
Research shows that stepwise therapy can reduce high blood pressure in patients with HCM. In a study of 115 HCM patients, including 94 with obstructive HCM, stepwise antihypertensive therapy effectively controlled both obstructive HCM symptoms and hypertension. Average systolic pressure in the obstructive HCM group was reduced from 137 to 131 mm Hg, and uncontrolled hypertension was reduced from 56% at the first visit to 37% at the last.[13, 14]
Mavacamten, a first-in-class allosteric inhibitor of cardiac myosin, gained approval form the FDA for adults with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve exercise capacity and symptoms. Mavacamten modulates number of myosin heads that can enter “on actin” (power-generating) states, thus reduces probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM.
Approval of mavacamten was based on results from the multicenter, phase 3 EXPLORER-HCM trial (n = 251). Of 123 patients randomly assigned to mavacamten, 92 (75%) completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and week 30 and of the 128 patients randomly assigned to placebo 88 (69%) completed the KCCQ at baseline and week 30. At 30 weeks, the change in KCCQ-OS score was greater with mavacamten than placebo (mean score 14.9 vs 5·4 13.7; difference +9.1; p < 0.0001), with similar benefits across all KCCQ subscales. The proportion of patients with a very large change (KCCQ-OS 20 points or more) was 36% in the mavacamten group versus 15% in the placebo group, with an estimated absolute difference of 21%. These gains returned to baseline after treatment was stopped.[15]
Additionally, the EXPLORER long-term extension trial (EXPLORER-LTE) projected mavacamten was associated with an increase of 4.17 additional quality-adjusted life-years compared with placebo (with or without beta-blocker or calcium channel blocker therapies).[16]
Avoid inotropic drugs if possible; also avoid nitrates and sympathomimetic amines, except in those patients with concomitant coronary artery disease. Avoid digitalis, because glycosides are contraindicated except in patients with uncontrolled atrial fibrillation. Cautious use of diuretics should be exercised because of their potential adverse effect on the LV outflow gradient and ventricular volume.
Transfer may be required for further diagnostic evaluation and electrophysiologic device or surgical intervention.
Patients must abstain from highly strenuous competitive athletic activity and highly strenuous physical exertion, such as shoveling snow or lifting very heavy objects, due to the high risk of arrhythmogenic sudden cardiac death. No acceptable medical recommendation deviates from total abstinence from these activities.
Consultations may be indicated with the following specialists:
No special diet is required. However, the patient should avoid excessive weight gain.
Left ventricular (LV) myomectomy is used for patients with severe symptoms refractory to therapy and an outflow gradient of more than 50 mmHg, either with provocation or with rest. The procedure typically is successful in abolishing the outflow gradient; most patients have symptomatic improvement for at least 5 years.
The reduction in LV outflow gradient may not correlate with a risk reduction for sudden death or overall mortality. Furthermore, the outflow gradient may increase gradually over time and return to the same level as before, requiring a repeat procedure or additional medical therapy.
Patients who have obstructive hypertrophic cardiomyopathy with low resting gradients and latent obstruction may have limiting symptoms similar to patients with more severe resting gradients. In a series of 749 patients undergoing septal myectomy, 249 had minimal gradients at rest but severe outflow tract obstruction with provocation testing. Symptom relief and survival in these patients was similar to that of patients with severe resting outflow obstruction undergoing myectomy. The authors suggest that septal myectomy may be recommended to patients who have severe outflow obstruction only on provocative testing because survival and symptom relief are excellent, suggesting that dynamic obstruction is the major hemodynamic problem and not diastolic dysfunction.[17]
In a retrospective study (1998-2010) that evaluated data from the Nationwide Inpatient Sample regarding the results of ventricular septal myectomy in patients with hypertrophic cardiomyopathy (HCM) with refractory LV outflow tract (OT) obstruction, Panaich et al found an overall mortality of 5.9%; there was an association between age and severity of comorbidities with higher rates of complications and mortality.[18]
In a prospective observational study (1991-2012) that evaluated the long-term outcomes (8.3 ± 6.1 y) of myectomy combined with anterior mitral leaflet extension in severely symptomatic patients with HCM, Vriesendorp et al reported no operative mortality, with symptomatic relief similar to the general population.[19] Cumulative survival rates at 1 year were 98%; 5 years, 92%; 10 years, 86%; and 15 years, 83%.[19]
In a systematic review and meta-analysis of 10 studies comprising 1824 patients for evaluating the efficacy and short- and long-term mortality of surgical myectomy (n = 1019) compared with alcohol septal ablation (n = 805}, Singh et al found no significant difference in symptomatic relief between the two procedures, and outcomes were similar for sudden cardiac death and short- and long-term mortality.[20] However, in a more recent study by Cui et al that assessed the long-term mortality of 3859 patients with obstructive HCM who underwent either alcohol septal ablation (n = 585) or septal myectomy (n = 3274), there was an association between alcohol septal ablation and long-term all-cause mortality relative to surgical myectomy, and its impact on survival was independent of other known factors.[21] The investigators suggest that the impact may be influenced by unmeasured confounding patient features.
Mitral valve replacement is reserved for patients with severe mitral regurgitation due to systolic anterior movement of the mitral valve, particularly when mitral regurgitation (large regurgitant fraction) is associated with the development of congestive heart failure or severe pulmonary hypertension.
Pacemaker implantation has been a proposed treatment for patients with hypertrophic cardiomyopathy (HCM). Studies have shown that pacing the right ventricular (RV) apex to maintain atrioventricular synchrony results in a decrease of the left ventricular outflow tract (LVOT) gradient, with symptomatic and quality-of-life improvements.[22, 1] A Cochrane review suggested that the benefits of pacing are based on physiologic measures and lacks clinically relevant end-points.[23]
Transvenous catheter ablation of the septal region has been performed using selective arterial ethanol infusion to destroy myocardial tissue.[24] The procedure involves infusing 96% ethanol down the first septal branch of the left anterior descending artery and inducing a therapeutic infarction of the proximal interventricular septal myocardium.
This leads to a remodeling of the septum, which decreases the marked septal thickening characteristic of hypertrophic cardiomyopathy (HCM) and results in a decrease of the gradient across the left ventricular outflow tract (LVOT). In this manner, the procedure is analogous to a surgical myomectomy, in attempting to decrease the amount of septal ventricular myocardium and thereby reducing the LVOT gradient.
The procedure has been used in clinical practice since the early 1990s and the reported results have been excellent, with significant reduction in symptoms, particularly in the incidence of heart failure.[25, 26] In many centers, it is the surgical procedure of choice for HCM.
Alcohol septal ablation offers some advantages over surgical myectomy in that (1) it does not require surgical incision and/or general anesthesia, (2) the recovery time is shorter, and (3) its results lead to less discomfort and greater patient satisfaction than are reported with surgical myectomy.[22, 1] In addition, older patients who often have multiple comorbidities may better tolerate alcohol septal ablation than septal myectomy, which has high postoperative risks and complications in this patient population. Note that alcohol septal ablation is not indicated for the pediatric population.[22, 1]
Complications of alcohol septal ablation and comparison to surgical myectomy
The European Society of Cardiology (ESC) indicates that the main nonfatal complication of alcohol septal ablation is atrioventricular block (7-20%); in addition, it is associated with 4-5–fold increased risk for permanent pacemaker, as well as right rather than left bundle branch block, compared to septal myectomy.[9] Moreover, although clinical and hemodynamic effects are seen immediately after septal myectomy, they may be delayed for up to 3 months following alcohol septal ablation.
There appears to be little benefit to alcohol septal ablation in patients whose septal thickness is 30 mm or more (ie, severe HCM), as compared to septal myectomy.[9] The septal myectomy treatment approach visually assesses the anatomy of the LVOT and the mitral apparatus, whereas the alcohol septal ablation approach indirectly ablates the septal perforator artery distribution.
Overall, the procedural mortality for both procedures are similar.[9]
Sudden cardiac death occurs in approximately 1% of patients with hypertrophic cardiomyopathy (HCM) each year, and pharmacotherapy has not shown protection against sudden cardiac death.[22, 1] However, high-risk individuals in whom prophylactic therapy may be indicated may potentially benefit from placement of an implantable cardioverter defibrillator (ICD), which can effectively terminate life-threatening ventricular tachyarrhythmias in the setting of HCM.[22, 1]
There is a 4% reported rate of ICD-associated complications (procedural and over the long term) per year.[22, 1, 27] Early complications include the possibility of pneumothorax, pericardial effusion, pocket hematoma, acute pocket infection, and/or lead dislodgment. Complications that may arise late include upper extremity deep venous thrombosis, lead dislodgment, infection, a high defibrillation threshold that may require revision of the lead, and receipt of inappropriate shocks.[22, 1, 27]
Pediatric patients appear to suffer a higher rate of inappropriate shocks and lead fractures than adults do, predominantly owing to the strain placed on the leads as the children grow and are active.[22, 1, 27]
Although the procedure to place ICDs is generally safe, defective generators have been known to cause death, high-voltage leads with small diameters have a tendency to fracture, and patients with severe hypertrophy or who are receiving amiodarone may need high-energy output generators or epicardial lead systems.[22, 1, 27]
Heart transplantation is recommended in specific situations for patients with hypertrophic cardiomyopathy (HCM). The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines indications for heart transplantation include advanced heart disease and New York Heart Association (NYHA) functional class III or IV symptoms that are refractory to all other interventions.[22, 1] In addition, transplant referral for refractory symptoms does not require a reduced ejection fraction (EF), and heart transplantation is performed in the presence of preserved EF.[22, 1]
HCM patient outcome after heart transplant is not different from that of other patients with other heart diseases.[22, 1]
Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM). During the clinical course of HCM, approximately 25% of patients will experience AF or atrial flutter. AF is diagnosed by electrocardiography (ECG) during an AF episode, on ambulatory Holter monitoring, or on an event monitor.[22, 1] AF causes significant worsening of congestive heart failure, especially in patients with left ventricular (LV) outflow tract (OT) obstruction. Amiodarone is most effective in controlling AF recurrence; however, long-term use of this agent is limited due to its side effects. An alternative antiarrhythmic agent to use in this setting is sotalol.
AF is associated with an increased risk for embolic stroke. Prevalence of AF is 6% and incidence is 0.8% per year. In patients with paroxysmal or chronic AF, prophylactic anticoagulation is recommended. Prior to starting anticoagulation, determine the individual patient's bleeding risk and compliance. The CHADS2 score (Congestive heart failure, Hypertension, Age [>65 y = 1 point, >75 y = 2 points], Diabetes, previous Stroke/transient ischemic attack [2 points]) has not been specifically validated in HCM. Anticoagulants to be considered are warfarin or newer oral agents such as dabigatran or rivaroxaban.
In patients with symptomatic AF that fails antiarrhythmic therapy, pulmonary vein catheter-based ablation (radiofrequency or cryoablation) should be considered.
In general, women with HCM can safely undergo pregnancy and labor with minimal risks.[22, 1] However, preconception genetic counseling is advised, and it is essential that the expectant mothers receive careful prepregnancy and pregnancy evaluation and functional assessment. Cesarean delivery is usually not required.[22, 1]
If the patient's HCM is controlled with medical therapy, then such management should be continued with careful maternal-fetal monitoring. In setting of advanced disease (eg, progressive heart failure, severe diastolic dysfunction, ventricular tachycardia, supraventricular tachycardia, marked left ventricular outflow tract obstruction [LVOT]), management with a multidisciplinary team that includes a maternal-fetal specialist and cardiologist is crucial.[22, 1]
Pillarisetti et al reported that predictors of improvement in left ventricular dysfunction in patients with peripartum cardiomyopathy appear to include postpartum diagnosis and white/Hispanic race.[28]
Data spanning 2 decades and 160,000 deliveries from an institutional review of pregnant women with hypertrophic cardiomyopathy showed a small number of completed pregnancies (23 completed in 14 patients) and no maternofetal deaths.[29] The overall morbidity was 26%, with a 13% incidence of peripartum congestive heart failure.[29]
The Federal Motor Carrier Safety Administration (FMCSA) sets medical standards and guidelines for commercial motor vehicle drivers. Current guidelines state that individuals with hypertrophic cardiomyopathy (HCM) should not be certified to drive CMV. However, the Medical Expert Panel (MEP) recommends that the guidelines be changed to reflect the fact that not all individuals with HCM are at risk for sudden incapacitation or death. Specifically, the panel recommends that individuals who meet all the following criteria are at low risk and may be certified to drive[30] :
However, low-risk individuals must be closely monitored for changes in their risk status.[30]
The Federal Aviation Administration (FAA) sets the criteria for aircraft pilots with medical conditions, including cardiovascular diseases.[31] Currently, HCM is incompatible with the highest grade aviation license for commercial pilots due to its unpredictable risk for impairment in the cockpit.[32, 33, 34]
Avoid strenuous exercise. Competitive-level sports should not be permitted if any of the following is present:
Although avoidance of intense physical exertion is probably appropriate, participation in noncompetitive-level recreational sports activities is not believed to be contraindicated.
Cardiovascular screening before participation in competitive sports appears to reduce the frequency of unexpected sudden death from HCM, although whether large-scale screening of athletes is administratively feasible or cost-effective remains to be determined.[35, 36]
Sudden death often occurs during exercise, but it also demonstrates a circadian distribution, with clustering of deaths in the morning and early evening.
The following organizations have released guidelines for the management of hypertrophic cardiomyopathy (HCM):
Select class I recommendations regarding the diagnosis of hypertrophic cardiomyopathy (HCM) from the 2020[37] and 2024 American Heart Association and American College of Cardiology (AHA/ACC) guidelines[38] as well as the 2023 European Society of Cardiology (ESC)[39] are summarized below.
It is recommended that diagnostic testing be carried out in patients with HCM and systolic dysfunction to evaluate for concomitant causes of systolic dysfunction (such as CAD).[37, 38]
The ESC recommends considering endomyocardial biopsy in individuals with suspected cardiomyopathy to facilitate diagnosis and management in the setting of clinical study findings that suggest myocardial inflammation, infiltration, or storage that is unidentifiable by other modalities.[39]
All clinically stable patients with cardiomyopathy should undergo routine follow-up with a multiparametric approach, such as with ECG and echocardiography every 1-2 years.[39] In the setting of a substantial or unexpected symptomatic change in individuals with cardiomyopathy, use ECG and multimodality imaging for clinical assessment.[39]
Genetic testing and family screening
As part of the initial diagnostic assessment in patients with HCM, perform a comprehensive assessment of familial inheritance, including a three- (to four-) generation family history.[38, 39]
Genetic testing is of benefit to patients with HCM to determine the genetic basis for ease of identifying at-risk family members for developing HCM (cascade testing).[37, 38] The ESC recommends genetic testing in index patients with diagnostic criteria for cardiomyopathy when it allows for the patient's diagnosis, prognostication, treatment stratification, or reproductive management, or when it allows for cascade genetic evaluation of their relatives who would otherwise undergo long-term monitoring.[39]
Genetic testing for HCM and other causes of unexplained cardiac hypertrophy (HCM phenotypes) is recommended in the setting of atypical HCM presentation or when the etiology is suspected to be due to another genetic condition.[37, 38]
It is recommended that patients who are genotype-positive, phenotype-negative for HCM undergo serial clinical assessment, electrocardiography (ECG), and cardiac imaging at periodic intervals according to age (every 1-2 years in children and adolescents; every 3-5 years in adults) and clinical status change.[37, 38]
An expert in genetic counseling is recommended to review and discuss risks, benefits, test results, and their clinical significance with patients who have HCM.[37, 38]
In probands with HCM undergoing genetic testing, the initial tier of genes tested should include those with strong evidence to be disease-causing in HCM.[37, 38]
Offer first-degree relatives of patients with HCM both clinical screening (ECG, two-dimensional echocardiography) and cascade genetic testing (in the setting of an identified pathogenic/likely pathogenic variant).[37, 38]
In the setting of families in which there's a history of a sudden unexplained sudden death with a postmortem HCM diagnosis, it is of benefit for first-degree relatives to obtain postmortem genetic testing to facilitate cascade genetic testing and clinical screening[37, 38] as well as facilitate management of the surviving relatives.[39]
2023 ESC class I recommendations for family screening and follow-up assessment of relatives include the following[39] :
Serial reassessment of the clinical significance of identified variant(s) is recommended in those with HCM who have had genetic testing to evaluate for variant reclassification, which has the potential to affect diagnosis and cascade genetic testing in family members.[37, 38]
Offer preconception and prenatal reproductive and genetic counseling to affected families with HCM.[37, 38]
A transthoracic echocardiogram (TTE) is recommended in the initial evaluation of patients with suspected HCM.[37, 38] The ESC recommends the following[39] :
Repeat TTE is recommended every 1-2 years in patients with HCM who have experienced no change in clinical status or events to evaluate the degree of myocardial hypertrophy, dynamic LVOTO, MR, and myocardial function.[37]
Repeat TTE is also recommended in patients with HCM in whom a change in clinical status or new clinical event has occurred.[37]
A TTE with provocative maneuvers is recommended for patients with HCM who have a resting LV outflow tract (LVOT) gradient below 50 mmHg.[37]
It is recommended that exercise TTE be performed for the detection and quantification of dynamic LVOTO in symptomatic patients with HCM in whom the resting or provocable outflow tract gradient is at or above 50 mmHg on TTE.[37]
Intraoperative transesophageal echocardiogram (TEE) is recommended to evaluate mitral valve anatomy and function, as well as the adequacy of septal myectomy, in patients with HCM in whom surgical septal myectomy is being performed.[37]
TTE or intraoperative TEE, with intracoronary ultrasonogram-enhancing contrast injection of the septal perforator(s), is recommended for patients with HCM in whom alcohol septal ablation is being performed.
TTE within 3-6 months after septal reduction therapy (SRT) is recommended to assess the results in patients with HCM who have undergone the procedure.
Screening with echocardiography is recommended in the following people[38] :
Consider cardiac computed tomography (CT) scanning when HCM is suspected in an adult but echocardiography results are not diagnostic and cardiac magnetic resonance imaging (MRI) is not available.[37]
CMRI is indicated to clarify the diagnosis when, in patients suspected of having HCM, echocardiography is inconclusive.[37]
CMRI is useful for patients with LV hypertrophy (LVH) when an alternative diagnosis such as infiltrative or storage disease or athlete's heart is suspected.[37]
CMRI is a beneficial means of evaluating for maximum LV wall thickness, ejection fraction (EF), LV apical aneurysm, and the extent of myocardial fibrosis with late gadolinium enhancement (LGE), in patients who have not otherwise been identified as being at high SCD risk or in whom a decision to employ an implantable cardioverter-defibrillator (ICD) remains uncertain after a clinical assessment that includes personal/family history, echocardiography, and ambulatory ECG monitoring.[37]
CMRI is indicated to inform the selection and planning of SRT when, in patients with obstructive HCM, the anatomic mechanism of obstruction is inconclusive on echocardiography.[37]
The ESC recomends contrast-enhanced CMRI in the presence of cardiomyopathy at initial evaluation.[39]
It is recommended that in their initial evaluation (and as part of periodic follow-up, every 1-2 years), patients with HCM undergo a 12-lead ECG study.
To identify individuals at SCD risk and guide arrhythmia management, it is recommended that patients with HCM undergo 24- to 48-hour ambulatory ECG monitoring during their initial evaluation and periodically (every 1-2 years).
It is recommended that patients with HCM who develop palpitations or lightheadedness undergo extended (>24 hours) ECG monitoring or event recording determine arrhythmia and clinical correlation.[38]
It is recommended that first-degree relatives of patients with HCM undergo a 12-lead ECG study as part of the screening algorithm.
In patients with HCM considered at high risk for development of atrial fibrillation (AF) on the basis of risk factors or with a validated risk score, and who are candidates for anticoagulation, the 2024 AHA/ACC guidelines recommend screening for AF with extended ambulatory monitoring as part of the initial evaluation and annual follow-up.[38]
It is recommended that invasive hemodynamic assessment with cardiac catheterization be used in patients with symptomatic HCM in whom the results of noninvasive imaging studies are uncertain regarding the presence or severity of LVOTO.
It is recommended that coronary angiography (CT or invasive) be performed in patients with HCM who are symptomatic or have evidence of myocardial ischemia.
In the setting of coronary atherosclerosis risk, it is recommended that patients with HCM undergo coronary angiography (CT or invasive) prior to surgical myectomy.
Exercise TTE is recommended for the detection and quantification of dynamic LVOTO in patients with HCM who are symptomatic and who lack a resting or provocable outflow track peak gradient of 50 mmHg or above on TTE.
Patients with nonobstructive HCM and advanced heart failure (HF) (New York Heart Association [NYHA] functional class III-IV) should undergo cardiopulmonary exercise stress testing to quantify the degree of functional limitation and to help select patients for heart transplantation or mechanical circulatory support.[38]
The 2024 AHA/ACC guidelines recommend exercise stress testing in pediatric patients with HCM, regardless of their symptom status, to establish their functional capacity and well as provide prognostic information.[38]
The AHA/ACC recommend that a comprehensive, systematic, noninvasive SCD risk assessment be performed on adult, pediatric, and adolescent patients with HCM at initial evaluation and every 1-2 years thereafter, with assessment of the following risk factors included[37, 38] :
CMRI is beneficial for the evaluation of maximum LV wall thickness, EF, LV apical aneurysm, and extent of myocardial fibrosis with LGE in adult, pediatric, and adolescent patients with HCM who have not otherwise been identified as being at high SCD risk, or in whom it is still not certain after clinical assessment—including evaluation of personal/family history, echocardiography, and ambulatory ECG monitoring—whether ICD placement should proceed.[38]
The ESC recommends that at initial evaluation, every 1-2 years thereafter, or in the presence of a change in clinical status, assess the patients 5-year risk of SCD.[39]
For primary prevention, the ESC recommends use of the HCM risk-SCD calculator to estimate the risk of sudden death at 5 years in patients aged 16 years and older.[39] For primary prevention in those younger than 16 years, validated pediatric-specific risk prediction models are recommended to estimate the risk of sudden death at 5 years.[39]
Select AHA/ACC guidelines class I recommendations regarding medical management of patients with hypertrophic cardiomyopathy (HCM) are summarized below.[37, 38]
It is recommended that nonvasodilating beta blockers, titrated to effectiveness or maximally tolerated doses, be used in patients with obstructive HCM and symptoms attributable to left ventricular (LV) outflow tract obstruction (OTO). In the setting of ineffective or nontolerated beta blockers in patients with obstructive HCM and symptoms attributable to LVOTO, substitute nondihydropyridine calcium channel blockers (CCBs) (eg, verapamil, diltiazem) for beta blockers. (The 2023 European Society of Cardiology guidelines have similar class I recommendations.[39]
If, despite the use of beta blockers or nondihydropyridine CCBs, patients with obstructive HCM have persistent symptoms attributable to LVOTO, add a myosin inhibitor (adult patients only) or disopyramide (in combination with an atrioventricular nodal blocking agent), or perform septal reduction therapy (SRT) at an experienced center.[38]
In the setting of obstructive HCM and acute hypotension not responsive to fluid administration, use intravenous phenylephrine (or other vasoconstrictors without inotropic activity) alone or in combination with beta-blocking drugs.[38]
It is recommended that patients with nonobstructive HCM with preserved EF and symptoms of exertional angina or dyspnea be treated with beta blockers or nondihydropyridine CCBs.[37, 38]
In the setting of HCM and clinical atrial fibrillation (AF)—as well as in the setting of HCM and subclinical AF detected by internal or external cardiac device or monitor of over 24 hours' duration for a given episode—anticoagulation with direct-acting oral anticoagulants (DOAC; as a first-line option) and vitamin K antagonists (as a second-line option) is recommended, independent of the CHA2DS2-VASc score.
Similarly, the 2023 European Society of Cardiology recommends oral anticoagulation to lower the risk of stroke and thromboembolic events in the following[39] :
It is recommended that beta blockers, verapamil, or diltiazem be used in individuals with AF in whom a rate-control strategy is planned, with the selected agent chosen according to patient preferences and comorbid conditions.
Antiarrhythmic drug therapy (eg, amiodarone, dofetilide, mexiletine, or sotalol) is recommended in adults with HCM who have symptomatic ventricular arrhythmias or recurrent ICD shocks despite beta-blocker use.[38] The agent should be chosen based on factors such as age, underlying comorbidities, severity of disease, patient preferences, and the balance between efficacy and safety.
Antiarrhythmic drug therapy (amiodarone, mexiletine, sotalol) is recommended in children with HCM who have recurrent ventricular arrhythmias despite beta-blocker use.[38] The agent should be chosen based on factors such as age, underlying comorbidities, severity of disease, patient preferences, and the balance between efficacy and safety.
It is recommended that guideline-directed therapy for HF with reduced EF be employed in patients with HCM who develop systolic dysfunction with an LVEF below 50%.[37, 38]
The updated 2024 AHA/ACC recommends discontinuation of cardiac myosin inhibitors those those with HCM who develop persistent systolic dysfunction (LVEF < 50%).[38]
Recommendations from the 2024 updated AHA/ACC guidelines regarding invasive therapies in patients with hypertrophic cardiomyopathy (HCM) are summarized below.[38]
Class I recommendations
Perform septal reduction therapy (SRT) in the setting of an experienced HCM center for eligible patients with obstructive HCM with persistent symptoms despite guideline-directed medical therapy (GDMT) for relief of left ventricular outlet tract obstruction (LVOTO). (Level of evidence: B)
Perform surgical myectomy in the setting of an experienced HCM center for symptomatic patients with obstructive HCM with associated cardiac disease that necessitates surgical intervention (eg, associated anomalous papillary muscle, markedly elongated anterior mitral leaflet, intrinsic mitral valve disease, multivessel coronary artery disease, valvular aortic stenosis). (Level of evidence: B)
Perform alcohol septal ablation in the setting of an experienced HCM center for eligible persistently symptomatic adults with obstructive HCM despite GDMT and who are contraindicated for surgery or whose risk is deemed unnacceptable owing to serious comorbidities or advanced age. (Level of evidence: C)
Class IIb recommendations
In comprehensive HCM centers, it may be reasonable to perform earlier (NYHA class II) surgical myectomy in patients with obstructive HCM in the setting of additional clinical factors, such as the following: (1) severe and progressive pulmonary hypertension deemed secondary to LVOTO or associated mitral regurgitation; (2) left atrial enlargement with one or more episodes of symptomatic atrial fibrillation (AF); (3) documented poor functional capacity attributed to LVOTO on treadmill exercise testing; and (4) very high resting LVOT gradients (>100 mg Hg) pediatric and young adult patients. (Level of evidence: B)
Consider SRT in the setting of an experienced HCM center for eligible symptomatic patients with obstructive HCM as an alternative to escalating medical therapy, once shared decision making has occurred, including discussion of the risks and benefits of all treatment options. (Level of evidence: B)
Precautions (class III recommendations)
Note the following to prevent harm to patients with HCM:
Select 2014 and 2023 ESC guidelines class I recommendations for septal reduction therapy (SRT) are summarized below.[9, 39]
Class I recommendations
Septal reduction therapies should be performed by experienced operators, working as part of a multidisciplinary team expert in the management of HCM.[9, 39] (Level of evidence: C)
Perform SRT for symptomatic improvement in patients with a resting or maximum provoked LVOT gradient of at least 50 mmHg, who are in NYHA/Ross functional class III–IV, despite maximum tolerated medical therapy.[9, 39] (Level of evidence: B)
Septal myectomy, rather than alcohol septal ablation (ASA) is recommended in pediatric patients with an indication for SRT and in adults with an indication with SRT as well as other lesions requiring surgical intervention (eg, mitral valve anomalies).[39] (Level of evidence: C)
The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding alcohol septal ablation in patients with HCM are summarized below.[1, 22]
Class I recommendations
As discussed earlier, it is reasonable to consult with centers experienced in performing alcohol septal ablation and surgical septal myectomy for treatment-eligible patients with HCM with severe drug-refractory symptoms and LVOT obstruction.
Use transthoracic (TTE) or transesophageal (TTE) echocardiography for intraoperative guidance of alcohol septal ablation (level of evidence: B) and TTE for assessing the outcomes of alcohol septal ablation (or surgical myectomy) in patients with obstruct HCM (level of evidence: C).
Class IIa recommendations
For clinical decision making and evaluation for the feasibility of alcohol septal ablation, use TEE when TTE findings are unclear.
Class IIb recommendations
In experienced centers, following a detailed discussion with eligible adult patients with HCM and severe drug-refractory symptoms and LVOT obstruction, alcohol septal ablation may be a treatment option to surgical myectomy when the patient indicates a preference for septal ablation. (Level of evidence: B)
In general, alcohol septal ablation is discouraged in patients with HCM and marked (ie, >30 mm) septal hypertrophy owing to uncertainty regarding its efficacy in these patients. (Level of evidence: C)
Class III recommendations
To prevent harm, avoid performing alcohol septal ablation in (1) patients with HCM and comorbid conditions that also require surgical repair, in whom myectomy can be performed concomitantly; (2) pediatric patients with HCM (age < 21 years); and (3) adults younger than 40 years in whom myectomy is a feasible alternative therapy. (Level of evidence: C)
The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding pacing in patients with HCM are summarized below.[1, 22]
Class IIa recommendation
For patients with HCM who previously underwent dual-chamber device implantation for non–HCM-related causes, the ACCF/AHA believe a trial of dual-chamber atrial-ventricular pacing (from the right ventricular apex) for symptomatic relief from LVOT obstruction can be considered. (Level of evidence: B)
Class IIb recommendation
Permanent pacing is an option in symptomatic patients with medically refractory obstructive HCM who are not good candidates for septal reduction therapy. (Level of evidence: B)
Select patients in whom permanent pacemaker implantation is of no benefit (class III recommendations)
The 2011 ACCF/AHA guidelines indicate pacemaker implantation is not beneficial in the following scenarios for patients with HCM[1, 22] :
The 2012 HRS/ACCF expert consensus statement on pacemaker device and mode selection offer the following guidance[40] :
Class IIa recommendation
Dual-chamber pacing can be useful for patients with medically refractory, symptomatic hypertrophic, cardiomyopathy with significant resting, or provoked left ventricular outflow obstruction. (Level of evidence: C)
Class III recommendation
Single-chamber (VVI or AAI) pacing is not recommended for patients with medically refractory, symptomatic hypertrophic cardiomyopathy. (Level of evidence: C)
In its 2013 guidelines for cardiac pacing and cardiac resynchronization therapy[41] and its 2014 guidelines for management of hypertrophic cardiomyopathy,[9] the European Society of Cardiology (ESC) recommends considering sequential AV pacing, with optimal AV interval to reduce the LV outflow tract gradient or to facilitate medical treatment with ß-blockers and/or verapamil in select patients who have contraindications for septal alcohol ablation or septal myectomy. (Class IIb; Level of evidence: C)[9]
Recommendations from the 2020 and 2024 AHA/AC) guidelines[37, 38] regarding implantable cardioverter-defibrillator (ICD) placement in patients with hypertrophic cardiomyopathy (HCM) are included below with select 2011 ACCF/AHA guidelines recommendations.[1, 22]
An ICD is recommended to be placed in patients with HCM and previous, documented cardiac arrest or sustained ventricular tachycardia (VT).[37, 38] Single-coil, rather than dual-coil, ICD leads are recommended in patients with HCM who are receiving an ICD.
Class I recommendations
ICD placement decision making in patients with HCM should involve a comprehensive discussion between clinicians and patients.[1, 22] (Level of evidence: C) In addition, use individual clinical judgment to evaluate the prognostic strength of conventional risk marker(s) of each patient's clinical profile in this decision-making process,[37] (level of evidence: C) with a thorough and balanced discussion with the patient of the evidence, benefits, and estimated risks.[38]
This procedure is recommended for patients with HCM who have documentation of having suffered cardiac arrest or sustained ventricular fibrillation (VF).[37] (Level of evidence: B)
The AHA/ACC recommends either a single-chamber transvenous ICD or a subcutaneous ICD in patients with HCM undergoing ICD placement, after evaluation of patient preferences, age, lifestyle, and the potential need for pacing for bradycardia or VT termination.[37, 38] Level of evidence: B) In addition, when patients undergo transvenous ICD placement, single-coil ICD leads are preferred over dual-coil leads,[37] if the defibrillation threshold is considered adequate.[38] (Level of evidence: B)
Program antitachycardia pacing in HCM patients with pacing-capable ICDs to minimize shock risk.[37] (Level of evidence: C).
Class IIa recommendations
ICD placement is a reasonable intervention for patients with HCM who also have at least one major risk factor for sudden cardiac death (SCD), such as: (1) one or more first-degree or close relatives aged 50 years or younger who suffered sudden cardiac death (SCD) definitively or likely related to HCM, (2) massive left ventricular (LV) hypertrophy (LVH) of 30 mm or more in any LV segment, (3) one or more recent syncopal events suspected to be arrhythmic on the basis of the clinical history, (4) LV apical aneurysmwith transmural scar or late gadolinium enhancement (LGE), and (5) LV systolic dysfunction with an ejection fraction below 50%.[37, 38] (Level of evidence: B)
In pediatric patients with HCM with one or more conventional risk factors (eg, unexplained syncope, massive LVH, nonsustained ventricular tachycardia [NSVT], family history of early HCM-related SCD), it is reasonable to place an ICD following evaluation of the relatively high complication rates of long-term ICD placement in this population.[37, 38] (Level of evidence: B)
Share the decision making for ICD placement with HCM patients who have one or more SCD risk factors, and discuss the estimated 5-year risk of sudden death and mortality.[38] (Level of evidence: B)
It is reasonable to use dual-chamber ICDs in HCM patients undergoing ICD placement who have a need for atrial or atrioventricular sequential pacing for bradycardia/conduction anomalies, or to attempt symptomatic relief of obstructive HCM (predominantly in those aged >65 y).[37, 38] (Level of evidence: B)
It is reasonable to use cardiac resynchronization therapy for symptomatic reduction in select adults with nonobstructive HCM undergoing ICD placement who have New York Heart Association (NYHA) class II to ambulatory class IV heart failure, left bundle branch block, and an LV ejection fraction below 50%.[37, 38] (Level of evidence: C)
Class IIb recommendations
ICD effectiveness remains unclear in patients with HCM who do not have other risk factors for sudden cardiac death but do have either (1) isolated bursts of nonsustained VT or (2) exercise-induced blood pressure anomalies, especially in the setting of significant left ventricular outflow tract (LVOT). (Level of evidence: C)
After clinical evaluation in select adults with HCM without major SCD risk factors or for whom it is undecided whether to proceed with ICD placement, consider the procedure in those who have extensive late gadolinium enhancement on enhanced CMRI or nonsustained VT on ambulatory monitoring.[37] (Level of evidence: B)
In select pediatric patients with HCM whose risk stratification is otherwise less certain, consider additional risk stratifcation factors (eg, extensive late gadolinium enhancement on cardiac magnetic resonance imaging [MRI], systolic dysfunction).[37] (Level of evidence: C)
Dual-chamber ICDs may be reasonable in those with HCM who have decided on ICD placement and who have paroxysmal atrial tachycardias or atrial fibrillation—however, balance this decision against the higher complication rates of dual-chamber devices.[37, 38] (Level of evidence: C)
Precautions (class III recommendations)
To prevent harm to patients with HCM, do not place and ICD in the absence of risk factors.[37] (Level of evidence: B) In addition, placing an ICD for the sole purpose of competitive athletics participation in patients with HCM is not recommended.[37] (Level of evidence: B)
In its 2013 guidelines for cardiac pacing and cardiac resynchronization therapy[41] and its 2014 guidelines for management of HCM[9] , the European Society of Cardiology (ESC) recommended considering a dual-chamber ICD (instead of a single-lead device) to reduce the LV outflow tract gradient or to facilitate medical treatment with ß-blockers and/or verapamil in patients with resting or provocable LVOTO ≥50 mm Hg, sinus rhythm and drug refractory symptoms. (Class IIb; Level of evidence: C)[9]
Class IIb recommendations
ICD effectiveness remains unclear in patients with HCM who do not have other risk factors for sudden cardiac death but do have either (1) isolated bursts of nonsustained VT or (2) exercise-induced blood pressure anomalies, especially in the setting of significant LVOT. (Level of evidence: C)
After clinical evaluation in select adults with HCM without major SCD risk factors or in whom it is undecided whether to proceed with ICD placement, consider the procedure in those who have extensive LGE on enhanced cardiac magnetic resonance imaging [CMRI] or NSVT on ambulatory monitoring.[37, 38] (Level of evidence: B)
In pediatric patients with HCM, it may be useful to consider additional risk stratifcation factors (eg, extensive LGE on CMRI, systolic dysfunction).[37] (Level of evidence: B)
Precautions (class III recommendations)
To prevent harm to patients with HCM, do not place an ICD in the absence of risk factors.[37, 38] (Level of evidence: B) In addition, placing an ICD for the sole purpose of competitive athletics participation in patients with HCM is not recommended.[37, 38] (Level of evidence: B)
In its 2013 guidelines for cardiac pacing and cardiac resynchronization therapy[41] and its 2014 guidelines for management of hypertrophic cardiomyopathy[9] , the European Society of Cardiology (ESC) recommends considering a dual-chamber ICD (instead of a single-lead device) to reduce the LV outflow tract gradient or to facilitate medical treatment with ß-blockers and/or verapamil in patients with resting or provocable LVOTO ≥50 mm Hg, sinus rhythm and drug refractory symptoms. (Class IIb; Level of evidence: C)[9]
Class IIb recommendations
ICD effectiveness remains unclear in patients with HCM who do not have other risk factors for sudden cardiac death but do have either (1) isolated bursts of nonsustained VT or (2) exercise-induced blood pressure anomalies, especially in the setting of significant LVOT. (Level of evidence: C)
After clinical evaluation in select adults with HCM without major SCD risk factors or who it is undecided whether to proceed with ICD placement, consider the procedure in those who have extensive late gadolinium enhancement on enhanced CMRI or nonsustained VT on ambulatory monitoring.[37] (Level of evidence: B)
In select pediatric patients with HCM whose risk stratification is otherwise less certain, consider additional risk stratifcation factors (eg, extensive late gadolinium enhancement on cardiac magnetic resonance imaging [MRI], systolic dysfunction).[37] (Level of evidence: C)
Precautions (class III recommendations)
To prevent harm to patients with HCM, do not place and ICD in the absence of risk factors.[37] (Level of evidence: B) In addition, placing an ICD for the sole purpose of competitive athletics participation in patients with HCM is not recommended.[37] (Level of evidence: B)
In its 2013 guidelines for cardiac pacing and cardiac resynchronization therapy[41] and its 2014 guidelines for management of hypertrophic cardiomyopathy[9] , the European Society of Cardiology (ESC) recommends considering a dual-chamber ICD (instead of a single-lead device) to reduce the LV outflow tract gradient or to facilitate medical treatment with ß-blockers and/or verapamil in patients with resting or provocable LVOTO ≥50 mm Hg, sinus rhythm and drug refractory symptoms. (Class IIb; Level of evidence: C)[9]
Select class I ESC recommendations are outlined below.[39]
ICD placement is recommended in the following:
For primary prevention, perform comprehensive SCD risk stratification in all patients with cardiomyopathy without a history of a previous cardiac arrest or sustained ventricular arrhythmia at the initial evaluation and 1-2 year intervals, or when a change in clinical status occurs. When available, use validated SCD algorithms/scores when ICD placement is offered to patients with HCM.
When an ICD is recommended, evaluate whether cardiac resynchronization therapy may be beneficial to the patient.
Class I recommendations from the 2020[37] and 2024[38] American Heart Association and American College of Cardiology (AHA/ACC) guidelines recommend that patients with nonobstructive HCM and advanced HF (NYHA functional class III to class IV despite guideline-directed therapy [GDMT]) undergo a cardiopulmonary exercise test (CPET) to quantify the degree of functional limitation and to help in patient selection for heart transplantation or mechanical circulatory support.
Evaluation for heart transplantation in accordance with current listing criteria is recommended when patients with nonobstructive HCM have advanced HF (NYHA class III-IV despite GDMT) or when life-threatening ventricular arrhythmias are refractory to maximal GDMT.[37, 38] The 2023 European Society of Cardiology (ESC) recommendations agree.[39]
Evaluation for heart transplantation in accordance with current listing criteria is recommended when patients have HCM and recurrent, poorly tolerated life-threatening ventricular tachyarrhythmias refractory to maximal antiarrhythic pharmacotherapy and ablation.[38]
The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding heart transplantation in patients with HCM are also summarized below.[1, 22]
Class I recommendations
Heart transplantation should not be considered in the setting of advanced heart failure (end stage) and nonobstructive HCM not otherwise amenable to other treatment intervention, in the presence of an ejection fraction (EF) that is at or below 50% (or, occasionally, with preserved EF). (Level of evidence: B)
Pediatric heart transplant candidates include those with symptomatic HCM with a restrictive physiology who are not responsive to or appropriate candidates for other therapeutic interventions. (Level of evidence: C)
Precautions (class III recommendations)
To prevent harm, do not perform heart transplantation in mildly symptomatic patients of any age with HCM. (Level of evidence: C)
The 2014 ESC guidelines recommendations regarding heart transplantation in patients with HCM are summarized below.[9]
Class I recommendation
For severely symptomatic patients with systolic and/or diastolic LV dysfunction being evaluated for heart transplantation or mechanical support, cardiopulmonary exercise testing, with simultaneous measurement of respiratory gases should be performed. (Level of evidence: B)
Class IIa recommendation
Orthotopic cardiac transplantation should be considered in eligible patients who have an LVEF < 50% and NYHA functional Class III–IV symptoms despite optimal medical therapy or intractable ventricular arrhythmia.(Level of evidence: B)
Class IIb recommendation
Orthotopic cardiac transplantation may be considered in eligible patients with normal LVEF ( 50%) and severe drug refractory symptoms (NYHA functional Class III–IV) caused by diastolic dysfunction.(Level of evidence: B)
The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding management of atrial fibrillation in patients with HCM are summarized below.[22, 1]
Class I recommendations
Use vitamin K antagonists (ie, warfarin, to an international normalized ratio [INR] of 2-3) for anticoagulation in patients with paroxysmal, persistent, or chronic atrial fibrillation AF and HCM. (Data are not available in the setting of HCM for anticoagulation with direct thrombin inhibitors such as dabigatran in reducing the risk of thromboembolism). (Level of evidence: C)
Control the ventricular rate in patients with HCM and atrial fibrillation who have rapid ventricular rates. High doses of beta antagonists and nondihydropyridine calcium channel blockers may need to be administered. (Level of evidence: C)
Class IIa recommendations
The ACCF/AHA indicates it is reasonable to use disopyramide (with ventricular rate–controlling agents) and amiodarone for atrial fibrillation in patients with HCM. (Level of evidence: B)
Radiofrequency ablation can be beneficial in the setting of HCM with refractory atrial fibrillation or patients unable to take antiarrhythmic agents. (Level of evidence: B)
Maze procedure with closure of the left atrial appendage is a reasonable intervention in patients with HCM and a history of atrial fibrillation. The procedure may be performed during septal myectomy or as an isolated procedure in select patients. (Level of evidence: C)
Class IIb recommendations
Alternative antiarrhythmic agents for patients with HCM and atrial fibrillation include sotalol, dofetilide, and dronedarone, particularly in those with an implantable cardioverter defibrillator. (Level of evidence: C)
The 2020 and 2024 American Heart Association/American College of Cardiology (AHA/ACC) guidelines class I recommendations regarding management of comorbidities in patients with hypertrophic cardiomyopathy (HCM) are summarized below.[37, 38]
To decrease the risk of cardiovascular events, patients with HCM should adhere to the ACC/AHA guideline on primary prevention of atherosclerotic cardiovascular disease.
Counseling and comprehensive lifestyle interventions are recommended for patients with HCM who are overweight or obese to lose weight and maintain weight loss and potentially lower the risk of developing left ventricular outflow tract obstruction, heart failure, and atrial fibrillation.
Lifestyle modifications and medical therapy for hypertension are recommended for individuals with HCM and hypertension. Beta blockers and nondihydropyridine calcium channel blockers preferred in patients with obstructive HCM.
It is recommended that patients with HCM be evaluated for symptoms of sleep-disordered breathing. If such symptoms are present, refer the patient to a sleep medicine specialist for assessment and treatment.
The 2020 and 2024 AHA/ACC class I recommendations regarding management of pregnancy in patients with hypertrophic cardiomyopathy (HCM) are summarized below.[37, 38]
For stroke prevention in pregnant women with HCM and atrial fibrillation (AF) or other indications for anticoagulation, administer low–molecular-weight heparin (LMWH) or vitamin K antagonists (at maximum therapeutic dose of < 5 mg daily).
Administer selected beta blockers to pregnant women with HCM for symptoms associated with outflow tract obstruction (OTO) or arrhythmias, with monitoring of fetal growth.
Mavacamten is contraindicated in gravida owing to potential teratogenicity.[38]
It is recommended that vaginal delivery be the first-choice delivery option in the majority of pregnant women with HCM.
Offer preconceptional and prenatal reproductive and genetic counseling to affected families with HCM.
Patients' cardiologists and obstetricians should coordinate care for pregnant women with HCM. It is advised that pregnant individuals with HCM considered high risk consult with an expert in maternal-fetal medicine.
The 2011 ACCF/AHA recommendations regarding management of pregnancy and/or delivery in women with HCM are summarized below.[1, 22]
Class I recommendations
Pregnancy is not contraindicated in asymptomatic women with HCM; perform a careful evaluation for pregnancy risks. Asymptomatic women or those whose symptoms are controlled with beta-blocking drugs should continue pharmacotherapy during their pregnancy, and close monitoring for fetal bradycardia or other complications is important. (Level of evidence: C)
Male and female patients with HCM should receive genetic counseling before planned conception. (Level of evidence: C)
Management by a high-risk obstetric team is essential for women with HCM and resting or provocable LVOT obstruction of 50 mm Hg or greater and/or cardiac symptoms not controlled by medical therapy alone. (Level of evidence: C)
Class IIa recommendations
Management by an expert maternal-fetal team is advised for women with HCM whose symptoms are controlled (mild to moderate). Such specialist care includes cardiovascular and prenatal monitoring. (Level of evidence: C)
Precautions (class III recommendations)
Women with advanced heart failure symptoms and HCM have an increased risk of excess morbidity/mortality in pregnancy. (Level of evidence: C)
Select class I recommendations from the 2023 ESC guidelines are outlined below.[39]
Offer pre- and posttest genetic counseling to all individuals receiving genetic testing for cardiomyopathy.
In families pursuing prenatal diagnostic testing, perform such testing early in the pregnancy to allow decision making about continuation or coordination of the pregnancy.
The 2014 ESC guidelines recommendations are summarized below.[9]
Class I recommendations (Level of evidence C for all)
Class IIa recommendations
The 2020 American Heart Association/American College of Cardiology (AHA/ACC) guidelines recommendations regarding pregnancy in patients with hypertrophic cardiomyopathy (HCM) are summarized below.[37]
Mild- to moderate-intensity recreational exercise is beneficial in most patients with HCM as a means of improving cardiorespiratory fitness, physical functioning, and quality of life, and as a strategy for aiding overall health, in keeping with physical activity guidelines for the general population.
It is recommended that, via an expert provider, athletes with HCM undergo a comprehensive evaluation and participate in a shared discussion of the potential risks of sports participation.
The updated 2024 AHA/ACC guidelines does not indicate universal restriction from vigorous physical activity or competitive sports for most individuals with HCM (class III).[38]
Level I recommendations from the 2024 updated American Heart Association(AHA) and American College of Cardiology (ACC) guidelines for individuals with hypertrophic cardiomyopathy (HCM) regarding recreational physical activity and competitive sports are as follows[38] :
In 2015, the AHA/ACC released a scientific statement containing eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities. The recommendations for athletes with HCM are summarized below.[42]
Class IIa recommendation
Participation in competitive athletics for asymptomatic, genotype-positive HCM patients without evidence of LV hypertrophy by 2-dimensional echocardiography and CMR is reasonable, particularly in the absence of a family history of HCM-related sudden death (Level of evidence C).
Class III recommendations
Athletes with a probable or confirmed diagnosis of HCM should not participate in most competitive sports, with the exception of those of low intensity (class IA sports). (Level of evidence C).
Pharmacologic agents (eg, β-blockers) to control cardiac-related symptoms or ventricular tachyarrhythmias should not be administered for the sole purpose of permitting participation in high-intensity sports. (Level of evidence C).
Prophylactic ICDs should not be placed in athlete-patients with HCM for the sole or primary purpose of permitting participation in high-intensity sports competition because of the possibility of device-related complications. ICD indications for competitive athletes with HCM should not differ from those in nonathlete patients with HCM.(Level of evidence B).
The purpose of pharmacologic therapy is to reduce the pressure gradient across the LV outflow tract by reducing the inotropic state of the left ventricle, improving compliance of the left ventricle, and reducing diastolic dysfunction. Mavacamten, a first-in-class allosteric inhibitor of cardiac myosin, has gained FDA approval for adults with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve exercise capacity and symptoms. Amiodarone has been shown to reduce the incidence of arrhythmogenic sudden cardiac death.[43, 44]
Clinical Context: This is a first-line therapy in the treatment of obstructive and nonobstructive hypertrophic cardiomyopathy (HCM). Rarely, patients may require up to 200 mg orally twice daily to achieve the desired effect. The dose is titrated to a heart rate of between 50 and 60 bpm.
Clinical Context: Atenolol selectively blocks beta1 receptors, with little or no effect on beta2 types.
Clinical Context: This is a class III antiarrhythmic agent that blocks K+ channels, prolongs action potential duration, and lengthens the QT interval. Sotalol is a noncardiac selective beta-adrenergic blocker that may be helpful in the conversion of atrial fibrillation and flutter to normal rhythm. It may also suppress the recurrence of atrial fibrillation and flutter.
Clinical Context: Propranolol is a class II antiarrhythmic nonselective beta-adrenergic receptor blocker with membrane-stabilizing activity that decreases the automaticity of contractions. The
dose is titrated to a heart rate of between 50 and 60 bpm.
These reduce the inotropic state of the left ventricle. They decrease diastolic dysfunction and increase LV compliance, thereby reducing the pressure gradient across LV outflow tract. Beta-adrenergic blocking agents decrease heart rate, thus lowering myocardial oxygen consumption and reducing the potential for myocardial ischemia.
Clinical Context: Disopyramide decreases the inotropic state of the left ventricle. It decreases ventricular and supraventricular arrhythmias. The drug decreases diastolic dysfunction and increases LV compliance, thereby reducing the pressure gradient across the LV outflow tract. Disopyramide raises the threshold for atrial and ventricular ectopy.
Clinical Context: Amiodarone is the only agent proven to reduce the incidence and risk of cardiac sudden death, with or without obstruction to LV outflow. It is very effective at converting atrial fibrillation and flutter to sinus rhythm and at suppressing the recurrence of these arrhythmias.
These agents alter the electrophysiologic mechanisms responsible for arrhythmia.
Clinical Context: During depolarization, verapamil inhibits calcium ions from entering slow channels or voltage-sensitive areas of the vascular smooth muscle and myocardium. The drug provides an alternative to beta-blocker therapy. It is useful in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
The use of short-acting calcium channel blockers is being discouraged because of numerous reports of adverse cardiac and hemodynamic events associated with their use, particularly in patients with known coronary artery disease.
An alternative to beta blockers, calcium channel blockers decrease the inotropic state of the left ventricle, decrease the gradient across the LV outflow tract, decrease diastolic dysfunction, and increase diastolic filling of the left ventricle by improving LV diastolic relaxation. These agents may have a better effect on exercise performance.
Clinical Context: Warfarin is a competitive, direct thrombin inhibitor. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade, thereby preventing thrombus development. It inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation. Warfarin is indicated for the prevention of stroke and thromboembolism associated with nonvalvular atrial fibrillation.
Clinical Context: Indicated for symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve exercise capacity and symptoms in adults. Mavacamten is a selective allosteric inhibitor of cardiac myosin. Modulates number of myosin heads that can enter “on actin” (power-generating) states, thus reduces probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Mavacamten shifts overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In patients with HCM, myosin inhibition with mavacamten reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures.
Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM.