Hypertrophic Obstructive Cardiomyopathy (HOCM) Topic Review

Diagnosis | Physical Examination | Treatment – ICD Implantation • Medical Therapy • Mechanical Therapy

Introduction

Hypertrophic obstructive cardiomyopathy results in abnormal thickening of the myocardium, most commonly in the interventricular septum, with pathologic “myocardial disarray” upon microscopic inspection. HOCM can lead to clinical heart failure, life-threatening arrhythmias, mitral regurgitation and sudden cardiac death. 

HOCM is an autosomal dominant genetic disorder in about 60% of cases. The remainder are related to spontaneous mutations. Several different genes are involved that can result in HOCM. Most of these encode for sarcomere proteins in the contractile apparatus of the myocardial cells. The most common gene affected is the cardiac myosin binding protein C, followed by mutations in the cardiac beta-myosin heavy chain.

In patients with HOCM, the myocardial muscle cells are abnormally thickened related to mutations in the genes, encoding contractile proteins in the sarcomere. The myocytes are not able to align properly and the typical description, pathologically, of heart specimens is that of “myocardial disarray.” Over time, the myocytes are replaced with fibrous tissue which can lead to systolic heart failure, or “burnt out HOCM.”

The causes of heart failure in HOCM are listed below.

  1. Diastolic dysfunction
  2. Mitral regurgitation (due to the Venturi effect)
  3. Arrhythmia
  4. End-stage HOCM results in systolic dysfunction, or “burnt out HOCM”

Diagnosis HOCM

The diagnosis is made with echocardiography, which will directly visualize the hypertrophied interventricular septum.

The ECG in a patient with HOCM will show left ventricular hypertrophy. The classic finding is large, dagger-like “septal Q waves” in the inferior and lateral leads due to the abnormally hypertrophied interventricular septum.

Below are links to two ECG examples of HOCM.

Physical Examination HOCM

The murmur of HOCM is important to detect due to its clinical implications. The murmur is a high-pitched, crescendo-decrescendo, midsystolic murmur heard best at the left lower sternal border.  The murmur of HOCM does not radiate to the carotids like that of aortic stenosis. The important auscultatory features of HOCM that distinguish it from AS relate to dynamic auscultation.

The murmur of HOCM becomes quite loud with Valsalva maneuver. This maneuver effectively acts to decrease left ventricular filling, which results in worsened left ventricular outflow tract obstruction in patients with HOCM, making the murmur louder. Standing from the squatting position has a similar effect; this results in sudden pooling of blood in the legs, decreasing venous return. In patients with aortic valvular stenosis, the murmur will get softer with Valsalva or standing from squatting because less blood is being ejected through the aortic valve. Rapid squatting from a standing position forces increased venous return and would have the opposite effect of Valsalva or rapid standing.

A beat post-premature ventricular contraction, or PVC, allows more time for the left ventricle to fill. The more blood in the left ventricle, the more will be ejected. This results in decreased intensity of the murmur of HOCM. If there is more blood in the left ventricle, the hypertrophied interventricular septum is pushed out of the left ventricular outflow tract, relieving the obstruction to some degree and decreasing the intensity of HOCM.

HOCM

Treatment HOCM

Implantable Cardioverter Defibrillator (ICD)

Patients with hypertrophic obstructive cardiomyopathy have a high risk for sudden cardiac death; however, an ICD is not recommend in all patients with HOCM.

If any of the criteria below are present, an ICD should be implanted.

  1. Syncope
  2. Interventricular septal thickness of 30 millimeters or greater
  3. Documented ventricular tachycardia and/or cardiac arrest
  4. Family history of sudden cardiac death
  5. Left ventricular systolic dysfunction in the setting of wall thinning, also known as “burnt out” left ventricle

Medical Therapy

There are no large randomized clinical trials available to evaluate different drug therapy in symptomatic patients with HOCM. Since most symptoms from HOCM are related to left ventricular outflow tract obstruction, which occurs during systole, medical therapy is aimed at lowering the heart rate to allow better diastolic filling and using negative inotropic agents to decrease the force of contractility.

Non-dihydropyridine calcium channel blockers such as verapamil are commonly used. These drugs slow the heart rate and decrease the inotropic force of left ventricular contraction, relieving the symptoms of HOCM.

Beta-blockers act similarly in mechanism as the above in HOCM patients.

Disopyramide is the historical treatment for HOCM. This drug has significant negative inotropic effects but is considered an antiarrhythmic drug. It is currently recommended only for persistent symptoms if non-dihydropyridine calcium channel blockers and beta-blockers fail. Patients on disopyramide should also take one of the above concomitantly, as disopyramide enhances atrioventricular, or AV, nodal conduction and, should atrial fibrillation/flutter develop, it will very rapidly conduct to the ventricles.

Disopyramide can prolong the QT interval, resulting in polymorphic ventricular tachycardia in some patients. There are significant anticholinergic side effects including xerostomia (dry mouth), urinary retention, visual disturbances and decreased perspiration.

Mechanical Therapy

The two mechanical therapies to treat HOCM are surgical myomectomy and catheter-based alcohol septal ablation.

The indications for mechanical therapy for HOCM are simply persistent symptoms despite optimal medical therapy (New York Heart Association functional class III and IV) or recurrent syncope despite medical therapy.

Surgical myectomy, also known as septal myectomy, is simply performed when the surgeon removes the hypertrophied part of the interventricular septum, relieving the outflow tract obstruction. Complications include a ventricular septal defect (if too much tissue is removed), LV dysfunction (if other myocardial segments are damaged during surgery) or the development of complete heart block (due to injury of the AV node).

Alcohol (ethanol) septal ablation is a catheter-based, minimally-invasive intervention during which the septal perforator coronary arteries are identified and alcohol is infused. This results in thrombosis and infarction of the interventricular septum. This causes the infarcted tissue to thin, thus relieving the outflow tract obstruction. Complications can be serious and include complete heart block, ventricular arrhythmias, sudden cardiac death, coronary dissection/perforation resulting in pericardial effusion and LV systolic dysfunction.

The above two procedures have never been compared head-to-head in any clinical trials. Observational data suggest that alcohol septal ablation has more variable results, with some patients achieving excellent results and others having no benefit. Both procedures have similar mortality rates. Cardiovascular complications (complete heart block) are lower with surgical myectomy, but surgical complications (infection) are higher. Both procedures similarly improve symptoms of heart failure. Alcohol septal ablation is more likely to result in the need for a second procedure.