Hypertrophic Obstructive Cardiomyopathy

1 Clinical practice This journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors clinical recommendations. n engl j med 350;13 25, 2004 The new england journal of medicine 1320 Hypertrophic Obstructive Cardiomyopathy Rick A. Nishimura, , and David R. Holmes, Jr., From the Division of Cardiovascular Dis-eases and Internal medicine , Mayo Clinic,200 First St.

2 SW, Rochester, MN 55905,where reprint requests should be addressedto Dr. Engl M Med 2004;350:1320-7. Copyright 2004 Massachusetts Medical Society. A 28-year-old man presents with a two-year history of increasing dyspnea on strenu-ous exertion and is found to have Hypertrophic Cardiomyopathy , with a septal thick-ness of 23 mm and a left ventricular outflow gradient of 80 mm Hg. There is no familyhistory of Hypertrophic Cardiomyopathy or sudden death. Forty-eight-hour Holtermonitoring shows infrequent premature ventricular contractions.

3 How should thispatient be treated? Hypertrophic Cardiomyopathy is a genetic cardiac disorder caused by a missense muta-tion in 1 of at least 10 genes that encode the proteins of the cardiac sarcomere. The phe-notypic expression of Hypertrophic Cardiomyopathy , which occurs in 1 of every 500adults in the general population, includes massive hypertrophy involving primarily theventricular septum. 1-5 Although the majority of patients are asymptomatic throughoutlife, some present with severe limiting symptoms of dyspnea, angina, and syncope;some may even die suddenly from cardiac causes.

4 The mechanisms of hypertrophiccardiomyopathy are complex and include dynamic left ventricular outflow tract ob-struction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, and cardi-ac arrhythmias. Treatment strategies are directed at symptom relief and the preventionof sudden death. 2,6,7 Therapy for Hypertrophic Cardiomyopathy is directed at the dynamic left ventricularoutflow tract obstruction (which is present in 30 to 50 percent of patients) (Fig. 1).Some patients have labile obstruction that is absent at rest but provoked with changesin preload, afterload, and contractility.

5 Thus, the obstruction may become manifestonly when certain drugs ( , vasodilator or diuretic agents) are given or when hypo-volemia occurs. In other patients, the obstruction is present at rest, with its magnitudedependent on loading conditions. The obstruction causes an increase in left ventricu-lar systolic pressure, which leads to a complex interplay of abnormalities that includeprolongation of ventricular relaxation, increased left ventricular diastolic pressure,myocardial ischemia, and decreased cardiac output. 3 Secondary mitral regurgitationcan occur in patients with severe obstruction due to systolic anterior motion of the mi-tral overall mortality among patients with Hypertrophic Cardiomyopathy is less than1 percent per year.

6 2,7 However, a subgroup of patients is at high risk for sudden death,primarily as a result of ventricular arrhythmias. 8 Hypertrophic Cardiomyopathy is themost common cause of sudden death among young athletes. 9 The propensity for sud-den death appears to be genetic, but there are clinical risk factors that should be rou-tinely evaluated (Table 1). Other complications that may occur include atrial fibrilla-tion, infective endocarditis, and end-stage heart failure. 2,6,7the clinical problemCopyright 2004 Massachusetts Medical Society.

7 All rights reserved. Downloaded from at COLUMBIA UNIV HEALTH SCIENCES LIB on September 24, 2006 . n engl j med 350;13 25, 2004 clinical practice 1321 diagnostic evaluation Hypertrophic Cardiomyopathy may be suspected onthe basis of abnormalities found on cardiac exami-nation or electrocardiography. Classic findings in-clude a systolic ejection murmur that becomes in-creasingly loud during maneuvers that decreasepreload (such as a change in the patient s positionfrom squatting to standing) and evidence of leftventricular hypertrophy on diagnosis can be confirmed by two-dimension-al echocardiography, which shows hypertrophy ofthe myocardium that is usually asymmetric, with theseptal thickness greater than the thickness of thefree wall (Fig.)

8 2). Continuous-wave Doppler echo-cardiography is used to diagnose resting obstruc-tion, which is evident as a high-velocity, late-peak-ing jet across the left ventricular outflow tract. Inpatients with no obstruction or only slight obstruc-tion (gradient, 30 mm Hg), provocative maneuvers(such as the Valsalva maneuver or exercise) shouldbe performed to identify latent the diagnosis is made, the patient s familyhistory (with special attention to Hypertrophic car-diomyopathy or sudden death) should be carefullyobtained. All first-degree family members shouldundergo periodic screening with echocardiogra-phy every five years for this autosomal dominantdisorder, since hypertrophy may not be appreciableuntil the sixth to seventh decade of life.

9 Annualscreening is recommended for adolescents 12 to18 years of age. In the future, the diagnosis of hyper-trophic Cardiomyopathy may be based on the identi-fication of mutations in the genes encoding thesarcomeric proteins, but this technique is not cur-rently the standard of care. 4 Patients should undergoan evaluation that includes 48-hour Holter moni-toring and exercise testing, which provide prog-nostic information. All patients should be offeredinstructions for prophylaxis against infective endo-carditis and should be advised to avoid dehydrationand strenuous exertion (intense physical activity in-volving bursts of exertion or repeated isometric ex-ercise).

10 Pharmacologic therapy The first-line approach to the relief of symptoms ispharmacologic therapy designed to block the ef-fects of catecholamines that exacerbate the outflowtract obstruction and to slow the heart rate so thatdiastolic filling is enhanced 2,3,6,7 (Table 2). Al-though no data from long-term randomized, con-trolled trials are available, beta-blockers are gener-ally the initial choice for patients with symptomatichypertrophic Obstructive Cardiomyopathy and areinitially effective in 60 to 80 percent of patients. 10,11 The calcium-channel blocker verapamil can also beused and is associated with a similar rate of im-provement in symptoms.