Dyspnea and Palpitations in a Varsity Athlete

Recently, a 21-year-old man has experienced dyspnea with strenuous exertion when he practices with his varsity basketball team. On several occasions, he has also had a sensation of pressure in his chest, and once or twice he has had palpitations. The symptoms abate quickly when he rests and are not associated with routine daily activity. HISTORY The patient is otherwise healthy and takes no long-term medications. Until the advent of his recent symptoms, he actively participated in strenuous athletics with no problems. His father sustained a myocardial infarction at age 57 years. His 4 older siblings are healthy. PHYSICAL EXAMINATION Heart rate is 80 beats per minute; respiration rate, 12 breaths per minute; and blood pressure, 115/75 mm Hg. Head and neck are normal; chest is clear. Cardiac examination reveals a grade 2 systolic ejection murmur at the apex that becomes significantly louder when the patient changes from a recumbent to an upright position. Results of the remainder of the physical examination are normal. RESULTS OF DIAGNOSTIC STUDIES ECG shows voltage criteria for left ventricular hypertrophy (LVH). Two-dimensional echocardiography reveals asymmetric hypertrophy of the left ventricle, with a septum thickness of 3 cm and a free-wall thickness of 1.5 cm. Flow studies demonstrate a left ventricular outflow gradient of 40 mm. Forty-eight–hour Holter monitoring reveals episodes of sustained ventricular tachycardia. Which of the following interventions is likely to have the greatest effect on this patient’s prognosis? A. Beta-Blocker therapy. B. Septal myomectomy to relieve outflow obstruction. C. Calcium channel blocker therapy. D. Implantation of an automatic defibrillator device. Answer on next page , CORRECT ANSWER: D, Implantation of an automatic defibrillator device This patient displays typical symptoms and signs of hypertrophic obstructive cardiomyopathy. This relatively common condition (estimated prevalence in the general population, 1 in 500) has a heterogeneous clinical, morphologic, and genetic expression.1,2  Most of those affected remain asymptomatic throughout life; however, in patients who do have symptoms, dyspnea, angina, and syncope are the most common. The results of this man’s cardiac examination—the systolic ejection murmur that becomes louder with maneuvers that decrease preload (eg, position change from lying to standing, Valsalva maneuvers) and ECG findings consistent with LVH—strongly suggest the diagnosis. The diagnostic test of choice is echocardiography; the characteristic findings are asymmetric hypertrophy of the left ventricle (septal thickness greater than free-wall thickness) and an obstructive left ventricular outflow gradient late in systole.2  Both are evident here. Hypertrophic cardiomyopathy and sudden death. A diagnosis of hypertrophic obstructive cardiomyopathy has prognostic as well as therapeutic implications. Certainly, therapy is indicated for relief of symptoms. However, the disease also causes sudden death. Although the overall mortality in affected persons is less than 1% per year, young age at onset magnifies this risk in many patients. In fact, in large autopsy studies in young athletes, hypertrophic cardiomyopathy was by far the leading cause of sudden death, accounting for 26.4% of cases.2  The pathophysiology of sudden death is complex; it seems most likely to result from an electrically unstable and unpredictable myocardial substrate in conjunction with sustained reentrant ventricular tachycardia.3 Therapy to relieve symptoms. The goals of therapy are the reduction of symptoms and the prevention of sudden death. For relief of symptoms, first-line therapy is pharmacologic; medications are used to reduce the effects of catecholamine (which worsen outflow obstruction) and to slow the heart rate (which enhances diastolic filling). Beta-Blockers (choice A) are the drugs of choice for relief of symptoms. They are highly effective and produce at least an initial response in most patients.1  Calcium channel blockers (choice C) have been used successfully in patients who cannot tolerate or who have not had a good response to Beta-blockers. However, calcium channel blockers are associated with serious, even fatal, complications in those who have severe symptoms and obstruction; thus, they must be used with care (eg, treatment initiated in hospital)—if at all—in such patients.1 Consider surgical septal myomectomy (choice B) in patients in whom pharmacologic therapy fails. Indications for this procedure include: •Resting gradient of 30 mm Hg or greater. •Provocable gradient of greater than 50 mm Hg. •Symptoms (dyspnea and angina) that interfere with or limit daily activity. When septal myomectomy is performed by experienced operators, the outcome is usually excellent. Clinical effectiveness exceeds 90%; operative mortality is less than 2%; and fewer than 3% of patients experience complications.4 Prevention of sudden death. Drugs and surgery that afford symptomatic relief may not reduce the risk of sudden death associated with hypertrophic obstructive cardiomyopathy. In natural history studies, features of hypertrophic cardiomyopathy that were associated with an increased risk of fatal cardiac events included: • Genetic factors (family history of sudden death, specific mutations in cardiac sarcomeric proteins). • Clinical features (recurrent syncope, episodes of ventricular tachycardia on monitoring). • Morphologic features (extreme degrees of LVH [greater than 3 cm]). • Hemodynamic factors (left ventricular outflow gradient greater than 30 mm, decreased blood pressure with exercise, demonstration of limited myocardial reserve).5 Current investigation focuses on the genetics of hypertrophic cardiomyopathy, and mutations in 10 genes that encode sarcomere proteins have been found. Genotyping seems to be effective in determining the risk of sudden death (ie, “malignant” genetic mutations have been identified); however, it is not yet widely available. Thus, the clinical criteria previously listed remain the most useful way to determine risk and decide whether implantation of an automatic defibrillator—the treatment of choice for the prevention of sudden death—is appropriate.1,5 This patient has at least 3 of the features associated with increased risk of sudden death: an extreme degree of LVH, outflow gradient greater than 30 mm, and episodes of ventricular tachycardia on monitoring. In addition to therapies that alleviate symptoms, most authorities would recommend the placement of a defibrillator in this case. Outcome of this case.  A defibrillator was placed, and atenolol (25 mg bid) was prescribed. The patient has taken a medical leave from the varsity basketball team, but he is able to perform all other daily activities—including participation in recreational sports—with no symptoms. He will be reevaluated in 3 months. THE TAKE-HOME MESSAGE: In addition to therapies that relieve the symptoms of hypertrophic obstructive cardiomyopathy, placement of a defibrillator is recommended to prevent sudden death in patients who have genetic, clinical, morphologic, or hemodynamic factors associated with increased risk of fatal cardiac events. REFERENCES: 1. Nishimura RA, Holmes DR Jr. Clinical practice. Hypertrophic obstructive cardiomyopathy. N Engl J Med. 2004;350:1320-1327. 2. Maron BJ. Sudden death in young athletes. N Engl J Med. 2003;349:1064-1075. 3. Cannon RO 3rd. Assessing risk in hypertrophic cardiomyopathy. N Engl J Med. 2003;349:1016-1018. 4. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA. 2002;287:1308-1320. 5. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med. 2000;342:365-373.