33-year-old man with syncope.

A 33-year-old man presented for evaluation of syncope. A few weeks earlier, he had become light-headed and developed mild chest discomfort and visual changes while running from home plate to first base during a softball game. A few days before evaluation, he had been running on his treadmill when he became light-headed, lost consciousness, fell, injured his nose, and broke his glasses. Bystanders observed no seizure-like activity. He experienced no bowel or bladder incontinence, tongue biting, or postevent confusion. He denied antecedent palpitations, chest pain, sneezing, coughing, Valsalva maneuver, or change in emotion. His medical history was remarkable for mild depression and gastroesophageal reflux disease. He was taking 20 mg/d of citalopram and 20 mg/d of pantoprazole. He denied use of illicit drugs or excessive alcohol. His family history was notable for the unexplained death of 3 siblings (at ages 3 days, 1 week, and 3 years) and the unexpected death of his father at age 44 years. No autopsies were performed. The patient's cardiac examination demonstrated a regular rhythm with a normal S1/S2 and a soft S4. At rest, no significant murmur was appreciated, but with the Valsalva maneuver a systolic ejection murmur appeared and reached a 3/6 intensity. Otherwise, findings on physical examination were unremarkable. Results of laboratory tests, including a complete blood cell count and an electrolyte panel, were within normal limits. Electrocardiography (ECG) showed normal sinus rhythm and biatrial enlargement. A 24-hour ambulatory ECG showed no significant atrial or ventricular dysrhythmia despite patient-reported episodes of light-headedness. Which one of the following is the most appropriate next diagnostic test? Tilt-table testing Electroencephalography Transthoracic echocardiography (TTE) Exercise ECG stress test Carotid ultrasonography Although neurocardiogenic syncope can often be detected using tilt-table testing, exertional syncope is not usually due to a vasovagal event. Electroencephalography is a reasonable choice when a generalized seizure is suspected as the cause of syncope, but in this case no convulsive activity or postictal state was reported by event observers. In a patient with exertional syncope, TTE is an appropriate diagnostic test, especially if there is auscultatory evidence of dynamic outflow tract obstruction.1 Exercise ECG stress testing can evaluate for cardiac ischemia but would not be the best next step given the patient's age and lack of risk factors. Carotid ultrasonography is not the best choice because the patient's lack of neurologic deficit and young age make a cerebrovascular event an unlikely cause of his syncope. Evidence of increased ventricular septal thickness (18 mm) with systolic anterior motion of the mitral valve apparatus was noted on TTE. Left ventricular outflow tract (LVOT) obstruction was noted at rest (36 mm Hg) and became severe with the Valsalva maneuver (88 mm Hg). These findings were consistent with a diagnosis of obstructive hypertrophic cardiomyopathy (HCM). Which one of the following is the best initial treatment option for this patient? β-Blocker Digoxin Angiotensin-converting enzyme inhibitor Long-acting nitrate Spironolactone A negative inotropic medication such as a β-blocker or non-dihydropyridine calcium channel blocker would be the most appropriate initial therapeutic intervention. Both β-blockers and calcium channel blockers can decrease the obstructive gradient in HCM by decreasing catecholamine-mediated contractility.2 These agents also increase diastolic filling by decreasing the heart rate. Digoxin is not appropriate in most patients with HCM because it has the opposite effect of a β-blocker, acting as an inotropic agent and increasing LVOT obstruction by increasing contractility. Angiotensin-converting enzyme inhibitors decrease preload and afterload and thus exacerbate the obstructive gradient in HCM. Likewise, diuretics and long-acting nitrates decrease cardiac preload, which also can exacerbate symptoms secondary to outflow tract obstruction. In contrast, patients with HCM should be instructed to avoid dehydration. The patient was prescribed metoprolol, titrated to 100 mg twice daily. He continued to experience presyncope and syncope and developed new symptoms of exertional dyspnea and chest pain. Despite dose titration and combination therapy with verapamil and later disopyramide, he did not improve. Follow-up TTE confirmed persistent LVOT obstruction, and 24-hour ambulatory ECG showed no evidence of arrhythmia. Which one of the following therapies would be most appropriate given the patient's continued symptoms despite maximal medical therapy? Heart transplant Percutaneous alcohol septal ablation Initiation of amiodarone therapy Surgical septal myectomy Dual-chamber pacemaker Heart transplant would not be indicated at this stage but should be considered in patients with end-stage HCM refractory to medical and surgical therapy.3 Percutaneous alcohol septal ablation involves administration of ethanol into a septal perforator branch of the left anterior descending coronary artery supplying the involved hypertrophic segment. This causes a controlled myocardial infarction and subsequent atrophy of the obstructing myocardium. Complications from the procedure include infarction of an uninvolved segment or of an undesirable size (due to variations in coronary anatomy and distribution) and a relatively high incidence of complete heart block. Because of these potential complications and the lack of long-term follow-up, alcohol ablation is not considered the primary therapy for medically refractory HCM.3 Amiodarone would not be indicated in the absence of atrial fibrillation or ventricular arrhythmia.2 Surgical septal myectomy is the primary treatment option for symptomatic HCM refractory to medical therapy.2-4 Dual-chamber pacemakers have been used for drug-refractory, symptomatic HCM. However, they are not the primary treatment option, and their efficacy has been disputed in clinical trials.5 Which one of the following is an established major risk factor for sudden death (SD) in patients with HCM? Male sex First-degree family member with a history of SD Atrial fibrillation (AF) Presence of established HCM-associated gene mutation European ancestry In patients with HCM, sex is not associated with SD.6 A first-degree family member with SD is a significant risk factor and should prompt consideration of an implantable cardioverter-defibrillator (ICD). 3,5,6 Atrial fibrillation has been associated with inappropriate ICD shocks, but no clear evidence suggests that it is a predictor of SD.3,6 It was hoped that the identification of certain genetic mutations would assist in the risk stratification of HCM. Unfortunately, considerable phenotypic variation among patients with genetic mutations has, to date, precluded widespread clinical use for risk stratification in HCM. No clear association has been established between race and SD risk.6 Given the patient's recurrent syncopal episodes, significant LVOT obstruction, and family history of SD, an ICD was implanted for primary prophylaxis. Which one of the following would be an additional recommendation for this patient? Infective endocarditis prophylaxis with dental procedures Vigorous exercise regimen Anticoagulation Clinic follow-up in 3 years Echocardiographic screening for HCM in first-degree family members Infective endocarditis prophylaxis is no longer routinely recommended for patients with HCM.7 Patients with HCM are generally advised to abstain from high-intensity exercises.3 Anticoagulation is not indicated for HCM in the absence of another indication. Although follow-up intervals should be based on clinical symptoms and risk factors, patients should be seen at least annually for symptom assessment and ongoing screening for SD. Screening for HCM is strongly recommended in first-degree family members.3 The patient underwent a surgical septal myectomy without perioperative complications. He had a marked reduction in exertional dyspnea and chest pain and no recurrent syncope. He continued receiving β-blocker therapy and experienced no ICD discharges during 4 years of follow-up.