Mid cavity obstruction Patients with mid ventricular obstruction have hypertrophy with hyperkinetic LV wall motion. Mid cavity obstruction is due to systolic apposition of the ventricular walls. Often hypertrophied papillary muscles are involved with obstruction at this level. The obstruction can trap blood in a small apical cavity from mid-systole on. This area can infarct. Medical treatment of mid ventricular obstruction is with negative inotropes, similar to HCM with SAM and mitral-septal contact. Treatment of non-obstructive hypertrophic cardiomyopathy VERAPAMIL THERAPY Verapamil is the most often used medication in non-obstructive patients. There are features of HCM that make use of calcium channel blockers appealing. Verapamil was first introduced for HCM by Kaltenbach and colleagues in 1978 Of 22 adult patients treated with oral verapamil, (mean dose of 480mg/day and mean duration of treatment 15 months) symptom relief occurred in 11pts and LV outflow tract (LVOT) gradient decreased in 5 patients. Side effects were mild and it was concluded that verapamil appeared to be more effective and better tolerated than beta-blockers. Numerous clinical studies followed, both in adult and pediatric cohorts. In various studies verapamil improved symptoms by 1 or more NYHA-class in 60% of patients after 14 months of treatment, in 43% after 25 months and in 57% after 40 months. Exercise duration increased in the majority of patients, by an average of 53%. This effect was sustained at 1 year, and 2 years and decreased after verapamil withdrawal. Hopf and Kaltenbach reported results of more than 10-years follow-up on verapamil (average dose 515mg/d): annual mortality was 2% ; exercise tolerance improved in 84% of patients. Gregor however, reported less durable effects, diminishing to equivocal benefit after 4 months. Most investigators have found an increase in treadmill exercise time on verapamil. Acute and subacute hemodynamic effects of verapamil in HCM have been studied extensively in order to elucidate mechanisms of its beneficial and adverse effects. A limitation has been that almost all investigations have included both obstructed and non-obstructed patients. Since LV relaxation improves when systolic overload is relieved, the direct effect of verapamil on diastolic dysfunction is difficult to prove in patients with dynamic gradients. There is some evidence that verapamil's clinical benefit in mild to moderately obstructed patients may be through its benefits in diastole. Using radionuclide angiography, Bonow and others found that verapamil decreased regional non-uniformity of relaxation and improved relaxation synchronicity. Enhanced peak LV filling was due to enhanced early synchrony after drug and correlated with increased exercise capacity. This beneficial effect, and its correlation with improved exercise capacity have been observed by others. Symptoms of angina due to ischemia are generally treated with verapamil, which improves scintigraphic evidence of ischemia. In a study of 29 patients, about 50% had exercise perfusion defects. Verapamil improved exercise perfusion in more than 70%. The usual dose is 360 mg/day as tolerated. The effect of verapamil on LV hypertrophy varied in the several studies, with no convincing effect shown. Arrhythmias Atrial fibrillation is a troubling complication for HCM patients and can precipitate an acute decompensation with dyspnea or collapse. Generally, the first therapeutic maneuver is slowing the ventricular response with beta blockade, orally, or if circumstances dictate, intravenously. However, if the patient is hypotensive or hypoperfusing, emergency cardioversion is indicated. Since HCM patients are prone to cerebrovascular accidents from thromboembolism in atrial fibrillation, we anticoagulate all patients with heparin and then coumadin. If atrial fibrillation does not revert, we cardiovert electrically. For preservation of sinus rhythm, amiodarone is the drug of choice. If a patient has significant obstruction, disopyramide is another option and will also improve obstruction. Patients with symptomatic syncopal ventricular tachycardia are generally treated in the United States with an implanted cardioverter-defibrillator (ICD). This device can terminate ventricular tachycardia by antitachycardia pacing as well as defibrillate ventricular fibrillation, should it occur. In the areas of the world with limited resources, amiodarone is the antiarrhythmic of choice for such patients. Sotolol can be substituted if amiodarone toxicity occurs. Non-sustained ventricular tachycardia, without syncope. In patients referred for tertiary care, non-sustained ventricular tachycardia without syncope has been found to be a risk factor for sudden death. However, in the asymptomatic or only mildly symptomatic patient, managed in the community, non-sustained ventricular tachycardia has not been found to be an important risk factor. Treatment of asymptomatic runs of ventricular tachycardia is controversial; some advocate prophylactic treatment with amiodarone (26). However, no controlled trials of this strategy have been done. Patients who have HCM symptoms, who have frequent, long runs of non-sustained ventricular tachycardia, and who also have other risk factors such as a positive family history for sudden death, exercise induced hypotension, a high gradient, or massive hypertrophy with a segment > 35 mm thick should be considered for prophylactic ICD implantation. Conclusion Medical therapy for patients with HCM is a rewarding endeavor for the clinician. There are no other syndromes in clinical cardiology where severe intraventricular pressure gradients and their symptoms can be abolished with medication. Antiarrhythmic therapy with amiodarone is often successful for atrial and ventricular arrhythmias alike, although with the price of side effects. Perhaps the future will bring better treatment for diastolic dysfunction, identification and preventative treatment of patients at risk for sudden death, and with progress in gene therapy, curative intervention. References 1. 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