Evidence that pharmacological strategies lack efficacy for the prevention of sudden death in hypertrophic cardiomyopathy.

OBJECTIVE: To determine the efficacy of pharmacological treatment in the prevention of sudden cardiac death in hypertrophic cardiomyopathy (HCM). DESIGN: Clinical outcome was assessed retrospectively in 293 patients with HCM, including 173 who were taking cardioactive medications. SETTING: Department of Cardiology, University of Padua, Padua, Italy; a tertiary HCM Centre. INTERVENTIONS: Medical treatment with beta blockers, verapamil, sotalol and amiodarone. MAIN OUTCOME MEASURE: HCM-related sudden cardiac death. RESULTS: 17 of 173 (10%) patients died suddenly or had aborted cardiac arrest, while being treated continuously with drugs having antiarrhythmic properties, over a period of 62 (56) months. Sudden death occurred in 20% of patients administered amiodarone (6/30), 9% each of patients taking verapamil (4/46) or beta blockers (7/76), and 0% of those taking sotalol (0/21). Patients taking cardioactive drugs (n = 173) and those without pharmaceutical therapy (n = 120) did not differ with respect to sudden death mortality. CONCLUSION: Medical treatment is not absolutely protective against the risk of sudden death in HCM. The present data inferentially support the use of the implantable defibrillator as the primary treatment choice for prevention of sudden death in high-risk patients with HCM.

Bosentan therapy of pulmonary arterial hypertension in connective tissue diseases.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening and debilitating complication of several connective tissue diseases. We aimed to evaluate the effects of long-term treatment with bosentan, an oral dual endothelin ET(A)/ET(B) receptor antagonist, in a cohort of patients with PAH related to connective tissue diseases. MATERIALS AND METHODS: In the present prospective, noncontrolled study, 13 patients (nine with systemic sclerosis, two with systemic lupus erythematosus, one with mixed connective tissue disease and one with overlap syndrome including scleroderma and myositis), mostly nonresponders to prostanoids therapy, were treated for 1 year with bosentan. Cardiac haemodynamics and the diagnosis of PAH were performed by Doppler ultrasound examination. Exercise capacity was assessed by 6-min walking test at baseline and at 3, 6 and 12 months of therapy. RESULTS: During bosentan treatment, progressive improvement of exercise capacity was observed. Walk distance increased in seven patients, remained unchanged in three and slightly decreased in three patients. A progressive significant decrease of right ventricular systolic pressure was also observed, whereas pulmonary artery mean pressure remained unchanged. Adverse effects related to bosentan (elevation of hepatic aminotransferases) were noted in two patients. CONCLUSION: Long-term treatment with bosentan was effective in improving exercise capacity and pulmonary haemodynamics in patients with PAH related to connective tissue diseases.

Ventricular arrhythmias and autonomic profile in patients with primary pulmonary hypertension.

The aim of our study was to assess the arrhythmic profile in patients with primary pulmonary hypertension (PPH) and its correlation with autonomic features, echocardiographic indexes and pulmonary function. We studied 9 subjects with a mean age of 42 +/- 11 years. All underwent echocardiography, 24-hour Holter monitoring, and cardiopulmonary exercise testing. Left ventricle ejection fraction was normal (65 +/- 6%). The right ventricle end diastolic volume was increased (108 +/- 32 ml/m2) with a slight reduction of ejection fraction (49 +/- 5%). Right ventricle systolic pressure was increased (91 +/- 25 mmHg). Heart rate variability analysis showed evidence of a reduced standard deviation of all NN intervals (SDNN) compared with the control group (102.8 +/- 32 versus 156.1 +/- 32, p < 0.005). Patients with significant ventricular arrhythmias had a lower SDNN, and lower baseline and effort PO2 (SDNN: 87.0 +/- 15 versus 115.4 +/- 38; baseline PO2: 63.2 +/- 12% versus 78.8 +/- 7%; effort PO2: 50.7 +/- 13% versus 68.7 +/- 19%). The patients with SDNN lower than 90 ms were characterized by a higher right ventricle systolic pressure (115.0 +/- 22.9 mmHg versus 79.2 +/- 17.8 mmHg, p = 0.035). The patients who experienced syncope had higher SDNN (131.7 +/- 36 versus 88.4 +/- 20, p < 0.05), higher effort PO2 (77.5 +/- 14 mmHg versus 52.3 +/- 14 mmHg, p < 0.03). The patients with PPH evidenced an increased sympathetic activity. Premature ventricular beats were more frequent in those subjects with higher adrenergic drive and lower oxygen saturation. Patients with episodes of syncope seem to have a relatively higher vagal activity, and effective mechanisms of adjustment in blood oxygenation during effort.