Homozygous mutation in cardiac troponin T: implications for hypertrophic cardiomyopathy.

BACKGROUND: Mutations in the gene that encode cardiac troponin T (cTnT) account for approximately 15% of cases of familial hypertrophic cardiomyopathy (HCM). These mutations are associated with a particularly severe form of HCM characterized by a high incidence of sudden death and a poor overall prognosis, despite subclinical or mild left ventricular hypertrophy. METHODS AND RESULTS: We evaluated a family with HCM and multiple occurrences of sudden death in children. DNA samples were isolated from peripheral blood or paraffin-embedded tissue, and all protein-encoding exons of the cTnT gene were sequenced. A mutation was identified in exon 11 and is predicted to substitute a phenylalanine-for-serine mutation at residue 179 (Ser(179)Phe) in cTnT. Both parents and 3 of 4 surviving and clinically unaffected children were heterozygous for this mutation; another clinically unaffected child did not carry the mutation. Genetic analysis of DNA from a child who died suddenly at age 17 years demonstrated he was homozygous for this mutation. A review of his echocardiogram revealed profound left and right ventricular hypertrophy. CONCLUSIONS: An homozygous Ser(179)Phe mutation in cTnT causes a severe form of HCM characterized by striking morphological abnormalities and juvenile lethality. In contrast, the natural history of the heterozygous mutation is benign. These studies emphasize the relevance of genetic diagnosis in hypertrophic cardiomyopathy and provide a new perspective on the clinical consequences of troponin T mutations.

Efficacy and safety of procainamide in preventing arrhythmias after coronary artery bypass surgery.

Arrhythmias are common after cardiac surgery and are associated with hemodynamic compromise, stroke, and prolonged hospitalization. Beta blockers prevent atrial fibrillation postoperatively, but there are few data regarding the prophylactic use of type 1 antiarrhythmic agents or the prevention of ventricular arrhythmias. Accordingly, we performed a randomized, double-blind, placebo-controlled study of the effects of oral procainamide on 100 patients undergoing elective coronary artery bypass surgery. Procainamide was received for 4 days; the dosage was adjusted for body weight. Patients receiving procainamide had a significant reduction in atrial fibrillation (16 vs 29 patient-days, p < 0.05) and ventricular tachycardia (2% vs 20%, p < 0.01). However, the incidence of atrial fibrillation was not significantly reduced (38% vas 26%). In the group achieving therapeutic serum procainamide levels, there was reduction in all measured postoperative arrhythmias. No serious cardiac or noncardiac adverse events were noted during procainamide therapy, although there was a significant increase in the incidence of nausea. We conclude that procainamide reduces arrhythmias in the early postoperative period after coronary artery bypass surgery, most prominently in patients who achieve therapeutic serum levels. This was associated with no serious cardiac adverse reactions.

Fatal intracerebral hemorrhage following thrombolytic therapy of embolic myocardial infarction in unsuspected infective endocarditis.

Cerebral hemorrhage occurs in 0.2% of patients under the age of 60 years treated with thrombolytic therapy for acute myocardial infarction. A case of fatal cerebral hemorrhage following TPA therapy for myocardial infarction due to probable coronary artery embolism during unsuspected native valve infective endocarditis is reported.

Transient left ventricular aneurysm in a patient with hypertrophic cardiomyopathy and myocarditis.

Left ventricular wall motion abnormalities, aneurysm formation, and progression to global hypokinesis have been described in patients with myocarditis and in patients with hypertrophic cardiomyopathy. We document a case of reversible aneurysm formation, cardiogenic shock, and complete recovery in a patient with myocarditis and hypertrophic cardiomyopathy. Pathophysiologic mechanisms of myocardial injury and recovery are discussed.

Stroke following coronary-artery bypass surgery. A case-control estimate of the risk from carotid bruits.

The causes of stroke following coronary-artery bypass surgery are largely unknown. To determine whether carotid bruits increase the risk of these events, we compared 54 patients with postoperative stroke or transient ischemic attacks with 54 randomly selected control patients. Both groups were drawn from 5915 consecutive patients who had coronary bypass surgery at our hospital from 1970 to 1984. Carotid bruits were noted preoperatively in 13 patients with postoperative stroke and in 4 control patients. Case-control analysis showed that the presence of carotid bruits increased the risk of stroke or transient ischemic attacks by 3.9-fold (95 percent confidence interval, 1.2 to 12.8; P less than 0.05). This increased risk remained essentially unchanged after adjustment for potentially confounding variables in a multiple logistic regression analysis. Other factors associated with a significantly increased risk (P less than 0.05) of these neurologic deficits were a history of stroke or transient ischemic attack (odds ratio, 6.0; 95 percent confidence interval, 1.6 to 22.1), a history of congestive heart failure (odds ratio, 5.3; confidence interval, 1.6 to 17.0), mitral regurgitation (odds ratio, 4.3; confidence interval, 1.4 to 12.9), postoperative atrial fibrillation (odds ratio, 3.0; confidence interval, 1.4 to 6.7), a cardiopulmonary-bypass pump time of more than two hours (odds ratio, 2.7; confidence interval, 1.1 to 6.7), and a previous myocardial infarction (odds ratio, 2.3; confidence interval, 1.1 to 5.1). We conclude that the presence of carotid bruits increases the risk of stroke after coronary-artery bypass surgery. However, the absolute magnitude of this risk, 2.9 percent, is small and comparable to the reported risk of stroke from carotid endarterectomy.

Spectrum of conditions initially suggesting acute aortic dissection but with negative aortograms.

Between 1963 and 1983, 55 patients presented to our hospital with a clinical picture that suggested aortic dissection but with aortograms that were interpreted as negative for that entity. In 4 patients, the aortographic findings subsequently proved to be false negative. The remaining 51 patients had the following diagnoses: myocardial infarction in 9 patients; aortic regurgitation in 5; thoracic nondissecting aneurysm in 4; musculoskeletal pain in 4; mediastinal tumor in 4; pericarditis in 3; acute coronary insufficiency in 3; cholecystitis in 2; miscellaneous in 3; and unknown in 14. The clinical features in these patients were compared with those of 125 patients with true aortic dissection. Three features were significantly more prevalent in patients with than without dissection: prior systemic hypertension, pain for 24 hours or less, and migratory pain. Patients without dissection were younger than those with distal dissection and had significantly less systemic hypertension, posterior thoracic pain and migratory pain. Patients without dissection had significantly less frequent congestive heart failure, pulse deficits and aortic regurgitation, and more frequent hypertension and pain for more than 24 hours than patients with proximal dissection. This study defines the actual differential diagnosis of aortic dissection at our hospital, the frequency of false-negative aortographic findings and contrasts the clinical features of patients with and without dissection.

Long-term survival of patients with treated aortic dissection.

Retrospective data on the treatment of aortic dissection at the Massachusetts General Hospital from 1963 to 1978 are reported. During this period, 160 patients with spontaneous aortic dissection were treated by definitive medical or definitive surgical therapy. Patients were classified according to type (proximal versus distal) and duration (acute versus chronic) of dissection. Long-term follow-up (mean 48 months, range 1 to 147) was available in 156 cases. Hospital and late survival in each of the categories of dissection were evaluated in relation to those features of the dissection itself and of the subsequent therapy that correlated with ultimate survival. Results show that: 1) chronic presentation was the most significant determinant of both hospital and late survival; 2) in acute dissection, prognosis was determined largely by the presence or absence of major complications, regardless of ultimate therapy; the only complication without adverse effect on survival was aortic insufficiency; 3) late survival after discharge from the hospital was similar for patients with all types of dissection and modes of therapy; and 4) the incidence of late complications from aortic dissection was lower than previously reported. Thus, the success of early definitive medical and surgical treatment was sustained on long-term follow-up.