Events in the cardiac arrhythmia suppression trial: baseline predictors of mortality in placebo-treated patients.

Patients randomized to placebo in the encainide and flecainide arms of the Cardiac Arrhythmia Suppression Trial (CAST) have been found to have a relatively low 1-year mortality rate of 3.9% in comparison with previous studies of patients in the postmyocardial infarction period. To determine the comparability of CAST with previous studies, baseline variables were examined in the 743 patients randomized to placebo in the flecainide and encainide arms of CAST. Twenty-three baseline characteristics were correlated with major outcome events: arrhythmic death (16 events), total mortality (26 events) and congestive heart failure (51 events). On multivariate analysis the risk of new or worsening congestive heart failure was significantly associated with diuretic use, diabetes, high New York Heart Association functional class, age, prolonged QRS duration and low ejection fraction. The risk of arrhythmic death or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, history of heart failure, use of digitalis, diabetes and prolonged QRS duration. Total mortality or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, diabetes, ST segment depression, high functional class, prolonged QRS duration and low ejection fraction. The variables at baseline associated with mortality from all causes or arrhythmic death or resuscitated cardiac arrest and heart failure in the CAST placebo-treated patients are similar to those identified in previous postmyocardial infarction studies. Thus, the observation of increased mortality in CAST associated with the administration of encainide and flecainide for suppression of ventricular premature depolarizations is probably applicable to any comparably defined group of patients in the postmyocardial infarction period.

Efficacy and safety of pravastatin in African Americans with primary hypercholesterolemia.

BACKGROUND: Coronary artery disease strikes early and may prove particularly severe in persons of African-American descent. Therefore, we studied the lipid-lowering efficacy and safety of pravastatin sodium (20 mg/d), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in 245 African-American patients with primary hypercholesterolemia. METHODS: After 4 weeks on an American Heart Association phase I low-fat diet, patients were randomized in a double-blind manner to either pravastatin or placebo in a 3:1 ratio. RESULTS: After 12 weeks of pravastatin treatment, low-density lipoprotein cholesterol levels declined 25.8%, total cholesterol levels 20.3%, and triglyceride levels 6.2%, while high-density lipoprotein cholesterol levels remained essentially unchanged. Overall, 72% of pravastatin-treated patients achieved reductions in low-density lipoprotein cholesterol level in excess of 20%, and 44% attained declines in excess of 30% (both P < .01 vs placebo). Pravastatin was generally well tolerated in this population, with one patient (0.5%) exhibiting a reversible myopathy with creatine kinase elevations to 10 times the upper limit of normal. No substantial elevations of aminotransferase levels of two to three times the upper limit of normal occurred in either the pravastatin or the placebo group. Drug compliance was high, exceeding 90%. CONCLUSION: Pravastatin appears to be an effective and safe lipid-lowering agent and is the first 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be studied extensively in this underrepresented population.

Time course of regression of left ventricular hypertrophy in treated hypertensive patients.

In a prospective study, 32 hypertensive patients with echocardiographic evidence of left ventricular hypertrophy were treated with methyldopa, hydrochlorothiazide, or methyldopa and hydrochlorothiazide combined. Echocardiograms and electrocardiograms were obtained in each of the 32 patients before treatment, at the point of initial blood pressure control, and then one, three, and six months thereafter; in 27 patients these studies were also obtained after 12 and 18 months. Left ventricular end-diastolic posterior wall thickness decreased in seven patients whose blood pressure was controlled with methyldopa alone (p less than 0.01) and in 17 patients whose blood pressure was controlled with methyldopa and hydrochlorothiazide combined (p less than 0.01); in both groups, the reduction in left ventricular posterior wall thickness at end-diastole was apparent one month after blood pressure control was established (p less than 0.05). In contrast, no significant reduction in left ventricular posterior wall thickness at end-diastole was observed in eight patients who had equivalent control of blood pressure with hydrochlorothiazide alone (p = 0.34). During the 18-month follow-up period, ventricular septal thickness at end-diastole decreased in the group treated with methyldopa and hydrochlorothiazide combined (p = 0.03); whereas, ventricular septal thickness at end-diastole appeared to increase in the group treated with hydrochlorothiazide alone (p less than 0.01). These results suggest that evidence of regression of left ventricular hypertrophy may be detected as early as one month after blood pressure is controlled with methyldopa or methyldopa and hydrochlorothiazide combined; whereas, long-term control of hypertension with hydrochlorothiazide alone was not associated with evidence of regression of left ventricular hypertrophy. Although the patient number are small, these data suggest that there are differences in the long-term effects of diuretics and sympatholytic drugs on left ventricular anatomy, which may, in part, relate to divergent effects on the sympathetic nervous system.

Systolic honks in young children.

Three children with loud systolic honks were studied noninvasively with phonocardiography and echocardiography. It was shown that the precordial honk, like the late systolic mitral murmur and the clicking apical systolic sound, is part of a continuum of auscultatory sounds that result from a defect of mitral valve support and are classified under the general heading of mitral valve prolapse syndrome. Prolapse of one or both of the mitral valve leaflets is believed to cause the characteristic auscultatory findings of click, murmur or honk. The timing of these sounds in systole varies with different physiologic or pharmacologic maneuvers. Variations in the onset of prolapse are associated with changes in left ventricular end-diastolic dimensions.

Transcutaneous method of measuring Doppler cardiac output--I. Comparison of transcutaneous and juxta-aortic Doppler velocity signals with catheter and cuff electromagnetic flowmeter measurements in closed and open chest dogs.

Cardiac output values obtained by thermodilution technique in 20 closed and open chest dogs were compared with values obtained by multiplying the integral of Doppler systolic velocity signals of aortic flow in 1 minute by the cross-sectional area of the aortic root. Doppler velocity signals were measured either from immediately outside the proximal aortic wall or from outside the chest wall during (1) the baseline state, (2) after 500 ml of hemorrhage, and (3) after reinfusion, (4) after administration of propranolol, and (5) during infusion of dopamine. In addition, Doppler "stroke volume" waveforms were compared with those obtained by electromagnetic flowmeter. Results showed a close similarity between Doppler signals and electromagnetic waveforms, and a close correlatin between Doppler and thermodilution values for cardiac output except at heart rates exceeding 160 beats/min. The studies showed the transcutaneous Doppler method of measuring cardiac output to be an accurate and reliable technique with application to clinical heart disease.

Echocardiogram of the porcine aortic bioprosthesis in the mitral position.

Echocardiography was performed in 10 consecutive patients who had a clinically normally functioning porcine aortic bioprosthesis in the mitral position. Strong well defined echoes were recorded from the anterior and posterior aspects of the xenograft stent. The maximal separation of the anterior and posterior stent echoes approximated the diameter of the stent at its base. The maximal excursion of the anterior stent was 5 to 10 mm (mean 7.5) with a mean systolic slope of 15 to 35 mm/sec (mean 22.2) and diastolic slope of 11 to 59 mm/sec (mean 21.5). In all 10 patients it was possible to record an anterior xenograft leaflet with anterior movement at the onset of diastole and posterior movement at the onset of systole and with appropriately steep (more than 200 mm/sec) slopes. The diastolic (E-F) slope of the anterior leaflet in 9 of the 10 patients ranged from 9 to 38 mm/sec (mean 19). In 6 of the 10 patients a posterior xenograft leaflet with a movement pattern symmetric with that of the anterior leaflet was recorded. In two patients, the central aortic leaflet was recorded with little diastolic displacement. These two patients also had mild aortic regurgitation, which was associated with diastolic shudder of the xenograft leaflets. Echocardiography was also performed in one patient who was later shown to have a 10 cm3 thrombus on the ventricular surface of a xenograft valve. The echocardiogram in this patient revealed the following abnormalities: (1) excessive anterior stent movement and systolic slope suggesting paravalvular leak in the presence of abnormal cinefluoroscopic valve tilt, and (2) multiple dense nonhomogeneous echoes between the anterior and posterior aspects of the valve stent, with an early diastolic clear space behind the anterior stent and abnormal echoes behind the posterior stent during systole. Echocardiography therefore appears to be useful in evaluating the porcine aortic bioprosthesis in the mitral position.

Echocardiographic diagnosis of tetralogy of Fallot.

The echocardiographic features of tetralogy of Fallot were defined in 25 patients with this malformation proved by cardiac catheterization. The echocardiographic characteristic that was present in all patients and that was most sensitive was the abrupt ending of the interventricular septal echoes with the aorta overriding the ventricular septal defect. The following additional echocardiographic features were frequently demonstrated in these 25 patients: right ventricular enlargement (20 patients), hypertrophy of the interventricular septum (20 patients), diminution of the right ventricular outflow tract (21 patients) and widening of the aorta (24 patients). The suggestion is made that the most specific echocardiographic pattern of tetralogy of Fallot is the finding of several echocardiographic abnormalities rather than the single feature of aortic overriding. Recognition of the altered anatomic relation coupled with a complete echocardiographic evaluation of all cardiac structures is a reliable means of diagnosing tetralogy of Fallot.

Echocardiographic study of cardiac dimensions and function in the endurance-trained athlete.

Adaptive cardiac responses to isotonic training were studied with echocardiographic measurement of cardiac dimensions and function in 20 endurance runners whose maximal aerobic capacity on the treadmill was 4.88 +/- 0.13 (mean standard error of mean) liters of oxygen/min. They were compared with 26 young sedentary control subjects whose capacity was 3.34 +/- 0.11 liters of oxygen/min (P less than 0.001). A modest degree of right and left ventricular chamber enlargement and left ventricular hypertrophy was observed in endurance runners (left ventricular mass index 140 +/- 6 g/m2 compared with 107 +/- 4 g/m2 in sedentary control subjects, (P less than 0.001). Resting heart rate was slower in endurance runners (51 +/- 2 versus 62 +/- 2 beats/min, P less than 0.001) and resting left ventricular function as evaluated with ejection fraction and maximal posterior wall shortening velocity and mean circumferential shortening velocity (VCF) was comparable or slightly depressed in endurance runners (0.98 +/- 0.03 versus 1.02 +/- 0.05 circumferences/sec [difference not significant]). This study suggests that isotonic training results in adaptive changes in ventricular volume and mass, slower heart rates that may be associated with more efficient pumping function (that is, increasing stroke volume) and insignificant alterations in resting ejection phase indexes of left ventricular function.

Reversal of left ventricular hypertrophy by drug treatment of hypertension.

Both essential hypertension and the development of left ventricular hypertrophy are multifactorial. Several types of hypertrophy may develop. There is evidence that different agents used to treat hypertension may cause varying degrees of regression of left ventricular hypertrophy. In many instances in which regression of left ventricular hypertrophy has occurred in human subjects, there has been an associated improvement in echocardiographic evidence of ventricular function. Although most current evidence suggests that therapy should aim at both the control of blood pressure and the regression of left ventricular hypertrophy, one should be aware that an individual who is successfully treated for hypertension with a regimen that also produces regression of the compensatory left ventricular hypertrophy may be more susceptible to left ventricular failure if the severe hypertension should ever recur from whatever cause.

Echocardiography in the diagnosis of idiopathic hypertrophic subaortic stenosis coexisting with pericardial effusion.

Of 89 patients with idiopathic hypertrophic subaortic stenosis who had M-mode echocardiagrams recorded, seven patients with coexisting moderate to large pericardial effusions were identified. The clinical profile, M-mode echocardiograms, and cardiac catheterization and angiocardiographic studies in two of the seven patients were analyzed. That the two entities were not associated was suggested by the identification of an etiology for the pericardial effusion in four of the patients. Although the "swinging heart" phenomenon was exhibited in the echocardiograms of each patient, the presence of a significant pericardial effusion did not preclude the ability to establish a diagnosis of idiopathic hypertrophic subaortic stenosis by M-mode echocardiography.

Aortic and mitral valve replacement in a patient with osteogenesis imperfecta.

We report a patient with severe aortic and mitral regurgitation secondary to osteogenesis imperfecta who successfully underwent double valve replacement in spite of the collagen defect and a bleeding diathesis.

A technique for unknotting an intracardiac flow-directed balloon catheter.

Described is an unusual complication occurring during right-sided cardiac catheterization using a 7F flow-directed balloon catheter. During an attempt to direct the catheter from the main pulmonary artery into the pulmonary wedge position, the tip became entangled in a loop of catheter and knotted. Initially, all attempts to unknot or remove the catheter failed. A movable core guide wire was passed through the major lumen of the catheter, resulting in the immediate unknotting of the catheter, thus allowing its withdrawal.

Idiopathic perforation of a porcine aortic bioprosthesis in the aortic position.

The report of a failure of glutaraldehyde-preserved porcine aortic xenograft bioprosthesis in the aortic position after 13 months is presented. Severe aortic regurgitation resulted from three "idiopathic" perforations in one of the cusps, and a linear tear in another cusp. Light and electron microscopy showed generalized degeneration of collagen thoughout the faulty valve. The absence of a platelet-fibrin coat on edges of the tear suggested a recent origin, compatible with cardiac catheter manipulation during unsuccessful attempts to cross the valve. The histopathologic data from this valve correlate with previously reported failures with formaldehyde preserved xenograft valves.

Current therapeutic options for the patient with a recent myocardial infarction.

The treatment of acute myocardial infarction continues to change rapidly. The mortality of many subgroups of patients sustaining acute myocardial infarction has significantly decreased. Current therapeutic modalities provide the physician with many agents that favorably influence the course of acute myocardial infarction. Improving diagnostic techniques provide the physician with the means to identify subsets of patients who are at very low risk or very high risk of recurrent myocardial infarction and to improve the management of these subsets.

The echocardiographic association of mitral valve prolapse and mitral anulus calcification.

Mitral anulus calcification (MAC) and mitral valve prolapse (MVP) are frequently diagnosed conditions. We studied two patients with mild or moderate mitral regurgitation who demonstrated both MAC and MVP on angiography and echocardiography. M-mode echocardiography is probably the definitive test for confirming the presence of MVP. Echocardiography is moderately sensitive in the diagnosis of cardiac calcification, such as MAC, but M-mode echocardiography may not detect the MAC in the majority of patients with both MVP and MAC demonstrated by angiography.

Mitral valve prolapse.

Mitral valve prolapse (MVP) now is a commonly recognized syndrome with an apparent prevalence of approximately 4-6%. It appears to occur more frequently in females and occasionally it is familial. In most instances, the syndrome is idiopathic, although it occurs in association with many other conditions, particularly Marfan's syndrome, rheumatic heart disease, coronary heart disease, congestive cardiomyopathy, ostium secundum atrial septal defect, Ehlers-Danlos syndrome or abnormalities of the thoracic cage. The majority of patients with the syndrome have minimal, if any, symptoms and have a benign course. When symptoms do occur, more frequently they are palpitations, chest pain, dyspnea on exertion or fatigue. Neuropsychiatric symptoms or even transient ischemic episodes may occur rarely. Very rarely, complications such as severe mitral regurgitation, arrhythmias or infective endocarditis may occur. Characteristically, patients have a midsystolic click, occasionally followed by a systolic murmur. The timing of the click and the onset of the murmur usually is variable, depending on the ventricular volume. The electrocardiogram frequently shows ST-T wave changes. The diagnosis usually can be confirmed by echocardiography or left ventricular angiography. Most patients with MVP require no treatment other than reassurance. If a systolic murmur is present, prophylaxis against infective endocarditis during dental work probably is useful. Patients with palpitations or chest pain usually respond well to treatment with propranolol. Patients with progressive severe mitral regurgitation require mitral valve replacement.