John H. Wertheimer

Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: Results of the survival and ventricular enlargement trial

BACKGROUND Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, longterm therapy with the angiotensin-converting--enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. METHODS Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive doubleblind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. RESULTS Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group. The reduction in risk was 21 percent (95 percent confidence interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37 percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for the development of severe heart failure, 22 percent (95 percent confidence interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent; P = 0.015) for recurrent myocardial infarction. CONCLUSIONS In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction.

Effect of Captopril on Mortality and Morbidity in Patients with Left Ventricular Dysfunction after Myocardial Infarction

BACKGROUND Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, longterm therapy with the angiotensin-converting--enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. METHODS Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive doubleblind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. RESULTS Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group. The reduction in risk was 21 percent (95 percent confidence interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37 percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for the development of severe heart failure, 22 percent (95 percent confidence interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent; P = 0.015) for recurrent myocardial infarction. CONCLUSIONS In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction.

Effect of Amlodipine on Morbidity and Mortality in Severe Chronic Heart Failure

BACKGROUND Previous studies have shown that calcium-channel blockers increase morbidity and mortality in patients with chronic heart failure. We studied the effect of a new calcium-channel blocker, amlodipine, in patients with severe chronic heart failure. METHODS We randomly assigned 1153 patients with severe chronic heart failure and ejection fractions of less than 30 percent to double-blind treatment with either placebo (582 patients) or amlodipine (571 patients) for 6 to 33 months, while their usual therapy was continued. The randomization was stratified on the basis of whether patients had ischemic or nonischemic causes of heart failure. The primary end point of the study was death from any cause and hospitalization for major cardiovascular events. RESULTS Primary end points were reached in 42 percent of the placebo group and 39 percent of the amlodipine group, representing a 9 percent reduction in the combined risk of fatal and nonfatal events with amlodipine (95 percent confidence interval, 24 percent reduction to 10 percent increase; P=0.31). A total of 38 percent of the patients in the placebo group died, as compared with 33 percent of those in the amlodipine group, representing a 16 percent reduction in the risk of death with amlodipine (95 percent confidence interval, 31 percent reduction to 2 percent increase; P=0.07). Among patients with ischemic heart disease, there was no difference between the amlodipine and placebo groups in the occurrence of either end point. In contrast, among patients with nonischemic cardiomyopathy, amlodipine reduced the combined risk of fatal and nonfatal events by 31 percent (P=0.04) and decreased the risk of death by 46 percent (P<0.001). CONCLUSIONS Amlodipine did not increase cardiovascular morbidity or mortality in patients with severe heart failure. The possibility that amlodipine prolongs survival in patients with nonischemic dilated cardiomyopathy requires further study.

Effect of amlodipine on mode of death among patients with advanced heart failure in the praise trial

Investigations of calcium antagonists in patients with advanced heart failure have raised concern over an increased risk of worsening heart failure and heart failure deaths. We assessed the effect of amlodipine on cause-specific mortality in such patients enrolled in a randomized, double-blind, placebo-controlled trial. In total, 1,153 patients in New York Heart Association class IIIb or IV heart failure were randomized to receive amlodipine or placebo, along with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median 14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for 89% of fatalities, 50% of which were sudden deaths and 45% of which were due to pump failure, with fewer attributed to myocardial infarction (3.3%) or other cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When patients were classified by etiology of heart failure (ischemic or nonischemic), cause-specific mortality did not differ significantly between treatment groups in the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus, when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors in patients with advanced heart failure, amlodipine appears to have no effect on cause-specific mortality in ischemic cardiomyopathy, but both pump failure and sudden deaths appear to be decreased in nonischemic heart failure patients treated with amlodipine.

Circadian rhythm and sudden death in heart failure: results from Prospective Randomized Amlodipine Survival Trial.

OBJECTIVE The purpose of this study was to address the timing of sudden death in advanced heart failure patients. BACKGROUND Sudden death is a catastrophic event in cardiovascular disease. It has a circadian pattern prominent in the early AM, which has been thought to be due to a surge of sympathetic stimulation. We postulated that the distribution of events in advanced heart failure, with chronic sympathetic activation, would be more uniform implicating other potential mechanisms. METHODS We analyzed data from Prospective Randomized Amlodipine Survival Trial (PRAISE). Sudden deaths were analyzed by time of death in 4-h and 1-h blocks for uniformity of distribution in the entire cohort, and in the prespecified ischemic and nonischemic stratum. Further analyses were undertaken in the treatment groups of amlodipine and placebo, and among those receiving background therapy of aspirin and warfarin. RESULTS Sudden deaths in the overall cohort showed a nonuniform distribution with a PM peak but not an AM peak. The ischemic stratum also showed a PM peak, but sudden deaths within the nonischemic stratum were uniformly distributed. Neither amlodipine treatment nor aspirin or warfarin use altered the distribution. CONCLUSIONS Sudden death in advanced heart failure did not show an AM peak, suggesting that circadian sympathetic activation did not strongly influence these events. The PM peak noted is likely complex in origin and was not affected by antiischemic or antithrombotic medications.

The STICH trial (Surgical Treatment for Ischemic Heart Failure): mode-of-death results.

OBJECTIVES This study sought to assess the effect of the addition of coronary artery bypass grafting (CABG) to medical therapy on mode of death in heart failure. BACKGROUND Although CABG therapy is widely used in ischemic cardiomyopathy patients, there are no prospective clinical trial data on mode of death. METHODS The STICH (Surgical Treatment for Ischemic Heart Failure ) trial compared the strategy of CABG plus medical therapy to medical therapy alone in 1,212 ischemic cardiomyopathy patients with reduced ejection fraction. A clinical events committee adjudicated deaths using pre-specified definitions for mode of death. RESULTS In the STICH trial, there were 462 deaths over a median follow-up of 56 months. The addition of CABG therapy tended to reduce cardiovascular deaths (hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.68 to 1.03; p = 0.09) and significantly reduced the most common modes of death: sudden death (HR: 0.73; 95% CI: 0.54 to 0.99; p = 0.041) and fatal pump failure events (HR: 0.64; 95% CI: 0.41 to 1.00; p = 0.05). Time-dependent estimates indicate that the protective effect of CABG principally occurred after 24 months in both categories. Deaths post-cardiovascular procedures were increased in CABG patients (HR: 3.11; 95% CI: 1.47 to 6.60), but fatal myocardial infarction deaths were lower (HR: 0.07; 95% CI: 0.01 to 0.57). Noncardiovascular deaths were infrequent and did not differ between groups. CONCLUSIONS In the STICH trial, the addition of CABG to medical therapy reduced the most common modes of death: sudden death and fatal pump failure events. The beneficial effects were principally seen after 2 years. Post-procedure deaths were increased in patients randomized to CABG, whereas myocardial infarction deaths were decreased.

Cardiac tamponade following perforation of the left anterior descending coronary system during percutaneous transluminal coronary angioplasty: Successful treatment by pericardial drainage

Percutaneous transluminal coronary angioplasty (PTCA) is an effective and increasingly utilized modality in the treatment of coronary artery disease. Its complications include prolonged angina, myocardial infarction, coronary occlusion, dissection, spasm, embolism, and perforation.’ When these complications occur, immediate aortocoronary bypass surgery is usually performed. We report the occurrence of perforation of a diagonal branch of the left coronary artery with associated cardiac tamponade treated successfully in the Cardiac Catheterization Laboratory without surgical repair of the perforated artery. A 69-year-old white man had a 3-week history of chest pain at rest, which was relieved by nitroglycerin. The patient had nonsustained ventricular tachycardia on an otherwise negative exercise thallium examination. Coronary arteriography revealed a 90% stenosis in the mid-left anterior descending coronary artery and multiple areas of noncritical disease in branches of the left circumflex coronary artery (Fig. 1). PTCA of the left anterior descending artery was performed. Following the intra-arterial administration of 10,000 units of heparin, the standard technique employing a No. 9 FL 4 USC1 (USCI, Billerica, Mass.) guiding catheter was used via the right femoral artery. The left anterior descending coronary artery was entered with a standard steerable ACS (Advanced Cardiovascular Systems, Inc., Temeculla, Calif.) guidewire (size 0.014 inch diameter, 175 cm long) and a 2.5 mm ACS dilatation catheter crossed the lesion. Four dilatations, at a maximum pressure of 8 atm and maximum duration of 15 seconds, were performed. In order to better opacify the area of dilatation and in anticipation of the use of a larger-sized dilatation catheter, with the tip of the dilatation catheter held distal to the area of angioplasty, the steerable guidewire was replaced with a 300 cm long ACS exchange guidewire (0.018 inch diameter). The original dilatation catheter was removed. Angiography of the left coronary artery demonstrated successful angioplasty of the left anterior descending lesion and extravasation of contrast into the pericardial cavity at a site near the tip of the exchange guidewire, several centimeters distal to the area of angioplasty and in the area of a small diagonal branch (Fig. 2). The patient was stable hemodynamically,

Surgical Treatment for Ischemic Heart Failure (STICH) Trial: Mode of Death Results

OBJECTIVES This study sought to assess the effect of the addition of coronary artery bypass grafting (CABG) to medical therapy on mode of death in heart failure. BACKGROUND Although CABG therapy is widely used in ischemic cardiomyopathy patients, there are no prospective clinical trial data on mode of death. METHODS The STICH (Surgical Treatment for Ischemic Heart Failure ) trial compared the strategy of CABG plus medical therapy to medical therapy alone in 1,212 ischemic cardiomyopathy patients with reduced ejection fraction. A clinical events committee adjudicated deaths using pre-specified definitions for mode of death. RESULTS In the STICH trial, there were 462 deaths over a median follow-up of 56 months. The addition of CABG therapy tended to reduce cardiovascular deaths (hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.68 to 1.03; p = 0.09) and significantly reduced the most common modes of death: sudden death (HR: 0.73; 95% CI: 0.54 to 0.99; p = 0.041) and fatal pump failure events (HR: 0.64; 95% CI: 0.41 to 1.00; p = 0.05). Time-dependent estimates indicate that the protective effect of CABG principally occurred after 24 months in both categories. Deaths post-cardiovascular procedures were increased in CABG patients (HR: 3.11; 95% CI: 1.47 to 6.60), but fatal myocardial infarction deaths were lower (HR: 0.07; 95% CI: 0.01 to 0.57). Noncardiovascular deaths were infrequent and did not differ between groups. CONCLUSIONS In the STICH trial, the addition of CABG to medical therapy reduced the most common modes of death: sudden death and fatal pump failure events. The beneficial effects were principally seen after 2 years. Post-procedure deaths were increased in patients randomized to CABG, whereas myocardial infarction deaths were decreased.

Lisinopril Versus Placebo in the Treatment of Heart Failure: The Lisinopril Heart Failure Study Group

Lisinopril, a long‐acting, angiotensin‐converting enzyme inhibitor, was compared with placebo in a randomized, parallel, double‐blind, 12‐week study of 193 patients with heart failure. All patients were New York Heart Association Functional Class II, III, or IV and had remained symptomatic despite optimal dosing with digoxin and diuretics. After 12 weeks of therapy, the improvement in treadmill exercise duration was greater in the lisinopril group (113 seconds) compared with the placebo group (86 seconds). This improvement in exercise duration was particularly evident in patients with left ventricular ejection fractions less than 35% (lisinopril = 130 seconds; placebo = 94 seconds). In patients receiving lisinopril, the increase in exercise duration was accompanied by an improvement in quality of life as measured by the Yale Scale Dyspnea/Fatigue Index and in signs and symptoms of heart failure. In addition, the lisinopril group had a larger mean increase (3.7%) in left ventricular ejection fraction when compared with the placebo group (1.3%). Thus, lisinopril, administered once daily for 12 weeks, was well tolerated and efficacious in the treatment of heart failure when used concomitantly with diuretics and digoxin.

Assessment of aortic regurgitation by transesophageal echocardiography: correlation with angiographic determination.

Transthoracic echocardiographic studies have shown that color Doppler mapping of the aortic regurgitation (AR) jet correlated well with the severity of regurgitation as assessed by contrast aortography. The present study was performed to assess whether these parameters could be similarly applied to measurements determined by transesophageal echocardiography (TEE). In order to determine and validate criteria for the assessment of AR severity, 39 clinically stable patients with a TEE color Doppler study and contrast aortography within a 2‐week period were identified. The ratio of the jet area (JA) to left ventricular diastolic area (LVDA) had the best correlation to AR severity as determined by contrast aortography (r = 0.89). Jet length, JA, the ratio of jet width to the width of the left ventricular outflow tract and jet width had r values of 0.88, 0.88, 0.83, and 0.84, respectively. The best sensitivity and specificity for the assessment of AR by TEE were obtained as follows: JA/LVDA ratio of 0%‐7% predicts 0‐1 + AR; 8%‐20% 2‐3 + AR, and > 20% 4 + AR. Of the three patients miscategorized, none was misgraded by more than one angiographic grade of AR. Jets that measure more than 6 cm in length or have an area of > 10 cm2 have a 100% sensitivity and specificity for diagnosing 4 + AR. In the present study the ratio of JA to LVDA area correlates best with AR severity as determined by angiography.