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.

Effect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial. Prospective Randomized Amlodipine Survival Evaluation.

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.

Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group.

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.

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 greater than 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 greater than 10 cm 2 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.

Quantification of mitral regurgitation: a comparison of transesophageal echocardiography and contrast ventriculography.

Transesophageal echocardiography (TEE) allows an unobscured view of the left atrium for the assessment of mitral regurgitation (MR). However, criteria for assessing MR by TEE have not been carefully validated. In order to determine and validate criteria for the assessment of MR severity, 65 clinically stable patients with a TEE color Doppler study and contrast ventriculography within a 2-week period were identified. Maximal or peak mitral regurgitation jet area to left atrial area ratio (MR/LA) derived solely from TEE imaging had the best correlation to MR severity by contrast ventriculography (r = 0.89). Utilizing MR jet area without correction for LA size resulted in r = 0.72 to 0.75. Utilizing LA area data from transthoracic echocardiograms in a subset of 29 patients resulted in r = 0.77. Best sensitivity and specificity for the assessment of MR by TEE were obtained using the following criteria: Peak MR/LA of 0%-9% predicts 0 + MR; 10%-28% 1 + MR; 29%-54% 2 + to 3 + MR; and greater than 55% 4 + MR. Best sensitivity and specificity occurs for assessment of 0 + and 4 + MR. Considerable overlap in data occurs in the 1 + and 3 + MR range utilizing the above stated criteria. Peak MR/LA ratio derived from a single TEE view in which the MR jet is maximally imaged is the best determinant of MR severity.

Pericardial tamponade associated with pacemaker catheter manipulation.

Three patients developed cardiac tamponade following postpacemaker catheter manipulation. Although regarded as a rare complication, this entity has to be recognized immediately on clinical grounds and confirmed by echocardiography. Prompt recognition and urgent pericardial drainage is lifesaving in this acute cardiac emergency.

Conjunctival oxygen monitoring: relationship to ventricular arrhythmias.

The results of conjunctival oxygen monitoring in a critically ill patient whose cardiac rhythm changed from sinus tachycardia to ventricular tachycardia and ventricular fibrillation and back to sinus tachycardia are described. Monitoring revealed a significant decrease in conjunctival oxygen tension 2 minutes before ventricular tachycardia was manifested by continuous electrocardiography, and an immediate rise in conjunctival oxygen tension was seen with the resumption of sinus tachycardia. This monitoring modality may be a useful adjunct in the hemodynamic evaluation of critically ill patients.

High risk percutaneous transluminal coronary angioplasty in the treatment of severe coronary artery disease.

We report on 27 "high risk" patients out of 171 consecutive patients undergoing percutaneous transluminal coronary angioplasty from June 1984 to August 1985. The ages ranged from 31-80 years (mean 62.7 +/- 10) years. High risk percutaneous transluminal coronary angioplasty was defined as: salvage cases (3 patients) where the patients presented in cardiogenic shock or the vessels were not bypassable; multivessel coronary artery disease (22 patients) where a large area of jeopardized myocardium was dependent on the angioplasty vessel(s); left ventricular dysfunction (7 patients) as defined by two of the three criteria: left ventricular end-diastolic volume index greater than 100 ml/m2; ejection fraction less than 30%; and left ventricular end-diastolic pressure greater than 20 mm Hg. The initial success rate in the high risk patients was 85.2%. Emergency coronary artery bypass surgery in these patients was 7.4%. There was one death in the high risk group, as one of the salvage cases died 24 hours after successful percutaneous transluminal coronary angioplasty due to severe underlying myocardial disease. In conclusion percutaneous transluminal coronary angioplasty can be successfully performed in high risk patients with a low complication rate and should be considered as an alternative to coronary artery bypass graft surgery in selected high risk patients.

Percutaneous transluminal coronary angioplasty of the "very proximal" coronary artery stenosis.

We report on 11 patients with "very proximal" lesions out of a total of 300 consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA). Eight patients had native left anterior descending (LAD) lesions and three had LAD saphenous vein grafts lesions. Lesions were considered to be "very proximal" when one half or more of the balloon was inflated in the left main coronary artery for the native LAD lesions or the aorta for the LAD coronary artery saphenous vein bypass graft (CABG) lesions. There was a mean reduction in stenosis from 88.3% (range 75-99) to 13.8% (range 0-60) and a mean reduction in transtenotic gradient from 47.2 mmHg (range 20-80) to 8.3 mmHg (range 0-20). The initial success rate was 90.9% (10 out of 11 patients) with a partial success in the other patient. No complications occurred in any of the patients. Two patients had restenosis (18.2%) at 3 months and 6 months, respectively, post-PTCA. It is concluded that "very proximal" lesions can be successfully dilated with a high initial success rate and low complication rate. Nevertheless, these lesions may present problems with guiding catheter stability and, because of the potential risk of circumflex (CX) occlusion, this vessel may have to be protected with a second guidewire.

"Crossing balloons:" a new technique for complex angioplasty.

A new technique is described for complex percutaneous transluminal coronary angioplasty of a lesion at the bifurcation of the obtuse marginal branch of the left coronary artery, just distal to a venous bypass graft insertion. Two separate angioplasty guide wire and catheter systems were used and the coronary artery side branch was protected in a "crossing" manner.

A new device and method for rapid emergency pacing: clinical use in 10 patients.

A new multipurpose transthoracic pacing device is described that will simultaneously enable transthoracic electrode insertion, intracardiac drug infection, and blood sample removal for blood gas determination, all via a single myocardial needle insertion. The device proved efficacious and safe in trials in an animal model. In clinical use in 10 emergency room patients with brady-asystolic cardiac arrest, pacing was achieved in all 10 with one short-term survivor. Median insertion time was 30 seconds. Median threshold in 6 patients was 2.5 mA (1 to 6). This new device enables reliable and rapid emergency treatment of brady-asystolic cardiac arrest.

Efficacy of nifedipine in rest angina refractory to propranolol and nitrates in patients with obstructive coronary artery disease.

Nineteen patients with recurrent rest angina were given oral nifedipine. All patients had chest discomfort refractory to propranolol and oral or topical nitrates given to tolerance. The addition of nifedipine, 30 to 120 mg daily, abolished rest angina in 14 patients, decreased its frequency in two, and had no effect in three patients. Five of seven patients on long-term nifedipine (mean, 6.2 +/- 3.4 months) remained free of rest pain. Of seven patients who had their nifedipine dose decreased or discontinued, five had recurrent rest angina. Of the 19 patients, 16 had coronary angiography. Five had three- vessel obstructive disease (greater than 75% lesion), six had two-vessel obstructive disease, and five had one-vessel obstructive disease. The remaining three unstudied patients had pathologic Q waves in the ECG. Thus nifedipine appears to be an efficacious agent in the treatment of refractory rest angina in patients with obstructive coronary artery disease.