Bepridil hydrochloride compared with placebo in patients with stable angina pectoris.

Bepridil is a calcium antagonist with a unique chemical composition and a long elimination half-life (42 hours). We evaluated the efficacy of bepridil 300 mg once/day in a crossover comparison with placebo in 45 patients with angina. Patients had an average of 7.6 anginal episodes/week during the placebo baseline phase of the trial. After 4 weeks of bepridil therapy, anginal frequency decreased to 2.9 episodes/week (p less than 0.05). Likewise, mean nitroglycerin consumption declined from 7.4 tablets/week during the placebo baseline phase to 4.0 tablets/week during bepridil therapy (p less than 0.05). Statistically significant increases over the previous period (placebo baseline or double-blind placebo) were seen in total exercise time, time to angina, and total work (p less than 0.05). During bepridil therapy, 13 of 45 patients (29%) no longer experienced angina as an exercise end point despite the increase in work and exercise time. Bepridil significantly prolonged both the QT and corrected QT (QTc) intervals; the mean increases were 10.0% and 5.6%, respectively. Side effects were reported with equal frequency in the placebo and bepridil arms of the trial, and no serious side effects were reported. In an intermediate fixed dose of 300 mg/day, bepridil relieved anginal symptoms with few side effects. Bepridil appears to be a safe and effective treatment for stable angina.

Echocardiographic criteria to distinguish reversible from irreversible myocardial ischaemia.

This treatise reviews two-dimensional echocardiographic criteria which have been developed to describe and distinguish reversible vs irreversible myocardial ischaemia. It also discusses the new pathophysiologic concepts such as 'hibernating' and 'decapitated' myocardium, and also 'reperfusion injury' and 'stunned' myocardium, complications which may supervene following reperfusion of jeopardized ischaemic myocardium. Computerized regional and global wall-motion analysis is now usually measured from enhanced endocardial edges. Provocative interventions can contribute information regarding viability of jeopardized ischaemic regions by testing contractile response of the myocardium to afterload reducing agents such as nitroglycerine or nitroprusside. They can also validate viability by demonstrating that post-extrasystolic beats can still cause potentiation. Ultrasonic contrast washout half-life of the myocardium which is compromised by stenotic coronary arteries provides a promising method for supplying information about the coronary perfusion defects and flow reserve. The decrease in global or regional ejection fraction following exercise echocardiography may show if jeopardized ischaemic myocardium is irreversibly damaged. A new hypercontractility phenomenon is described following brief coronary occlusions such as during percutaneous transluminal angioplasty, or after sudden release of angiospasm, and this should be considered a sign of viability. Increase in end-diastolic wall thickness and echo amplitudes immediately after reperfusion of ischaemic segments is often associated with reversibly damaged myocardium.

Coronary artery bypass grafts: visualization with MR imaging.

To evaluate the use of magnetic resonance (MR) imaging in the detection of coronary artery bypass grafts (CABGs), 20 patients with grafts underwent electrocardiographic-gated MR study. The number and location of CABGs in each patient were not known at the time of study. The number of grafts seen with MR imaging was compared with the actual number of grafts determined from the operative or angiographic report. On the prospective review of the images, 54 of 64 grafts (84%) were detected, with three false-positive results. When the images were reevaluated with knowledge of the type and number of grafts in each patient, 56 of 64 grafts (88%) were detected. Forty-one of the 46 (89%) left grafts, 15 of the 18 (83%) right grafts, and five of the 11 (45%) internal mammary grafts were detected. Although resolution was not adequate to determine the presence of graft stenosis, this early experience indicates that patent CABGs can be seen with MR imaging.

Attenuation correction in echocardiography.

A commercial two-dimensional echo unit, modified to permit digital acquisition (2.2 MHz) of echo signals prior to time-gain-compensation (TGC), was ratiometrically calibrated. Simulating the TGC in software, we demonstrated improvements in image quality as compared to conventional video methods. A path-dependent attenuation correction (PDAC) algorithm, utilizing the gray level image statistics to assign one of three attenuation coefficients (for chest, myocardium or blood) to each image pixel, was then developed. Using it on left ventricular (LV) short axis images obtained in nine healthy closed chest dogs, we demonstrated that the backscatter intensity at end diastole (ED) was 2.0 +/- 0.5 dB (mean +/- SEM) higher (p less than 0.01) than at end systole (ES), in circumferential segments of the myocardium oriented anteriorly and posteriorly, relative to the transducer. In seven of the dogs, subsequently occluded for one hour in the anterior descending branch of the left coronary artery (LAD), this normal phasic myocardial backscatter (PMB) variation decreased or was reversed in ischemic segments, relative to preocclusion values, suggesting utility of the method for sequential study of myocardial ischemia and its treatment.

Validation of a computerized edge detection algorithm for quantitative two-dimensional echocardiography.

An edge detection algorithm used in conjunction with digitized two-dimensional echocardiograms was applied to validate computerized two-dimensional echocardiographic (2DE) quantitation of cross-sectional areas of canine left ventricular chambers. Images were enhanced by space-time smoothing and dynamic range expansion, after which automatic edge detection was performed by convolving a Laplacian operator with the enhanced image. In an in vitro study of 29 myocardial slabs, computer-derived 2DE measurements of short-axis sections of the left ventricle were compared with manually derived 2DE data and validated against direct measurements of intraluminal areas of myocardial slabs. Correlations of both manually and computer-derived 2D echocardiograms vs direct measurements were equally satisfactory (r = .95 for both). Computer-derived measurements of perimeters tended to underestimate actual perimeters of the endocardial outlines of left ventricular sections. In 13 closed-chest anesthetized dogs, manually and computer-derived left ventricular short-axis areas measured by 2DE techniques showed a good correlation at both end-diastole (r = .91) and end-systole (r = .92). Left ventricular volumes reconstructed from 2DE images were compared with angiographically determined volumes. The computer-enhanced 2DE method correlated against angiography, with r = .93 for end-diastolic and r = .93 for end-systolic volumes. Left ventricular volume correlations between manually and computer-derived 2D echocardiograms were satisfactory, with r = .87 for end-diastole and r = .87 for end systole. We conclude that computerized enhancement and edge detection of 2D echocardiograms obtained in dogs provided accurate analysis of actual left ventricular cross-sectional areas and left ventricular volumes.

Advances in clinical management of acute myocardial infarction in the past 25 years.

The management of acute myocardial infarction in the past 25 years has emerged from a state of masterful inactivity to one of intensive care based on a new discipline of aggressive management. This has increased the chances of survival of the victim of infarction and could well be one of the major reasons for the decline in mortality due to coronary heart disease in the United States since 1968. Because resuscitative techniques must be instituted within 4 minutes after the onset of cardiac arrest, the attendant nurse had to learn the new emergency lifesaving techniques and assume a crucial role as a physician's assistant. The various stages in the evolution of coronary care discipline began with cardiopulmonary resuscitation and were followed by pacemaker application, arrhythmia prophylaxis and insertion of pulmonary venous flow-directed catheters and arterial lines that permit monitoring and control of ventricular filling pressures. Other developments in better management of the failing heart have included methods to salvage jeopardized myocardium, strategies for the prevention of sudden death, the application of revascularization techniques after acute coronary occlusion and new noninvasive computerized technology to provide enhanced contrast images of cardiac perfusion that can be directly integrated with measurement of function.