The effect of acebutolol on cardiac arrhythmias in patients with chronic coronary artery disease

The effect of the beta-blocking drug acebutolol on the severity of cardiac arrhythmias and the incidence of exercise-induced arrhythmias was studied in 15 patients with chronic coronary artery disease using ambulatory Holter monitoring and bicycle ergometry. We found a significantly lower grading of arrhythmias both on long-term ECGs and during and after exercise. Furthermore, there was a significant decrease in the incidence of VPBs during and after exercise (18.15 +/- 7.7 on placebo vs. 3.46 +/- 1.7 on acebutolol). It is concluded that acebutolol favorably influences the incidence and severity of ventricular arrhythmias in patients with chronic coronary artery disease.     

Suppression of high-grade ventricular ectopic activity by antiarrhythmic drug treatment as a marker for survival in patients with chronic coronary artery disease

In order to investigate the relationship between the ease of suppression of complex (frequent multiform, repetitive, and early) ventricular premature beats (VPBs) and subsequent survival, 50 consecutive patients with chronic coronary artery disease (CAD) were followed retrospectively during a mean observation period of 16 months. A total of 124 drug trials were performed using single or combined class I, II, and III antiarrhythmic drugs. Thirty-nine patients were considered "responders" (elimination of Lown classes greater than or equal to IVa and reduction of greater than 30 multiform VPBs to occasional unifocal VPBs during Holter monitoring), whereas in 11 patients VPBs could not be adequately suppressed ("nonresponders"). There were no significant differences in age and congestive heart failure in the two groups. There were three deaths (one sudden) in the 39 "responders" but five deaths (three sudden) in the 11 "nonresponders" (p less than 0.01 for all deaths, p less than 0.05 for sudden deaths). Cumulative probability of survival at 12 months was 0.93 for "responders" and 0.64 for "nonresponders" (p less than 0.005). Significant side effects necessitated drug withdrawal in four patients. Our data suggest that survival in patients with CAD is better when complex VPBs can be suppressed.     

Echocardiographic features of the correctly functioning St. Jude Medical valve prosthesis

The St. Jude Medical valve (SJM) is a new low-prfile bileaflet prosthesis with central flow. We investigated 10 patients with aortic valve replacement and 11 with mitral valve replacement by means of combined echocardiography and phonocardiography. In patients with aortic valve replacement, echocardiography revealed during systole the anterior and posterior part of the ring together with both leaflets. During diastole, patients with mitral valve replacement showed part of the anterior leaflet and the entire posterior leaflet together with the posterior ring. Distinctive opening sounds were missing. In aortic prostheses, maximal opening followed S₁ 0.06 ± 0.02 second. An amplitude of the posterior leaflet of 9.8 ± 1.3 mm and a leaflet separation of 4.8 ± 0.9 mm were measured. In mitral prostheses the maximal opening followed A₂ 0.10 ± 0.02 second, the Q-closure interval was 0.07 ± 0.03 second and leaflet separation was 4.4 ± 0.8 mm. In both aortic and mitral positions, high values for opening and closing velocities were measured, and closing velocities exceeded opening rates. These findings establish the normal pattern and values in echocardiography and phonocardiography for patients with aortic valve replacement as well as mitral valve replacement with SJM prostheses.     

Noninvasive assessment of myocardial function in young patients with mitral valve prolapse.

To evaluate myocardial function in patients with documented mitral valve prolapse (MVP) 14 patients (six men and eight women with a mean age of 28 +/- 6.3 years) were examined noninvasively. Systolic time intervals were recorded at rest (in the supine and upright position) and after bicycle ergometry (upright position) and were compared with 10 healthy control subjects of similar age. Tracings were coded with random numbers and were evaluated by two blinded investigators. Contractility indices such as pre-ejection period index (PEPc) and ratio pre-ejection period/left ventricular ejection time (PEP/LVET) revealed no significant differences between patients and controls both at rest and after exercise. We conclude that young patients with MVP have no evidence for impaired myocardial function, provided there is no significant mitral incompetence or associated heart disease.     

Progression of mild mitral stenosis and incidence of restenosis after open commissurotomy: a study using echocardiography.

Thirteen patients with mild mitral stenosis and 21 asymptomatic patients after commissurotomy were studied by echocardiography in order to assess the rate of progression of mitral stenosis and the incidence of restenosis after successful open mitral commissurotomy. In the group with mitral stenosis there was a decrease of the diastolic closing velocity (E-F slope) from 35.7 to 29.5 mm./sec. (p less than 0.0005) over a period of 37 months. In 23% of the patients the stenosis increased significantly (p less than 0.0005) by echocardiographic parameters. Forty-eight months after commissurotomy we noted a significant over-all slowing of the diastolic closing velocity (from 52.6 to 44.8 mm./sec., p less than 0.0005) and a decrease of the mitral valve closure index DE/MAIC (from 1.7 to 1.5, p less than 0.0025). Five of 21 patients (24%) showed a change in one or both of these parameters which was greater than 2 standard deviations of the mean change. Based on echocardiographic criteria, we conclude that patients with mild mitral stenosis and asymptomatic patients following successful commissurotomy need only be checked approximately every 3 years.     

Combined acebutolol/nifedipine therapy in patients with chronic coronary artery disease: Additional improvement of ischemia-induced left ventricular dysfunction

To assess acute hemodynamic effects of combined oral nifedipine (10 mg) and acebutolol (100 mg), 21 patients with angiographically documented coronary artery disease and stable angina pectoris were studied (three groups of seven randomized patients). Simultaneous hemodynamic and equilibrium radionuclide ejection fraction measurements were performed at rest and during exercise before treatment, 1 hour after administration of nifedipine, acebutolol or a combination of the two and again 1 hour after combined nifedipine and acebutolol. At the same exercise level achieved without drugs, angina, subjectively scored by the patients, decreased significantly after nifedipine, acebutolol and a combination of the two in association with a significant improvement in left ventricular ejection fraction (p < 0.01). There was an additive effect of both drugs on heart rate, systolic blood pressure and therefore the double product (p < 0.01 each). The negative effects of acute beta receptor blockade on cardiac index, resting ejection fraction and total peripheral resistance were balanced by the vasodilatory action of nifedipine. In patients with borderline heart failure no untoward effects were seen after combined therapy. Thus, acute combined acebutolol/nifedipine therapy in patients with stable angina proved to be hemodynamically superior to therapy with either drug alone and safe even in patients with moderately depressed left ventricular function. This finding provides a basis for appropriately designed long-term studies.     

Sustained effectiveness of chronic prazosin therapy in severe chronic congestive heart failure

Twelve patients with severe chronic congestive heart failure (CHF) (NYHA class III and IV) resistant to digitalis and diuretics were treated with the postsynaptic alpha-blocking agent prazosin (PZ) (3 to 20 mg/day). In 11 patients oral PZ treatment was well tolerated; the agent was discontinued in the remaining patient because of orthostatic dizziness. After 4 weeks of PZ, total systemic vascular resistance decreased from 2245 ± 792 to 1603 ± 355 dyn sec cm^?5, mean blood pressure declined from 100 ± 15 to 90 ± 14 mm Hg, and pulmonary capillary wedge pressure decreased from 29 ± 8 to 25 ± 9 mm Hg. Cardiac index increased from 1.92 ± 0.63 to 2.30 ± 0.41 l/min/m². The increase of stroke volume index correlated with the fall in peripheral vascular resistance (r = ?0.79, p < 0.01) and the decline in pulmonary capillary wedge pressure (r = ?0.75, p < 0.05). In parallel, exercise tolerance increased significantly. Four patients improved from functional class IV to II, four from class IV to III, and one from class III to II, while two patients were unchanged. In the eight patients followed for 6 months, the beneficial effects of ambulatory PZ were maintained throughout the expansive observation period. Three patients died as their disease process progressed during the study (sudden death, pneumonia, and post-PZ withdrawal pump failure). Prazosin is a valuable vasodilator for long-term treatment of otherwise refractory congestive heart failure with the agent given in sufficient individualized dosage.     

Human pharmacology studies with a new, orally active stimulant of cardiac adrenergic beta-receptors.

The effects of single oral doses of 5, 10, and 20 mg. of a new cardioselective β-stimulant, preparation C $\text{50,005}\text{A-Ba}$, were tested and compared with the response to placebo in eight healthy volunteers (four aged 23 to 26 years and four aged 49 to 55 years). The compound induced a doserelated increase in myocardial contractility (reduction of 17 to 24 msec. in PEP_c) and in heart rate, which was accelerated by 8 to 20 beats/minute by comparison with the placebo values. The rise in systolic pressure observed in response to C $\text{50,005}\text{A-Ba}$ was both dose-related and dependent on the age of the subjects; in the younger group there was an increase of 16 to 31 mm. Hg and in the older group an increase of 7 to 21 mm. Hg. A slight decrease in diastolic pressure was noted, which was likewise more prominent in the younger subjects. These changes were ascribed to a decrease due to aging in the responsiveness of the adrenergic β-receptors to stimulation. The effects of the compound set in quickly, reached their maximum within 30 to 60 minutes, and persisted for about 4 hours. The only side effects observed were slight palpitations. Depression of the ST segment was noted in one 55-year-old subject and was interpreted as a manifestation of latent coronary disease. In view of this finding, it seems possible that the preparation could be used as a diagnostic agent for a simple test of coronary function. Continuous E.C.G. recordings over a period of $\text{5}\text{3}\text{4}\text{hours}$, including three ergometer tests at submaximum effort, showed that by comparison with placebo, C $\text{50,005}\text{A-Ba}$ caused a slight increase in the frequency of isolated ventricular and supraventricular premature contractions, and also in the incidence and intensity of sinus arrhythmias not due to respiration. Essentially the same changes in cardiac rhythm were observed in four young volunteers during continuous E.C.G. recordings over a period of 9 hours in response to the repeated administration of C $\text{50,005}\text{A-Ba}$ in a dosage of 15 mg. three times a day on two consecutive days. The differences from the corresponding placebo values were, however, not statistically significant.C $\text{50,005}\text{A-Ba}$ is thus an orally active cardiostimulant agent with a high degree of β₁-receptor selectivity and with only a very slight arrhythmogenic potential. It is well tolerated and could afford beneficial effects in the treatment of heart failure or as a countermeasure in therapy with β-blockers.     

Impact of radionuclide techniques on evaluation of patients with ischemic heart disease

Radiotracer studies of the heart have become clinically important in the last decade, especially for evaluation of patients with known or suspected ischemic heart disease. Radionuclide ventriculography provides quantitative measures of biventricular function and regional wall motion. Recent technical advances include the development of computer programs for analyzing diastolic function, parametric imaging methods such as "phase" analysis and methods for calculating absolute ventricular volumes. Thallium-201 scans provide maps of regional myocardial perfusion. Recent advances include development of computer programs to quantitate regional thallium-201 uptake and to calculate thallium-201 turnover rates and the development of tomographic imaging systems. Technetium-99m pyrophosphate localizes in irreversibly damaged myocardium and provides a method for diagnosing, localizing and sizing acute myocardial infarcts. Recent applications include tomographic imaging to improve image contrast and development of criteria to identify high risk patients after infarction. Two important trends affecting the application of all the radionuclide studies in clinical cardiologic practice are the increasing use of decision analysis for incorporating results of multiple tests into single diagnostic probability statements, and the use of diagnostic algorithms that include the radionuclide studies to optimize the cost effectiveness of evaluation of patients with ischemic heart disease.     

Conduction defects in aortic valve disease

Serial electrocardiograms of 426 patients undergoing homograft replacement of the aortic valve were analyzed with respect to the presence or absence of conduction defects (CD) in an attempt to define more precisely their etiology and relationship to prognosis. The dominant lesion was aortic stenosis in 249 patients and aortic regurgitation in 177 patients. Preoperative CD were present in 69 patients (28 per cent) with aortic stenosis and in 43 patients (24 per cent) with aortic regurgitation. In those with aortic stenosis, calcification in the ventricular septum or impaired left ventricular function were common and could have been important etiological factors. In those with aortic regurgitation, impaired left ventricular function was the dominant feature. Coronary artery disease was present in a minority of patients in both groups. In patients with aortic stenosis, there were three early deaths (4.4 per cent) and 11 late deaths (15.9 per cent). In those with aortic regurgitation, there were four early deaths (9.3 per cent) and four late deaths (9.3 per cent). Of 275 patients with normal conduction throughout the pre- and postoperative period, there were 15 early deaths (5.4 per cent) and 13 late deaths (4.7 per cent). (Follow-up 3 to 84 months. Mean, 36 months). Reversal of CD following operation occurred in more than half of those patients with first-degree A.V. block regardless of the initial hemodynamic lesion and was associated with improvement in left ventricular function. Reversal of left anterior hemiblock (LAH) occurred in approximately 30 per cent of cases. Progression of LAH and the combination of left axis deviation with left bundle block (LBBB) were associated with a poor prognosis. Fresh CD following operation occurred in 19 patients within 1 month of surgery and in 20 patients beyond this period of time. In this group there were two early deaths (5.1 per cent) and four late deaths (10.3 per cent). Of 20 patients developing late conduction defects, six were associated with valve failure and the development of poor left ventricular function. In the remainder no apparent cause could be determined and this group may represent fibrosis occurring in the region of the conducting pathways.     

Silent myocardial ischemia: hemodynamic changes during dynamic exercise in patients with proven coronary artery disease despite absence of angina pectoris

The hemodynamic changes during exercise occurring in 36 patients with proven coronary artery disease (10 without and 26 with previous myocardial infarction) who tolerated the stress test without angina were analyzed and compared with changes observed in a control group of 36 carefully matched patients whose exercise was limited by angina. All patients were exercised to the same extent, reaching a similar rate-pressure product at the end of the stress test (19,508 +/- 4,828 [SD] versus 19,247 +/- 4,117 beats/min X mm Hg [NS] in the study and control groups without prior infarction, and 19,665 +/- 3,950 versus 17,701 +/- 4,600 beats/min X mm Hg [NS] in the respective groups with infarction). In all groups left ventricular end-diastolic pressure increased from rest to exercise (from 18 +/- 4 to 36 +/- 11 and from 13 +/- 5 to 29 +/- 9 mm Hg, respectively, in the study and control groups without prior infarction and from 17 +/- 7 to 32 +/- 13 and from 19 +/- 7 to 36 +/- 9 mm Hg in the respective groups with prior infarction). Left ventricular ejection fraction decreased (from 59 +/- 7 to 50 +/- 15 and from 60 +/- 4 to 52 +/- 9% in the study and control groups without prior infarction and from 54 +/- 9 to 47 +/- 10 and 55 +/- 9 to 50 +/- 4% in the respective groups with prior infarction). Whereas the changes from rest to exercise were highly significant within each group, no significant differences were noted between the corresponding groups. Regional de novo hypokinesia appeared in all patients without prior infarction and in 25 and 22 patients, respectively, of the groups with prior infarction. Thus, under similar physical stress conditions, comparable hemodynamic changes indicative of ischemia are observed in patients with significant coronary artery lesions with or without previous myocardial infarction irrespective of the occurrence of angina. Therefore, angina pectoris cannot be considered a prerequisite for hemodynamically significant ischemia during exertion.     

The management of anticoagulation during noncardiac operations in patients with prosthetic heart valves

Based on previous thromboembolic complications associated with the interruption of anticoagulation during subsequent noncardiac operations in patients with nonbilogical mitral prostheses, a protocol was developed for this high risk group. We report the successful management of 26 such operations in which anticoagulation was interrupted for 12 hours and then rapidly restored by means of heparin in the postoperative period. Since an earlier study suggested no adverse effect from the interruption of chronic anticoagulants for three to five days among patients with isolated aortic valve prostheses, simple interruption was again employed during 16 subsequent noncardiac operative procedures in this group with no complications. There were three episodes of hemorrhage observed in patients receiving therapeutic doses of heparin postoperatively, but only one required blood replacement.     

Evaluation of aortocoronary venous bypass grafting for prevention of cardiac arrhythmias.

The influence of ACB on cardiac arrhythmias was examined in 27 patients. Eight-hour Holter monitoring was performed 8 days preoperatively and 100 days postoperatively. Arrhythmias were divided into 3 groups (Class I: NSR +/- occasional APBs; Class II: less than five unifocal VPBs per minute; Class II: more than five VPBs per minute, multifocal VPBs, VPBs in a row or VT). Preoperative classification disclosed that 13 patients (48.1 per cent) were in Class I, six patients (22.2 per cent) were in Class II, and eight patients (29.6 per cent) were in Class III. The corresponding values after surgery were 10 patients (37.0 per cent), 13 patients (48.1 per cent), and four patients (14.8 per cent). These differences were not statistically significant (p less than 0.1). In view of the tendency of arrhythmias of Class III to improve after ACB, we feel that further investigations in this area are needed. At the present time ventricular arrhythmias alone constitute no indication for bypass surgery.