Effects of verapamil on coronary hemodynamic function and vasomobility relative to its mechanism of antianginal action

The effect of intravenous verapamil on systemic and coronary hemodynamic function was studied at cardiac catheterization in 12 patients with coronary artery disease. Verapamil was administered as a 2-minute bolus (0.145 mg/kg) followed by an infusion (0.005 mg/kg/min). Cardiac output and coronary sinus blood flow were measured by thermodilution techniques. Caliber of the large coronary arteries and of diseased segments was determined from the coronary angiogram using a computer-assisted method. Verapamil reduced mean arterial pressure 14% (p less than 0.001), systemic vascular resistance 21% (p less than 0.01), and stroke work index 16% (p less than 0.001). Coronary vascular resistance decreased 24% (p less than 0.01) with a small increase in coronary sinus blood flow (+13%, difference not significant [NS]). Myocardial oxygen consumption determined in 5 patients showed no significant change with verapamil. Luminal area in 39 coronary lesions was measured in the "normal" portion of the diseased segment and at its maximal constriction, and an estimate of flow resistance in the stenosis was computed. Overall, 50% of "normal" and of diseased coronary segments dilated significantly with verapamil. Stenosis dilation resulted in an average 14% reduction (p less than 0.01) in estimated flow resistance. In 8 patients, the luminal changes (n = 27) induced by sublingual nitroglycerin were compared with those induced by verapamil. Nitroglycerin induced a significantly greater increase in coronary caliber in both normal and diseased segments; estimated stenosis flow resistance decreased 28% with nitroglycerin compared with 14% with verapamil (p less than 0.01). Thus, verapamil moderately dilates the systemic and coronary small vessel resistance bed without apparently increasing myocardial metabolic demand. Furthermore, verapamil mildly dilates large coronary conductance vessels in both "normal" and diseased segments, although significantly less than does nitroglycerin.     

Influence of severity of ventricular dysfunction on hemodynamic responses to intravenously administered verapamil in ischemic heart disease

The effects of verapamil, 0.145 mg/kg body weight, administered intravenously in a bolus injection followed by 0.005 mg/kg per min, on cardiovascular hemodynamics and on ventricular ejection fraction, determined with gated cardiac blood pool scanning, were studted in 25 patients, 8 with acute myocardial infarction and 17 with symptomatic coronary artery disease who were undergoing diagnostic cardiac catheterization. The mean (± standard deviation) plasma verapamil level, determined with a gas liquid chromatographic technique utilizing a nitrogen detector, was 161 ± 47 ng/ml (n = 8) during steady state conditions of drug infusion. In 15 patients with stable coronary artery disease having a normal or moderately reduced ejection fraction, verapamil reduced mean arterial pressure (?16 percent, probability [p] < 0.001), systemic vascular resistance (?23 percent, p < 0.001), stroke work index (?13 percent, p < 0.02), with no significant change in pulmonary vascular resistance, ejection fraction or heart rate; cardiac index was increased (+11 percent, p < 0.001) as was the stroke volume index (+7 percent, p < 0.01) and mean capillary wedge pressure (+10 percent, p < 0.01). In the seven patients with uncomplicated infarction, there was no effect on ejection fraction, heart rate or pulmonary vascular resistance. There was a decrease in systemic vascular resistance (?22 percent, p < 0.01) and mean arterial pressure (?16 percent, p < 0.01) with an increase in cardiac index (+27 percent, p < 0.05), stroke volume index (+4 percent, p < 0.05) and mean capillary wedge pressure (+17 percent, p < 0.02). In three patients, one wlth acute infarction and two with coronary artery disease, having a severely reduced ejection fraction and elevated mean capillary wedge pressure (20 mm Hg or greater), mean arterial pressure decreased markedly with a fall in stroke volume index and an abrupt increase in the mean pulmonary capillary wedge pressure. These findings were associated with clinical evidence of heart failure and dyspnea.It is concluded that (1) in patients with cardiac disease having a mild to moderate decrease in left ventricular ejection fraction accompanied by a normal or mildly elevated mean pulmonary capillary wedge pressure, the intrinsic depressant effect of verapamil is offset almost entirely by its potent vasodilator proporties, but (2) in patients with a severely reduced ejection fraction and a high pulmonary capillary wedge pressure, the depressant effects of the compound become clinically apparent with sudden further increases in pulmonary capillary wedge pressure and a decrease in stroke volume and mean arterial pressure.     

Verapamil in chronic stable angina: amelioration of pacing-induced abnormalities of left ventricular ejection fraction, regional wall motion, lactate metabolism and hemodynamics

The effects of intravenously administered verapamil (bolus dose of 0.145 mg/kg body weight, followed by continuous infusion at 0.005 mg/kg per min) on myocardial ischemia induced by incremental coronary sinus pacing were investigated in 12 patients with coronary artery disease undergoing diagnostic angiography. The effects were determined with respect to differences between changes under control pacing conditions and after verapamil in the transmyocardial gradients of lactate, systemic hemodynamics and in left ventricular ejection fraction and regional wall motion abnormalities measured with gated radionuclide ventriculography. Control and drug data could not be matched for four patients because of the development of atrioventricular (A-V) Wenckebach block at lower pacing rates during verapamil infusion. In the remaining eight patients, under control conditions, pacing to a mean maximal heart rate of 120.6 ± 10.8 beats/min produced moderate to severe chest pain in all; the left ventricular ejection fraction decreased from 0.59 ± 0.08 to 0.47 ± 0.07 (?20.2 percent, p < 0.001) with the development of new regional wall motion abnormalities in seven patients and an accentuation of the preexisting abnormality in the remainder. During verapamil administration, the left ventricular ejection fraction decreased from 0.55 ± 0.07 to 0.52 ± 0.04 (?5.5 percent, difference not significant); no regional wall motion abnormalities developed. Four patients had no chest pain; in the other four, the pain at maximal pacing was minimal or mild in intensity. Under control conditions, the maximal pacing rate led to a decrease in myocardial lactate extraction in all patients, with metabolism becoming anaerobic in four. During administration of verapamil, identical pacing rates produced no abnormalities of the transmyocardial lactate gradient while preventing the increases in pulmonary capillary wedge pressure and in pulmonary and systemic arterial pressures observed under control conditions.The overall data, demonstrating that verapamil, when given under steady state conditions of drug administration, prevents or greatly attenuates the ischemic consequences of incremental coronary sinus pacing in patients with coronary artery disease, provide objective evidence for the clinical utility of the compound in exertional angina. Controlled clinical trials during oral therapy with the drug are therefore indicated.     

Clinical features and prognosis of patients with out of hospital cardiac arrest and a normal electrophysiologic study

Nineteen patients survived a cardiac arrest not associated with an acute myocardial infarction, and had a normal electrophysiologic study with no inducible ventricular tachycardia despite programmed stimulation with one to three extrastimuli at two or more ventricular sites. Among 14 patients who had obstructive coronary artery disease, cardiac arrest occurred during exertion or an episode of angina pectoris in 11; 24 hour ambulatory electrocardiographic recordings demonstrated infrequent or no premature ventricular complexes in 10 and an ischemic response occurred during stage I or II (Bruce protocol) in 6 of 9 patients who underwent exercise testing. Treatment of these patients consisted of myocardial revascularization (eight patients) or antianginal medications (six patients). Only three patients were also treated with an antiarrhythmic drug. Over a follow-up period of 26 +/- 15 months (mean +/- standard deviation), only one patient died suddenly. Two patients who had coronary artery spasm were treated with coronary vasodilator medications and had no recurrence of cardiac arrest over 7 and 36 months of follow-up, respectively. Three patients who had cardiomyopathy or no identifiable structural heart disease were treated with nadolol or amiodarone and had no recurrence of cardiac arrest over 3 to 27 months of follow-up. Among patients who survive a cardiac arrest and have a normal electrophysiologic study, those with obstructive coronary artery disease or coronary artery spasm generally have an excellent prognosis with treatment directed primarily at the underlying heart disease. The clinical features of these patients suggest that cardiac arrest was related to ischemia rather than a primary arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Echocardiographic evaluation of normal and prolapsed tricuspid valve leaflets

The tricuspid valve was examined by 2-dimensional (2-D) echocardiography in 14 patients with tricuspid valve prolapse (TVP) and in 16 normal subjects. Individual leaflets were identified anatomically and for frequency of prolapse. Maximal and minimal anular sizes were measured. Multiple tomograms of the tricuspid anulus were recorded at 30 degrees intervals around the tricuspid anulus with the transducer placed at the right ventricular apex. Anuli were reconstructed from the 6 planes and corrected for body surface area. Three leaflets of the tricuspid valve could be anatomically identified in all patients. Prolapse of all 3 leaflets was observed in 6 patients, 2 leaflets in 5 and 1 in 3. Frequency of individual leaflet prolapse was 93% for the septal cusp, 86% for the anterior and 43% for the posterior. Maximal anular circumference and area in TVP were 7.9 +/- 0.6 and 8.9 +/- 1.3 cm2/m2, respectively--significantly larger than values in normal subjects (6.4 +/- 0.5 cm/m2 and 6.1 +/- 0.9 cm2/m2, respectively) (p less than 0.001). Percent reductions in circumference and area in TVP were 14 +/- 3 and 25 +/- 5%, respectively--significantly smaller values than in normal subjects (19 +/- 4 and 33 +/- 4%, respectively). Tricuspid regurgitation (TR) was detected by contrast echocardiography in 7 of 14 patients with TVP. The severity of TR appeared to be minimal in 6 of the 7 patients, and was not associated with an increase in anular size. Thus, TVP is associated with anular dilatation irrespective of associated TR, probably as a primary pathologic characteristic.     

Chronic effects of myocardial infarction on right ventricular function: a noninvasive assessment

To assess the chronic effects of myocardial infarction on right ventricular function, 48 subjects were studied utilizing radionuclide angiography and two-dimensional echocardiography. Ten were normal subjects (group I), 11 had previous inferior wall myocardial infarction (group II), 10 had previous anteroseptal infarction (group III), 11 had combined anteroseptal and inferior infarction (group IV) and 6 had extensive anterolateral infarction (group V). The mean (+/- standard deviation) left ventricular ejection fraction was 0.66 +/- 0.03 in group I, 0.58 +/- 0.02 in group II, 0.52 +/- 0.02 in group III, 0.33 +/- 0.03 in group IV and 0.33 +/- 0.01 in group V. No systematic correlation between left and right ventricular ejection fraction was observed among the groups. The mean right ventricular ejection fraction was significantly reduced in the presence of inferior myocardial infarction (0.30 +/- 0.03 in group II and 0.29 +/- 0.03 in group IV compared with 0.43 +/- 0.02 in group I [p less than 0.001]). The group II and IV patients also had increased (p less than 0.001) right ventricular end-diastolic area and decreased (p less than 0.001) right ventricular free wall motion by two-dimensional echocardiography. In the presence of anteroseptal infarction (group III), right ventricular free wall motion was increased (p less than 0.05) compared with normal subjects (group I). Thus, the effects of prior myocardial infarction on right ventricular function depend more on the location of infarction than on the extent of left ventricular dysfunction. Inferior infarction was commonly associated with reduced right ventricular ejection fraction and increased right ventricular end-diastolic area. The right ventricular free wall excursion was increased in the presence of anteroseptal infarction, suggested loss of contribution of interventricular septal contraction to right ventricular ejection.     

Atypical echocardiographic and angiographic presentation of a postoperative pseudoaneurysm of the left ventricle after repair of a true aneurysm

Subsequent to the repair of a true aneurysm from the posteromedial-basal aspect of the left ventricle, a 58 year old man developed a draining wound at the site of the sternotomy. Two-dimensional echocardiography revealed recurrence of the aneurysm at the site of the previous aneurysm repair. This aneurysm had a wide neck and looked similar in appearance to the previous true aneurysm. However, at surgery the patient was found to have a ventricular pseudoaneurysm with a cardiocutaneous fistula.     

Reproducibility of left ventricular internal dimensions with M mode echocardiography: Effects of heart size,body position and transducer angulation

Analysis was made of the variables of heart size, body position and transducer angle affecting the reproducibility of left ventricular internal dimensions as measured with M mode echocardiography. Echocardiograms were recorded in 24 subjects as the thorax was incrementally rotated and tilted. Transducer angle was noted from a three plane level attached to the probe. Constants were the technician, transducer placement and the interpreter. Heart rates varied insignificantly; respirations were held. Groups A and B were defined by their initial left ventricular internal dimensions at end-diastole (LVID_d): 49 ± 5.9 and 73 ± 8.6 mm (group mean ± standard deviation). With body position constant the measurement error between duplicate recordings of LVID_d was ± 1.2 mm (coefficient of variation = 1.8 percent) in Group A and ±4.5 mm (coefficient of variation = 4.6 percent) in Group B (p <0.001). Transducer angle varied 12 ° between duplicate recordings in both groups. As the position of the thorax changed, the transducer followed, maintaining approximately the same incline with the chest wall. In both groups errors for combined LVID_d recorded with rotation and tilt, respectively, were unchanged from the duplication error. Thus, when the spatial orientation between the transducer and heart is held constant, it is the size of the heart that determines the reproducibility of the measurement of left ventricular internal dimensions.     

Pharmacologic and hemodynamic mechanisms underlying the antianginal actions of verapamil

The pharmacologic and hemodynamic effects of verapamil are the result of its selective inhibitory action on the slow channel in cardiac muscle and its propensity to block transmembrane calcium influx in vascular smooth muscle and to nonspecifically antagonize sympathetic excitation. In patients with normal or moderately reduced ventricular function, verapamil's ability to reduce afterload counteracts its intrinsic negative inotropic effects and therefore a reduction in ventricular performance is not seen. In patients with a severely reduced ventricular ejection fraction and high ventricular filling pressures, however, the drug may produce clinical and hemodynamic deterioration. Computer-assisted angiographic analysis shows that verapamil dilates normal as well as narrowed epicardial coronary vessels and reverses ergonovineand sympathetically provoked coronary vasoconstriction. Intravenous administration of verapamil reduces coronary arterial resistance and enhances coronary sinus flow with variable effects on myocardial oxygen consumption. The drug prevents the ischemic consequences of angina produced by atrial pacing; after verapamil administration, pacing-induced lactate production is lessened, and ischemia-related declines in left ventricular ejection fraction are prevented. During chronic therapy the effects of verapamil on regional and global ventricular function are similar to those of propranolol during supine bicycle exercise. However, verapamil has significantly less effect on rate-pressure product at rest and during exercise, which suggests that its antianginal mechanism of action, unlike that of beta-blocking agents, may not be related solely to a reduction in oxygen demand. These data indicate that the mechanisms underlying the antianginal effects of verapamil are complex and are likely to be multifactorial.     

Exercise-induced regional wall motion abnormalities on radionuclide angiography: Lack of reliability for detection of coronary artery disease in the presence of valvular heart disease

Exercise-induced regional wall motion abnormalities on radionuclide angiography have been thought to be a reliable indicator of coronary artery disease. To evaluate their reliability, particularly in patients with valvular heart disease, exercise radionuclide angiography was performed in 12 normal subjects, 35 patients with coronary artery disease and 19 patients with valvular heart disease and normal coronary arteries. Exercise-induced regional wall motion abnormalities were found in none of the normal subjects, 63 percent of the patients with coronary artery disease and 42 percent of those with valvular heart disease and were predominantly inferoapical in location in the group with valvular heart disease. We conclude that exercise-induced regional wall motion abnormalities are not reliable for the detection of coronary artery disease in patients with valvular heart disease.     

Effects of flecainide on ventricular function: clinical and experimental correlations

Flecainide has unusual electrophysiologic properties and a high potency for the suppression of ventricular tachyarrhythmias. Little is known about its inotropic and hemodynamic actions. In isolated rabbit papillary muscle, it produced a concentration-dependent depression of contractile force, the threshold concentration being 1.0 micrograms/ml. In patients undergoing coronary angiography for ischemic heart disease and given 1 (n = 11) and 2 mg/kg (n = 11) of flecainide acetate i.v., there was no change in heart rate or mean arterial pressure. The vehicle in which i.v. flecainide was suspended had no significant effects in 6 patients in whom it was tested. Both doses produced comparable hemodynamic effects irrespective of the level of the left ventricular ejection fraction. The mean right atrial pressure increased by 12% (p less than 0.05) after 1 mg/kg and by 15% (p less than 0.01) after 2 mg/kg of the drug. The corresponding increases in mean wedge pressure were 44% (p less than 0.05) and 33% (p less than 0.05), in mean pulmonary artery pressure 27% (p less than 0.01) and 28% (p less than 0.05), in systemic vascular resistance 10% (p less than 0.05) and 9% (not significant [NS]) and in pulmonary vascular resistance 6% (NS) and 49% (p less than 0.05). Significant decreases in cardiac index (8 and 12%, p less than 0.05), stroke volume index (11 and 15%, p less than 0.01) and stroke work index (12%, p less than 0.05, and 21%, p less than 0.01) as well as in left ventricular ejection fraction (15 and 16%, p less than 0.01) were also induced by the 2 doses of flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of tricuspid regurgitation by directional analysis of right atrial systolic linear reflux echoes with contrast M-mode echocardiography

Twenty-seven individuals were studied for diagnostic assessment of tricuspid regurgitation (TR) using directional analysis of echo contrast lines on M-mode echocardiograms (MME). Group I consisted of 12 patients with physical findings, as well as phonocardiogram and jugular venous pulse tracings, compatible with TR. Group II consisted of five normal volunteers and 10 control patients without any evidence of congestive heart failure or TR. Following peripheral venous injection of contrast material, all 12 patients in group I demonstrated linear reflux contrast echoes in the right atrium (RA) on MME consisting of multiple posteriorly directed echo lines throughout systole behind the tricuspid valve. In addition, linear reflux contrast echoes in the hepatic vein directed away from its entry into the inferior vena cava were noted in 8 of the 12 patients by a cursor-placed MME. The remaining 15 patients in group II showed none of the above findings on contrast echocardiography. These observations indicate that linear systolic reflux contrast echoes in the RA behind the tricuspid valve on MME may be a specific and sensitive sign of TR.     

Noninvasive detection and localization of coronary stenoses in patients: Comparison of resting dipyridamole and exercise thallium-201 myocardial perfusion imaging

Two noninvasive tests to detect and localize coronary stenoses were compared in a fully blinded protocol. Thallium²⁰¹ myocardial perfusion imaging (MPI) following maximal treadmill exercise and pharmacologic coronary vasodilation with intravenous dipyridamole (DP) was performed in 33 patients. Thallium²⁰¹ imaging defects in six myocardial perfusion regions were correlated with stenoses in their respective vascular distributions. Disease severity was determined with coronary arteriograms using a computer-assisted method, 198 myocardial regions were evaluated; 101 were supplied by at least one major artery with a ≥ 50% stenosis (luminal diameter narrowing). The sensitivity and specificity for detecting a ≥50% stenosis were 85% and 64% (p < 0.005), respectively, for DP and 84% and 68% (p < 0.005) for exercise-thallium²⁰¹ imaging. A particular combination of anterior and septal imaging defects was useful in detecting left anterior descending artery stenoses proximal to its first septal branch. DP administration was safe in this group of patients; however, 42% experienced transient chest pain. Although the overall sensitivity and specificity of the two methods were not significantly different, DP-MPI appeared more sensitive than exercise-MPI (70% vs 52%, p < 0.01) in detecting coronary stenoses in the 40% to 60% range. DP-thallium²⁰¹ MPI provides a useful alternative test for potential coronary disease patients unable to perform maximal exercise.     

Assessment of right ventricular function using two-dimensional echocardiography

With the use of two-dimensional echocardiography (2DE), we analyzed apical and subcostal four-chamber views for evaluation of right ventricular (RV) function in 30 individuals as compared to RV ejection fraction (RVEF) obtained by radionuclide angiography. In addition to previously reported parameters of changes in areas and chords, a new simple measurement of tricuspid annular excursion was correlated with RVEF. A close correlation was noted between tricuspid annular plane systolic excursion (TAPSE) and RVEF (r = 0.92). The RV end-diastolic area (RVEDA) and percentage of systolic change in area in the apical four-chamber view also showed close correlation with RVEF (r = -0.76 and 0.81); however, the entire RV endocardium could only be traced in about half of our patients. The end-diastolic transverse chord length and the percentage of systolic change in chord length in the apical view showed a poor correlation with RVEF. The correlation between RVEF and both areas and chords measured in the subcostal view was poor. It is concluded that the measurement of TAPSE offers a simple echocardiographic parameter which reflects RVEF. This measurement is not dependent on either geometric assumptions or traceable endocardial edges. When the endocardial outlines could be traced, the apical four-chamber view was superior to the subcostal view in assessment of RV function.     

Comparative evaluation of segmental asynergy in remote myocardial infarction by radionuclide angiography,two-dimensional echocardiography,and contrast ventriculography

Radionuclide angiography (RNA), two-dimensional echocardiography (2DE), and contrast ventriculography (CVG) were compared in the evaluation of regional wall motion (RWM) in 58 patients with remote myocardial infarction (MI). All 58 patients were studied by 2DE, 52 by RNA, and 24 by CVG. Severe degrees of segmental asynergy (akinesia/dyskinesia) were noted more often by 2DE (56% of all segments, p < 0.005) and CVG (52%, p < 0.05) than by RNA (39%). The apex was the most frequent site of akinesia/dyskinesia by all techniques (43% by RNA, 36% by 2DE, and 45% by CVG). 2DE and RNA agreed in 64% of regions (p < 0.005), 2DE and CVG agreed in 68% (p < 0.005), and RNA and CVG agreed in 70% (p < 0.005); the highest agreement was for the apical region. Dyskinesia was noted in 77% of patients by RNA, in 71% by 2DE, and in 79% by CVG. RNA and CVG agreed in 89% of patients and in 57% of regions, 2De and CVG agreed in 67% of patients and in 53% of regions, and RNA and 2DE agreed in 71% of patients and in 38% of regions. Combined RNA and 2DE detected dyskinesia in 94% of the 16 patients with dyskinesia by CVG who underwent all three techniques and in 90% of the 52 patients studied by RNA and 2DE. We conclude that (1) RNA, 2DE, and CVG agree significantly in the evaluation of regional wall motion; (2) there is better agreement concerning the presence or absence of dyskinesia in a given patient than the exact region involved; and (3) the combination of RNA and 2DE is more useful than either alone as a screening procedure for the detection of ventricular dyskinesia.