The efficacy of the addition of nifedipine in patients with mixed angina compared to patients with classic exertional angina: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Episodes of myocardial ischemia in patients with coronary artery disease may be due to transient increases in coronary vasomotor tone superimposed on a fixed atherosclerotic obstruction. The purpose of this study was to determine whether identification of the clinical pattern of angina could predict the therapeutic response to the addition of nifedipine to a regimen of beta blockers and/or long-acting nitrates. Seventy-two patients with stable exertional angina were divided into two groups: "classic exertional angina" (17 patients), defined as exertional angina with a stable threshold; and "mixed angina" (55 patients), defined as exertional angina provoked by a variable threshold and/or at least two episodes of rest angina within the 3 months prior to screening. Patients were studied with nifedipine and placebo in a 6-week, double-blind, crossover design that used serial anginal diaries, exercise treadmill tests, and 24-hour ambulatory ECG monitoring. In patients with mixed angina, nifedipine reduced the frequency of angina compared to that during placebo treatment (13.1 vs 9.9 episodes/3 weeks, p less than 0.01) and reduced nitroglycerin consumption (11.7 vs 7.5 tablets/3 weeks, p less than 0.05); while in patients with classic exertional angina, nifedipine had no symptomatic effect (7.9 vs 6.8 anginal episodes/3 weeks, NS; 6.4 vs 5.8 nitroglycerin tablets/3 weeks, NS). Patients in both groups experienced a significant decrease in the manifestations of ischemia during exercise testing. Patients with mixed angina experienced a reduction in the daily frequency of painful episodes of ST segment depression during nifedipine treatment compared to placebo (0.6 vs 0.2 episodes, p less than 0.05), but there was no effect on the frequency of episodes of silent ischemia (4.2 vs 3.4 episodes, NS). In patients with classic exertional angina, the addition of nifedipine had no effect on any measure of ambulatory ischemia. We conclude that patients with mixed angina are more likely to benefit symptomatically from the addition of nifedipine therapy than patients with classic exertional angina. The lack of a consistently preferential response to nifedipine in patients with mixed angina, however, suggests that episodic coronary vasoconstriction may not be the only mechanism responsible for ischemia in these patients, and/or that nifedipine may not necessarily provide additional therapeutic benefit beyond that conferred by a regimen of beta blockers and/or nitrates.

Rest and exercise hemodynamics following aortic valve replacement. A comparison between 19 and 21 mm Ionescu-Shiley pericardial and Carpentier-Edwards porcine valves.

When aortic valve replacement is performed in a patient with a small anulus, significant obstruction of the left ventricular outflow tract may remain. Most prostheses are obstructive in the smaller sizes, and enlargement of the aortic anulus may be required to allow placement of a larger valve. To evaluate the hemodynamic performance of two commonly used tissue prostheses, the Ionescu-Shiley pericardial and Carpentier-Edwards porcine valves, 22 patients with either the 19 or 21 mm size were electively studied at rest and after exercise at a mean of 15 months after operation. The resting mean transvalvular gradient for 19 mm Ionescu-Shiley pericardial valves (n = 7), 10.6 +/- 9.2 mm Hg, was significantly lower than that for 19 mm Carpentier-Edwards valves (n = 3), 33.3 +/- 2.1 mm Hg, p less than 0.01. Following exercise, the mean gradient for 19 mm Ionescu-Shiley pericardial valves rose only to 13.8 +/- 8.5 mm Hg. No exercise data were available for the 19 mm Carpentier-Edwards valve. Among patients with 21 mm Ionescu-Shiley pericardial valves (n = 7), the mean transvalvular gradient at rest was 5.6 +/- 9.5 mm Hg, not significantly different from that of patients with 21 mm Carpentier-Edwards valves (n = 5), 9.8 +/- 18.3 mm Hg. After exercise, the gradients rose to 16.0 +/- 10.0 mm Hg and 25.5 +/- 23.8 mm Hg for the Ionescu-Shiley pericardial and Carpentier-Edwards valves, respectively (no statistical significance). Cardiac index was not different between groups. Gradients were not significantly higher in patients with body surface areas greater than 1.5 m2. It is concluded that the 19 and 21 mm Ionescu-Shiley pericardial valves possess excellent hemodynamics, even after exercise. This valve appears hemodynamically superior to the Carpentier-Edwards valve, particularly in the 19 mm size. Procedures to enlarge the aortic anulus are usually unnecessary when small Ionescu-Shiley pericardial valves are used, even in patients who have large body surface areas.

Supraventricular arrhythmias following coronary artery bypass. The effect of preoperative digitalis.

Supraventricular arrhythmias continue to complicate the postoperative course of patients undergoing myocardial revascularization. In a previous study, we showed a decrease in arrhythmias if patients were given digitalis prior to operation. Since that time we have made two changes-- propranolol is no longer discontinued prior to operation and cold hyperkalemic cardioplegic solution is routinely used. To assess the affect of these changes on arrhythmias, we repeated the previous study. One hundred twenty patients all receiving preoperative and postoperative propranolol were randomized into a control group and a digitalis-treated group. The incidence of supraventricular arrhythmia postoperatively was 21.4% in the control group and 3.1% in the digitalis group (p less than 0.005). Therefore, we continue to advise preoperative digitalization in patients requiring coronary artery bypass and continue to maintain beta blocker and digitalis therapy in the postoperative period.

Effect of verapamil on basal and pentagastrin-stimulated gastric acid secretion.

The role of calcium in gastric acid secretion is still uncertain. The effect of verapamil on basal and pentagastrin-stimulated gastric acid secretion was evaluated in eight normal men. Submaximal pentagastrin tests (2 micrograms/kg/hr) were performed after pretreatment with intravenous verapamil at a concentration of 0.1 mg/kg and followed 1 hr later with a second bolus injection of 0.15 mg/kg. On a separate day, subjects received a placebo injection of saline solution at the same designated times as the verapamil. Verapamil did not alter basal or stimulated gastric acid secretion. All subjects showed ECG evidence of significant calcium-channel blocking (i.e., prolongation of PR interval). Data indicate that therapeutic doses of a calcium slow-channel antagonist do not alter gastric acid secretion in normal subjects. Results support the concept that in vivo, secretory function of the human parietal cell is not affected by alteration in cellular calcium flux.

Prognostic significance of the development of left bundle conduction defects following aortic valve replacement.

The association of intraventricular conduction defects and aortic valvular disease is widely recognized. This study was undertaken to evaluate the effects on survival of left bundle conduction defects (LBCDs) as a consequence of aortic valve replacement. A total of 133 patients were followed between 1 and 70 months after operation, with a mean follow-up of 32.1 months. The incidence of intraoperative LBCDs was 31.6% or 42 patients. There were 13 deaths in the group of 42 patients with LBCDs compared to eight deaths in the group of 91 patients without such abnormalities (p less than 0.01). Sudden death occurred in five of 42 patients with postoperative LBCDs and two of 91 patients with normal intraventricular conduction (p less than 0.025). The survival rate in these patients with significant aortic stenosis and normal intraventricular conduction was 89.9%, whereas if LBCD had occurred after operation, the survival rate was 65.7% (p less than 0.005). If the LBCD was accompanied by a left axis deviation, the survival rate was 21.7%. Sudden death may be due either to a tachyarrhythmia or perhaps to progression from LBCD to complete heart block or trifascicular block. It is important that this group of patients be monitored closely after operation. There may be an indication to insert prophylactic permanent pacemakers in this group.

Vectorcardiographic manifestations of experimental right ventricular necrosis.

This study was carried out to evaluate the possible usefulness of the VCG in the diagnosis of right ventricular necrosis. Myocardial necrosis was produced by injecting 40% formalin into the ventricular walls of 21 open-chest mongrel dogs. The injections were made in the inferior wall of the left ventricle in eight dogs (Group A) and in the inferior wall of the right ventricle in 13 dogs (Group B). Analysis of vectorcardiographic QRS loops obtained before and two hours after the injections revealed that both left and right ventricular necrosis resulted in a decrease in: maximum inferior amplitude, inferior amplitude at 10 and 20 msec. and maximum frontal plane angle. In Group A, six dogs had counterclockwise initial forces in the frontal plane before the injections and these became clockwise following the injections. In Group B, nine dogs had counterclockwise initial forces in the frontal plane before the injections and these remained counterclockwise following the injections. The only consistent QRS change in scalar ECGs that occurred after the injections was the development of small Q waves in the six dogs in Group A that manifested clockwise initial forces in the frontal plane. The VCG performed in serial fashion may be more sensitive than the 12 lead ECG for detecting right ventricular inferior wall necrosis in the experimental animal. Application of these findings to the diagnosis of myocardial infarction in humans requires further investigation.

Left ventricular function following aortic valve replacement: assessment by radionuclide ventriculography.

Left ventricular function following aortic valve replacement has been evaluated in 15 consecutive patients. Cold potassium cardioplegia was utilized for myocardial preservation. Left ventricular function was assessed by radionuclide ventriculography performed preoperatively and 3 months postoperatively. The predominant lesion was aortic insufficiency in 10 patients and aortic stenosis in five patients. All patients demonstrated improved ejection fractions at 3 months. The mean increases of ejection fraction in the aortic insufficiency group were 20% from the anterior (Ant.) position and 12.5% from the left anterior oblique (LAO) position; in the aortic stenosis group they were 15.2% (Ant.) and 14.8% (LAO). It is our contention that cold potassium cardioplegia is an effective means of myocardial preservation and that it showed no measurable deleterious effect on left heart function in this group of patients.

An evaluation of the results of left ventricular aneurysmectomy: use of a simplified method for analysis of the left ventriculogram.

Twenty-three patients underwent left ventricular aneurysmectomy without coronary artery bypass or other surgical procedure. Fourteen patients (Group 1) benefitted from surgery, and nine fared poorly (Group 2), including the four postoperative deaths. Among the 19 survivors, 17 had postoperative catheterizations. Pre- and postoperative left ventriculograms in the right anterior oblique projection were analyzed by planimetry of the aneurysmal and non-aneurysmal areas. This method provided data favorably altered by surgery in the improved patients and unchanged in the others. None of the preoperative ventriculographic measurements effectively separated the postoperative patient groups. The poor results in the Group 2 patients were of heterogeneous origin arising from pre-, peri- and postoperative factors. The more important factors were the largest and smallest aneurysms, surgically induced mitral insufficiency, and progressive coronary artery disease. Thus, the improvement in surgical results from better angiographic preoperative case selection is possible, but limited.

Sodium nitroprusside therapy in congestive cardiomyopathy-variability in hemodynamic response.

Twelve of 17 patients (group A) with congestive cardiomyopathy improved hemodynamically during sodium nitroprusside (NP) infusion. Five patients (group B) failed to increase their cardiac output. The two groups were identical in clinical presentation and had comparable cardiomegaly and left ventricular filling pressure (LVFP). However, group A had a baseline cardiac index (CI) lower than 2.5 L/min/m2 and high peripheral systemic (PSR) and total pulmonary vascular resistance (PR). In contrast, group B had a control of CI of higher than 2.5 L/min/m2 and near normal PSR and PR. Furthermore, a highly significant correlation was observed between the calculated levels of control PSR and their subsequent reduction during NP infusion. The higher the initial resistance, the more marked was its fall on NP as documented in group A. In group B, the PSR was probably not high enough for NP to be effective in increasing the cardiac output further by vasodilatation. We conclude that NP infusion may not increase cardiac output in congestive cardiomyopathy, in spite of a high LVFP, if the PSR is near normal.

Elevated ejection fractions in patients with the anginal syndrome and normal coronary arteriograms.

The etiology of chest pain in patients with the anginal syndrome and normal coronary arteriograms has not been established. There has been no explanation for the association of electrocardiographic, hemodynamic, and myocardial metabolic abnormalities consistent with myocardial ischemia observed in some patients with this disorder. Historical, clinical, laboratory, and hemodynamic data of 45 patients (24 females, 21 males), mean age 47.5 years, with chest pain and normal coronary arteriograms are reviewed. Left ventriculograms were analyzed utilizing the single-plane cineangiographic measurement of left ventricular volume. Systolic ejection fractions for the 45 patients ranged from 0.66 to 0.91 (mean 0.80 +/- 0.01 SEM). Ventricular volumes determined angiographically revealed mean end-diastolic and end-systolic volumes of 83 +/- 5 ml and 18 +/- 2 ml, respectively. The mean changes in longitudinal and transverse segmental axis shortening that occurred during ventricular systole were 28.8% and 50.7%, respectively. These elevated values for ejection fraction, and reduced measurements of ventricular volumes, indicate that some patients with chest pain and normal coronary arteriograms may have small hearts with hyperdynamic ventricular contraction. These findings suggest that hyperdynamic ventricular contraction may play a causative role in the development of transient, angina-like chest pain in these patients. The etiology of the proposed hyperdynamic ventricle is unknown, but it may be attributable to increased beta-sympathetic stimulation of the myocardium.

Hemodynamic and plasma renin effects of propranolol in essential hypertension.

Hemodynamics and plasma renin activity were measured in 20 ambulatory hospital inpatients with untreated mild to moderate essential hypertension. The control measurements were made after a period of four to seven days just on a diet containing 10 mEq sodium per day. The measurements were repeated following a week of oral propranolol hydrochloride therapy plus the low salt diet. Heart rate (P less than .001), mean arterial pressure (P less than .001), cardiac output (P less than .05), and plasma renin activity (P less than .05) were reduced in the majority of these patients following propranolol therapy but stroke volume increased (P less than .05). Corrected ejection time and total peripheral resistance did not show significant change. The antihypertensive effect of propranolol could not be related to its hyporeninemic effect or to the fall in cardiac output. Under the experimental conditions of this study, no single parameter, either hemodynamic or plasma renin activity, was predictive of a definite antihypertensive response to propranolol therapy.

Prophylactic digitalization for coronary artery bypass surgery.

One hundred and twenty patients undergoing aortocoronary bypass procedures were randomly placed into control and digitalized groups. All were initially in normal sinus rhythm and without evidence of congestive heart failure. Supraventricular arrhythmias occurred in 17 of 66 controls and in only three of 54 digitalized patients (P less than 0.01). There was no evidence of digitals toxicity. Based on this evidence we recommend prophylactic digitalization for patients having aortocoronary bypass operations.

Effect of digitalis on skeletal muscle in man.

Although an inotropic effect of digitalis on skeletal muscle has been demonstrated in animals, it has not been shown in man. Digitalis, in previous studies, has failed to improve voluntary exercise performance. In this investigation the strength of nerve-stimulated involuntary thumb adduction was measured before, during and after infusion of ouabain into the brachial artery. With this experimental design, the many uncontrolled factors that govern ordinary exercise tolerance were avoided. Large doses of ouabain (0.5 mg) produced significant augmentation of peak strength of thumb adduction whereas smaller doses (75 mug) more likely to reach the thumb during systemic digitalization produced only suggestive increases in peak contraction strength. In patients previously digitalized for heart failure, the large doses of ouabain did not significantly change contractility. The findings suggest that skeletal muscle is less sensitive than cardiac muscle to ouabain, and that systemic digitalization has a minor effect on skeletal muscle. When the differences between skeletal and cardiac muscle in excitation-contraction coupling are considered, the reduced effect of ouabain on skeletal muscle contraction is compatible with cell membrane locus of action in both tissues.

Follow-up catheterization of patients with myocardial infarction during coronary artery bypass surgery.

Of 197 consecutive patients having aortocoronary bypass grafts over a 30 month period, 38 (19 per cent) had ECG evidence of myocardial infarction. The infarctions occurred more commonly in patients receiving multiple grafts. The infarctions were usually in areas supplied by grafted vessels. The infarctions occurred most often in the inferior wall, even when multiple vessels were grafted. Eleven patients with intraoperative infarction have had repeat postoperative coronary arteriograms. Seven had all grafts patent; three of these patients had hypokinesis of the infarcted wall. Four of the 11 patients had one or more occluded grafts; three of these patients had an area of hypokinesis. We conclude that intraoperative myocardial infarction is a common problem in aortocoronary bypass surgery and is not necessarily caused by graft occlusion.

Cine angiographic diagnosis of patent foramen ovale in paradoxical embolism,.

A case of paradoxical embolism is presented in which the antemortem diagnosis was facilitated by a new simple angiographic technique that demonstrated a patent foramen ovale. An additional 14 patients were studied by this technique, and one had a patent foramen ovale. The mechanism of reversal of the normal intraatrial pressure gradient and subsequent right to left shunt through a patent foramen ovale is discussed. This angiographic technique may be readily applied in any diagnostic catheterization laboratory and complements existing methods for detecting patency of the foramen ovale in patients with suspected paradoxidal embolism.

Varied manifestations of left atrial myxoma and the relationship of echocardiographic patterns of tumor size.

Four cases of left atrial myxoma with varied clinical manifestations were diagnosed with echocardiographic studies prior to cardiac catheterization and surgery. The unusual clinical features include Raynaud's phenomenon and intermittent claudication. The echocardiographic features of the atrial myxoma appear to be related to tumor size. Systematic echocardiographic evaluation of patients with mitral valvular disease and systemic and cerebral vascular insufficiency will undoubtedly increase the positive diagnostic results in patients with atrial myxomas. Removal of these tumors results in normalization of the echocardiographic pattern.

Fluid therapy in severe systemic reaction to radiopaque dye.

Two patients developed severe vascular collapse after left ventriculography with organic iodides. Hemodynamic monitoring showed marked reduction in systemic pressures. In one patient there was no response to the standard therapeutic measures in anaphylactic reactions, and prompt response to fluid administration was obtained. In the second patient response was prompt to fluids, adrenalin, and hydrocortisone.

Effects of coronary artery ligation and release and perfusion with glucose on cardiac energy metabolism in dogs.

Adenosine triphosphate (ATP), glycogen, and inorganic phosphorus (Pi) were assayed in myocardial tissues obtained from beating dog hearts subjected to the following procedures: Group 1. Ligation of anterior descending coronary artery(AD) for 60 min. Group 2. Perfusion of the AD with 20 mM glucose in Ringer's solution containing 1 mU regular insluin/ml, for 60 min. Group 3. Ligation of the AD for 60 min, followed by release of the ligature with re-establishment of blood flow for 30 min. Group 4. Perfusion of the AD with 20 mM glucose in Ringer's solution containing 1 mU/ml regular insulin for 60 min, followed by re-establishment of blood flow for 30 min. Samples from normal myocardium (N zone) and from the area supplied by the AD (I zone) were simultaneously obtained and the level of metabolites compared. In all four groups, ATP was significantly lower in I than N zone. However, ATP values were lower in N zone in group 1 as compared with the other groups (p less than 0.05) and higher in I zone in group 3 versus groups 1 and 2 (p less than 0.05). Glycogen was lower in I than N zones to a similar degree in all the groups. However, it was higher in the I zone in group 3 than in group 1 (p less than 0.05). Pi was significantly higher in I zone versus N zone only in group 1 (p less than 0.05). These data suggest that, the the beating dog heart, ATP and glycogen preservation in a myocardial segment rendered ischemic for 1 hour is best achieved by re-establishing circulation. Glucose infusion into the ischemic segment did not contribute significantly to the ATP stores in that segment but may have exerted a protective effect on the nonischemic zones, possibly by providing a high glucose level in the circulating blood. This protection was equally well achieved by release of the ligature with or without prior glucose infusion. The increase in Pi in the ischemic zone in the dogs with coronary ligation only is probably related to accumulation of the ion under ischemic and hypoxic conditions.