David R. Redwood

Coronary Artery Narrowing in Coronary Heart Disease: Comparison of Cineangiographic and Necropsy Findings

Of 10 patients with fatal coronary heart disease undergoing coronary angiography 0 to 69 d (average, 21) before necropsy, the amount of narrowing in 61 coronary arteries observed angiographically (diameter reduction) during life by three angiographers was compared with that observed histologically (cross-sectional area) at necropsy. No overestimations of the degree of narrowing were made angiographically. Of 11 coronary arteries or their subdivisions narrowed 0 to 50% in cross-sectional area histologically, none were underestimated angiographically; of eight narrowed 51% to 75% histologically, seven had been underestimated, and of 42 narrowed 76% to 100% histologically, 17 were underestimated angiographically. The coronary atherosclerotic plaquing was diffuse (greater than 25% cross-sectional area narrowing) in 90% of 467 five-millimetre segments of coronary artery examined (24 cm per patient), and this diffuseness of the atherosclerotic process seems to be the major reason for angiographic underestimation of coronary narrowings.

Electrical Stability of Acutely Ischemic Myocardium Influences of Heart Rate and Vagal Stimulation

Previous investigations have shown that a slower heart rate (HR) and myocardial ischemia independently diminish the electrical stability of the heart. It therefore was suggested that increasing heart rate during myocardial infarction might diminish the incidence of serious ventricular arrhythmias. However, since increased HR during experimental acute myocardial ischemia augments the degree of ischemia, an evaluation of the presumed “protective” effects of increased HR on the electrical stability of acutely ischemic myocardium was undertaken. The differences in refractory periods (RP) of eight contiguous areas of the left ventricle were determined as a function of HR. In nonischemic myocardium, the disparity of RP was less at an HR of 180 than 60. However, in ischemic myocardium the disparity increased in three of six animals as the HR was increased from 60 to 90, in seven of 10 animals as HR was increased from 60 to 120, and in all animals when the HR was increased from 60 to 180. The increased disparity of RP is believed to favor development of reentrant arrhythmia. The vulnerability of the heart to develop ventricular fibrillation was assessed by determining ventricular fibrillation threshold (VFT). During ischemia, VFT was not only an inverse function of HR but also was found to be independently influenced by electrical stimulation of the cervical vagus nerves. In the absence of vagal stimulation VFT was lowered in only one of four dogs as HR was increased from 50 to 90, but decreased 30% (P < 0.01) as HR reached 120 and 74% at 180 beats/min. When vagal stimulation was used to control HR VFT was lowered 37% as HR was increased from 50 to 60 to 90 (P < 0.05). We conclude that increasing HR within a physiologic range by diminishing vagal tone during myocardial ischemia decreases electrical stability of the ventricle by (1) increasing ischemia consequent to the rate-induced increase in myocardial oxygen requirements, and (2) a direct electrophysiologic action of the vagus on the ventricular myocardium.

Observations on the optimum time for operative intervention for aortic regurgitation. I. Evaluation of the results of aortic valve replacement in symptomatic patients.

A recent echocardiographic study of symptomatic patients who had aortic valve replacement for isolated aortic regurgitation indicated that patients in whom preoperative left ventricular end–systolic dimension (LVD[SYS]) exceeded 55 mm or fractional shortening (%FS) was less than 25% were at high risk of developing congestive heart failure and dying after an otherwise successful operation. Because indices of left ventricular systolic function might identify asymptomatic patients with aortic regurgitation who might benefit from earlier operation, 37 such patients were evaluated with serial echocardiograms (mean follow–up 34 months). Fourteen patients (38%) subsequently developed symptoms and were recommended for operation (SUBSQ OP). Twenty–three patients (62%) remain asymptomatic during follow–up (NON OP). LVD(SYS) and %FS were the most sensitive measurements for distinguishing on initial examination the patients who subsequently required operation from those who have not (LVD[SYS] 53.0 mm SUBSQ OP vs 44.3 mm NON OP, p = 0.001; %FS 28.8% SUBSQ OP vs 33.9% NON OP,p = 0.002). During serial studies, the maximum rate of change in end–systolic dimension exceeded 7 mm per year in only one patient. Four of five patients (80%) with end–systolic dimension greater than 55 mm developed symptoms and came to operation during a mean follow–up of 39 months. Of the 20 patients whose initial end–systolic dimension was 50 mm or less, only four patients (20%) developed symptoms and required operation, and none died during follow–up. Thus, an asymptomatic patient with aortic regurgitation whose end–systolic dimension is less than 50 mm appears to be at low risk and can be safely followed with echocardiograms at yearly intervals. Asymptomatic patients with end–systolic dimension of 50–54 mm are being followed with serial echocardiograms every 4–6 months. Operation is now being recommended to patients with end–systolic dimensions of 55 mm or greater, even in the absence of symptom.

Operative treatment in hypertrophic subaortic stenosis. Techniques, and the results of pre and postoperative assessments in 83 patients.

The results of operative treatment in 83 patients with idiopathic hypertrophic subaortic stenosis (IHSS) are described. Most patients with the disease are asymptomatic, or derive satisfactory symptomatic improvement from nonoperative therapy: administration of propranolol, exercise limitation, control of arrhythmia, etc. Operation is required, however, in 10-15% of patients, those who remain severely symptomatic after nonoperative treatment or who become refractory to it. Operation relieves symptoms in IHSS by relieving obstruction to left ventricular outflow, and for a patient to be considered an operative candidate severe obstruction must be documented at left heart catheterization either under resting conditions or after provocative interventions. All 83 patients were severely incapacitated — 58 in Class III and 24 in Class IV. Seventy had obstruction at rest (average gradient 96 mm Hg), and 13 had only provocable obstruction. At operation the hypertrophic interventricular septum was exposed via an aortotomy, and a vertical bar of muscle was resected between parallel myotomy incisions. There were six operative deaths (7%); no patient has died since 1970. Seven patients have died late after operation, five of them from causes unrelated to their heart disease or the operation. All surviving patients describe symptomatic improvement. Fifty-two patients with obstruction at rest preoperatively (average gradient 95 mm Hg) have been studied postoperatively: no resting gradient was evident in 47, while in the remaining five the gradient was less than 25 mm Hg. Recurrence of obstruction has never been observed at late catheterization (21 pts) or late echocardiographic examination (37 pts). Obstruction could not be provoked postoperatively in ten of the 11 patients who had large gradients only with the Valsalva maneuver or isoproterenol administration preoperatively. Obstructed and provocable obstructed patients had similar symptomatic improvement after operation. A variety of rhythm and conduction abnormalities were observed both pre and postoperatively, and these are described in detail. The results of operation in these 83 patients with IHSS demonstrate that gratifying symptomatic and hemodynamic improvement uniformly follows left ventriculomyotomy and myectomy. Relief of obstruction and amelioration of symptoms have proved to be long-lasting during postoperative observation periods extending to 14 years. Continued application of the operative procedure in properly selected patients appears to be indicated.

Blood Fibrinolytic Activity in Man Diurnal Variation and the Response to Varying Intensities of Exercise

This investigation was undertaken in normal subjects to define the relationship between the intensity of exercise and magnitude of fibrinolytic response and to examine the effect of diurnal variations on the exercise response. Fibrinolytic activity was measured on fibrin plates and expressed as mm2. Diurnal variations occurred with lowest activity at 8:00 AM (mean, 66 mm2), and peak activity between 5:00 and 8:00 PM (mean, 266 mm2, P<0.001). Five minutes of maximal treadmill exercise caused a marked increase in mean activity from 90 to 658 mm2 (P<0.001). Five minutes of 70% maximal exercise produced no significant increase, but 30 minutes increased activity to 626 mm2 (P<0.005). In contrast, 30 minutes of 40% maximal exercise produced a small elevation from 80 to 173 mm2 (P<0.005). Maximal and 40% maximal exercise evoked greater responses at 4:00 PM than 8:00 AM. Exercise produces increases in fibrinolytic activity which are related to the relative intensity of exercise, its duration, and the time of day it is performed. Short bursts of intense exercise cause marked increases, but more prolonged bouts of moderate exercise are required to produce similar increases. The increases with prolonged mild exercise are small and comparable to those observed during resting diurnal variations.

Asymmetric Septal Hypertrophy

Abstract Studies by echocardiography and necropsy show that, with rare exception, all patients with idiopathic hypertrophic subaortic stenosis (or hypertrophic cardiomyopathy) have a ventricular se...

Clinical and Circulatory Effects of Isosorbide Dinitrate Comparison with Nitroglycerin

In order to resolve current controversies on isosorbide dinitrate (ISDN), we employed a particularly sensitive testing protocol to evaluate effects of sublingual ISDN and nitroglycerin on the exercise capacity of patients with angina. Ten minutes after ISDN 21 of 23 patients exercised longer (average 2.7 minutes, P < 0.001) than after placebo. Benefit was evident in only a minority of patients tested one hour and in none tested two hours after either ISDN or nitroglycerin. A given amount of exercise resulted in lower mean blood pressure (average 13 mm Hg, P < 0.001), higher heart rate (average 10 beats/min, P < 0.001), and shorter ejection time (average 0.04 second, P < 0.001) after ISDN. Similar changes were seen after nitroglycerin. The product of blood pressure, heart rate, and ejection time, an index of myocardial O2 consumption, was unchanged at angina after ISDN or nitroglycerin despite the increased exercise capacity, suggesting that clinical improvement after these drugs may be due to circulatory changes causing decreased myocardial O2 demand. We conclude that sublingual ISDN closely resembles nitroglycerin in its alteration of circulatory responses to exercise and in the duration of the resultant improvement in exercise capacity.

Sustained Effects of Nitroglycerin Ointment in Patients with Angina Pectoris

Cutaneous absorption of nitroglycerin is a well-documented phenomenon which may have unique advantages for the sustained prophylaxis of angina pectoris. Therefore, we have examined the effects of nitroglycerin ointment and placebo on exercise capacity in 14 patients with angina pectoris. Nitroglycerin ointment produced a significant increase in exercise capacity which persisted for at least three hours. Concomitant sustained changes in systolic blood pressure and resting heart rate were observed. Electrocardiographic evidence of myocardial ischemia was significantly reduced. Chronic administration in six patients did not reduce the effects of either nitroglycerin ointment or sublingual nitroglycerin. Nitroglycerin ointment appears to be a truly long-acting nitrate. While evidence of nitrate toxicity or tolerance was not observed in the present study, additional information is required before the widespread use of this agent can be recommended.

Differences in Distribution of Myocardial Abnormalities in Patients with Obstructive and Nonobstructive Asymmetric Septal Hypertrophy (ASH) Light and Electron Microscopic Findings

Patients with typical idiopathic hypertrophic subaortic stenosis (IHSS) represent only one subgroup of a cardiac disease in which the characteristic anatomic abnormality is asymmetric septal hypertrophy (ASH). In most patients with ASH, left ventricular outflow obstruction is absent and cardiac dysfunction presumably is due to widespread involvement of the left ventricle by an underlying myocardial abnormality. In other patients with ASH, left ventricular outflow obstruction is present (typical IHSS) and constitutes a major feature of the hemodynamic and physical findings. To determine whether patients with outflow obstruction also have the underlying myocardial abnormality diffusely involving the left ventricle, the gross morphology of hearts from patients with and without outflow obstruction were studied both by necropsy and by echocardiography. Echocardiographic studies revealed that the ventricular septum was thicker in obstructive ASH, a finding confirmed by the postmortem studies. The necropsy studies also indicated that although the left ventricular free wall was thickened in both obstructive and nonobstructive ASH, the configuration of the left ventricular free wall was distinctly different in the two groups. In obstructive ASH, the free wall was hypertrophied and identical in appearance to that seen in valvular aortic stenosis. Moreover, echocardiographic studies indicated that the thickening of the free wall behind posterior mitral leaflet appeared to regress after operative relief of the outflow obstruction. In contrast, the left ventricular free wall of severely symptomatic patients without outflow obstruction had a markedly different and unique appearance; the free wall of left ventricle directly behind the posterior mitral leaflet was of normal or less than normal thickness, whereas the remaining free wall was nonuniformly thickened. On the basis of these findings and the microscopic data presented in the companion paper, we conclude that the myocardial abnormality in obstructive ASH (typical IHSS) is localized largely to the ventricular septum, with left ventricular free wall thickening occurring as a consequence of outflow obstruction. In symptomatic patients with nonobstructive ASH, however, the data suggest that the left ventricle, including free wall, is extensively involved with a primary myocardial abnormality.

Reduction in Myocardial Ischemia with Nitroglycerin or Nitroglycerin plus Phenylephrine Administered during Acute Myocardial Infarction

Nitroglycerin reduces ischemic injury during acute myocardial infarction (AMI) in dogs--an effect that is potentiated when drug-induced hypotension and tachycardia are prevented with phenylephrine. To determine the effectiveness of nitroglycerin, alone or with phenylephrine, during AMI in man, 12 patients (five or whom had left heart failure) were evaluated by summing ST-segment abnormalities (sigmaST) from 35 precordial electrodes. The seven patients without heart failure did not benefit consistently from nitroglycerin alone; however, addition of phenylephrine to abolish nitroglycerin-induced arterial pressure reduction uniformly diminished sigmaST (4.9 to 3.2 mv; P less than 0.05). In patients with heart failure, nitroglycerin alone consistently reduced ischemia (5.8 to 4.4 mv, P less than 0.05); addition of phenylephrine often partially reversed this effect. Thus, administration of nitroglycerin, alone or with phenylephrine, can reduce myocardial ischemic injury during AMI in man; however, the response to phenylephrine depends on the presence or absence of left ventricular failure before treatment.