Marvin L. Murphy

Observer agreement in evaluating coronary angiograms.

The reliability of interpretation of coronary arteriography as a diagnostic tool was investigated in a sub study of the VA Cooperative Study of Surgical Treatment for Coronary Arterial Occlusive Disease. Twenty two physicians with varying levels of experience read 13 cine angiograms — blind — on two different oc casions. Analysis of inter- and intraobserver variability showed that angiographic items about which observers were most inconsistent from one reading to the other had the largest interobserver disagreement as well. They were the distal portions of the left anterior descending and left circumflex arteries. Among the items on which there was most consistent agreement — namely, the right main coronary artery and presence of ven tricular aneurysm — there was most often agreement between observers as well. When individual readers were evaluated, some observers were far more consistent in their own readings of all the angiographic items than others. This intraobserver agreement in turn correlated fairly well with how often they agreed with the other observers and with how much experience they reported having in reading coronary cineangiograms.

Treatment of chronic stable angina. A preliminary report of survival data of the randomized Veterans Administration cooperative study.

We evaluated the effect of saphenous-vein-bypass grafting on survival in patients with chronic stable angina by comparing medical and surgical treatment in a large-scale, prospective randomized study. Excluding patients with left-main-coronary-artery disease who have already been reported, a total of 596 patients were entered into this study; when randomized into a medical group (310 patients) and a surgical group (286 patients), entry clinical and angiographic base lines were comparable. Operative mortality at 30 days was 5.6 per cent. At an average of one year after operation, 69 per cent of all grafts were patent, and 88 per cent of the surgical patients had atleast one patent graft. There was no statistically significant difference in survival, at a minimal follow-up interval of 21 months, between patients treated medically and those treated with saphenous-vein-bypass grafting. At 36 months, 87 per cent of the medical group and 88 per cent of the surgical group were alive.

Effect of bypass surgery on survival in patients in low- and high-risk subgroups delineated by the use of simple clinical variables.

A multivariate risk function was developed on data from all 508 medical patients in the Veterans Administration (VA) randomized study of coronary bypass surgery. The variables, in order of importance, were ST-segment depression on resting ECG, history of myocardial infarction, history of hypertension and New York Heart Association functional classification III or IV. These noninvasive variables have been reported to be risk factors in natural-history studies of coronary heart disease (CHD). Applying the risk function to medical and surgical patients of the 1972–1974 cohort yielded a 5-year probability of dying for each patient. Investigation of treatment effects in approximate terciles obtained by collapsing the probability distribution into low-, middle- and high-risk groups showed that surgery was beneficial for patients in the high-risk tercile even after removal of patients with left main coronary artery disease (17% surgical vs 34% medical mortality at 5 years; p < 0.01). This finding was accentuated when patients in the 10 hospitals with the lowest operative mortality (3.3%) were compared. Mortality results in the low-risk tercile favored medical treatment (medical vs surgical mortality 7% vs 17%; p < 0.05).The risk function predicted mortality well not only for the VA medical group, but also for an independent symptomatic CHD population from the University of Alabama arteriography registry.This report further delineates the advantages and limitations of coronary bypass surgery in CHD patients with chronic stable angina.

Mitochondrial function, oxygen extraction, epicardial S-T segment changes and tritiated digoxin distribution after reperfusion of ischemic myocardium

This study examines the effect of 2 hours of reperfusion on transiently ischemic myocardium in pigs. Indexes of myocardial viability measured were mitochondrial function, oxygen extraction, epicardial S-T segment change and distribution of tritiated digoxin. Results were as follows: (1) Mitochondrial function was markedly impaired in the reperfused area after 60 minutes or more of coronary occlusion. The defect would seem to be a block in electron flow near site I, which can be partially bypassed with succinate. (2) An apparent inability of the reperfused myocardium to extract oxygen did not improve with 2 hours of reperfusion. (3) Epicardial S-T segment mapping suggested that necrosis occurred during reperfusion. (4) There was an altered distribution of tritiated digoxin in the reperfused area. The results show that reperfusion for 2 hours did not improve myocardial viability after 60 minutes or more of ischemia.

Myocardial lesions in idiopathic and alcoholic cardiomyopathy: Study by ventricular septal biopsy☆

Abstract Myocardial biopsy specimens from 20 patients with cardiomyopathy were examined by electron and light microscopy. In 11 of 12 patients with idiopathic cardiomyopathy, loss of contractile elements and closely related sarcoplasmic reticulum was seen. Glycogen increase was common. Structural damage of mitochondria was inconsistently present in 5 patients. Examination revealed normal myocardium in 1 patient. In all 8 patients with alcoholic cardiomyopathy, loss of contractile elements and sarcoplasmic reticulum was present. In 5 alcoholic subjects, generalized dilatation of the sarcoplasmic reticulum was a prominent abnormality and in areas of some myofibers was the only structural abnormality. Glycogen increase was common. Mitochondria were structurally normal in 7 patients. Contractile element-sarcoplasmic reticulum disorganization and loss was a consistent ultrastructural abnormality common to both idiopathic and alcoholic cardiomyopathy. This change, whether secondary or primary, represented the major ultrastructural lesion correlating with myocardial dysfunction in our patients. Generalized swelling of the sarcoplasmic reticulum without disorganization appears to be an early manifestation of myocardial damage in alcoholic cardiomyopathy. Similar change was focal and inconsistent in idiopathic cardiomyopathy. This represented the only consistent difference noted in comparing the 2 groups of patients. Structural damage of mitochondria did not appear to be a major lesion in either idiopathic or alcoholic cardiomyopathy; however, in both conditions mitochondrial numbers were decreased in extensively damaged myofibers. Microtubules were identified in human myocardium and were most commonly observed in areas of contractile element-sarcoplasmic reticulum damage.

Left Ventricular Hypertrophy in Patients with Chronic Bronchitis and Emphysema

Abstract The causes and prevalence of left ventricular hypertrophy in 72 patients with an unequivocal clinical diagnosis of chronic bronchitis and emphysema associated with severe hypoxemia and hyp...

Reevaluation of electrocardiographic criteria for left, right and combined cardiac ventricular hypertrophy

Cardiac chamber weight was determined at necropsy in 323 men to develop correlative studies of electrocardiographic criteria for ventricular hypertrophy. Thirty recommended criteria for left ventricular (LV) hypertrophy, 10 for right ventricular (RV) hypertrophy, and combinations of both criteria for combined hypertrophy were evaluated. Four methods for electrocardiographic diagnosis of LV hypertrophy were derived: (1) a modification of the Romhilt-Estes point system; (2) the presence of any 1 of 3 criteria: (a) S V1 + R V5 or V6 greater than 35 mm, (b) left atrial abnormality, or (c) intrinsicoid deflection in lead V5 or V6 greater than or equal to 0.05 second; (3) a combination of any 2 criteria or of 1 criterion (above) plus at least 1 of the following 3 additional criteria: (a) left-axis deviation greater than -30 degrees, (b) QRS duration greater than 0.09 second, or (c) T-wave inversion in lead V6 of 1 mm or more; and (4) the use of a single criterion--left atrial abnormality. Sensitivity varied from 57 to 66% and specificity from 85 to 93% among these 4 methods. Myocardial infarction increased sensitivity of the foregoing methods, but the specificity was reduced. Method 2 is preferred for the electrocardiographic diagnosis of LV hypertrophy. Two methods were useful for right ventricular (RV) hypertrophy: (1) the use of any 1 of 4 criteria: (a) R/S ratio in lead V5 or V6 less than or equal to 1; (b) S V5 or V6 greater than or equal to 7 mm; (c) right-axis deviation of more than +90 degrees, or (d) P pulmonale; and (2) use of any 2 combinations of the foregoing criteria. Sensitivity ranged from 18 to 43% and specificity from 83 to 95%. Combined hypertrophy was best diagnosed using left atrial abnormality as the sole criteria of LV hypertrophy, plus any 1 of 3 criteria of RV hypertrophy: (a) R/S ratio in lead V5 or V6 less than or equal to 1, (b) S V5 or V6 greater than or equal to 7 mm, or (c) right axis deviation greater than +90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Ectopic Ventricular Prematurity and Its Relationship to Ventricular Tachycardia in Acute Myocardial Infarction in Man

In order to determine the role of the coupling interval of a premature ventricular contraction (PVC) in the development of paroxysmal ventricular tachycardia (PVT) during the early phase of acute myocardial infarction in man, 52 male patients with documented acute myocardial infarction had 24-hour Holter monitoring commenced within 24 hours of the onset of prolonged chest pain. Review of the tape recordings revealed that 27 patients had PVT documented, while 25 patients did not. Analysis of the data on the two groups showed that the frequency of PVCs, coupled PVCs, and accelerated idioventricular rhythm (AIVR) were found to be associated with a significantly increased incidence of ventricular tachycardia.The mean coupling interval of the PVCs initiating episodes of ventricular tachycardia was not significantly different from either the mean coupling interval of the isolated PVCs in the patients with PVT or the mean coupling interval of the PVCs in the patients without PVT. This suggests that the coupling interval of a ventricular ectopic is a poor predictor of ventricular tachycardia in the early phases of acute myocardial infarction.

Abnormal mitochondrial oxidative phosphorylation of ischemic myocardium reversed by Ca2+-chelating agents.

Mitochondria isolated from ischemic and ischemic-reperfused myocardium have been shown to have a defect in electron transport and in energy-linked 45 Ca 2+ uptake. In this study, the influence of Ca 2+ on the efficiency of oxidative phosphorylation by mitochondria isolated from ischemic and ischemic-reperfused myocardium was studied by directly measuring ATP production in the presence and absence of Ca 2+ -chelating agent—EDTA and EGTA. Results demonstrate the following. (a) Mitochondria isolated from ischemic myocardium have a low rate of ATP production, reduced ATP/O ratios and lower net ATP production. These functions are improved by EDTA. (2) Mitochondria from ischemic-reperfused myocardium are totally incapable of phosphorylating ADP in the absence of Ca-chelating agents. Addition of EDTA or EGTA either to the isolation medium or to the incubation medium restores the ability of these mitochondria to phosophorylate all added ADP, although the rate of this phosphorylation remained very slow. (3) The Ca 2+ content of mitochondria from ischemic-reperfused myocardium was higher than the Ca 2+ levels of mitochondria from either normal or ischemic myocardium. These results suggest that phosphorylation of ADP by mitochondria from ischemic and ischemic-reperfused myocardium is inhibited by endogeneous ionic Ca 2+ and that this inhibition can be partially reversed by the addition of Ca 2+ -chelating agents.

Improvement of mitochondrial energy production in ischemic myocardium by in vivo infusion of ruthenium red.

Reperfusion of acutely ischemic myocardium results in deficient energy production and abnormal Ca2+ deposition. This study evaluates mitochondrial energy production in ishemic reperfused myocardium following an in vivo infusion of a Ca2+ antagonist, ruthenium red. Results are summarized as follows: (1) In vivo infusion of ruthenium red increases adenosine diphosphate-induced respiration threefold and adenosine triphosphate (ATP) production fivefold compared with those mitochondria derived from myocardium which had been occluded 2 hr and reperfused 2 hr without ruthenium red. (2) Infusion of ruthenium red improves state 3 respiration and ATP production to nearly normal levels by mitochondria isolated from myocardium which had been occluded 30 min and reperfused 2 hr. However, mitochondrial respiration and ATP production from nonischemic myocardium are not altered by in vivo ruthenium red infusion. (3) Ruthenium red infusion decreases both tissue and mitochondrial Ca2+ content in ischemic-reperfused myocardium. (4) The partial improvement in energy production in ischemic-reperfused myocardium by ruthenium red is probably related to a decrease in intracellular Ca2+ concentration.