H. William Strauss

Sudden death in the year following myocardial infarction. Relation to ventricular premature contractions in the late hospital phase and left ventricular ejection fraction

Both depressed left ventricular ejection fraction and ventricular arrhythmias have been associated with a poor prognosis following acute myocardial infarction. To assess the relative role of each of these parameters in predicting mortality in the early period after hospitalization for myocardial infarction, 24 hour ambulatory electrocardiographic tape recordings and gated cardiac blood pool scans were obtained in 81 patients approximately two weeks after their admission to the hospital for myocardial infarction. Lown class 0 to II ventricular premature contractions during this period were classified as uncomplicated ventricular arrhythmias and Lown class III to V ventricular premature contractions were classified as complicated ventricular arrhythmias. Ejection fraction was calculated from biplane images of gated cardiac blood pool scans. In 35 patients the ejection fraction was greater than or equal to 0.40; only three of these had complicated ventricular arrhythmias. In 45 patients the ejection fraction was less than 0.40; 26 of these had complicated ventricular arrhythmias. Eight patients had documented ventricular fibrillation or instantaneous death during a mean 7.0 moonth (range 2 to 16 months) follow-up period outside the hospital. Although the number of patients studied was small, and there were only eight sudden deaths, life table analysis projected a one year mortality of 66 per cent in patients with complicated ventricular arrhythmias and 31 per cent in patients with an ejection fraction less than 0.40. All eight patients who died suddenly were in the subgroup of 26 patients with an ejection fraction less than 0.40 and complicated ventricular arrhymias; none was in the subgroup of 19 patients with an ejection fraction less than 0.40 and uncomplicated ventricular arrhythmias (P less than 0.02). Although a low ejection fraction may suggest a poor prognosis following myocardial infarction, the presence of complicated ventricular arrhythmias significantly increases the risk of sudden cardiac death in the early period after hospitalization in patients with low ejection fraction.

The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: Contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis☆

Abstract Patients with diabetes mellitus experience a more adverse outcome after acute myocardial infarction compared with nondiabetic patients, although the mechanisms responsible for these findings are not clear. From the Multicenter Investigation of the Limitation of Infarct Size (MILIS) study, the course of acute infarction in 85 diabetic patients was compared with that in 415 nondiabetic patients, all of whom had serial assessments of left ventricular function. The diabetic patients experienced a more complicated in-hospital and postdischarge course than did the nondiabetic patients, including a higher incidence of postinfarction angina, infarct extension, heart failure and death, despite the development of a smaller infarct size and similar levels of left ventricular ejection fraction. Although diabetic patients had a worse profile of cardiovascular risk factors at the time of the index infarction, the increased incidence of adverse outcomes among them persisted despite adjustment for these baseline imbalances. Diabetic women had a poor baseline risk profile compared with the other groups categorized by gender and diabetic status, and experienced an almost twofold increase in cardiac mortality despite development of the smallest infarct size during the index event. The duration of diabetes and the use of insulin at the time of the index infarction were associated with a better in-hospital mortality rate, but the duration of diabetes did not exert a major influence on the outcome of the diabetic patients. The factors responsible for the increased incidence of adverse outcomes among diabetic patients may be related to an acceleration of the atherosclerotic process, diastolic left ventricular dysfunction associated with diabetic cardiomyopathy or other unidentified unfavorable processes.

Effects of gender and race on prognosis after myocardial infarction: Adverse prognosis for women, particularly black women

Controversy has arisen concerning whether gender influences the prognosis after myocardial infarction. Although some studies have shown there to be no difference between the sexes, most have indicated a worse prognosis for women, attributing this to differences in baseline characteristics. It has been further suggested that black women have a particularly poor prognosis after infarction. To determine the contribution of gender and race to the course of infarction, 816 patients with confirmed myocardial infarction who were enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS) were analyzed. Of those patients, 226 were women and 590 were men, 142 were black and 674 were white. The cumulative mortality rate at 48 months was 36% for women versus 21% for men (p less than 0.001, mean follow-up 32 months). The cumulative mortality rate by race was 34% for blacks versus 24% for whites (p less than 0.005). Both women and blacks exhibited more baseline characteristics predictive of mortality than did their male or white counterparts. It was possible to account for the greater mortality rate of blacks by identifiable baseline variables; however, even after adjustment, the mortality rate for women remained significantly higher (p less than 0.002). The poorer prognosis for women was influenced by a particularly high mortality rate among black women (48%); the mortality rate for white women was 32%, for black men 23% and for white men 21%. The mortality for black women was significantly greater than that of the other subgroups. Thus, findings in the MILIS population indicate that the prognosis after myocardial infarction is worse for women, particularly black women.

Heart failure in outpatients: a randomized trial of digoxin versus placebo.

The view that digitalis clinically benefits patients with heart failure and sinus rhythm lacks support from a well-controlled study. Using a randomized, double-blind, crossover protocol, we compared the effects of oral digoxin and placebo on the clinical courses of 25 outpatients without atrial fibrillation. According to a clinicoradiographic scoring system, the severity of heart failure was reduced by digoxin in 14 patients; in nine of these 14, improvement was confirmed by repeated trials (five patients) or right-heart catheterization (four patients). The other 11 patients had no detectable improvement from digoxin. Patients who responded to digoxin had more chronic and more severe heart failure, greater left ventricular dilation and ejection-fraction depression, and a third heart sound. Multivariate analysis showed that the third heart sound was the strongest correlate of the response to digoxin (P less than 0.0001). These data suggest that long-term digoxin therapy is clinically beneficial in patients with heart failure unaccompanied by atrial fibrillation whose failure persists despite diuretic treatment and who have a third heart sound.

Prognostic value of exercise thallium-201 imaging in patients presenting for evaluation of chest pain

Accurate prognostic information is important in determining optimal management of patients presenting for evaluation of chest pain. In this study, the ability of exercise thallium-201 myocardial imaging to predict future cardiac events (cardiovascular death or nonfatal myocardial infarction) was correlated with clinical, coronary and left ventricular angiographic and exercise electrocardiographic data in 139 consecutive, nonsurgically managed patients followed-up over a 3 to 5 year period (mean follow-up, 3.7 +/- 0.9), using a logistic regression analysis. Among patients without prior myocardial infarction (100 of 139), the number of myocardial segments with transient thallium-201 defects was the only statistically significant predictor of future cardiac events when all patient variables were evaluated. Among patients with myocardial infarction before evaluation (39 of 139), angiographic ejection fraction was the only significant predictor of future cardiac events when all variables were considered. This study suggests an approach to evaluate the risk of future cardiac events in patients with possible ischemic heart disease.

TUMOUR-INFILTRATING LYMPHOCYTES AND INTERLEUKIN-2 IN TREATMENT OF ADVANCED CANCER

Tumour-infiltrating lymphocytes (TIL) were isolated and expanded from small tumour biopsy samples of twenty-eight patients (thirteen with malignant melanoma, seven with renal cell carcinoma, and eight with non-small-cell lung cancer). The patients were treated with autologous expanded TIL (about 10(10)) and continuous infusions of recombinant human interleukin-2(1-3 x 10(6) U/m2 per 24 h). 29% of the patients with renal cell cancer and 23% of those with melanoma achieved objective tumour responses lasting 3-14 months. Toxic side-effects were limited, and no patient required intensive-care monitoring. Adoptive immunotherapy with TIL and interleukin-2 may be an effective systemic approach to the treatment of some patients with malignant melanoma and renal cell carcinoma.

Increased lung uptake of thallium-201 during exercise myocardial imaging: Clinical, hemodynamic and angiographic implications in patients with coronary artery disease☆

Abstract To determine the clinical significance of increased thallium-201 activity in the lung immediately after exercise stress, the thallium-201 scans in 227 patients undergoing cardiac catheterization were reviewed. Thallium lung activity on the Initial anterior view images were graded qualitatively as follows: 0 (none) in 175 patients (77 percent); 1+ (moderate—increased activity in the lungs but less intense than that in left ventricular myocardium) in 37 patients (16 percent); and 2+ (severe—activity equal to or greater in intensity than left ventricular myocardlal activity) in 15 patients (7 percent). Increased (1+ or 2+) lung activity was related to (1) a greater number of myocardial segmental thallium defects (probability [p]

Myocardial imaging with thallium-201: A multicenter study in patients with angina pectoris or acute myocardial infarction

A multicenter study of rest and exercise thallium-201 myocardial imaging in 190 patients from five centers was performed. Exercise images were obtained after graded treadmill or bicycle stress with use of five different gamma camera models and were interpreted by the originating investigator without knowledge of other clinical data. Of 42 patients with less than 50 percent coronary stenosis, 4 (10 percent) had a resting image defect, 1 (2 percent) a new exercise defect and 5 (12 percent) either a resting or an exercise image defect, or both. Of 148 patients with coronary stenosis of 50 percent or greater, 64, (45 percent) had an image defect in the study at rest, 90 (61 percent) had new or increased defects after exercise, and 115 (78 percent) had resting or exercise defects, or both. New exercise image defects were more common than exercise S-T depression (90 of 148 [61 percent] versus 62 of 148[42 percent]; P less than 0.01). In a second group of 111 patients with acute myocardial infarction studied at three centers, 90 patients (81 percent) had image defects compared with 71 (64 percent) two had new electrocardiographic Q waves (P less than 0.01). Smaller infractions, as assessed with serum enzyme values, and diaphragmatic infarctions were less commonly detected than larger or anterior infarctions. These findings suggest that myocardial imaging complements the electrocardiographic identification of acute myocardial infarction of exericse-induced myocardial ischemia.

Imaging Atherosclerotic Plaque Inflammation by Fluorodeoxyglucose With Positron Emission Tomography : Ready for Prime Time?

Inflammation is a determinant of atherosclerotic plaque rupture, the event leading to most myocardial infarctions and strokes. Although conventional imaging techniques identify the site and severity of luminal stenosis, the inflammatory status of the plaque is not addressed. Positron emission tomography imaging of atherosclerosis using the metabolic marker fluorodeoxyglucose allows quantification of arterial inflammation across multiple vessels. This review sets out the background and current and potential future applications of this emerging biomarker of cardiovascular risk, along with its limitations.

Therapeutic lymphangiogenesis with human recombinant VEGF-C

Chronic regional impairments of the lymphatic circulation often lead to striking architectural abnormalities in the lymphedematous tissues. Lymphedema is a common, disabling disease that currently lacks a cure. Vascular endothelial growth factors C and D mediate lymphangiogenesis through the VEGFR‐3 receptor on lymphatic endothelia. The purpose of this study was to investigate the therapeutic potential for lymphangiogenesis with VEGF‐C. We developed a rabbit ear model to simulate human chronic postsurgical lymphatic insufficiency. Successful, sustained surgical ablation of the ear lymphatics was confirmed by water displacement volumetry. After complete healing, the experimental animals (n=8) received a single, s.c. 100 μg dose of VEGF‐C in the operated ear; controls (n=8) received normal saline. Radionuclide lymphoscintigraphy was performed to quantitate lymphatic function. Immunohistochemistry (IHC) was performed 7–8 days following treatment. After VEGF‐C, there was a quantifiable amelioration of lymphatic function. IHC confirmed a significant increase in lymphatic vascularity, along with reversal of the intense tissue hypercellularity of untreated lymphedema. This study confirms the capacity of a single dose of VEGF‐C to induce therapeutic lymphangiogenesis in acquired lymphedema. In addition to improving lymphatic function and vascularity, VEGF‐C can apparently reverse the abnormalities in tissue architecture that accompany chronic lymphatic insufficiency.