T. B. Levine

Bio: T. B. Levine is an academic researcher from University of Minnesota. The author has contributed to research in topics: Heart failure & Mean arterial pressure. The author has an hindex of 12, co-authored 19 publications receiving 4852 citations.

Plasma Norepinephrine as a Guide to Prognosis in Patients with Chronic Congestive Heart Failure

Abstract: Hemodynamics, plasma norepinephrine, and plasma renin activity were measured at supine rest in 106 patients (83 men and 23 women) with moderate to severe congestive heart failure. During follow-up lasting 1 to 62 months, 60 patients died (57 per cent); 47 per cent of the deaths were sudden, and 45 per cent were related to progressive heart failure. Statistically unrelated to the risk of mortality were cause of disease (60 patients had coronary disease, and 46 had cardiomyopathy), age (mean, 54.8 years), cardiac index (mean, 2.11 liters per minute per square meter of body-surface area), pulmonary wedge pressure (mean, 24.5 mm Hg), and mean arterial pressure (mean, 83.2 mm Hg). A multivariate analysis of the five significant univariate prognosticators--heart rate (mean, 84.4 beats per minute), plasma renin activity (mean, 15.4 ng per milliliter per hour), plasma norepinephrine (mean, 700 pg per milliliter), serum sodium (mean, 135.7 mmol per liter), and stroke-work index (mean, 21.0 g-meters per square meter)--found only plasma norepinephrine to be independently (P = 0.002) related to the subsequent risk of mortality. Norepinephrine was also higher in patients who died from progressive heart failure than in those who died suddenly. These data suggest that a single resting venous blood sample showing the plasma norepinephrine concentration provides a better guide to prognosis than other commonly measured indexes of cardiac performance.

The neurohumoral axis in congestive heart failure.

Abstract: The incidence of congestive heart failure is increasing in the United States. This common syndrome is characterized not only by impaired ventricular function but also by an increase in some endogenous vasoconstrictor substances, including norepinephrine, angiotensin II, and arginine vasopressin. Although activation of the systems that release these substances is presumed to be compensatory (to maintain perfusion pressure during inadequate flow), the sympathetic nervous system, renin-angiotensin-aldosterone system, and arginine vasopressin may contribute to the pathogenesis of the syndrome. The excessive vasoconstriction present in heart failure likely produces a further burden on the failing myocardium. New strategies in therapy are being developed to counteract the activation of vasoconstrictor forces in congestive heart failure. Data indicate that selective blockade of the renin-angiotensin system is useful. Preliminary data suggest that inhibition of the sympathetic nervous system may be helpful, and inhibition of vasopressin in animals with heart failure is being studied. New and more selective therapy for heart failure may come from these studies.

Acute Vasoconstrictor Response to Intravenous Furosemide in Patients with Chronic Congestive Heart Failure: Activation of the Neurohumoral Axis

Abstract: Hemodynamic and neurohumoral responses to acute diuretic therapy were measured in 15 patients with severe chronic heart failure given intravenous furosemide, 1.3 +/- 0.6 (SD) mg/kg body weight. Left ventricular pump function deteriorated by 20 minutes, as indicated by a fall in stroke volume index (27 +/- 8 to 24 +/- 7 mL/min X m2 body surface area, p less than 0.01) and an increase in left ventricular filling pressure (28 +/- 7 to 33 +/- 9 mm Hg, p less than 0.01). Increases occurred in heart rate (87 +/- 13 to 91 +/- 16 beats/min, p less than 0.01), mean arterial pressure (90 +/- 15 to 96 +/- 15 mm Hg, p less than 0.01), systemic vascular resistance (1454 +/- 394 to 1676 +/- 415 dynes X s X cm-5, p less than 0.01), plasma renin activity (9.9 +/- 8.5 to 17.8 +/- 16 ng/mL X h, p less than 0.05), plasma norepinephrine level (667 +/- 390 to 839 +/- 368 pg/mL, p less than 0.01), and plasma arginine vasopressin level (6.2 +/- 1.3 to 8.3 +/- 2.0 pg/mL, p less than 0.01). During the next 3.5 hours the patients had diuresis (2085 +/- 1035 mL) and the expected fall in filling pressure (28 +/- 7 to 22 +/- 10 mm Hg, p less than 0.01). Neurohumoral indicators also returned toward the control levels. Intravenous furosemide, in patients with severe chronic heart failure, is associated with acute pump dysfunction temporally related to activation of the neurohumoral axis.

Acute and long-term response to an oral converting-enzyme inhibitor, captopril, in congestive heart failure.

Abstract: Captopril (SQ 14,225), an oral angiotensin converting-enzyme inhibitor, was administered to 11 patients with severe congestive heart failure (CHF). Peak effect was observed at 1.5 hours after administration. At peak effect right atrial pressure fell from 3.4 to 0.0 mm Hg, pulmonary capillary wedge pressure (PCW) fell from 22.7 to 12.3 mm Hg, mean arterial pressure (MAP) fell from 79.5 to 62.1 mm Hg, systemic vascular resistance (SVR) fell from 1989 to 1370 dyn-sec-cm-5, pulmonary vascular resistance fell from 843 to 523 dyn-sec-cm, and cardiac index (CI) rose from 1.96 to 2.43 1/min/m2. These were all statistically significant. Control plasma renin activity (PRA) was elevated (25.9 ng/ml/hr) and correlated with resting PCW (r = 0.65). The acute hemodynamic response was related to PRA: a fall in MAP (r = 0.74), a fall in PCW (r = 0.80), a fall in SVR (r = 0.45) and a rise in CI (r = 0.45). Eight patients were placed on chronic captopril therapy. After 2 or more months, their exercise time was significantly increased, from 6.8 to 11.7 minutes. Their cardiothoracic ratios showed a significant decrease, from 0.55 to 0.52, and most patients reported symptomatic improvement. Chronic response was not predicted by acute hemodynamic response. Captopril is therefore a vasodilator with both arterial and venous effects that are at least partially caused by inhibition of the renin-angiotensin system. It may be useful for the treatment of CHF.

Hemodynamic and clinical response to enalapril, a long-acting converting-enzyme inhibitor, in patients with congestive heart failure.

Abstract: Enalapril, a new oral angiotensin converting-enzyme inhibitor, was administered to nine patients with severe congestive heart failure. Short-term hemodynamic response was noted within 2 hr and persisted for up to 24 hr. At peak effect mean arterial pressure fell from 83.4 +/- 10(SD) to 72.1 +/- 16.2 mm Hg (p less than .01), right atrial pressure from 13.6 +/- 6.0 to 10.4 +/- 7.5 mm Hg (p less than .01), pulmonary arterial pressure from 38.9 +/- 4.8 to 31.9 +/- 4.8 mm Hg (p less than .01), pulmonary capillary wedge pressure from 28.2 +/- 3.5 to 22.1 +/- 5.1 mm Hg (p less than .01), and total pulmonary resistance from 875 +/- 304 to 697 +/- 291 dynes-sec-cm-5 (p less than .05). Cardiac index was not changed, but there was a significant redistribution of regional blood flow with an increase of renal blood flow after enalapril. Plasma renin activity rose significantly from 6.2 to 28.6 ng/ml/hr, whereas plasma norepinephrine did not change after enalapril. Seven patients were treated with enalapril for 4 weeks. Five patients reported symptomatic improvement. Five of six patients tested had an increase in both exercise time (NS) and maximum oxygen consumption (NS). Repeat hemodynamic evaluation in six patients after long-term enalapril therapy showed a persistent effect with significant reductions in right atrial pressure from 13.8 +/- 7.2 to 7.1 +/- 4.7 mm Hg and in mean arterial pressure from 82.5 +/- 10.4 to 76.6 +/- 5.3 mm Hg and a significant increase in cardiac index from 2.1 +/- 0.5 to 2.5 +/- 0.5 l/min/m2 (all p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased heart rate variability and its association with increased mortality after acute myocardial infarction

Abstract: A high degree of heart rate (HR) variability is found in compensated hearts with good function, whereas HR variability can be decreased with severe coronary artery disease, congestive heart failure, aging and diabetic neuropathy. To test the hypothesis that HR variability is a predictor of long-term survival after acute myocardial infarction (AMI), the Holter tapes of 808 patients who survived AMI were analyzed. Heart rate variability was defined as the standard deviation of all normal RR intervals in a 24-hour continuous electrocardiogram recording made 11 +/- 3 days after AMI. In all patients demographic, clinical and laboratory variables were measured at baseline. Mean follow-up time was 31 months. Of all Holter variables measured, HR variability had the strongest univariate correlation with mortality. The relative risk of mortality was 5.3 times higher in the group with HR variability of less than 50 ms than the group with HR variability of more than 100 ms. HR variability remained a significant predictor of mortality after adjusting for clinical, demographic, other Holter features and ejection fraction. A hypothesis to explain this finding is that decreased HR variability correlates with increased sympathetic or decreased vagal tone, which may predispose to ventricular fibrillation.

The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure

Abstract: Background Controlled clinical trials have shown that beta-blockers can produce hemodynamic and symptomatic improvement in chronic heart failure, but the effect of these drugs on survival has not been determined. Methods We enrolled 1094 patients with chronic heart failure in a double-blind, placebo-controlled, stratified program, in which patients were assigned to one of four treatment protocols on the basis of their exercise capacity. Within each of the four protocols patients with mild, moderate, or severe heart failure with left ventricular ejection fractions ≤0.35 were randomly assigned to receive either placebo (n = 398) or the beta-blocker carvedilol (n = 696); background therapy with digoxin, diuretics, and an angiotensin-converting–enzyme inhibitor remained constant. Patients were observed for the occurrence of death or hospitalization for cardiovascular reasons during the following 6 months (12 months for the group with mild heart failure). Results The overall mortality rate was 7.8 percent in t...

The Effect of Carvedilol on Morbidity and Mortality in Patients With Chronic Heart Failure

Abstract: Background Controlled clinical trials have shown that beta-blockers can produce hemodynamic and symptomatic improvement in chronic heart failure, but the effect of these drugs on survival has not been determined. Methods We enrolled 1094 patients with chronic heart failure in a double-blind, placebo-controlled, stratified program, in which patients were assigned to one of four treatment protocols on the basis of their exercise capacity. Within each of the four protocols patients with mild, moderate, or severe heart failure with left ventricular ejection fractions ≤0.35 were randomly assigned to receive either placebo (n = 398) or the beta-blocker carvedilol (n = 696); background therapy with digoxin, diuretics, and an angiotensin-converting–enzyme inhibitor remained constant. Patients were observed for the occurrence of death or hospitalization for cardiovascular reasons during the following 6 months (12 months for the group with mild heart failure). Results The overall mortality rate was 7.8 percent in t...

A Comparison of Enalapril with Hydralazine–Isosorbide Dinitrate in the Treatment of Chronic Congestive Heart Failure

Abstract: Background and Methods. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator—Heart Failure Trial. Results. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine—isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was m...

Narrative review: the management of acute decompensated heart failure.

Abstract: Acute decompensated heart failure (ADHF) is the most common reason for hospitalization in Western nations. The prognosis of patients admitted to hospital with ADHF is poor, with up to 64% being readmitted within the first 90 days after discharge and with a 1-year mortality approximating 20%. Epidemiological studies suggest that the majority of patients hospitalized with ADHF receive treatment that is inadequate and which is not based on scientific evidence. Furthermore, emerging data suggest that the "conventional" therapeutic interventions for ADHF including morphine, high-dose diuretics, and inotropic agents may be harmful. The goal of this review is to provide evidence-based recommendations for the diagnosis and management of ADHF.