Showing papers by "Arthur M. Feldman published in 1994"

Sudden cardiac death in heart failure. The role of abnormal repolarization.

Abstract: Congestive heart failure is a common, highly lethal cardiovascular disorder claiming over 200,000 lives a year in the United States alone. Some 50% of the deaths in heart failure patients are sudden, and most of these are probably the result of ventricular tachyarrhythmias. Methods designed to identify patients at risk have been remarkably unrewarding, as have attempts to intervene and prevent sudden death in these patients. The failure to impact favorably on the incidence of sudden death in heart failure patients stems largely from a lack of understanding of the underlying mechanisms of arrhythmogenesis. This article explores the role of abnormalities of ventricular repolarization in heart failure patients. We will examine evidence for the hypothesis that alteration of repolarizing K+ channel expression in failing myocardium predisposes to abnormalities in repolarization that are arrhythmogenic. The possible utility of novel electrophysiological and ECG measures of altered ventricular repolarization will be explored. Understanding the mechanism of sudden death in heart failure may lead to effective therapy and more accurate identification of patients at greatest risk.

Ventricular systolic assessment in patients with dilated cardiomyopathy by preload-adjusted maximal power: Validation and noninvasive application

Abstract: BACKGROUNDNoninvasive cardiac-specific analysis of contractile function in patients with dilated heart failure remains problematic. This study tests whether maximal power divided by the square of end-diastolic volume (PWRmx/EDV2, or preload-adjusted PWRmx) can provide such assessment.METHODS AND RESULTSTo validate the load insensitivity of the PWRmx index and determine its response to contractile change, 24 subjects with chronic dilated cardiomyopathy underwent invasive pressure-volume catheterization study using the conductance catheter technique. Preload was transiently reduced by 30% using balloon occlusion of the inferior vena cava, and afterload impedance was lowered by 50%, induced by a bolus injection of nitroglycerin. Contractile state was varied by intravenous dobutamine, verapamil, or esmolol. PWRmx was calculated from the simultaneous product of ventricular pressure and rate of volume change (dV/dt), the latter derived from the volume catheter signal. PWRmx varied directly with preload but was ...

Endomyocardial gene expression during development of pacing tachycardia-induced heart failure in the dog.

Abstract: Selective and specific changes in gene expression characterize the end-stage failing heart. However, the pattern and relation of these changes to evolving systolic and diastolic dysfunction during development of heart failure remains undefined. In the present study, we assessed steady-state levels of mRNAs encoding a group of cardiac proteins during the early development of left ventricular dysfunction in dogs with pacing-induced cardiomyopathy. Corresponding hemodynamic assessments were made in the conscious state in the same animals and at the same time points at baseline, after 1 week of ventricular pacing, and at the onset of clinical heart failure. Systolic dysfunction dominated after 1 week of pacing, whereas diastolic dysfunction was far more pronounced with the onset of heart failure. Atrial natriuretic factor mRNA was undetectable in 7 of 12 hearts at baseline but was expressed in all hearts at 1 week (P < .01 by chi 2 test), and it increased markedly with progression to failure (P = .05). Creatine kinase-B mRNA also rose markedly with heart failure (P < .01). Levels of mRNA encoding beta-myosin heavy chain, mitochondrial creatine kinase, phospholamban, and sarcoplasmic reticulum Ca(2+)-ATPase did not significantly change from baseline, despite development of heart failure. Additional analysis to determine if these mRNA changes were related to the severity of diastolic or systolic dysfunction revealed that phospholamban mRNA decreased in hearts with larger net increases in end-diastolic pressure (+19.2 +/- 1.9 mm Hg) compared with those hearts in which it did not change (+4.0 +/- 4.9, P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

New therapeutic agents for the management of congestive heart failure.

Abstract: During the past year, several important studies have strongly supported the use of what we now view as the three-pronged, "standard" approach to the treatment of symptomatic heart failure: diuretics, digoxin, and angiotensin-converting enzyme inhibitors. New information regarding the latter two agents is reviewed elsewhere in this issue of Current Opinion in Cardiology. However, despite obvious advances in our management of this important clinical syndrome and the substantial body of evidence supporting the beneficial effects of the angiotensin-converting enzyme inhibitors, the prognosis for patients with symptomatic congestive heart failure remains abysmal. For this reason, new and novel agents for the pharmacologic treatment of patients with heart failure continue to be developed and clinically evaluated. This article reviews the results of recent clinical trials with some of these new investigational pharmacologic agents. To facilitate categorization of these new agents, they will be grouped according to their primary pharmacologic action. However, it should be noted that those pharmacologic actions may not necessarily be responsible for either the beneficial or deleterious effects associated with these agents.

Regulation of Gene Expression in the Failing Myocardium: Evidence for a Heart Failure Gene Program

Abstract: Over the past decade the availability of failing human myocardium obtained at the time of cardiac transplantation has led to the identification of a variety of both structural and biochemical abnormalities in the end-stage failing heart. These studies have identified profound abnormalities in the s-receptor-G protein adenylyl cyclase transmembrane signaling system in both humans with congestive heart failure as well as in selected animal models [1,2]; abnormalities that explain at least in part the insensitivity of the failing myocardium to adrenergic stimulation. At the level of the sarcoplasmic reticulum, investigators have identified a diminution of Ca2 + uptake sites [3], abnormal Ca2 + uptake [4], impaired Ca2 + handling [5], and an impairment in Ca2 + release [6].