Showing papers by "David A. Kass 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)

Effects of acute changes in canine LV-chamber volume and shape on accuracy of impedance catheter estimates of LV-chamber volume

Abstract: The accuracy with which a multiple-electrode impedance catheter (IC) tracks instantaneous global, in-situ left ventricular (LV) volumes was tested in 13 anesthetized dogs scanned in the Dynamic Spatial Reconstructor (DSR), a fast volumetric computed tomographic (CT) scanner. All dogs were scanned during control conditions and during an acute hemodynamic intervention. Hypertonic saline calibrations were performed for the IC prior to each DSR scan. In six of the dogs the IC-derived LV end-diastolic volume (Y) correlated with the DSR-derived global LV end-diastolic volume (X) as follows: end-diastolic volume, Y = 1.01X - 9.9, r = 0.812. The IC-derived LV end-diastolic volume, under control conditions, correlated with the DSR-derived truncated (i.e., that region of the LV chamber between the proximal and distal electrodes of the IC catheter) LV end-diastolic volume, Y = 1.00X + 17.4, r = 0.803. Under reduced preload the relation was Y = 1.3X - 15.26, r = 0.911. The segmental volume (between adjacent sensing electrodes on the IC) at the basal portion of the LV correlated poorly (Y = 1.88X + 3.3, r = 0.459 etc.), but correlated better at mid- and more apical LV levels (Y = 0.97X + 2.7, r = 0.762). Correlations between segmental stroke volumes were similar at basal (Y = 1.31X + 1.60, r = 0.815) and mid- and more apical levels (Y = 1.42X + 0.11, r = 0.763). Stroke volume during acute ischemia (two dogs) was Y = 1.33X - 1.41, r = 0.717; during acutely decreased preload (four dogs) it was Y = 1.24X - 2.88, r = 0.572). Thus, the IC tracks the changes in LV-chamber volume throughout a cardiac cycle quite well under a variety of conditions, but accuracy deteriorates as the shape of the LV chamber changes in response to changes in hemodynamic loading or local myocardial ischemia.

Mechanisms of Ventricular Reserve Limitation in Cardiac Hypertrophy

Abstract: Ventricular hypertrophy is usually characterized by resting abnormalities of diastolic function with preserved systolic performance. However, there are often profound limitations of both diastolic and systolic functional reserve to physiologic stress. One of the most well studied reserve limitations is to chronotropic stress. Rapid atrial pacing can result in marked elevation of diastolic pressure and stiffness in animal hypertrophy models and in humans with idiopathic asymmetric hypertrophy presenting with chest pain syndrome. In other patients with severe hypertrophy and congestive failure symptoms, diastolic function does not deteriorate with rapid pacing, suggesting that underlying etiology and severity of disease are important factors to this response. Systolic reserve limitations to pacing stress are also found in both animal and human hypertrophy. Raising heart rate from 80 to 160 min—1 increases endsystolic elastance by nearly 100% in normal humans, while it is virtually unchanged in hypertrophied hearts. Mechanisms that may underlie the loss of contractile reserve to chronotropic challenge are abnormal subendocardial perfusion, altered calcium cycling, and changes in myofilament proteins. Each mechanism is reviewed. In addition to chronotropic reserve limitations, the hypertrophied heart has limited preload and inotropic reserve due to increased end-systolic chamber stiffness. A high end-systolic stiffness results in minimal augmentation of pump function (i. e., cardiac output) when contractility is increased. Furthermore, such a heart is highly sensitive to preload change, with marked alterations in systolic pressure generation and thus wall stress resulting from relatively small changes in chamber diastolic filling. Current and future therapeutic approaches to this disorder need to consider all of these reserve limitation mechanisms.