Sustained Sympathoinhibitory Effects of Cardiac Resynchronization Therapy in Severe Heart Failure

Abstract

Abstract-Evidence is available that in heart failure, cardiac resynchronization therapy by biventricular pacing improves myocardial function and exercise capacity. Whether this is accompanied by a sustained inhibition of heart failure-dependent sympathoexcitation is uncertain. In 11 heart failure patients (meanϮSEM age, 68.4Ϯ1.5 years) in New York Heart Association (NYHA) class III and IV under medical treatment with an intraventricular conduction delay (QRS duration Ն130 ms), with a markedly depressed left ventricular ejection fraction, and undergoing implantation of a biventricular pacemaker, we measured beat-to-beat blood pressure and muscle sympathetic nerve traffic. Measurements, which also included echocardiographic and clinical variables, were performed before and Ϸ10 weeks after successful resynchronization therapy. Ten age-and NYHA class-matched heart failure patients who were under medical treatment for the same time period served as controls. Long-term resynchronization therapy improved cardiac function and caused a significant increase in systolic blood pressure coupled with an improvement in maximal oxygen consumption and exercise capacity. These effects were coupled with a significant and marked reduction in sympathetic nerve traffic when expressed both as burst frequency over time (44.1Ϯ3.6 vs 30.7Ϯ3.0 bs/min, Ϫ30.5%, PϽ0.02) and as burst frequency corrected for heart rate (68.3Ϯ5.9 vs 47.3Ϯ4.3 bs/100 beats, Ϫ32.1%, PϽ0.02). No significant change in the aforementioned parameters was seen in the control group. These data provide the first direct evidence that in severe heart failure, resynchronization therapy exerts a marked and sustained sympathoinhibition. Because in heart failure sympathetic overactivity adversely affects prognosis, this may have important clinical implications. Key Words: electrical stimulation Ⅲ heart failure Ⅲ sympathetic nervous system Ⅲ autonomic nervous system C ardiac resynchronization therapy (CRT) by biventricular pacing exerts favorable effects in patients with congestive heart failure (CHF) and intraventricular conduction delay in whom it improves symptoms, functional class, and quality of life with an increase in exercise tolerance. [1][2][3] Whether the favorable effects include a reduction in the enhanced sympathetic cardiovascular drive characterizing CHF 4 -6 is uncertain, however, because the studies that have addressed this issue so far had either methodological or design limitations. That is, they assessed adrenergic function only indirectly by plasma norepinephrine assay 3,7 or used direct measurement of muscle sympathetic nerve activity (MSNA) that was confined, however, to the acute phase of biventricular pacing. 8,9 The present study was designed to determine the longterm sympathetic effects of CRT in CHF patients with an intraventricular conduction delay by using a design similar to the 1 used in the MIRACLE trial, which had shown CRT to be accompanied by a sustained improvement in patient clinical status. 3 Sympathetic activity was quantified both indire...

Sympathetic activation in congestive heart failure: Reproducibility of neuroadrenergic markers

“…These data for sensitivity are similar to those reported by others [25]. During each experimental session, BP was monitored by a finger photopletismographic device (Finapres 2300, Ohmeda) capable of providing accurate beat-to-beat systolic and diastolic values [6][7][8][12][13][14][15]17,18]. Heart rate was monitored beat-to-beat by a cardiotachometer triggered by the R wave of an EKG lead.…”

“…Multiunit recording of MSNA was obtained from a microelectrode inserted in a peroneal nerve posterior to the fibular head, as reported previously [6][7][8]12,13,17,18]. Integrated nerve activity was monitored by a loud-speaker, displayed on a storage oscilloscope (model 511A, Tektronix), and continuously recorded with BP and heart rate on an ink polygraph.…”

“…Integrated nerve activity was monitored by a loud-speaker, displayed on a storage oscilloscope (model 511A, Tektronix), and continuously recorded with BP and heart rate on an ink polygraph. The muscle nature of MSNA was established according to criteria described in previous studies [6][7][8]12,13,17,18], and nerve recording was accepted only if the signal:noise ratio was N3. In the two experimental sessions, MSNA was quantified as bursts incidence corrected for heart rate values (bursts per 100 heart beats).…”

“…This is also the case for some of the studies aimed at investigating the effects of non-pharmacological or pharmacological interventions on adrenergic function [17,18]. Among the reasons suggested to explain the reduced ability of NE to reliably reflect sympathetic drive in CHF, a likely one is the limited reproducibility of the approach [19], as suggested by data obtained in essential hypertension, another condition characterized by a hyperadrenergic state [20].…”

Acute effects of cardiac resynchronization therapy on arterial distensibility and serum norepinephrine levels in advanced heart failure

“…Cha et al [25] found that clinical and cardiac functional improvements were paralleled by significant improvements in NE reuptake function as measured by metaiodobenzylguanidine ( 123 I-MIBG), an NE analog, uptake and retention after CRT for advanced cardiomyopathy. Also, CRT inhibits arterial baroreflex mediated sympathoexcitation occurring in CHF, and, therefore, reduces adrenergic nerve outflow measured by microneurography [26,27].…”