What is the clinical evidence from this study?

Study design: Observational. Population: End-stage heart failure (n=44). Primary outcome: Correlation between Na+-Ca2+ exchanger protein and norepinephrine levels (r=0.64, p=0.01).

What does this research mean for the field?

Sympathetic activation, indicated by elevated plasma norepinephrine, is significantly correlated with increased Na+-Ca2+ exchanger expression in end-stage heart failure, which is associated with a higher incidence of ventricular tachycardia. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

July 15, 2002Open Access

Importance of sympathetic activation for the expression of Na+-Ca2+ exchanger in end-stage failing human myocardium

Key Result

Plasma norepinephrine levels significantly correlated with Na+-Ca2+ exchanger expression (r=0.64; P=0.01), which was elevated in heart failure patients with ventricular tachycardia (P<0.05).

Study Design

Type

Observational (n=44)

Structured PICO

Is the expression of the Na+-Ca2+ exchanger in end-stage human heart failure regulated by sympathetic activation and associated with ventricular arrhythmias?

Population

23 patients suffering from end-stage cardiac failure examined in the hours preceding cardiac transplantation, and 21 healthy control subjects.

Comparator

21 healthy control subjects

Outcome

Protein levels of the Na+-Ca2+ exchanger and sarcoplasmic reticulum (SR) Ca2+-ATPase in left ventricles, and correlation with neurohumoral levelssurrogate

Sympathetic activation in end-stage heart failure is associated with increased expression of the Na+-Ca2+ exchanger, which may favor malignant ventricular arrhythmias.

Main Result

Effect estimate: r=0.64

p-value: p=0.01

Abstract

AIMS: In end-stage heart failure, an alteration in the expression of the Na+-Ca2+ exchanger has been reported. Regulation of its expression is largely unknown. We sought to find out whether Na+-Ca2+ exchanger in human heart failure is regulated by sympathetic activation. In addition, since Na+-Ca2+-exchange is electrogenic, we conjectured whether increased expression of Na+-Ca2+ exchanger is associated with an increased incidence of cardiac arrhythmias. METHODS AND RESULTS: Twenty-three patients suffering from end-stage cardiac failure were examined in the hours preceding cardiac transplantation. Plasma levels of norepinephrine, epinephrine, atrial natriuretic peptide, renin activity, aldosterone, tumour necrosis factor (TNF)-alpha, and TNF-receptors were measured. All parameters were elevated relative to 21 healthy control subjects. As determined by immunoblots, protein levels of the Na+-Ca2+ exchanger were increased by 56% and protein levels of sarcoplasmic reticulum (SR) Ca2+-ATPase were decreased by 20% in left ventricles of the explanted failing hearts. A significant correlation between protein and neurohumoral levels was exclusively found for the Na+-Ca2+ exchanger with norepinephrine (r=0.64; P=0.01). Recent Holter ECGs revealed that patients with sustained or non-sustained ventricular tachycardia (more than three consecutive beats) had significantly higher Na+-Ca2+ exchanger protein and plasma norepinephrine levels than patients with a maximum of two consecutive beats (Na+-Ca2+ exchanger: 109+/-10 vs 83+/-7, n=11 each, P<0.05; norepinephrine: 1359+/-159 vs 656+/-88 pg. ml(-1), n=9 each, P<0.001). CONCLUSIONS: Sympathetic activation may enhance the expression of Na+-Ca2+ exchanger in end-stage heart failure. The data support the hypothesis that increased Na+-Ca2+-exchange could favour malignant ventricular arrhythmias.