Baroreflex sensitivity normalization after cardiac resynchronization therapy

Abstract

Neurohormonal activation is a key factor in the development and progression of chronic heart failure. Abnormalities in arterial baroreceptors has long been hypothesized to play an important pathogenic role by reducing the restraining influence on efferent autonomic neural activity to the cardiovascular system eventually leading to sympathetic hyperactivity and parasympathetic withdrawal. The arterial baroreflex sensitivity is tested by estimating the extent of change in heart rate following spontaneous, or pharmacologically induced systemic arterial blood pressure alterations and has been proposed as a valid index of the cardiovascular system capability to reflexly increase parasympathetic activity. In the clinical setting the methodology most extensively used relies on intravenous administration of phenylephrine, a pure alpha-agonist drug that activates arterial baroreceptors and leads to a reflex bradycardia, which can be measured as pulse interval prolongation: baroreflex sensitivity is quantified in ms of pulse interval prolongation for each mm Hg of arterial pressure increase elicited by the drug. In patients with chronic heart failure alterations in baroreceptor have been shown to provide information on the risk of death [ [1] Mortara A. La Rovere M.T. Pinna G.D. et al. Arterial baroreflex modulation of heart rate in chronic heart failure: clinical and hemodynamic correlates and prognostic implications. Circulation. 1997; 96: 3450-3458 Crossref PubMed Scopus (401) Google Scholar ]. Although optimization of medical treatment partially restores autonomic imbalance [ [2] Marin-Neto J.A. Pintya A.O. Gallo Jr., L. Maciel B.C. Abnormal baroreflex control of heart rate in decompensated congestive heart failure and reversal after compensation. Am J Cardiol. 1991; 67: 604-610 Abstract Full Text PDF PubMed Scopus (41) Google Scholar ], even with optimal pharmacotherapy a number of patients remain symptomatic. In this setting, a novel approach is cardiac resynchronization therapy, an intervention that, reducing the mechanical ventricular dissynchrony, has been shown to favorably impact on morbidity and functional capacity, as demonstrated by reduced hospitalization rate, improved quality of life, left ventricular ejection fraction, New York Heart Association class, mean distance walked in 6 min [ 3 Cazeau S. Leclercq C. Lavergne T. et al. MUSTIC Study InvestigatorsEffects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med. 2001; 344: 873-880 Crossref PubMed Scopus (2516) Google Scholar , 4 Abraham W.T. Fisher W.G. Smith A.L. et al. MIRACLE Study GroupCardiac resynchronization in chronic heart failure. N Engl J Med. 2002; 346: 845-853 Google Scholar ]. Recent data indicate that cardiac resynchronization therapy can also improve heart rate variability [ [5] Adamson P.B. Kleckner K.J. VanHout W.L. Srinivasan S. Abraham W.T. Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure. Circulation. 2003; 108: 266-269 Crossref PubMed Scopus (130) Google Scholar ], a marker of autonomic nervous system activity. However, the effect of cardiac resynchronization therapy on the reflex control of the heart has not been yet investigated.