Prediction of the Chemoreflex Gain by Common Clinical Variables in Heart Failure.

Gianluca Mirizzi,Andrea Ripoli,Michele Emdin,Claudio Passino,Francesca Bramanti,Giovanni Iudice,Alberto Giannoni,Giuseppe Rengo

doi:10.1371/journal.pone.0153510

Gianluca Mirizzi, Andrea Ripoli + Show 6 more

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https://doi.org/10.1371/journal.pone.0153510

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Abstract

BackgroundPeripheral and central chemoreflex sensitivity, assessed by the hypoxic or hypercapnic ventilatory response (HVR and HCVR, respectively), is enhanced in heart failure (HF) patients, is involved in the pathophysiology of the disease, and is under investigation as a potential therapeutic target. Chemoreflex sensitivity assessment is however demanding and, therefore, not easily applicable in the clinical setting. We aimed at evaluating whether common clinical variables, broadly obtained by routine clinical and instrumental evaluation, could predict increased HVR and HCVR.Methods and results191 patients with systolic HF (left ventricular ejection fraction—LVEF—<50%) underwent chemoreflex assessment by rebreathing technique to assess HVR and HCVR. All patients underwent clinical and neurohormonal evaluation, comprising: echocardiogram, cardiopulmonary exercise test (CPET), daytime cardiorespiratory monitoring for breathing pattern evaluation. Regarding HVR, multivariate penalized logistic regression, Bayesian Model Averaging (BMA) logistic regression and random forest analysis identified, as predictors, the presence of periodic breathing and increased slope of the relation between ventilation and carbon dioxide production (VE/VCO2) during exercise. Again, the above-mentioned statistical tools identified as HCVR predictors plasma levels of N-terminal fragment of proBNP and VE/VCO2 slope.ConclusionsIn HF patients, the simple assessment of breathing pattern, alongside with ventilatory efficiency during exercise and natriuretic peptides levels identifies a subset of patients presenting with increased chemoreflex sensitivity to either hypoxia or hypercapnia.

Highlights

Modern therapies have improved the natural history of chronic heart failure (HF), mainly by tackling neurohormonal activation, the prognosis of HF is dismal [1,2,3] justifying the search for novel therapeutic targets in HF.Chemoreflex sensitivity (CS) represents a major determinant of neurohormonal imbalance in HF, being associated with reduced baroreflex sensitivity [4,5], heightened sympathetic outflow and periodic breathing (PB) [6,5,7]
In HF patients, the simple assessment of breathing pattern, alongside with ventilatory efficiency during exercise and natriuretic peptides levels identifies a subset of patients presenting with increased chemoreflex sensitivity to either hypoxia or hypercapnia
hypoxic ventilatory response (HVR) and hypercapnic ventilatory response (HCVR) were increased in 34% and 56% of patients, respectively

Summary

Introduction

Modern therapies have improved the natural history of chronic heart failure (HF), mainly by tackling neurohormonal activation, the prognosis of HF is dismal [1,2,3] justifying the search for novel therapeutic targets in HF.Chemoreflex sensitivity (CS) represents a major determinant of neurohormonal imbalance in HF, being associated with reduced baroreflex sensitivity [4,5], heightened sympathetic outflow and periodic breathing (PB) [6,5,7]. Modern therapies have improved the natural history of chronic heart failure (HF), mainly by tackling neurohormonal activation, the prognosis of HF is dismal [1,2,3] justifying the search for novel therapeutic targets in HF. CS impacted on prognosis mainly by increasing arrhythmic events and cardiac mortality, especially when both CS to hypoxia and hypercapnia were heightened (four-years survival 49%) compared to those with normal CS (survival 100%) [9]. Peripheral and central chemoreflex sensitivity, assessed by the hypoxic or hypercapnic ventilatory response (HVR and HCVR, respectively), is enhanced in heart failure (HF) patients, is involved in the pathophysiology of the disease, and is under investigation as a potential therapeutic target. We aimed at evaluating whether common clinical variables, broadly obtained by routine clinical and instrumental evaluation, could predict increased HVR and HCVR.

Methods

Results

Conclusion