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Respiratory Effects of β-blocker Therapy in Heart Failure

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Abstract

The present review focuses on the effects of β-blockers on lung function in HF patients. Indeed, historically, β-blockers have been considered not indicated in the presence of impaired lung function but recently this concept has been challenged. Lung function abnormalities are part of the chronic HF syndrome, as both lung mechanics and gas exchange are impaired. The regulation of ventilation and gas exchange is under sympathetic control and, therefore, a possible target of β-blockers. β-Blocker compounds differ in terms of pharmacological action blocking either both β1 and β2 receptors (carvedilol), or selectively the β1 receptors (nebivolol, bisoprolol, metoprolol). This difference is likely to explain a different action on lung function. Indeed, 90% of β-receptors in the lung are located on the alveoli and are mainly β2, whereas 10% are on the airways (mainly β1-receptors). Expiratory gases and ventilation kinetic analysis during exercise on top of standard spirometry and resting lung diffusion for carbon monoxide (DLCO) provide an integrate evaluation of the respiratory function in HF patients. Carvedilol reduces hyperventilation in HF patients during the entire exercise and proportionally increases patients´ quality of life. However, carvedilol has a negative action at altitude when, to counterbalance hypoxia, hyperventilation is needed. Indeed, when exercise is performed at a simulated altitude of 2,000 m, PO2 is 69 ± 3 mmHg and 64 ± 4, in placebo and carvedilol, respectively. Mechanical pulmonary function in HF patients at rest and during exercise is only slightly influenced by β-blockers. β-Blockers affect DLCO differently in chronic HF. Specifically, carvedilol reduces DLCO from 88 ± 15% to 74 ± 13% due to reduction of membrane diffusion, whereas bisoprolol does not influence DLCO, likely due to the absence of action by bisoprolol on alveolar β2-receptors, which preserve active Na+ transport processes across the alveolar-capillary membrane. In conclusion, it is possible to use β-blockers in HF patients even in the presence of lung function impairment, but their use should be guided by a combination of lung function evaluation and knowledge of the pharmacological properties of each molecule

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Abbreviations

MDC trial:

Metoprolol in Dilated Cardiomyopathy trial

CIBIS trial:

Cardiac Insufficiency Bisoprolol Study

ANZ trial:

Australia/New Zealand Heart Failure Research Collaborative Group

MERIT-HF:

Metoprolol CR/XL Randomised Intervention Trial in Heart Failure

CIBIS II:

Cardiac Insufficiency Bisoprolol Study II

COPERNICUS trial:

Carvedilol Prospective Randomised Cumulative Survival trial

CAPRICORN trial:

Carvedilol Post-infarct survival Control in left ventricular dysfunction

COMET study:

Carvedilol Or Metoprolol European Trial

BEST trial:

Beta-blocker Evaluation Survival Trial

SENIORS trial:

Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure

HF:

Heart failure

VO2 :

Oxigen uptake (oxigen consumption)

VCO2 :

Carbon dioxide output (carbon dioxide production )

VD/VT:

Physiological dead space/tidal volume ratio

VE:

Ventilation

PaCO2 :

Partial pressure of CO2 in arterial blood

DLCO:

Lung diffusion for carbon monoxide

DM:

Membrane diffusion capacity

VE/VCO2 :

Ventilatory equivalents for CO2

OUES:

Oxigen uptake efficiency slope

PetCO2 :

End-tidal CO2 tension

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Acknowledgement

We thank Elisabetta Salvioni PhD for the careful scientific support to the manuscript.

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Correspondence to Piergiuseppe Agostoni.

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Agostoni, P., Palermo, P. & Contini, M. Respiratory Effects of β-blocker Therapy in Heart Failure. Cardiovasc Drugs Ther 23, 377–384 (2009). https://doi.org/10.1007/s10557-009-6195-2

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