Effects of β2-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective
Mauro Contini1, Emanuele Spadafora1, Simone Barbieri1
1Centro Cardiologico Monzino, IRCCS, Milano, Italy.
Abstract:
Alveolar β2-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar β2-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) β-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO2 slope and lower maximal PETCO2 during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO2 31.8 ± 5.9 vs. 28.5 ± 5.6, p < 0.0001 and maximal PETCO2 36.7 ± 5.5 vs. 37.7 ± 5.8 mmHg, p < 0.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119 ± 34 vs. 113 ± 30 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise.
Insights
Beta-blockers worsen lung diffusion in heart failure (HF). Stimulating beta-2 receptors with indacaterol did not worsen lung diffusion and improved exercise ventilation in some HF patients.
Area of Science:
- Cardiology
- Pulmonology
- Pharmacology
Background:
- Beta-2 receptor blockade in the lungs can impair diffusion capacity in heart failure (HF) patients.
- Stimulating alveolar beta-2 receptors may counteract this negative effect.
Purpose of the Study:
- To assess the safety and efficacy of indacaterol in HF patients on beta-blockers.
- To evaluate indacaterol's impact on lung diffusion, mechanics, sleep, cardiac rhythm, and exercise performance.
Main Methods:
- A randomized, double-blind, cross-over study involving 44 HF patients (27 on bisoprolol, 17 on carvedilol).
- Patients received indacaterol or placebo, with assessments before and after treatment.
Main Results:
- Indacaterol was well-tolerated and did not negatively affect lung diffusion overall.
- In patients on bisoprolol, indacaterol increased ventilation response during exercise (higher VE/VCO2 slope, lower maximal PETCO2).
- In patients on carvedilol, indacaterol showed a trend towards higher peak heart rate and reduced sleep hypopnea prevalence.
Conclusions:
- Inhaled indacaterol is safe for HF patients on beta-blockers.
- Indacaterol does not worsen lung diffusion and may improve exercise ventilation in HF patients treated with bisoprolol.
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