Background:Cardiovascular comorbidities have a negative impact on the health status and prognosis of patients with COPD. We determined whether nocturnal noninvasive (positive) mechanical ventilation (NIMV) can improve heart rate variability (HRV), decrease circulating natriuretic peptide levels, and improve functional performance of patients with very advanced COPD.Methods:A randomized, double-blind, parallel controlled trial was conducted in 23 participants with stable but advanced COPD. Participants received standard medical therapy plus nocturnal NIMV or standard medical therapy plus sham NIMV for 3 months.Results:After 3 months of NIMV therapy, the 24-h triangular interpolation of N-N intervals increased from 322 to 473 ms (p = 0.034), the 24-h HRV index (HRVI) increased from 21.8 to 29.9 ms (p = 0.035), nocturnal HRVI increased from 6.1 to 8.0 ms (p = 0.026), and the SD of the average N-N interval increased from 37 to 41 ms (p = 0.020). None of these indexes changed significantly in the control group. Additionally, compared with the control group, the pro-atrial natriuretic peptide levels declined significantly in the NIMV group (p = 0.013).Conclusions:NIMV applied nocturnally over 3 months may improve HRV, reduce circulating natriuretic peptide levels, and enhance the functional performance of patients with advanced but stable COPD. While not definitive due to small sample size, these data suggest that nocturnal NIMV may reduce the impact of cardiac comorbidities in COPD patients.