Hypercapnia Attenuates Ventricular Ectopy during Wakefulness in a Young Man with Heart Failure

Abstract

Ventricular premature beats (VPBs) are common in heart failure (HF). Patients with HF often exhibit oscillations in breathing pattern (or Cheyne‐Stokes Respiration, CSR) that lead to increased VPBs during the hyperpneic phase. In such patients, CO2 inhalation during sleep eliminates CSR and reduces VPB prevalence. Whether this VPB‐lowering effect of CO2 occurs in awake HF patients without CSR remains unexplored. In a young CSR‐free HF patient (26 years; LVEF=20%; BMI=30 kg·m−2) with mild obstructive sleep apnea (AHI=17 events/h) and frequent ectopy, we compared the incidence of VPBs during: 1) resting breathing; 2) volitional hyperventilation; 3) and at standardized intervals (quartiles) during two CO2 rebreathing tests with end‐tidal O2 tension (PETO2) maintained at either 50 mmHg (hypercapnic‐hypoxia) or 150 mmHg (hypercapnic‐hyperoxia). Breath‐by‐breath ventilation, PETO2, and PETCO2 were measured by flowmeter and rapid gas analyzer and ECG and O2 saturation were monitored continuously. At rest (PETCO2=39 mmHg) and during hyperventilation (PETCO2=28 mmHg), VPBs occurred with 15% and 12% of all heart beats, respectively. With hyperoxic CO2 rebreathing (PETO2=148mmHg), as PETCO2 increased from 40, 46, 52, 57 mmHg in the first through fourth quartile, VPB incidence decreased from 11% to 6%, 3%, and 0%, respectively. Hypoxic rebreathing (PETO2=51mmHg) showed a similar trend: VPB incidence fell from 9% at a PETCO2 of 40 mmHg to 0% at 46 mmHg and remained at 0% thereafter. The hypercapnia‐induced reduction in VPB frequency was not dependent on heightened ventilation: VPBs were evident during volitional hyperventilation (12%) but not during the CO2 rebreathing quartiles with matched ventilation (0% for both hypoxia and hyperoxia). Furthermore, blood O2 also did not appear to modulate this response: VPB incidence at rest (15%) was similar to both hypoxic (11%; O2 saturation=86%) and hyperoxic (13%; O2 saturation=99%) CO2 rebreathing quartiles with matched ventilation (~9 L·min−1) and PETCO2 (~39 mmHg). These observations suggest that in HF, acute hypercapnia attenuates ventricular ectopy. The mechanism appears to be unrelated to increased respiratory or sympathetic drive, myocardial stretch accompanying large tidal volumes, or altered O2 availability. How hypercapnia exerts anti‐arrhythmic effects remain uncertain; we hypothesize that CO2 mediated increases in coronary flow may be involved.Support or Funding InformationExperiments were funded by a Project Grant from the Canadian Institutes of Health Research (PJT 159491).