Assessing the interaction of respiration and heart rate in heart failure and controls using ambulatory Holter recordings

Breathing is a critical component of cardiopulmonary function, but few tools exist to evaluate respiration in ambulatory patients. Holter monitoring allows accurate diagnosis of a host of cardiac issues, and several investigators have demonstrated the ability to detect respiratory effort on the electrocardiogram. In this study we introduce a myogram signal derived from 12-lead, high frequency Holter as a means of detecting respiratory effort. Using the combined myogram and ECG signal, four novel variables were created: total number of Cheyne-Stokes episodes; the BWRatio, the ratio of power (above baseline) measured one second after peak-to-peak respiratory power, an assessment of the "shape" of the respiratory effort; DRR, the change in RR interval centering around peak inspiration; and minutes of synchronized breathing, a fixed ratio of heart beats to respiratory cycles. These variables were assessed in 24-hour recordings from three cohorts: healthy volunteers (n = 33), heart failure subjects from the GISSI HF trial (n = 383), and subjects receiving implantable defibrillators with severely depressed left ventricular function enrolled in the M2Risk trial (n = 470). We observed a statistically significant 6-fold increase in the number of Cheyne-Stokes episodes (p = 0.01 by ANOVA), decreases in BWRatio (p < 0.001), as well as decrease in DRR in heart failure subjects; only minutes of synchronized breathing was not significantly decreased in heart failure. This study provides "proof of concept" that novel variables incorporating Holter-derived respiration can distinguish healthy subjects from heart failure. The utility of these variables for predicting heart failure, arrhythmia, and death risk in prospective studies needs to be assessed.