Ventricular arrhythmias not meeting criteria for terminating cardiopulmonary exercise testing stratify prognosis and disease severity in heart failure of preserved, midrange, and reduced ejection fraction

Background Continued high mortality in heart failure patients indicates the need for additional methods of risk stratification and phenotyping. Hypothesis We hypothesized that ventricular arrhythmias that do not meet test-termination criteria (non-terminating ventricular arrhythmias [NTVA]) during cardiopulmonary exercise testing (CPET) may help in phenotyping disease severity and prognosis in heart failure with reduced (HFrEF) and midrange (HFmrEF)/preserved (HFpEF) left ventricular ejection fraction (LVEF). Methods About 319 patients with heart failure (199 HFrEF; 80 HFmrEF; 41 HFpEF) underwent CPET. Tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) were measured by echocardiography. B-type natriuretic peptide (BNP) at rest and peak exercise was also determined. The patients were tracked for primary (cardiac death) and secondary composite outcomes (all-cause death, heart transplantation/left ventricular assist device implantation, hospitalization for cardiac reasons). Results Forty-seven (15%) of the patients demonstrated NTVA during CPET, regardless of coronary artery disease prevalence. Patients without arrhythmias had a significantly higher LVEF (P < .05), TAPSE/PASP ratio (P < .001), peak oxygen consumption (P < .01), lower resting and peak BNP (P < .001), and the minute ventilation/carbon dioxide production slope (P < .001) compared to those with NTVA. Seventy-one patients died during the tracking period, 54 for cardiac reasons. NTVA during CPET was a significant predictor of primary and secondary outcomes in the total heart failure cohort (HR: 5.3, 3.7; 95% CI: 3.1-9.1, 2.4-5.5; P < .001, respectively), as well as in subgroups categorized according to reduced and middle-range/preserved LVEF (P < .001). Conclusion Exercise-induced ventricular arrhythmias that do not reach test-termination criteria are nonetheless indicative of an advanced disease severity phenotype and worse prognosis.