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.