Risk stratification and survival in patients with HFmrEF: the role of cardiopulmonary exercise testing

Abstract

\n \n \n The prognostic value of cardiopulmonary exercise testing (CPET) is established for risk stratification in patients with heart failure (HF) and reduced ejection fraction (HFrEF). Since the introduction of HF with mid-range ejection fraction (HFmrEF) as an additional category in 2016, optimal management strategy and risk stratification for these patients is a field of ongoing research.\n \n \n \n Left ventricular ejection fraction (LVEF) is only one part of the picture when planning treatment and estimating long time risk for patients with HF. We planned to investigate the predictive long-term value of exercise intolerance as measured by CPET in patients with HFmrEF in comparison to HFrEF.\n \n \n \n We performed a single-center retrospective cohort study of ambulatory consecutive patients that showed signs of heart failure (NYHA functional class II or III) and had a LVEF of 49% or below as measured by echocardiography at the time of CPET. All patients underwent CPET evaluation with an upright bicycle between 2015–2017. The primary endpoint of all-cause mortality as well as the secondary composite endpoint of all-cause mortality or heart transplant/ventricular assist device implantation (transplant/VAD free survival) were assessed.\n \n \n \n For the primary analysis, 253 patients (mean age 61.2±13.0 years, 82.6% male) were included. 68 patients showed an LVEF between 40 and 49% (HFmrEF) whereas 185 patients had an LVEF of below 40% (HFrEF). HF etiology was in 31.3% ischemic. Mean BNP values were 788±1061 pg/ml while HFmrEF patients had on average lower values than HFrEF (322±676 vs. 945±1121, p<0.001). Patients were followed up for a median of 4.2 years (IQR: 3.5–5.0 years). Over this period, the primary and secondary end-point occurred in 22.5%/30.8% of patients.\n Patients in the HFmrEF group showed a higher mean peak oxygen uptake compared to HFrEF (pVO2; 17.3±4.6 vs 14.2±3.7 ml/min/kg, p<0.001), peak exercise power (Pmax; 111±49 vs 91±38 Watt, p=0.02) and peak oxygen pulse (pO2/HR; 12.6±4.2 vs 10.4±4.1 ml/min/kg, p<0.001). The Kaplan-Meier-Estimate showed a significant difference in survival for both HFmrEF and HFrEF who had pVO2 below 14 ml/min/kg (Log Rank: Chi2: 4.45, p=0.035 and Chi2: 10.05, p=0.02). In univariate Cox regression, pVO2 was predictive of the primary endpoint (HR per +1 mL/kg/min: 0.81; CI: 0.71–0.93; p=0.002 and HR per +1 mL/kg/min: 0.84; CI: 0.77–0.92; p<0.001) in both groups as was Pmax and pO2/HR (p<0.05 for both variables in both groups).\n \n \n \n As in HFrEF, CPET is a useful tool to stratify risk in HFmrEF as well. Our findings support the prognostic role of pVO2 as well as pO2/HR and Pmax in HF with mid-range LVEF. Using a cut off of pVO2 14 ml/min/kg selected patients at risk with similar long-term prognosis as in the HFrEF cohort. Further research to identify subgroups at risk within the heterogeneous group of HFmrEF is warranted for optimal risk stratification.\n \n \n \n Type of funding sources: None.\n