Background

The prognostic value of cardiopulmonary exercise testing (CPET) is established for risk stratification in patients with Heart Failure (HF) and reduced ejection fraction (HFrEF). Additionally right ventricular (RV) dysfunction or impairment is also associated with poor outcomes. 

Purpose

In this retrospective cohort analysis of a large single center heart failure cohort, we analyzed the combined value and interplay of RV impairment and exercise tolerance.

Methods

We included symptomatic patients with heart failure across the full spectrum of LVEF. All patients underwent CPET evaluation with an upright bicycle between 2015–2017. Peak power in W (Pmax), peak heart rate in bpm (HRmax), peak relative oxygen consumption in ml/min/kg (VO2max) and peak oxygen pulse in ml (O2HRmax) were assessed. Additionally all patients received standard two dimensional transthoracic echocardiography for assessment of RV functional impairment. The patients were follow up for up to 5 years and the primary endpoint of all-cause mortality was assessed. Patients were classified as impaired RV when evidence of right ventricular dilation (RVEDd >40mm or RVOT > 30mm) or decreased tricuspid annular systolic excursion (TAPSE < 17mm) was present. Additionally a Kaplan-Meier-analysis was performed to determine in presence of RV impairment improved stratification beyond a pre-defined cut-off of 14 ml/min/kg VO2max.

Results

For the primary analysis, 626 patients (mean age 59.9.7±13.8 years, 28.6% female) were included. Mean LVEF was 44.6 %. According to LVEF 282 or 46.1% of patients were classified as HFrEF, 82 or 13.4 % as HFmrEF and 248 or 40.5% as HFpEF. Mean BNP values were 514±827 pg/ml. Patients were followed up for a median of 4.0 years (IQR: 3.4-4.9 years). Over this period, the primary endpoint occurred in 110 (18.0%) patients. Overall, 135 (22.1%) of patients had evidence of RV dysfunction as defined above. Correspondingly these patients performed worse on CPET evaluation (Pmax: 105 W vs 85 W; HRmax 123 bpm vs 118 bpm; VO2max: 16.7 ml/min/kg vs. 13.3 ml/min/kg, O2HRmax: 11.3 ml vs. 9.8 ml). When entered into a multivariable COX regression model including left ventricular parameters like LVEF and LVEDd as well as baseline eGFR, BNP and body-mass-index (BMI) by backwards LR elimination RV dysfunction (categorial), VO2max and BMI remained in the model with the best fit, whereas markers of left ventricular dysfunction did not. In a final COX model using the three parameters, VO2max showed the greatest independent influence on survival (χ²: 83.6; p< 0.001; HR +1 ml/min/kg VO2max: 0.813; 0.772-0.856; p < 0.001). The Kaplan-Meier-estimator showed significant differences in survival for the four pre-specified groups (Figure 1; Log Rank Mantel-Cox: χ²: 56.7; p< 0.001).

Conclusion

In this retrospective monocentric analysis of a contemporary treated cohort a combined evaluation of exercise tolerance and right heart function highlighted the correlation between the two markers and hinted towards improved risk stratification for HF patients regardless of LVEF. The study is limited by its retrospective approach as well as the only two dimensional evaluation of RV impairment.

Figure 1. Kaplan-Meier-Estimator showing all-cause survival for the cohort stratified by VO2max (peak oxygen consumption) and RVD (right ventricular dysfunction).