Prognostic Value of Cardiopulmonary Exercise Testing in Heart Failure With Reduced, Midrange, and Preserved Ejection Fraction.

This study aimed to compare the independent and incremental prognostic value of peak oxygen consumption (VO2) and minute ventilation/carbon dioxide production (VE/VCO2) in heart failure (HF) with preserved (HFpEF), midrange (HFmEF), and reduced (HFrEF) ejection fraction (LVEF). In 195 HFpEF (LVEF ≥50%), 144 HFmEF (LVEF 40-49%), and 630 HFrEF (LVEF <40%) patients, we assessed the association of cardiopulmonary exercise testing variables with the composite outcome of death, left ventricular assist device implantation, or heart transplantation (256 events; median follow-up of 4.2 years), and 2-year incident HF hospitalization (244 events). In multivariable Cox regression analysis, greater association with outcomes in HFpEF than HFrEF were noted with peak VO2 (HR [95% confidence interval]: 0.76 [0.67-0.87] versus 0.87 [0.83-0.90] for the composite outcome, Pinteraction=0.052; 0.77 [0.69-0.86] versus 0.92 [0.88-0.95], respectively for HF hospitalization, Pinteraction=0.003) and VE/VCO2 slope (1.11 [1.06-1.17] versus 1.04 [1.03-1.06], respectively for the composite outcome, Pinteraction=0.012; 1.10 [1.05-1.15] versus 1.04 [1.03-1.06], respectively for HF hospitalization, Pinteraction=0.019). In HFmEF, peak VO2 and VE/VCO2 slope were associated with the composite outcome (0.79 [0.70-0.90] and 1.12 [1.05-1.19], respectively), while only peak VO2 was related to HF hospitalization (0.81 [0.72-0.92]). In HFpEF and HFrEF, peak VO2 and VE/VCO2 slope provided incremental prognostic value beyond clinical variables based on the C-statistic, net reclassification improvement, and integrated diagnostic improvement, with models containing both measures demonstrating the greatest incremental value. Both peak VO2 and VE/VCO2 slope provided incremental value beyond clinical characteristics and LVEF for predicting outcomes in HFpEF. Cardiopulmonary exercise testing variables provided greater risk discrimination in HFpEF than HFrEF.

Nadruz W Jr ，West E ，Sengeløv M ，Santos M ，Groarke JD ，Forman DE ，Claggett B ，Skali H ，Shah AM ... -  《Journal of the American Heart Association》

Heart Failure and Midrange Ejection Fraction: Implications of Recovered Ejection Fraction for Exercise Tolerance and Outcomes.

Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known. We studied 944 patients with HF who underwent clinically indicated cardiopulmonary exercise testing. The study population was categorized according to LVEF as follows: HF with reduced LVEF (HFrEF; LVEF<40%; n=620); HF with midrange ejection fraction and no recovered ejection fraction (LVEF was consistent between 40% and 55%; n=107); HF with recovered midrange ejection fraction (LVEF, 40%-55% but previous LVEF<40%; n=170); and HF with preserved LVEF (HFpEF; LVEF>55%; n=47). HF with midrange ejection fraction and no recovered ejection fraction and HF with recovered midrange ejection fraction had similar clinical characteristics, which were intermediate between those of HFrEF and HFpEF, and comparable values of predicted peak oxygen consumption and minute-ventilation/carbon dioxide production slope, which were better than HFrEF and similar to HFpEF. After a median of 4.4 (2.9-5.7) years, there were 253 composite events (death, left ventricular assistant device implantation, or transplantation). In multivariable Cox-regression analysis, HF with recovered midrange ejection fraction had lower risk of composite events than HFrEF (hazard ratio, 0.25; 95% confidence interval, 0.13-0.47) and HF with midrange ejection fraction and no recovered ejection fraction (hazard ratio, 0.31; 95% confidence interval, 0.15-0.67), and similar prognosis when compared with HFpEF. In contrast, HF with midrange ejection fraction and no recovered ejection fraction tended to show intermediate risk of outcomes in comparison with HFpEF and HFrEF, albeit not reaching statistical significance in fully adjusted analyses. Patients with HF with midrange LVEF demonstrate a distinct clinical profile from HFpEF and HFrEF patients, with objective measures of functional capacity similar to HFpEF. Within the midrange LVEF HF population, recovered systolic function is a marker of more favorable prognosis.

Nadruz W Jr ，West E ，Santos M ，Skali H ，Groarke JD ，Forman DE ，Shah AM ... -  《-》

Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure.

Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V̇E /V̇CO2 ) slope. The physiological correlates of the V̇E /V̇CO2 slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (VD /VT ) and arterial CO2 tension (PaCO2 ) differentially contribute to the V̇E /V̇CO2 slope in HFrEF vs. HFpEF. Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean ± standard deviation (SD) left ventricular ejection fraction: 22 ± 7% and 61 ± 9%, respectively; mean ± SD body mass index: 28 ± 4 kg/m2 and 33 ± 6 kg/m2 , respectively; P < 0.01] performed cardiopulmonary exercise testing with breath-by-breath ventilation and gas exchange measurements. PaCO2 was measured via radial arterial catheterization. We calculated the V̇E /V̇CO2 slope via linear regression, and VD /VT  = 1 - [(863 × V̇CO2 )/(V̇E  × PaCO2 )]. Resting VD /VT (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO2 (38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise VD /VT (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO2 (33 ± 6 mmHg vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇E /V̇CO2 slope was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance associated with the V̇E /V̇CO2 slope in HFrEF and HFpEF was explained by peak exercise VD /VT (R2  = 0.30 and R2  = 0.50, respectively) and PaCO2 (R2  = 0.64 and R2  = 0.28, respectively), but the relative contributions of each differed (all P < 0.01). Relationships between the V̇E /V̇CO2 slope and both VD /VT and PaCO2 are robust, but differ between HFpEF and HFrEF. Increasing V̇E /V̇CO2 slope appears to be strongly explained by mechanisms influential in regulating PaCO2 in HFrEF, which contrasts with the strong role of increased VD /VT in HFpEF.

Van Iterson EH ，Johnson BD ，Borlaug BA ，Olson TP ... -  《-》

A flattening oxygen consumption trajectory phenotypes disease severity and poor prognosis in patients with heart failure with reduced, mid-range, and preserved ejection fraction.

In heart failure (HF), a flattening oxygen consumption (VO2 ) trajectory during cardiopulmonary exercise test (CPET) reflects an acutely compromised cardiac output. We hypothesized that a flattening VO2 trajectory is helpful in phenotyping disease severity and prognosis in HF with either reduced (HFrEF), mid-range (HFmrEF), or preserved (HFpEF) ejection fraction. Overall, 319 HF patients (198 HFrEF, 80 HFmrEF, and 41 HFpEF) underwent CPET. A flattening VO2 trajectory was tracked and defined as an inflection of VO2 linearity as a function of work rate with a second slope downward inflection >35% extent of the first one. Peak VO2 , the minute ventilation/carbon dioxide production (VE/VCO2 ) slope, and the presence of exercise oscillatory ventilation (EOV) were also determined. Pulmonary artery systolic pressure (PASP) and tricuspid annular plane systolic excursion (TAPSE) were measured by echocardiography. A flattening VO2 occurred in 92 patients (28.8%). PASP and TAPSE at rest were significantly higher and lower (P < 0.001), respectively. The primary outcome was the combination of all-cause death, heart transplantation and left ventricular assist device implantation. The secondary outcome was the primary outcome plus hospitalization for cardiac reasons. In the multivariate model including peak VO2 , VE/VCO2 slope, EOV and VO2 trajectory, a flattening VO2 trajectory and EOV were retained in the regression for primary (X2 = 35.78, and 36.36, respectively; P < 0.001) and secondary (X2 = 12.45 and 47.91, respectively; P < 0.001) outcomes. Results point to a flattening VO2 trajectory as a likely new and strong predictor of events in HF with any ejection fraction. Given the relation of right-sided cardiac dysfunction to pulmonary hypertension, this oxygen pattern might suggest a real-time decrease in pulmonary blood flow to the left heart.

Popovic D ，Arena R ，Guazzi M 《-》

Cardiopulmonary exercise testing as prognostic indicators: Comparisons among heart failure patients with reduced, mid-range and preserved ejection fraction.

Sato T ，Yoshihisa A ，Kanno Y ，Suzuki S ，Yamaki T ，Sugimoto K ，Kunii H ，Nakazato K ，Suzuki H ，Saitoh SI ，Ishida T ，Takeishi Y ... -  《-》