Hemodynamic phenotyping based on exercise catheterization predicts outcome in patients with heart failure and reduced ejection fraction.
BACKGROUND
Exercise right heart catheterization (RHC) unmasks different phenotypes based on hemodynamic response to exertion in patients with heart failure. The prognostic relevance of this approach in patients with heart failure and reduced ejection fraction (HFrEF) is uncertain.


METHODS
We analyzed 167 patients with HFrEF from the Kerckhoff-Klinik Heart Failure Registry who underwent supine exercise RHC with constant external workload between September 2009 and August 2014. The primary outcome was heart transplant/assist device-free survival. Hemodynamic parameters that significantly predicted outcome were identified by multivariate Cox regression analysis and assessed further by Kaplan-Meier analysis after dichotomization using cutoffs derived from receiver operating characteristic analysis. Hemodynamic phenotypes were defined based on a dichotomized flow response (exercise-induced change in cardiac output [∆CO]) combined with a dichotomized pressure response (exercise-induced change in systolic [∆sPAP] or mean pulmonary arterial pressures).


RESULTS
∆CO independently predicted transplant/assist device-free survival (multivariate hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.09-2.58; p = 0.02). Patients with ∆CO ≥1.15 liter/min had significantly better 5-year transplant/assist device-free survival than patients with lower ∆CO (72.9% vs 22.5%; log-rank p < 0.001 [Kaplan-Meier analysis]). The hemodynamic phenotype of ∆CO <1.15 liter/min combined with ∆sPAP <17.5 mm Hg was associated with worse transplant/assist device-free survival than ∆CO ≥1.15 liter/min combined with ∆sPAP ≥17.5 mm Hg (multivariate HR 7.39; 95% CI, 2.27-24.05; p = 0.001).


CONCLUSIONS
Exercise RHC parameters are important prognostic indices in HFrEF. Hemodynamic phenotyping using ∆CO and ∆sPAP allows enhanced risk stratification.
Department of Cardiology Kerckhoff-Klinik, Bad Nauheim, Germany. Electronic address: a.rieth@kerckhoff-klinik.de.
Andreas
A
Rieth
Department of Pneumology, Kerckhoff-Klinik, Bad Nauheim, Germany; Department of Internal Medicine, Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Manuel Jonas
MJ
Richter
Department of Internal Medicine, Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Henning
H
Gall
Department of Internal Medicine, Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Werner
W
Seeger
Department of Pneumology, Kerckhoff-Klinik, Bad Nauheim, Germany; Department of Internal Medicine, Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Hossein A
HA
Ghofrani
Department of Cardiology Kerckhoff-Klinik, Bad Nauheim, Germany.
Veselin
V
Mitrovic
Department of Cardiology Kerckhoff-Klinik, Bad Nauheim, Germany; Department of Cardiology, Justus Liebig University Giessen, Universities of Giessen and Marburg, Giessen, Germany.
Christian W
CW
Hamm
D000368:Aged; D006328:Cardiac Catheterization / Q000379:methods*; D002302:Cardiac Output / Q000502:physiology; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008297:Male; D010641:Phenotype; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate / Q000639:trends
exercise right heart catheterization; heart failure with reduced ejection fraction; hemodynamic phenotype; prognostic factor; survival