TY - JOUR
TI - Novel endotypes in heart failure: effects on guideline-directed medical
therapy
AU - Tromp, J.
AU - Ouwerkerk, W.
AU - Demissei, B. G.
AU - Anker, S. D. and
AU - Cleland, J. G.
AU - Dickstein, K.
AU - Filippatos, G.
AU - van der Harst,
AU - P.
AU - Hillege, H. L.
AU - Lang, C. C.
AU - Metra, M.
AU - Ng, L. L. and
AU - Ponikowski, P.
AU - Samani, N. J.
AU - van Veldhuisen, D. J.
AU - Zannad,
AU - F.
AU - Zwinderman, A. H.
AU - Voors, A. A.
AU - van der Meer, P.
JO - EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
PY - 2018
VL - 39
TODO - 48
SP - 4269-4276
PB - Oxford University Press
SN - null
TODO - 10.1093/eurheartj/ehy712
TODO - Heart failure; Phenotypes; Heterogeneity; Medication
TODO - Aims We sought to determine subtypes of patients with heart failure (HF)
with a distinct clinical profile and treatment response, using a wide
range of biomarkers from various pathophysiological domains.
Methods and results We performed unsupervised cluster analysis using 92
established cardiovascular biomarkers to identify mutually ex elusive
subgroups (endotypes) of 1802 patients with HF and reduced ejection
fraction (HFrEF) from the BIOSTAT-CHF project. We validated our findings
in an independent cohort of 813 patients. Based on their biomarker
profile, six endotypes were identified. Patients with endotype 1 were
youngest, less symptomatic, had the lowest N-terminal pro-B-type
natriuretic peptide (NT-proBNP) levels and lowest risk for all-cause
mortality or hospitalization for HF. Patients with endotype 4 had more
severe symptoms and signs of HF, higher NT-proBNP levels and were at
highest risk for all-cause mortality or hospitalization for HF [hazard
ratio (HR) 1.4; 95% confidence interval (Cl) 1.1-1.8]. Patients with
endotypes 2, 3, and 5 were better uptitrated to target doses of
beta-blockers (P < 0.02 for all). In contrast to other endotypes,
patients with endotype 5 derived no potential survival benefit from
uptitration of angiotensin-converting enzyme-inhibitoriangiotensin-II
receptor blocker and beta-blockers (P-interaction <0.001). Patients with
endotype 2 (HR 1.29; 95% Cl 1.10-1.42) experienced possible harm from
uptitration of beta-bockers in contrast to patients with endotype 4 and
6 that experienced benefit (P-interaction for all <0.001). Results were
strikingly similar in the independent validation cohort.
Conclusion Using unsupervised cluster analysis, solely based on
biomarker profiles, six distinct endotypes were identified with
remarkable differences in characteristics, clinical outcome, and
response to uptitration of guideline directed medical therapy.
ER -