Penalized Model‐Based Unsupervised Phenomapping Unravels Distinctive HFrEF Phenotypes With Improved Outcomes Discrimination From Sacubitril/Valsartan Treatment Independent of MAGGIC Score

Figures

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  Figure 1. Key baseline differences of clinical characteristics (A) and cardiac features (B) among cluster based LCZ696 HFrEF phenogroups. HbA1c data were only available among 405 patients with diabetes and HFrEF in the present study. CAD indicates coronary artery disease; cESS, circumferential end‐systolic wall stress (unit, kdynes/cm2); eGFR, estimated glomerular filtration rate (unit, mL/min per 1.73 m2); LVEDVi, left ventricular end‐diastolic volume index (unit, mL/m2); LVH, left ventricular hypertrophy; and PG, phenogroup.

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  Figure 2. Linear relationships among various LV geometric measures as LV mass index (A) and LVEDVi (B) in relation to LV filling estimate (as E/e′, lateral) and linear relationship between relative wall thickness and LV wall stress (cESS) (C) among LCZ696 HFrEF phenogroups. cESS indicates circumferential end‐systolic wall stress (unit, kdynes/cm2); LV, left ventricular; LVEDVi, end‐diastolic left ventricular volume index (unit, mL/m2); PG, phenogroup; and RWT, relative wall thickness.

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  Figure 3. Intragroup comparisons for overall outcome differences among LCZ696 HFrEF phenogroups after age and sex adjustment. HF indicates heart failure; HFrEF, heart failure with reduced ejection fraction; HR, hazard ratio; and PG, phenogroup. *P<0.05 by Cox models.

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  Figure 4. Kaplan–Meier curves for overall outcome differences among LCZ696 HFrEF phenogroups and matched RASi control including (A) death from any cause, (B) HF hospitalization, (C) composite of death (any cause) and HF hospitalization, (D) cardiovascular death, (E) urgent HF visits, and (F) HF hospitalization among LCZ696 HFrEF phenogroups and matched RASi control. CTL indicates control group; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; and PG, phenogroup.

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  Figure 5. Summary of current study findings and potential clinical implications. The clinical, cardiac features, and clinical outcomes among 3 HFrEF phenogroups and potential diagnostic and therapeutic workup according to model‐based clustering phenotyping. ARNi indicates angiotensin receptor–neprilysin inhibitor; CV, cardiovascular; DM, diabetes mellitus; HFrEF, heart failure with reduced ejection fraction; LV, left ventricular; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; RWT, relative wall thickness; and sGLT2i, sodium–glucose cotransporter 2 inhibitor.