Abstract
BackgroundComorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes. Methods and resultsOf 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF. ConclusionHFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.
Highlights
Heart failure (HF) is a clinical syndrome characterized by severe morbidity and mortality [1]
HFmrEF and HFrEF had lower prevalence of chronic kidney disease (CKD) (48% and 46%, respectively), HFmrEF had intermediate prevalence of atrial fibrillation (AF) (58%), which was lowest in HFrEF (51%)
AF and/or CKD and/or T2DM, and across patients with different combinations of these comorbidities within each heart failure (HF) phenotype by t-test or ANOVA, Wilcoxon rank-sum test or Kruskal Wallis tests for continuous variables and by chi-square rest for categorical variables
Summary
Heart failure (HF) is a clinical syndrome characterized by severe morbidity and mortality [1]. A comprehensive and detailed characterization of HF according to EF, comorbidities and outcomes may improve phenotyping, prognostication, diagnosis and clinical management, and importantly, facilitate interventional trial design planning in HF. In this setting information on comorbidities and cause-specific outcomes is critical for setting up eligibility criteria, assessing feasibility of enrolment, and estimating cardiovascular (CV) and competing event rates. Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs mid-range/mildly-reduced (HFmrEF) vs reduced (HFrEF) ejection fraction (EF), complicating trial design. Conclusion: HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk
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