What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure (n=31344). Intervention: Heart failure with preserved ejection fraction (HFpEF) vs. Heart failure with reduced ejection fraction (HFrEF). Primary outcome: All-cause mortality (IRR 0.95, 95% CI 0.91-0.99, p=0.018).

February 20, 2019Open Access

Non-cardiac comorbidities and mortality in patients with heart failure with reduced vs. preserved ejection fraction: a study using the Swedish Heart Failure Registry

CEConstantinos ErgatoudesSahlgrenska University Hospital MSMaria SchaufelbergerHeart Failure & Transplant BABert AnderssonHeart Failure & Transplant

Key Result

Non-cardiac comorbidities contributed significantly to mortality in both heart failure phenotypes, with diabetes, renal failure, and liver disease having a higher impact in HFrEF.

Study Design

Type

Cohort (n=31,344)

Multicenter

Yes

Structured PICO

Do non-cardiac comorbidities differentially impact all-cause mortality in patients with HFrEF compared to HFpEF?

Population

31,344 patients with heart failure (24,856 with HFrEF [EF < 50%] and 6,488 with HFpEF [EF ≥ 50%]) from the Swedish Heart Failure Registry (2000-2012). Mean age 72.5, 64.9% male. Excluded: death during hospitalization, incomplete EF information, and significant valve disease.

Intervention

Presence of non-cardiac comorbidities (hypertension, diabetes, stroke/TIA, anemia, renal failure, pulmonary disease, liver disease, sleep apnea, gout, cancer)

Comparator

Absence of respective comorbidities, and comparison of comorbidity impact between HFrEF and HFpEF phenotypes

Outcome

All-cause mortalityhard clinical

Non-cardiac comorbidities significantly increase mortality in both HFrEF and HFpEF, but specific conditions like diabetes and renal failure confer a higher relative mortality risk in HFrEF, while pulmonary disease confers a higher risk in HFpEF.

Main Result

Effect estimate: IRR 0.95 (95% CI 0.91-0.99)

Absolute Event Rate: 40.3% vs 34.3%

p-value: p=0.018

Limitations

Observational study subject to confounding and selection bias
Potential residual confounding despite extensive adjustments
Limited information on comorbidities regarding the degree of severity, staging, or disease duration
Patients with significant valve disease were excluded without data on grade or type

Abstract

BACKGROUND: Heart failure (HF) and non-cardiac comorbidities often coexist and are known to have an adverse effect on outcome. However, the prevalence and prognostic impact of non-cardiac comorbidities in patients with HF with reduced ejection fraction (HFrEF) vs. those with preserved (HFpEF) remain inadequately studied. METHODS AND RESULTS: We used data from the Swedish Heart Failure Registry from 2000 to 2012. HFrEF was defined as EF < 50% and HFpEF as EF ≥ 50%. Of 31 344 patients available for analysis, 79.3% (n = 24 856) had HFrEF and 20.7% (n = 6 488) HFpEF. The outcome was all-cause mortality. We examined the association between ten non-cardiac comorbidities and mortality and its interaction with EF using adjusted hazard ratio (HR). Stroke, anemia, gout and cancer had a similar impact on mortality in both phenotypes, whereas diabetes (HR 1.57, 95% confidence interval CI 1.50-1.65 vs. HR 1.39 95% CI 1.27-1.51, p = 0.0002), renal failure (HR 1.65, 95% CI 1.57-1.73 vs. HR 1.44, 95% CI 1.32-1.57, p = 0.003) and liver disease (HR 2.13, 95% CI 1.83-2.47 vs. HR 1.42, 95% CI 1.09-1.85 p = 0.02) had a higher impact in the HFrEF patients. Moreover, pulmonary disease (HR 1.46, 95% CI 1.40-1.53 vs. HR 1.66 95% CI 1.54-1.80, p = 0.007) was more prominent in the HFpEF patients. Sleep apnea was not associated with worse prognosis in either group. No significant variation was found in the impact over the 12-year study period. CONCLUSIONS: Non-cardiac comorbidities contribute significantly but differently to mortality, both in HFrEF and HFpEF. No significant variation was found in the impact over the 12-year study period. These results emphasize the importance of including the management of comorbidities as a part of a standardized heart failure care in both HF phenotypes.

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