Long-Term Outcomes of Heart Failure With Preserved or Mid-Range Ejection Fraction in the United States

Abstract

Background: Approximately one-half of all heart failure (HF) consists of heart failure with preserved ejection fraction (HFpEF) or heart failure with mid-range ejection fraction (HFmrEF). Although several recent trials have investigated treatments for HFpEF/HFmrEF, there is limited insight on the long-term clinical trajectory of this population.

Objectives: The purpose of this study was to model clinical outcomes in patients with symptomatic (NYHA functional class II-IV) HFpEF/HFmrEF over 10 years.

Methods: We developed a Markov model with stable HF, HF hospitalization, and death states to follow a cohort of patients with HFpEF/HFmrEF treated with standard of care (SoC) recommended by the American Heart Association/American College of Cardiology/Heart Failure Society of America. Population characteristics and clinical event probabilities were derived from recent phase 3 HFpEF/HFmrEF trials. We used weighted averages for control and sodium-glucose cotransporter-2 inhibitor outcomes. SoC was informed by baseline treatments reported in clinical trials.

Results: In a cohort of U.S. patients with HFpEF/HFmrEF treated with SoC, our model estimated 0.53 cumulative HF hospitalizations per patient over 10 years. Overall, 37% had at least 1 HF hospitalization, and 26% experienced cardiovascular death. The model estimated 6.1 years of life expectancy from age 72 and total cost of care over this time of $123,900.

Conclusions: HFpEF/HFmrEF is associated with high rates of HF hospitalization and cardiovascular mortality based on contemporary clinical trials in this population. Furthermore, clinical trial results are likely to be more optimistic than real-world outcomes. Continuing to optimize care and treatment may reduce clinical burden and improve population health.

Keywords: HFmrEF; HFpEF; costs; heart failure; hospitalizations; mortality.

Graphical abstract

Figure 1

Model Structure A Markov model was developed with 3 health states and 1-month cycle lengths. Stable HF was defined as having no acute HF events. Patients who experienced an HF hospitalization transitioned to stable HF after 1 cycle unless they experienced death or readmission for HF within 30 days. While alive, all patients were at risk of discontinuing treatment, hyperkalemia adverse events, composite renal endpoint events, or death due to either a cardiovascular or noncardiovascular cause. HF = heart failure.

Central Illustration

Long-Term Outcomes of Heart Failure With Preserved or Mid-Range Ejection Fraction: A Markov Model The simulation model included outcomes of recent phase 3 clinical trials, assuming treatment with contemporary standards of care in HFpEF/HFmrEF. The cumulative incidence of HF hospitalizations and proportion of patients experiencing cardiovascular or noncardiovascular death are shown over a 10-year time horizon starting at age 72 years. Over a 10-year time horizon, a cohort of 1,000 patients experienced 528 HF hospitalizations, lived an additional 6.1 years on average, and accumulated a total cost of $123,900 related to HF. ACC = American College of Cardiology; AHA = American Heart Association; HF = heart failure; HFmrEF = heart failure with mid-range ejection fraction; HFpEF = heart failure with preserved ejection fraction; HFSA = Heart Failure Society of America; LVEF = left ventricular ejection fraction; SoC = standard of care; USD = United States dollars.

Figure 2

Tornado Diagrams for 1-Way Sensitivity Analyses One-way sensitivity analyses were conducted to identify the most impactful contributors to variation in (A) life expectancy and (B) total cost. The 2 factors that impacted life expectancy the most were noncardiovascular mortality and cardiovascular mortality, followed by mortality risk associated with HF hospitalization and treatment with SGLT2 inhibitors. Parameters that resulted in a life expectancy range of <0.01 years are not shown. Total cost was most sensitive to the proportion of patients treated with SGLT2 inhibitors, followed by the monthly cost of stable HF and costs of noncardiovascular death and cardiovascular death. eGFR = estimated glomerular filtration rate; HF = heart failure; SGLT2 = sodium-glucose cotransporter-2; SoC = standard of care.