Development of Advanced Heart Failure: A Population-Based Study

Anna V. Subramaniam, Susan A. Weston, Jill M. Killian, Phillip J. Schulte, Veronique L. Roger, Margaret M. Redfield, Saul B. Blecker, Shannon M. Dunlay

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Some patients with heart failure (HF) will go on to develop advanced HF, characterized by severe HF symptoms despite attempts to optimize medical therapy. The goals of this study were to examine the risk of developing advanced HF in patients with newly diagnosed HF, identify risk factors for developing advanced HF, and evaluate the impact of advanced HF on outcomes. METHODS: This was a population-based, retrospective cohort study of Olmsted County, Minnesota, residents with a new clinical diagnosis of HF between 2007 and 2017. Risk factors for the development of advanced HF (2018 European Society of Cardiology criteria) were examined using cause-specific Cox proportional hazard regression models. The associations of development of advanced HF with risks of hospitalization and mortality were examined using the Andersen-Gill and Cox models, respectively. RESULTS: There were 4597 residents with incident HF from 2007 to 2017. The cumulative incidence of advanced HF was 11.5% (95% CI, 10.5%–12.5%) at 6 years after incident HF diagnosis overall and was 14.4% (95% CI, 12.3%–16.9%), 11.4% (95% CI, 8.9%–14.6%), and 11.7% (95% CI, 10.3%–13.2%) in patients with incident HF with reduced, mildly reduced, and preserved ejection fraction, respectively. Key demographics, comorbidities, and echocardiographic characteristics were independently associated with the development of advanced HF. Development of advanced HF was associated with increased risks of all-cause hospitalization (adjusted hazard ratio, 3.0 [95% CI, 2.7–3.4]; P<0.001), HF hospitalization (hazard ratio, 10.2 [95% CI, 8.7–12.1]), all-cause mortality (hazard ratio, 5.0 [95% CI, 4.5–5.6]; P<0.001), and cardiovascular mortality (hazard ratio, 7.8 [95% CI, 6.7–9.1]). CONCLUSIONS: In this population-based study, development of advanced HF was common and was associated with markedly increased morbidity and mortality.

Original languageEnglish (US)
Pages (from-to)423-432
Number of pages10
JournalCirculation: Heart Failure
Issue number5
StatePublished - May 1 2022


  • cardiology
  • epidemiology
  • heart failure
  • hospitalization
  • mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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