Influence of Hospitalization for Cardiovascular Versus Noncardiovascular Reasons on Subsequent Mortality in Patients With Chronic Heart Failure Across the Spectrum of Ejection Fraction

Background—Noncardiovascular (non-CV) comorbidities may contribute to hospitalizations in patients with heart failure (HF). We examined the incidence of mortality following hospitalization for cardiovascular (CV) versus non-CV reasons in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program. Methods and Results—First hospitalizations for CV or non-CV reasons during the CHARM trial (N=7599) were related to subsequent risk of all-cause death using time-updated proportional hazards models. Over median 37.7 month follow-up, 2816 subjects (37.1%) were not hospitalized, 2893 (38.1%) were first hospitalized for CV reasons, and 1890 (24.9%) for non-CV reasons. The death rate (per 100 patient-years) among those not hospitalized was 2.8 compared with 17.8 after CV and 16.5 after non-CV hospitalization (both P<0.001 versus not hospitalized). Mortality at 30 days was higher after CV than non-CV hospitalization; however, among 30-day survivors of CV and non-CV hospitalization, rates of subsequent mortality were similar (14.5 versus 14.6 per 100 patient-years; P=0.62). Rates of CV hospitalization were higher for those with ejection fraction (EF) ⩽40% than those with EF >40% (P<0.001), but rates of non-CV hospitalization did not vary by EF. Low EF patients had higher risk for mortality than preserved EF patients after any hospitalization, but within each EF subgroup, mortality in 30-day survivors of CV versus non-CV hospitalization was similar. Conclusions—Non-CV hospitalization is frequent in patients with symptomatic heart failure and associated with risk of subsequent mortality similar to CV hospitalization across the spectrum of EF. These findings may have implications for developing strategies to prevent readmissions. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00634309 (CHARM-Added), NCT00634712 (CHARM-Preserved), NCT00634400 (CHARM-Alternative).

[1]  J. Cleland,et al.  Influence of concomitant disease on patterns of hospitalization in patients with heart failure discharged from Scottish hospitals in 1995. , 1998, European heart journal.

[2]  D. DeMets,et al.  Effect of Carvedilol on the Morbidity of Patients With Severe Chronic Heart Failure: Results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study , 2002, Circulation.

[3]  Karl Swedberg,et al.  Influence of Nonfatal Hospitalization for Heart Failure on Subsequent Mortality in Patients With Chronic Heart Failure , 2007, Circulation.

[4]  Hilary K. Wall,et al.  Costs of heart failure-related hospitalizations in patients aged 18 to 64 years. , 2010, The American journal of managed care.

[5]  S. Schneeweiss,et al.  Repeated hospitalizations predict mortality in the community population with heart failure. , 2007, American heart journal.

[6]  Karl Swedberg,et al.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial , 2003, The Lancet.

[7]  H. Krumholz,et al.  Spectrum of heart failure in older patients: results from the National Heart Failure project. , 2002, American heart journal.

[8]  H. Tsutsui [Candesartan in heart failure: assessment of reduction in mortality and morbidity]. , 2007, Nihon rinsho. Japanese journal of clinical medicine.

[9]  George A Mensah,et al.  Heart failure-related hospitalization in the U.S., 1979 to 2004. , 2008, Journal of the American College of Cardiology.

[10]  M. Pfeffer,et al.  Candesartan in heart failure--assessment of reduction in mortality and morbidity (CHARM): rationale and design. Charm-Programme Investigators. , 1999, Journal of cardiac failure.

[11]  M. Pfeffer,et al.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial , 2003, The Lancet.

[12]  T. Therneau,et al.  Hospitalizations after heart failure diagnosis a community perspective. , 2009, Journal of the American College of Cardiology.

[13]  A. Jha,et al.  Who Has Higher Readmission Rates for Heart Failure, and Why?: Implications for Efforts to Improve Care Using Financial Incentives , 2011, Circulation. Cardiovascular quality and outcomes.

[14]  Ulf Dahlström,et al.  Frequent non‐cardiac comorbidities in patients with chronic heart failure , 2005, European journal of heart failure.

[15]  Salim Yusuf,et al.  Predictors of mortality and morbidity in patients with chronic heart failure. , 2006, European heart journal.

[16]  Albert W Wu,et al.  Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure. , 2003, Journal of the American College of Cardiology.

[17]  C. Lang,et al.  Non-cardiac comorbidities in chronic heart failure , 2006, Heart.

[18]  C. O'connor,et al.  Causes of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: results from Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) program. , 2010, American heart journal.

[19]  Akshay S. Desai,et al.  Heart failure with preserved ejection fraction: time for a new approach? , 2013, Journal of the American College of Cardiology.

[20]  Sanjiv J Shah,et al.  Heart failure with preserved ejection fraction: treat now by treating comorbidities. , 2008, JAMA.

[21]  Mark D. Huffman,et al.  Heart disease and stroke statistics--2013 update: a report from the American Heart Association. , 2013, Circulation.

[22]  V. Roger,et al.  Lifetime Costs of Medical Care After Heart Failure Diagnosis , 2011, Circulation. Cardiovascular quality and outcomes.

[23]  D G Altman,et al.  Practical problems in fitting a proportional hazards model to data with updated measurements of the covariates. , 1994, Statistics in medicine.

[24]  D. Redelmeier,et al.  The treatment of unrelated disorders in patients with chronic medical diseases. , 1998, The New England journal of medicine.

[25]  Stefan Störk,et al.  Mode of Action and Effects of Standardized Collaborative Disease Management on Mortality and Morbidity in Patients With Systolic Heart Failure: The Interdisciplinary Network for Heart Failure (INH) Study , 2012, Circulation. Heart failure.

[26]  S. Normand,et al.  Patterns of Hospital Performance in Acute Myocardial Infarction and Heart Failure 30-Day Mortality and Readmission , 2009, Circulation. Cardiovascular quality and outcomes.

[27]  M. Pfeffer,et al.  Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme , 2003, The Lancet.

[28]  S. Janower Rosuvastatin in older patients with systolic heart failure. , 2007 .

[29]  Harlan M. Krumholz,et al.  Recent National Trends in Readmission Rates After Heart Failure Hospitalization , 2010, Circulation. Heart failure.

[30]  Sheila Roman,et al.  Public reporting and pay for performance in hospital quality improvement. , 2007, The New England journal of medicine.

[31]  M. Clearfield Rosuvastatin in older patients with systolic heart failure. , 2009, Current atherosclerosis reports.

[32]  P. Austin,et al.  Improved Outcomes With Early Collaborative Care of Ambulatory Heart Failure Patients Discharged From the Emergency Department , 2010, Circulation.

[33]  Karl Swedberg,et al.  Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial , 2003, The Lancet.

[34]  K. Swedberg,et al.  Risk following hospitalization in stable chronic systolic heart failure , 2013, European journal of heart failure.