Editor's Note: Commentary based on Tisminetzky M, Gurwitz JH, Fan D, et al. Multimorbidity burden and adverse outcomes in a community-based cohort of adults with heart failure. J Am Geriatr Soc 2018;66:2305-13.

Rationale for Study/Background: Multimorbidity has been associated with higher risks of hospitalization and death in individuals with heart failure (HF).^1-3 Applying guideline-directed therapies in management of patients with multiple chronic conditions is challenging and may lead to undesirable outcomes such as adverse interactions among drugs and diseases.² Older, multimorbid adults are often not included in clinical trials and therefore applicability of effectiveness of therapeutic agents is not often generalizable to this population.⁴ The authors of this study thought to delineate the association between multimorbidity burden and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF) and heart failure with borderline EF (HFbEF).

Funding: National Heart, Lung, and Blood Institute. Grant Number: RC1 HL099395 U19 HL91179; National Institute on Aging. Grant Number: R24 AG045050; Yale Claude D. Pepper Older Americans Independence Center. Grant Number: P30AG021342

Methods:

Design: Retrospective cohort study

Inclusion Criteria: Adults 21 years and older with HF admission, as defined by primary discharge diagnosis of HF or having three or more ambulatory visits (one or more with a cardiologist) coded for HF. The International Classification of Diseases, Ninth Edition (ICD-9) codes were used to identify the patients.

Exposure: Eligible participants from five participating healthcare delivery systems within the Cardiovascular Research Network were divided into quartiles based on overall burden of comorbidity (<5, 5-6, 7-8, ≥9) with respect to the presence of 26 chronic conditions. Follow-up occurred from the index date of meeting eligibility criteria through December 31, 2013. Deaths were identified from hospital and billing claims databases, administrative health plan databases, state death certificate registries, and Social Security Administration files as available at each site.

Primary Outcome(s): All-cause death and hospitalization for HF or any cause.

Statistical Analysis: Baseline characteristics and clinical variables across the groups were compared using chi-square tests for categorical variables and t-tests for continuous variables. Cox proportional hazards regression models were used to examine associations between burden of multimorbidity and each outcome of interest after adjustment for potential confounding variables.

Results: 114,553 eligible adults with HF comprised the study population. Mean age was 75.0±12.8 years, 45.9% were female and 73.5% were white. Subjects had a mean of 6.0 chronic conditions, with 26.4% having 0 to 4, 29.3% having 5 or 6, 26.9% having 7 or 8, and 17.4% having 9 or more at the time of study entry. 51.3% had HFpEF, 34.3% had HFrEF, and 14.4% had HFbEF. Use of all classes of cardiovascular medications was higher with increasing multimorbidity burden.

Higher comorbidity burden (>5) was associated with higher all-cause mortality compared to lower comorbidity burden (5-6: HR=1.59, 95% CI=1.55-1.63; 7-8: HR=2.20, 95% CI=2.15-2.26; ≥9: HR=3.17, 95% CI=3.09-3.25). A greater risk of death with greater morbidity burden remained after adjustment for demographic characteristics, laboratory and physiological variables, medications and study site. Higher comorbidity burden was also associated with more frequent HF-specific hospitalization and all-cause hospitalization. These findings were consistent across sex (men and women), age (list age groups) and heart failure subtype (HFpEF, HFrEF and HFbEF). Of note, the observed association was particularly prominent among those younger than 65 years old.

Conclusion: The authors concluded that greater comorbidity burden is associated with graded, increasing risk of adverse clinical outcomes. Worse clinical outcomes with multimorbidity were found among men and women, across a broad age spectrum, and in those with preserved, reduced and borderline ejection fraction findings.

Limitations of Study: Using ICD-9 codes to identify heart failure cases is imperfect, carries inherent bias and depends on coding practices. There were no individual adjudication of HF diagnoses in the study. Automated clinical databases were used for ascertainment of presence of comorbidities and use of medications, which may have led to some misclassification. Detailed information about the duration, severity, and extent of the chronic conditions studied was unavailable.

Geriatric Perspective for the Cardiovascular Clinician: There is an increasing amount of literature to support the association between the burden of multimorbidity and various clinical outcomes including mortality, hospitalization and quality of life in patients with HF and other cardiovascular diseases.^5-9 Tisminetzky and colleagues extend these observations by confirming the association between increasing burden of chronic comorbid conditions and clinical outcomes in a diverse cohort of patients inclusive of a broad range of age groups. While there is increased recognition of the importance of multimorbidity among older adults with HF, especially those with HFpEF, this study highlights that multimorbidity is a critically important factor across the entire spectrum of HF regardless of age, sex and HF subtype.¹⁰ This lends support to formally incorporate an assessment for multimorbidity in all HF patients. Future studies are needed to improve consensus on how to best assess and measure multimorbidity burden in HF patients, and how best to manage this particularly vulnerable population.

References

1. Saczynski JS, Darling CE, Spencer FA, Lessard D, Gore JM, Goldberg RJ. Clinical features, treatment practices, and hospital and long-term outcomes of older patients hospitalized with decompensated heart failure: the Worcester Heart Failure Study. J Am Geriatr Soc 2009;57:1587-94.
2. Masoudi FA, Krumholz HM. Polypharmacy and comorbidity in heart failure. BMJ 2003;327:513-4.
3. Braunstein JB, Anderson GF, Gerstenblith G, et al. Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries and chronic heart failure. J Am Coll Cardiol 2003;42:1226-33.
4. Rich MW, Chyun DA, Skolnick AH, et al. Knowledge gaps in cardiovascular care of the older adult population: a scientific statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society. J Am Coll Cardiol 2016;67:2419-40.
5. Tisminetzky M, Goldberg R, Gurwitz JH. Magnitude and impact of multimorbidity on clinical outcomes in older adults with cardiovascular disease: a literature review. Clin Geriatr Med 2016;32:227-46.
6. Buck HG, Dickson VV, Fida R, et al. Predictors of hospitalization and quality of life in heart failure: a model of comorbidity, self-efficacy and self-care. Int J Nurs Stud 2015;52:1714-22.
7. Ather S, Chan W, Bozkurt B, et al. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol 2012;59:998-1005.
8. Lichtman JH, Spertus JA, Reid KJ, et al. Acute noncardiac conditions and in-hospital mortality in patients with acute myocardial infarction. Circulation 2007;116:1925-30.
9. Chen HY, Saczynski JS, McManus DD, et al. The impact of cardiac and noncardiac comorbidities on the short-term outcomes of patients hospitalized with acute myocardial infarction: a population-based perspective. Clin Epidemiol 2013;5:439-48.
10. Tisminetzky M, Gurwitz JH, Fan D, et al. Multimorbidity burden and adverse outcomes in a community-based cohort of adults with heart failure. J Am Geriatr Soc 2018;66:2305-13.

Clinical Topics: Cardiovascular Care Team, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Geriatrics, International Classification of Diseases, Confounding Factors, Epidemiologic, United States Social Security Administration, Consensus, Pharmaceutical Preparations, Vulnerable Populations, Comorbidity, Stroke Volume, Follow-Up Studies, Retrospective Studies, Quality of Life, Morbidity, Hospitalization, Cause of Death, Registries, Heart Failure, Cardiovascular Diseases

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