Methods

The study population consisted of adult residents of the Worcester, Massachusetts, metropolitan area (2000 census estimate 478,000) who survived hospitalization for ADHF at all 11 central Massachusetts medical centers during the 4 study years of 1995, 2000, 2002, and 2004. These years were selected because of the availability of federal funding support. The present population was restricted to patients who had undergone clinically indicated echocardiography during their index ADHF-related hospitalizations (n = 3,604). Details of the WHFS have been described previously.

In brief, the patient population included in this investigation was not contacted directly but instead was identified through a systematic retrospective review of the computerized databases of all participating central Massachusetts hospitals, which were searched for patients hospitalized with possible diagnoses of ADHF. The inpatient medical records of patients with primary and/or secondary International Classification of Diseases, Ninth Revision, discharge diagnoses indicating the presence of HF were retrospectively reviewed by trained nurse and physician reviewers. Patients with discharge diagnoses of HF (International Classification of Diseases, Ninth Revision, code 428) comprised the primary diagnostic rubric reviewed. Confirmation of the diagnosis of HF, on the basis of the use of the Framingham criteria, included the presence of 2 major criteria or the presence of 1 major and 2 minor criteria. Patients in whom ADHF developed secondary to admission for another acute illness (e.g., acute myocardial infarction) or after an interventional procedure (e.g., coronary artery bypass surgery) were excluded because we were interested in studying de novo cases of ADHF. Residents of the Worcester metropolitan area with first hospitalizations for ADHF (incident cases) as well as those in whom ADHF had been previously diagnosed were included in this study population.

Information was collected about patients’ demographic characteristics, medical histories, clinical characteristics, and laboratory test results through the review of information contained in their medical records. Each of the cardiovascular and noncardiovascular co-morbidities examined were identified through the review of medical history data provided in hospital charts during the patient’s index hospitalization for ADHF. Data on EF measurements were recorded in 37% of the overall study cohort. On the basis of previously validated and clinically relevant criteria, we defined patients with HF with reduced EF (HF-REF) as those with EFs ≤40%, patients with HF with preserved EF (HF-PEF) as those with EFs ≥50%, and patients with HF with borderline EF (HF-BREF) as those with EFs during their index hospitalizations of 41% to 49%. EF measurements were not validated with other cardiac imaging techniques. In those cases in which a range for EF findings was reported, the average of the 2 values was recorded.

Physicians’ progress notes were reviewed, in addition to daily medication logs, for the prescription of selected medications at the time of hospital discharge. We examined physicians’ prescribing patterns for cardiac medications that have been shown to be of benefit in improving the long-term prognosis of patients with ADHF, namely, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β blockers, and aldosterone inhibitors, at hospital discharge. In addition, we examined medications shown to be effective in improving patients’ symptomatic status (digoxin and diuretics) and selected cardiac medications (lipid-lowering agents and nitrates). Long-term survival status was obtained by the review of medical records at all participating medical centers for further hospitalizations or medical care contacts and review of Social Security Death Index files and statewide death certificates.

We examined differences in the characteristics of patients with EFs ≤40%, 41% to 49%, and ≥50% using analysis of variance and chi-square tests for continuous and discrete variables, respectively. A life-table approach was used to examine long-term mortality after discharge from all central Massachusetts hospitals. Postdischarge case-fatality rates, multivariate-adjusted relative risks, and accompanying 95% confidence intervals were calculated in a standard manner. Multivariate-adjusted logistic regression analyses were used to examine the association between hospital EF findings and 1- and 2-year postdischarge mortality while controlling for several clinical and demographic factors of prognostic importance, including age, gender, history of previously diagnosed atrial fibrillation, diabetes, chronic lung disease, renal failure, and HF, and serum glucose findings during the acute hospitalization. We did not control for the receipt of various cardiac medications during the patient’s index hospitalization in these regression analyses, because of the potential for confounding by treatment indication and difficulty in the interpretation of resultant findings due to the nonrandomized nature of this descriptive observational investigation. The Committee for the Protection of Human Subjects in Research at the University of Massachusetts Medical School approved this study.

Results

Our study population consisted of 3,604 residents of the Worcester metropolitan area who were hospitalized at all central Massachusetts medical centers with ADHF during the 4 years under study and had EF data available. Their average age was approximately 75 years, most were Caucasian, 44% were men, and most had histories of HF (59%). In this population, 36.9% (n = 1,479) were classified as having HF-REF (average EF = 26.7%), 49.4% (n = 1,779) were classified as having HF-PEF (average EF = 59.9%), and the remaining 13.7% (n = 346) were classified as having HF-BREF (average EF = 43.6%).

Patients with HF-REF were slightly younger, were predominantly men, had the greatest co-morbid disease burden, and presented with lower systolic blood pressures, but higher blood urea nitrogen and serum hematocrit levels, than did patients with either HF-BREF or HF-PEF ( Table 1 ). They were also less likely to have histories of chronic lung disease but were more likely to have histories of previously diagnosed coronary heart disease, chronic kidney disease, and HF.

Patients with HF-PEF were generally older, were mostly women, and presented with higher estimated glomerular filtration rates at the time of hospital admission than patients in the other EF strata. Patients with HF-PEF were also more likely to have presented with first episodes of ADHF and to have histories of chronic lung disease and hypertension ( Table 1 ).

Patients with HF-BREF were slightly older than patients with HF-REF and included a higher percentage of women. In addition, they included a greater percentage of patients with previously diagnosed peripheral vascular disease compared with patients with either HF-REF or HF-PEF ( Table 1 ).

Overall, as well as over time, patients with ADHF and reduced EFs were more likely than those with preserved EFs to have received ACE inhibitors or ARBs, lipid-lowering agents, nitrates, diuretics, and digoxin at the time of hospital discharge ( Figure 1 ). Diuretics were more frequently prescribed to patients with HF-REF and to a similar extent in the other 2 categories in 2004 ( Figure 1 ). Patients with HF-PEF were more likely to have been prescribed calcium channel blockers but were less likely to have received combinations of ACE inhibitors or ARBs, β blockers, and aldosterone inhibitors in comparison with those with either HF-REF or HF-BREF ( Figure 1 ).

Trends in treatment practices according to EF findings. ( A ) Disease-modifying medications. ( B ) Symptom-modifying medications. ( C ) Cardiac medications. ( D ) Combined medications (ACE/ARBs, β blockers, aldosterone inhibitors).

Overall, the case-fatality rates at 1, 2, and 5 years after hospital discharge were approximately 35%, 49%, and 71% for patients with HF-REF; 27%, 42%, and 70% for those with HF-BREF; and 30%, 43%, and 69% for those with HF-PEF, respectively ( Table 2 , Figure 2 ). The overall median survival times were approximately 1.9 years for patients with HF-REF, 2.1 years for those with HF-BREF, and 2.3 years for those with HF-PEF ( Figure 2 ).

Trends in postdischarge survival rates according to EF findings. ( A ) Long-term survival for patients with HF-REF. ( B ) Long-term survival for patients with HF-BREF. ( C ) Long-term survival for patients with HF-PEF.

At 1, 2, and 5 years after hospital discharge, patients with HF-BREF had the highest crude relative risk for dying compared with patients in the other 2 groups ( Table 3 ). After adjustment for a variety of important demographic and clinical variables, the poorer long-term prognosis for patients with HF-BREF, and for those with HF-REF, remained, although these differences were no longer statistically significant at 5 years after hospital discharge ( Table 3 ).

Table 3

Relative risk (RRs) for dying after hospital discharge according to ejection fraction findings

	1-Year		2-Years		5-Years
	Crude RR	Mutivariable Adjusted RR ∗	Crude RR	Mutivariable Adjusted RR	Crude RR	Mutivariable Adjusted RR
HF-REF (EF ≤40%)	1.12 (1.02, 1.22) †	1.17 (1.07, 1.28)	1.10 (1.03, 1.18)	1.17 (1.09, 1.24)	1.03 (0.99, 1.08)	1.02 (0.99, 1.05)
HF-BREF (EF = 41–49%)	1.25 (1.04, 1.49)	1.37 (1.14, 1.65)	1.22 (1.06, 1.40)	1.36 (1.20, 1.55)	1.06 (0.97, 1.16)	1.04 (0.98, 1.10)
HF-PEF ‡ (EF ≥50%)	1.0	1.0	1.0	1.0	1.0	1.0

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