Factors Associated With Prolonged Hospitalization, Readmission And Death In Elderly Heart Failure Patiens Idocx

=== Factors associated with prolonged hospitalization, readmission and death in elderly heart failure patiens i ===

ORIGINAL RESEARCH

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Factors associated with prolonged hospitalization, readmission and death in elderly heart failure patients

Istvan Gyalai-Korpos et al

Factors associated with prolonged hospitalization, readmission and death in elderly heart failure patients in western Romania

Istvan Gyalai-Korpos1, Oana Ancusa1*, Tiberiu Dragomir1, Mirela Cleopatra Tomescu1* , Iosif Marincu2

1, “ V. Babes” University of Medicine and Pharmacy, Timisoara, Romania

2Department of Epidemiology and Infectious Diseases, “ V. Babes” University of Medicine and Pharmacy, Timisoara, Romania

Corresponding authors* :

Oana Ancusa, 2nd Eftimie Murgu Square, Timisoara- 300041. Phone (+40)722814024; fax (+40)256220636. E-mail: [anonimizat]

Mirela Cleopatra Tomescu, 2nd Eftimie Murgu Square, Timisoara- 300041. Phone (+40)722979516, fax: (+40)220636. E-mail: [anonimizat]

Abstract:

Purpose. The purpose of this prospective study was to identify factors associated with prolonged hospitalization , readmissions and death in elderly patients presenting heart failure with reduced ejection fraction (HFREF).

Patients and methods: all consecutive patients aged ≥ 65 years, discharged with a diagnosis of acute new-onset heart failure with LVEF 45%, were included and followed-up for 1 year. The variables associated with outcomes were analyzed in univariate and multivariate logistic regression. For the independent predictors identified by multivariate analysis, ROC analysis was performed.

Results: 71 patients were included. Mean age was 72.5 years, 50% were female, mean LVEF was 31.25±5.76. PH was found in 34 (48%) patients and was independently predicted by the rural of the patients (p=0.005), NYHA functional class 4 (p<0.001), the presence of comorbidities (p=0.023), COPD exacerbation (p<0.001) and chronic kidney disease (p=0.025). In multivariate analysis, only COPD exacerbation was independently associated with (p=0.003).

19 patients (27%) experienced readmissions during the 1 year follow-up, of which 12 (17%) had cardiovascular and 7 (10%) had non-cardiovascular causes. The variables associated with rehospitalizations were, in univariate analysis: infections (p<0.020), COPD exacerbation (p=0.015), comorbidities ≥1 (p<0.0001) and (p<0.0001). At multivariate analysis, independent predictors for readmissions were the presence of comorbidities (p<0.001 ) and (p<0.01). The 1 year mortality rate was 9.8%, with no significant difference between cardiovascular (5.6%) and non-cardiovascular (4.2%) deaths. The only independent predictive variable for mortality was NYHA functional class 4 at baseline hospitalization (p=0.001).

Conclusion: elderly patients are at high risk for prolonged hospitalization, readmission and death after a first hospitalization for HFREF. The most powerful predictors for outcomes are the severity of HF, the presence of comorbidities and baseline

Keywords: elderly, heart failure, reduced ejection fraction, outcome predictors

Introduction

Heart failure (HF) is the most common discharge diagnosis in patients older than 65 years and a usual cause of readmission to hospital and death, presenting a significant financial burden worldwide.1,2  Although HF is primarily a disorder of the elderly, there is a lack of evidence-based data from randomized clinical trials of HF. In most clinical trials, the elderly are under-represented, their proportion being between 30-50%.3 Despite significant progress in treatment strategies for HF in adults, the prevalence of HF is increasing and its prognosis is worsening in the elderly.4,5 A possible explanation for this facts is that most clinical trials have enrolled patients with a mean age of 60-65 years and not severely impaired renal function. In the real world, however, approximately two- thirds of elderly admitted for aggravated HF have stage 3 to 5 chronic kidney disease.6,7 The elderly present more frequent comorbidities and require the use of multiple drugs, polypharmacy being an important problem.8 Although the association of multiple drugs often represents the recommended strategy in the treatment of HF, the use of numerous drugs simultaneously may increase the risk of drug interactions and adverse effects. It also may reduce the adherence to pharmacological therapies.9 Thus, it is possible that treatment strategies found to be effective in adult HF patients with reduced LVEF are less applicable to elderly HF patients.

Accordingly, the purpose of this study was to identify factors associated with prolonged hospitalization, readmissions and death in elderly patients, based on variables obtained at the time of the first admission for heart failure with reduced LVEF.

Material and methods

Patient Selection

The study included all patients aged ≥ 65 years discharged from the Cardiology of the City Hospital Timisoara, with a diagnosis of acute new-onset heart failurefrom January until November 2013. Diagnosis of heart failure was based on symptoms, physical signs, chest radiography and echocardiographically determined LVEF < 45% (Simpson method).10 Exclusion criteria were acute myocardial infarction, acute myocarditis, acute pericarditis, acute pulmonary thromboembolism and the need for cardiovascular surgery.

The study was advised by the ethics commission at our hospital. Before enrollment, all patients signed the informed consent for participation in the study, according to Human Rights Declaration of Helsinki. Before obtaining the consent, the patient was given sufficient time and opportunity to inquire about details of the study and decide to study participation or not.

Data Extraction

Baseline data were extracted from hospital records and included age, gender, NYHA functional class on admission and primary cause of HF, laboratory data, chest X-ray, echocardiographic data, medical history. Medical history included data regarding smoking, obesity, coronary artery disease, hypertension, valvular disease, old myocardial infarction, atrial fibrillation, diabetes, COPD, chronic kidney disease (CKD), history of stroke, malignancy, psychiatric disorder, neurologic disorder, thyroid gland disorder, anemia, osteoporosis and infections. Types of infections included in the study were: COPD exacerbation, pneumonia, urinary tract infections, skin and soft tissue infections, infective endocarditis.

Definition of Covariates

Heart failure with reduced ejection fraction (HFREF) was defined as HF with LVEF 45%. Ischemic etiology of heart failure was considered in patients with a history of coronary artery disease, documented myocardial infarction or angina.12 Hypertensive etiology of heart failure was considered if the patient had a documented diagnosis of hypertension and presented an echocardiographic documented significant left ventricular hypertrophy.13 .14 Peripheral artery disease diagnosis was based on history, physical examination, ankle-brachial index and Duplex ultrasound.15 Chronic kidney disease was diagnosed in the presence of an estimated glomerular filtration rate ˂90 mL/min / 1.73 m².16 Diabetes mellitus was diagnosed according to World Health Organization (WHO)/IDF) besity as a body mass index 30 kg/m2.17 We used WHO’s criterion for anemia in adults as an hemoglobin value of less than 12.5 g/dL.18 COPD . exacerbation was defined as "a sustained worsening of the patient's condition, from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD”.

Follow-up and Outcomes

Prolonged hospitalizations , readmissions and deaths were assessed as adverse outcomes. were considered the 75th percentile of hospitalization length measured in days. All cause readmissions were registered during the follow-up period of 1 year. The causes of readmissions were assessed by documentation of hospital records. Readmissions due to worsening HF, atrial fibrillation, hypertensive crisis, acute coronary syndrome, pulmonary embolism, stroke or acute peripheral ischemia were considered as cardiovascular readmissions. Other causes of readmissions were classified as non-cardiovascular readmissions. Cardiovascular deaths were defined as deaths due to HF, acute myocardial infarction, malignant arrhythmias (sudden death) or aortic dissection. All other deaths were classified as non-cardiovascular deaths. The cause of death was ascertained from hospital records, or by contacting by phone the patient`s physician.

Statistical Analysis

Continuous data are expressed as mean ± standard deviation (SD) or median (interquartile range [IQR]). Categorical data are presented as number (%). The association of variables with follow-up outcomes was analyzed by calculating the odds ratio (OR) together with confidence intervals (CI), in univariate analysis. The multivariate analysis included the significant independent variables at univariate analysis. For the independent predictors identified by multivariate logistical regression, receiver operating characteristic (ROC) analysis was performed. Cumulative mortality throughout the first year after the baseline hospitalization was characterized with the use of Kaplan–Meier curves, with the log-rank test used for the comparison between groups. A p value less than 0.05 was considered statistically significant. Statistical analysis was performed using MedCalc 12.3.0.0 statistical software for Windows.

Results

Baseline Characteristics

All 71 consecutive elderly patients with a first hospitalization for acute new-onset HF with LVEF < 45% were included in the analysis. The mean age was 72.5±5.5 (range 65-84) years. The median age was 72 years (IQR 64-83). 50% of the patients were women, 42% were . The main demographic data are presented in Table 1.

The mean length of baseline hospitalization was 9 ± 4 (range 3-22) days, with a median of 8 (IQR 5-1) days. 34 patients (48%) had a prolonged hospitalization , defined as baseline hospitalization longer than 12 days (> 75 percentile of hospitalization length).

Table 1

Table 2

As presented in Table 2, in univariate analysis, rural (p=0.005), NYHA functional class 4 (p<0.001), the presence of comorbidities ≥ 1 (p=0.023), COPD exacerbation (p<0.001)chronic kidney disease (p=0.025) were significantly associated with a hospitalization length longer than 12 days.

In multivariate analysis, only COPD exacerbation was independently associated with sensitivity: 92.9; specificity: 64.9)

19 patients (27%) experienced readmissions during the 1 year follow-up, of which 12 (17%) had cardiovascular and 7 (10%) had non-cardiovascular causes. The variables associated with rehospitalizations were, in univariate analysis: yinfection (p<0.020), COPD exacerbation (p=0.015), comorbidities ≥1 (p<0.0001) and prolonged baseline hospitalization (p<0.0001). At multivariate logistic regression, independent predictors for readmissions were the presence of comorbidities (p<0.001 ) and (p<0.01).

Figure 1

Figure 2

Figure 3

Figure 4

During the 1 year follow-up period, 7 deaths occurred (9.8%), of which 4 deaths (5.6%) were assessed as having cardiovascular causes, while 3 (4.2%) were non-cardiovascular. The only independent predictive variable for mortality was NYHA functional class 4 at baseline hospitalization (sensitivity:85.7; specificity:65.6,

As shown by the Kaplan-Meier survival curves (Figure 4), there was no significant difference between the cardiovascular and non-cardiovascular 1-year mortality rates in elderly HF patients with LVEF <45% (log-rank p=0.943).

Discussion

Th a prospective cohort study involving 71 patients with acute new-onset HF with LVEF < 45%. 50% were male and the mean age was 72.5 years (range 65-84 years). patients w slightly the patients included in some registries JCARE-CRAD mean age 71 years,5 EuroHeart Failure Survey II mean age 70 years)7, but than in recently published French National Observational Study (mean age 78 years).

The baseline hospitalization for HF was . A prolonged hospitalization (> 12 days) was observed 34 patients (48%). In the absence of a standardized definition of prolonged hospitalization, we decided to use a cut-off at the 75th percentile of hospitalization length measured in days, this cut-off being used in other studies too. Factors associated with an index hospitalization longer than 12 days were: the rural of the patients, NYHA functional class 4, the presence of ≥ 1 comorbidities, chronic kidney disease and COPD exacerbation. At multivariate analysis, the only independent predictor for prolonged hospitalization was COPD exacerbation (AUC= 0.789, p<0.001). The close association between COPD and heart failure has been studied with attention in the last fifteen years. that patients with COPD are at a significant higher risk for congestive heart failurecute exacerbation of COPD may trigger HF aggravation, by means of a systemic inflammatory mechanism.

The readmission rate of the 71 elderly HFREF was 27% during the 1 year follow-up period, with slightly more frequent cardiovascular (17%) than non-cardiovascular (10%) causes (p=0.329). Factors associated with readmissions of elderly heart failure patients were, at univariate analysis, prolonged baseline hospitalizations, the presence of comorbidities, infections and COPD exacerbation. In multivariate analysis, we found two independent predictors for readmissions in the elderly: the presence of comorbidities (AUC=0.772), followed by prolonged initial hospitalization (AUC=0.732). A possible explanation of this finding is that patients that require prolonged hospitalization may have a worse health status and an increased need for post-discharge medical care.

The 1 year all-cause mortality rate in our study was 9.8%, with no significant difference between cardiovascular deaths (5,6%) and non-cardiovascular deaths (4.2%), log-rank p=0.943. The only independent predictor for 1 year mortality in the HFREF elderly patients included in our study was NYHA functional class 4 at baseline hospitalization (AUC=0.757, p=0.001). The mortality rate in our study was smaller comparative to other studies. Huynh et al found a 1-year mortality rate of 25% in patients79.2 years), after discharge. The Cardiovascular Health Study also reported high rates for death and readmissions among elderly patients with all forms of heart failure (normal and decreased left ventricular function). A recently published French national observational study reported a 1-year mortality rate of 29% after a first hospitalization for heart failure, the mean age being 78 years, while mortality rate in heart failure patients aged ≥ 85 was reported to be 44%. We have chosen to use the age of 65 years as a cut-off for the elderly, because it coincides with the retirement age in Romania and it is accepted by WHO as the definition of an elderly. The mean age of our elderly study is also representative for Romania, where life expectancy is 74.5 years (7 years for men, 78 years for women), lower than in central and western European countries

Conclusion

The results of this prospective, hospital based study, confirm that elderly (≥ 65 years) patients are at high risk for prolonged hospitalization, readmissions and death after a first hospitalization for

Multivariate logistic regression outlined following independent predictors for outcomes: COPD exacerbation for prolonged hospitalization, comorbidities and prolonged baseline hospitalization for 1-year readmissions, baseline NYHA functional class 4 for 1-year mortality.

Author contributions

IGK, OA, MCT – conception and design of the study, statistical analysis and interpretation of data, revising the manuscript for intellectual content, drafting the article; TD – design of the manuscript, help in drafting manuscript, interpretation of data. IM- acquisition and interpretation of data. All authors read and approved the final manuscript.

Disclosure

The author reports no conflicts of interest in this work

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Figure 1. Receiver operating characteristic (ROC) curve for COPD infectious exacerbation as independent predictor for prolonged baseline hospitalization in elderly patients with HFREF

Figure

Legend

COPD, chronic obstructive pulmonary disease; AUC, area under the curve; HFREF, heart failure with reduced ejection fraction

Figure 2. Receiver operating characteristic (ROC) curves for comorbidities and prolonged baseline hospitalization as independent predictors for 1- year readmissions in elderly patients with HFREF

Figure

Legend

AUC, area under the curve; PH, prolonged hospitalization; HFREF, heart failure with reduced ejection fraction

Figure 3. Receiver operating characteristic (ROC) curve for NYHA functional class 4 as independent predictor for 1- year mortality in elderly patients with HFREF

Figure

Legend

NYHA, New York Heart Association; AUC, area under the curve; HFREF, heart failure with reduced ejection fraction

Figure

Figure 4. Kaplan-Meier event-free survival curves for cardiovascular and non-cardiovascular deaths in elderly HFREF patients

Legend

CV, cardiovascular