There are few data comparing the patient characteristics and outcomes of heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced EF (HFrEF) in Asian cohorts. We aimed to evaluate the prevalence, clinical characteristics, and 1-year outcomes of a well-defined Southeast Asian HFpEF cohort in comparison to an HFrEF cohort. We conducted a retrospective observational study of 1,978 patients discharged from Changi General Hospital, Singapore with a primary diagnosis of HF from 2009 to 2013. About 29% of discharges had HFpEF. Patients with HFpEF were more likely to be women, older age, and have a higher prevalence of hypertension. There were no significant differences in the absolute rates of 30-day outcomes between the 2 groups. The absolute rate of death at 1 year was similar in HFrEF and HFpEF at 17% and 15%, respectively (p = 0.3). After multivariate adjustment, there was no difference in the outcomes of the 2 groups. Atrial fibrillation at baseline was a predictor of death or HF hospitalization in HFpEF but not HFrEF (interaction p = 0.003). In conclusion, in this study of a Southeast Asian population with well-defined HF, we found that the clinical profile of patients with HF was similar to that in the West and 30-day and 1-year mortality and morbidity were not significantly different between cohorts.
Heart failure (HF) is a major global health problem that imposes a significant burden on society and the individual. It is commonly categorized based on the underlying left ventricular ejection fraction (LVEF) as HF with reduced EF (HFrEF; EF <50%) and HF with preserved EF (HFpEF; LVEF ≥50%). In Western populations, HFpEF can account for up to 50% of hospital admissions for HF, and the proportion of patients presenting with HFpEF is on the increase. In these cohorts, HFpEF is not a benign entity and patients with HFpEF have similar outcomes to patients with HFrEF. Despite Asia making up 60% of the world’s population, most of the published data on HF comes from European and North American cohorts. In particular, there are sparse data comparing the characteristics and outcomes of patients with HFpEF and HFrEF in Asian cohorts. Clear racial differences in the epidemiology of HF have already been established. African-Americans have HFpEF less often than HFrEF, and patients in Asia have been shown to present with HF at a younger age and with more severe symptoms. Explosive population growth combined with an aging population is leading to an epidemic of HF in Asia. With that comes, an increasing need for data on Asian patients with HF and in particular the differences between HFpEF and HFrEF populations. The purpose of this study was to evaluate the prevalence, clinical characteristics, and 1-year outcomes of a well-defined Southeast Asian Multiethnic HFpEF cohort in comparison to an HFrEF cohort.
Methods
We conducted a retrospective observational study of patients discharged from Changi General Hospital with a primary diagnosis of HF from January 1, 2009 and December 31, 2013. Changi General Hospital is a 1,000-bed acute care hospital in eastern Singapore. It has a mature HF program incorporating a clinical management pathway protocol to manage patients admitted with a primary diagnosis of HF. Approval to conduct this study was obtained from our center’s centralized institutional review board.
All patients aged 21 years or older admitted to the department of cardiology with a principal discharge diagnosis of HF were included in this study. Only the first emergency admission for each patient during the specified period was included in the analysis. The diagnosis of HF was made if the patient satisfied the clinical Framingham Criteria, had elevated serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) above the age-specific cut-off level, and had evidence of cardiac dysfunction on transthoracic echocardiography. HFrEF was defined as HF with LVEF <50%. HFpEF was defined as HF with LVEF ≥50% and either cardiac structural changes (increased left atrial volume index or left ventricular hypertrophy) or evidence of diastolic dysfunction (E/e′>12). Age-specific cut-off criteria for NT-proBNP are as follows: <50 years, >450 pg/ml; 50 to 75 years, >900 pg/ml; and more than 75 years, >1,800 pg/ml. Patients were excluded if they had end-stage renal disease (estimated glomerular filtration rate <15 ml/min/1.73 m 2 or were on dialysis treatment). The diagnosis of HF was confirmed by the HF team. Cases excluded from this analysis included elective admissions; death during the index admission; death without admission; discharged against doctor’s advice; or discharged to other health care facilities.
All hospitalizations and deaths were determined by reviewing electronic medical records at the time points 30 days and 1 year after the index admission. Hospitalizations were based on discharge coding and categorized as HF, cardiovascular, and noncardiovascular. Routine data collection was conducted prospectively using a uniform case report form.
All echocardiograms were dual reported by a cardiac technologist and cardiology consultant specialized in echocardiography. LVEF was assessed either by Simpson’s biplane method or visual estimation if this was not available. If an LVEF was not measured during the admission (24%), then the nearest LVEF within 1 year was used. If not done within 1 year, the patient was excluded from the study.
Demographics and clinical characteristics of patients with HFpEF and HFrEF were compared using the 2-sample t test or Wilcoxon test for continuous variables and the Pearson chi-square test for categorical variables. Outcomes at 30 days and 1 year were analyzed using a logistic regression model including the following potential confounding covariates: age, gender, race, ischemic heart disease (IHD), previous myocardial infarction, hypertension, previous stroke cerebrovascular accident, hyperlipidemia, asthma, diabetes, systolic blood pressure (BP), diastolic BP, serum sodium (Na), serum creatinine, atrial fibrillation (AF). Interaction terms were included in the full multivariate model to examine the relation between HFpEF/HFrEF and significant predictors of outcome. Significance was accepted at the 0.05 level. All analyses were undertaken using the Statistical Package for Social Scientists (SPSS Inc., Chicago, Illinois).
Results
From 2009 to 2013, there were a total of 2,083 patients hospitalized with a primary diagnosis of HF. Of these, a small number were excluded from analysis: 20 patients had no available outcome data at 30 days; 63 patients had no LVEF data; and 22 patients died during the index admission. Overall, 1,978 patients were included in the final analysis. Patients with HFpEF made up 29% of discharges.
Table 1 describes the baseline demographics and clinical characteristics in the HFrEF and HFpEF groups. Patients with HFpEF were significantly older and more likely to be women than patients with HFrEF. They were also less likely to have a history of smoking. There were significant differences in the ethnic makeup of each group. Patients with HFpEF were more likely to be of Chinese ethnicity and less likely to be of Malay ethnicity.
| Variable | HFrEF (n = 1405) | HFpEF (n = 573) | P-Value |
|---|---|---|---|
| Age (Years) | 66.7 ± 13.4 | 74.6 ± 11.7 | <0.001 |
| Women | 458 (33%) | 360 (63%) | <0.001 |
| Current Smoker | 353 (35%) | 54 (9.5%) | <0.001 |
| Ex-smoker | 312 (22%) | 89 (16%) | <0.001 |
| Atrial fibrillation on electrocardiogram | 257 (18%) | 235 (41%) | <0.001 |
| Incident heart failure | 751 (54%) | 324 (57%) | <0.001 |
| Length of hospital stay (Days) | 4.8 ± 4.0 | 4.5 (3.6) | 0.11 |
| Chinese | 746 (53%) | 357 (62%) | 0.002 |
| Malay | 439 (31%) | 140 (24%) | |
| Indian | 125 (8.9%) | 40 (7.0%) | |
| Others | 95 (6.8%) | 36 (6.3%) | |
| Coronary heart disease | 1072 (77%) | 292 (51%) | <0.001 |
| Prior myocardial infarction | 574 (42%) | 94 (17%) | <0.001 |
| Previous stroke/ transient ischemic attack | 213 (15%) | 102 (18%) | 0.15 |
| Hypertension | 965 (69%) | 471 (82%) | <0.001 |
| Hyperlipidemia | 822 (59%) | 346 (60%) | 0.44 |
| Chronic obstructive airways disease/asthma | 141 (10%) | 49 (8.6%) | 0.31 |
| Diabetes mellitus | 766 (55%) | 264 (46%) | 0.001 |
| Peptic ulcer disease | 51 (3.6%) | 26 (4.5%) | 0.34 |
| Permanent pacemaker | 27 (1.9%) | 23 (4.0%) | 0.007 |
| Implantable cardioverter defibrillator | 21 (1.5%) | 0 | 0.003 |
| Cardiac resynchronization Therapy | 10 (0.7%) | 0 | 0.043 |
| Symptoms and signs at presentation | |||
| Paroxysmal nocturnal dyspnea | 498 (35%) | 141 (25%) | <0.001 |
| Orthopnea | 770 (55%) | 268 (47%) | 0.001 |
| Nocturnal cough | 78 (5.6%) | 28 (4.9%) | 0.55 |
| Dyspnea | 786 (56%) | 329 (57%) | 0.55 |
| Jugular venous pulse raised | 628 (45%) | 263 (46%) | 0.63 |
| Rales | 1051 (75%) | 453 (79%) | 0.11 |
| Cardiomegaly on chest X-ray | 665 (47%) | 254 (44%) | 0.22 |
| S3 | 45 (3.2%) | 19 (3.3%) | 0.90 |
| Edema | 923 (66%) | 414 (72%) | 0.005 |
| Hepatomegaly | 11 (0.8%) | 2 (0.3%) | 0.28 |
| Pleural effusion | 155 (11%) | 62 (11%) | 0.89 |
| Tachycardia | 32 (2.3%) | 12 (2.1%) | 0.80 |
| Physiology | |||
| Heart rate (bpm) | 94 ± 24 | 86 ± 25 | <0.001 |
| Systolic blood pressure (mmHg) | 141 ± 26 | 148 ± 27 | <0.001 |
| Diastolic blood pressure (mmHg) | 82 ± 17 | 77 ± 15 | <0.001 |
| Lab values | |||
| Sodium (mmol/l) | 137 ± 4 | 137 5 | 0.34 |
| Creatinine (umol./l) | 131 ± 72 | 118 ± 58 | <0.001 |
| Urea (mmol/l) | 7.5 ± 4.2 | 7.2 ± 3.9 | 0.22 |
| Hemoglobin (g/dl) | 12.9 ± 3.2 | 12.0 ± 1.9 | <0.001 |
| Troponin T (ng/ml) | 0.128 ± 0.362 | 0.070 ± 0.273 | 0.001 |
| NT Pro BNP (pg/ml) | 7227 ± 7227 | 4498 ± 5401 | <0.001 |
| Serum Albumin (g/l) | 32.6 ± 4.9 | 33.3 ± 4.8 | 0.003 |
| QRS duration (ms) | 102 ± 24 | 94 ± 20 | <0.001 |
| Treatment on discharge | |||
| Anti-coagulation | 176 (13%) | 121 (21%) | <0.001 |
| Angiotensin Converting Enzyme Inhibitor/ Angiotensin Receptor Blocker | 1098 (78%) | 375 (66%) | <0.001 |
| Aldosterone Antagonists | 661 (47%) | 17 (3.0%) | <0.001 |
| Beta-Blocker | 1206 (86%) | 437 (77%) | <0.001 |
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