Heart failure with preserved ejection fraction (HFpEF) has been described as a disease of elderly subjects with female predominance and hypertension. Our clinical experience suggests patients with HFpEF from an urban population are far more heterogenous, with greater co-morbidities and significant inhospital morbidity. There are limited data on the hospitalization course and outcomes in acute decompensated HFpEF. Hospitalizations for acute heart failure at our institution from July 2011 to June 2012 were identified by International Classification of Diseases, Ninth Revision , codes and physician review for left ventricular ejection fraction ≥50% and were reviewed for patient characteristics and clinical outcomes. Worsening renal function (WRF) was defined as creatinine increase of ≥0.3 mg/dl by 72 hours after admission. Hospital readmission and mortality data were captured from electronic medical records and the Social Security Death Index. Of 434 heart failure admissions, 206 patients (47%) with HFpEF were identified. WRF developed in 40%, the highest reported in HFpEF to date, and was associated with higher blood pressure and lower volume of diuresis. Compared to previous reports, hospitalized patients with HFpEF were younger (mean age 63.2 ± 13.6 years), predominantly black (74%), and had more frequent and severe co-morbidities: hypertension (89%), diabetes (56%), and chronic kidney disease (55%). There were no significant differences in 1- and 12-month outcomes by gender, race, or WRF. In conclusion, we found hospitalized patients with HFpEF from an urban population develop a high rate of WRF are younger than previous cohorts, often black, and have greater co-morbidities than previously described.
Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all hospitalized heart failure today, with clinical outcomes similar to heart failure with reduced ejection fraction (HFrEF) and no proven therapies to date. HFpEF has generally been described as a disease of elderly, predominantly female patients, with hypertensive heart disease from predominantly Caucasian cohorts. There are limited data on the population of patients with HFpEF who present with acute heart failure, the treatments they receive, and their hospitalization course. In particular, worsening renal function (WRF) has been associated with poor outcomes in HFrEF; however, to our knowledge, there is only a single report of WRF outcomes in hospitalized patients with HFpEF. In contrast to previous observational studies, our clinical experience with hospitalized patients with HFpEF from an urban population has been that these patients are younger, racially diverse, with more co-morbidities than previously described. To investigate this experience, we reviewed hospitalizations of patients with HFpEF with acute heart failure with the following objectives: (1) to describe the baseline characteristics and co-morbidities of hospitalized urban patients with HFpEF; and (2) to examine the hospitalization course and clinical outcomes of patients with HFpEF.
Methods
Patients hospitalized for acute heart failure on the Osler Internal Medicine services at The Johns Hopkins Hospital from July 2011 to June 2012 were identified by the primary discharge diagnosis code 428 according to the International Classification of Diseases, Ninth Revision, Clinical Modification . Of these patients, records of those with left ventricular ejection fraction measurement of ≥50% within 1 year before admission and without any suspected interval clinical event to suggest a decrease in left ventricular ejection fraction were reviewed. The diagnosis of heart failure was confirmed by Framingham criteria. If a patient was admitted more than once for heart failure within the study period, only data from the first admission were included for analysis. This study was approved by the Johns Hopkins Institutional Review Board.
Patients were excluded if they presented with active ischemic heart disease, primary hypertrophic, or other cardiomyopathy (e.g., active myocarditis, hypertrophic obstructive cardiomyopathy, severe valvular disease, restrictive or constrictive cardiomyopathy, including known amyloidosis, sarcoidosis, or hemochromatosis), complex congenital heart disease, constrictive pericarditis, or severe primary pulmonary hypertension. Patients with end-stage renal disease, defined as requiring dialysis, or with estimated glomerular filtration rate (eGFR) ≤15 ml/min/1.73 m 2 , determined by the Chronic Kidney Disease Epidemiology Collaboration equation were included in the overall study; however, they were not included in the analysis of renal outcomes, nor were they considered at risk for WRF.
eGFR (ml/min/1.73 m 2 ) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, GFR = 141 × min (serum creatinine/κ,1) α × max (serum creatinine/κ,1) −1.209 × 0.993 Age × 1.018 [if female] × 1.159 [if black], where κ is 0.7 for women and 0.9 for men, α is −0.329 for women and −0.411 for men, min indicates the minimum of serum creatinine/κ or 1, and max indicates the maximum of serum creatinine/κ or 1 (serum creatinine, mg/dl). Chronic kidney disease (CKD) was defined as eGFR <60 ml/min/1.73 m 2 at presentation. WRF was defined as a increase in serum creatinine by ≥0.3 mg/dl from admission to within 72 hours of admission.
All patients included in the study had undergone a clinically indicated comprehensive 2-dimensional echocardiography study with standard Doppler imaging during their index hospitalization or within 1 year before the index hospitalization. Standard echocardiographic views were obtained according to American Society of Echocardiography guidelines. Left ventricular (LV) mass was defined as LV mass = 0.8 (1.04 [(Dd + PW + VS) 3 − (Dd) 3 ]) + 0.6 g, where Dd = diastolic dimension, PW = posterior wall thickness, and VS = septal thickness. LV hypertrophy was defined by 2 criteria: (1) LV mass/height 2.7 with gender-specific reference values of at least 46.7 g/m 2.7 in women and at least 49.2 g/m 2.7 in men to define LV hypertrophy and (2) LV mass/body surface area, with cut points of 116 g/m 2 in men and 104 g/m 2 in women to identify LV hypertrophy of obesity independently. Early diastolic medial and lateral mitral annular tissue velocity (e′), E/A ratio of mitral inflow velocity, and the ratio of the early transmitral flow velocity (E) to e′ (E/e′) were used to estimate LV relaxation and LV filling pressure. Pulmonary artery systolic pressure was calculated from the peak tricuspid regurgitant velocity and the estimated right atrial pressure using the simplified Bernoulli equation.
Hospital readmission data were acquired through review of the Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center electronic medical record systems. One-year mortality data were captured from review of the Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center electronic medical record systems as well as linkage to the Social Security Death Index.
Summary statistics are presented as mean and standard deviation or median and interquartile range for continuous variables and percentages for categorical variables. Comparisons of demographics, co-morbidities, and risk factors for HFpEF were made by gender, race, and WRF status using t tests (for continuous variables) and chi-square tests (for categorical variables). Hospital readmission and mortality status over the year after discharge was analyzed by gender, race, and WRF status using Cox proportional hazards regression.
Results
Of 434 patients hospitalized for heart failure during the study period on the Osler Internal Medicine services at our institution, 206 patients (47%) met the predefined criteria for HFpEF. The baseline characteristics of hospitalized patients with HFpEF are summarized in Table 1 . The mean age was 63years ± 14 years, ranging from 31 to 91 years, with a female predominance at 62% of the cohort. Seventy-four percent of patients were black. Co-morbidities were common, particularly hypertension (89%), diabetes (56%), and CKD (55%), with 22 patients classified as end-stage renal disease at the time of admission. Just over half of the patients had been hospitalized before their index admission for heart failure.
| Variables | |
|---|---|
| Age (years) | 63 ± 14 |
| Women | 62% |
| Black | 74% |
| Hypertension | 89% |
| Diabetes mellitus | 56% |
| Atrial fibrillation | 25% |
| Coronary artery disease | 18% |
| Estimated glomerular filtration rate < 60 mL/min/1.73 m 2 | 55% |
| End-stage renal disease | 11% |
| Any prior heart failure hospitalization | 55% |
| NYHA Functional Classes | |
| I | 13% |
| II | 43% |
| III | 26% |
| V | 18% |
| Body mass index(kg/m 2 ) | 37.3 ± 12.6 |
| Systolic blood pressure (mm Hg) | 150 ± 34 |
| Diastolic blood pressure (mm Hg) | 76 ± 18 |
| Estimated glomerular filtration rate (mL/min/1.73m 2 ) | 62 ± 35 |
| Sodium (mEq/L) | 140 ± 3.5 |
| Creatinine(mg/dL) | 1.6 ± 1.1 |
| Hemoglobin (g/dL) | 11.0 ± 2.0 |
| Albumin (g/dL) | 3.8 ± 0.5 |
| Troponin I (ng/mL) | 0.1 ± 0.1 |
| Medication Use | |
| ACE inhibitor | 43% |
| Angiotensin receptor blocker | 12% |
| Diuretic | 74% |
| Beta-blocker | 56% |
| Aldosterone antagonist | 6% |
| Nitrates | 12% |
| Digoxin | 3% |
| Statin | 50% |
| Aspirin | 56% |
| Echocardiographic Characteristics | |
| E′, cm/s | 7.3 ± 2.7 |
| E/e′ | 16.2 ± 10.7 |
| E/A | 1.3 ± 0.7 |
| LA systolic diameter (cm) | 4.2 ± 0.9 |
| LV end-diastolic diameter (cm) | 4.6 ± 0.7 |
| LV end-systolic diameter (cm) | 3.1 ± 0.7 |
| LV mass (g) | 231 ± 85 |
| LV mass/body surface area (g/m 2 ) | 105 ± 35 |
| LV mass/Height 2.7 (g/m 2.7 ) | 56 ± 19 |
| Intraventricular septal diameter (cm) | 1.3 ± 0.3 |
| LV posterior wall diameter (cm) | 1.2 ± 0.3 |
| LV hypertrophy | 69% |
| Left bundle branch block | 2% |
| Right ventricular systolic pressure (mm Hg) | 48 ± 16 |
| Hospitalization Course and Outcomes | |
| Diuretic given | 98% |
| Furosemide dose(mg) | 83 ± 47 |
| Thiazide given | 14% |
| IV contrast received | 28% |
| Fluid removed (mL) | 5622 ± 8116 |
| Weight loss (kg) | 4.6 ± 8.2 |
| Change in creatinine (mg/dL) | 0.3 ± 0.3 |
| Development of WRF | 40% |
| Incident hemodialysis | 2% |
| Length of Stay (days) | 6.6 ± 9.2 |
| In-patient death | 1% |
| 1-year mortality | 13% |
On admission, mean systolic blood pressure was 150 ± 33 mm Hg and mean diastolic blood pressure was 76 ± 18 mm Hg. The mean body mass index was 37.3 ± 12.6 kg/m 2 , mean eGFR was 62 ± 35 ml/min/1.73 m 2 , and mean creatinine was 1.6 ± 1.1 mg/dl. Medication use before hospitalization included diuretics (74%), angiotensin-converting enzyme inhibitors (43%), β blockers (56%), statins (50%), and nitrates (12%). Echocardiographic findings showed normal LV dimensions, increased left ventricular mass (LVM) and left ventricular mass index, and impaired relaxation: LV end-diastolic diameter 4.6 ± 0.7 cm; LV end-systolic diameter 3.1 ± 0.7 cm; E/e′ 16.2 ± 10.7; E/A 1.3 ± 0.7; LVM 230.5 ± 85 g (range 92.6 to 635.0 g); and left ventricular mass index 105.3 ± 34.7 g/m 2 . LV hypertrophy was noted in 69% of patients based on prespecified echocardiographic criteria.
The hospital course and clinical outcomes for hospitalized patients with HFpEF are summarized in Table 2 . WRF developed in 40% of patients within 72 hours of hospitalization with 2% requiring new initiation of dialysis during the index admission. The mean change in creatinine was 0.3 ± 0.3 mg/dl (range −0.1 to 2.0 mg/dl); mean fluid removed during the hospitalization was 5.6 ± 8.1 l (range −5.8 to 56.8 l); and mean weight loss was 4.6 ± 8.2 kg (range −9.6 to 60.7 kg). Intravenous diuretics were administered in 98% of patients; the mean dose of furosemide administered at a time was 83 mg. Fourteen percent of patients received a thiazide diuretic in addition to a loop diuretic. Of note, 28% of patients received intravenous contrast for computed tomography studies on initial evaluation in the emergency department to evaluate for pulmonary embolism as a cause of dyspnea; none of these studies were diagnostic of pulmonary embolism. Thirty-seven percent of patients with HFpEF were readmitted to our hospital system in the year after their index admission; 9% were readmitted within 30 days after discharge. Two patients died during their index hospitalization; mortality rate at 1 year of the cohort was 13%.
| Clinical Course and Outcomes | By Gender | By Race | By WRF Status | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Male | Female | p-value | Non-black | Black | p-value | No WRF | Yes WRF | p-value | |
| 38% | 62% | 26% | 74% | 53% | 36% | ||||
| Age (years) | 61 | 64 | 0.1 | 66 | 62 | 0.1 | 63 | 65 | 0.4 |
| Women | … | … | 46% | 68% | 0.005 | 59% | 68% | 0.2 | |
| Black | 63% | 80% | 0.005 | … | … | 69% | 77% | 0.2 | |
| Hypertension | 87% | 90% | 0.6 | 83% | 91% | 0.1 | 85% | 92% | 0.2 |
| Diabetes | 49% | 60% | 0.1 | 44% | 60% | 0.05 | 54% | 59% | 0.5 |
| Atrial fibrillation | 31% | 21% | 0.1 | 35% | 21% | 0.039 | 28% | 23% | 0.5 |
| Estimated glomerular filtration rate < 60 mL/min/1.73 m 2 | 46% | 60% | 0.1 | 49% | 57% | 0.3 | 51% | 59% | 0.3 |
| LV hypertrophy | 65% | 71% | 0.4 | 57% | 73% | 0.033 | 66% | 73% | 0.3 |
| Body mass index (kg/m 2 ) | 36 | 38 | 0.4 | 38 | 37 | 0.5 | 39 | 37 | 0.3 |
| Systolic blood pressure (mm Hg) | 147 | 152 | 0.3 | 137 | 155 | <0.001 | 143 | 158 | 0.003 |
| Diastolic blood pressure (mm Hg) | 79 | 75 | 0.1 | 69 | 79 | <0.001 | 73 | 78 | 0.019 |
| Maximum Lasix dose (mg) | 80 | 85 | 0.5 | 86 | 82 | 0.6 | 78 | 88 | 0.1 |
| Continuous Lasix dose (mg) | 3 | 7 | 0.2 | 9 | 4 | 0.1 | 6 | 5 | 0.9 |
| Intermittent Lasix dose (mg) | 60 | 71 | 0.1 | 61 | 69 | 0.3 | 75 | 70 | 0.5 |
| Fluid removed/body surface area (ml) | 2638 | 2523 | 0.8 | 3036 | 2395 | 0.2 | 3173 | 2106 | 0.034 |
| Intravenous contrast given | 27% | 29% | 0.8 | 44% | 22% | 0.002 | 30% | 27% | 0.6 |
| Development of WRF | 35% | 44% | 0.2 | 33% | 43% | 0.2 | … | … | … |
| Length of Stay (days) | 6.8 | 6.4 | 0.8 | 9.8 | 5.4 | 0.003 | 7.1 | 6.5 | 0.7 |
| HF readmission within 30 days | 9% | 9% | 0.9 | 9% | 9% | 0.9 | 9% | 8% | 0.8 |
| HF readmission in 1 year | 38% | 37% | 0.8 | 35% | 38% | 0.7 | 33% | 41% | 0.3 |
| Any readmission within 1 year | 63% | 53% | 0.2 | 46% | 61% | 0.1 | 52% | 57% | 0.6 |
| 1-year mortality | 17% | 11% | 0.2 | 19% | 11% | 0.2 | 13% | 14% | 0.9 |
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