Abstract
Background
We assessed the prevalence of preserved left ventricular ejection fraction in patients with incident heart failure and differences in the demographic and clinical characteristics that may differentiate patients presenting with heart failure with preserved versus reduced left ventricular ejection fraction.
Methods
We identified all patients with newly diagnosed heart failure between 2005 and 2008 from 4 sites in the Cardiovascular Research Network on the basis of hospital discharge and ambulatory visit diagnoses, and assigned a category of preserved, borderline, or reduced left ventricular ejection fraction using data from electronic databases and chart review.
Results
We identified 11,994 patients with incident heart failure; of these, 6210 (51.8%) had preserved left ventricular ejection fraction, 1870 (15.6%) had borderline systolic dysfunction, and 3914 (32.6%) had reduced left ventricular ejection fraction. For those with heart failure with preserved left ventricular ejection fraction, the mean age was 74.7 years and 57.1% were women; for those with borderline systolic dysfunction, the mean age was 71.6 years and 38.4% were women; and for those with reduced left ventricular ejection fraction, the mean age was 69.1 years and 32.6% were women. Compared with white patients, black patients were less likely to have heart failure with preserved systolic function. Those with a history of coronary artery bypass surgery, mitral or aortic valvular disease, atrial fibrillation or flutter, or a diagnosis of hypertension were more likely to have heart failure with preserved systolic function, as were those with a diverse range of noncardiac comorbid conditions, including chronic lung disease, chronic liver disease, a history of a hospitalized bleed, a history of a mechanical fall, a diagnosis of depression, and a diagnosis of dementia. Patients with a history of acute myocardial infarction and a history of ventricular fibrillation or ventricular tachycardia were less likely to have heart failure with preserved left ventricular ejection fraction. Patients with higher systolic blood pressures at baseline and lower low-density lipoprotein levels were more likely to have heart failure with preserved left ventricular ejection fraction, as were those with lower hemoglobin levels and the lowest glomerular filtration rates.
Conclusions
Heart failure with preserved left ventricular ejection fraction is the most common form of the heart failure syndrome among patients newly presenting with this condition, and women and older adults are especially affected. Evidence-based treatment strategies apply to less than one third of patients with newly diagnosed heart failure.
Keywords
The heterogeneity of the heart failure syndrome is well appreciated, and the importance of heart failure with preserved left ventricular ejection fraction as a prominent contributor to the heart failure epidemic has been established unequivocally.
1
, 2
Heart failure with “normal ventricular performance” has been described in case reports and small hospital-based case series dating back to the 1970s.3
However, there have been few large population-based studies of this condition.Clinical Significance
- •Heart failure with preserved left ventricular ejection fraction is the most common form of the heart failure syndrome among patients newly presenting with this condition.
- •Women and older adults are especially affected.
- •Patients with ejection fractions less than 40% comprise less than one third of those with incident heart failure.
- •Evidence-based treatment strategies apply to only a minority of patients with newly diagnosed heart failure.
In a community-wide study of residents of Olmsted County, Minnesota, among 556 individuals with incident or prevalent heart failure identified in the early to mid-2000s, more than half had heart failure with preserved left ventricular ejection fraction.
4
Another study of patients hospitalized with decompensated heart failure at Mayo Clinic Hospitals from 1987 to 2001 determined that the prevalence of heart failure with preserved left ventricular ejection fraction increased from 38% to 47% to 54% over the 3 consecutive 5-year periods encompassed in the study.5
We conducted a large population-based study to provide a contemporary estimate of the prevalence of heart failure with preserved left ventricular ejection fraction and heart failure with reduced left ventricular ejection fraction among patients with newly diagnosed heart failure syndrome. An additional goal was to describe the demographic and clinical characteristics that may differentiate heart failure with preserved left ventricular ejection fraction from heart failure with reduced left ventricular ejection fraction at the time of initial clinical presentation. To address these questions, we identified all patients with newly diagnosed heart failure from 4 sites participating in the Cardiovascular Research Network (CVRN) between 2005 and 2008.
Materials and Methods
The source population included members from 4 participating health plans within the National Heart, Lung, and Blood Institute–sponsored CVRN.
6
Sites included Kaiser Permanente Northern California, Kaiser Permanente Colorado, Kaiser Permanente Northwest, and Fallon Community Health Plan. Contributing sites provide care to an ethnically and socioeconomically diverse population across varying clinical practice settings and geographically diverse areas. Each site also had a Virtual Data Warehouse,6
, 7
which served as the primary data source for subject identification and characterization. The Virtual Data Warehouse is a distributed standardized data resource composed of electronic datasets at each CVRN site, populated with linked demographic, administrative, ambulatory pharmacy, outpatient laboratory test results, and health care use (ambulatory visits and network and non-network hospitalizations with diagnoses and procedures) data for members receiving care at participating sites. Institutional review boards at participating sites approved the study, and waiver of consent was obtained because of the nature of the study.Study Sample and Characterization of Left Ventricular Systolic Function
We first identified all persons aged≥21 years with diagnosed heart failure based on having been hospitalized with a primary discharge diagnosis of heart failure or having>3 ambulatory visits coded for heart failure with at least 1 visit being with a cardiologist between January 1, 2005, and December 31, 2008. We used the following International Classification of Diseases, 9th Revision (ICD-9) codes: 398.91, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 428.0, 428.1, 428.20, 428.21, 428.22, 428.23, 428.30, 428.31, 428.32, 428.33, 428.40, 428.41, 428.42, 428.43, and 428.9. Prior studies have shown a positive predictive value of>95% for admissions with a primary discharge diagnosis of heart failure based on these codes when compared against chart review and Framingham clinical criteria.
8
, 9
, 10
We defined incident heart failure as having no hospitalization or ambulatory heart failure diagnosis at any time during the 5-year period before each patient's first heart failure diagnosis.We ascertained information on quantitative or qualitative assessments of left ventricular ejection fraction from the results of echocardiograms, radionuclide scintigraphy, other nuclear imaging modalities, and left ventriculography test results available from site-specific databases complemented by manual chart review. We classified patients into categories of preserved and reduced ejection fraction. We defined heart failure with preserved left ventricular ejection fraction as a reported left ventricular ejection fraction≥50% or a qualitative assessment of preserved or normal systolic function by a physician.
11
We defined heart failure with reduced left ventricular ejection fraction as a reported left ventricular ejection fraction≤40% or a qualitative assessment of moderate, moderate to severe, or severe systolic dysfunction by a physician. A third category termed “borderline” systolic dysfunction was defined as a left ventricular ejection fraction of 41% to 49% or a qualitative assessment of mildly reduced systolic function by a physician.Covariates
We ascertained information on coexisting illnesses on the basis of diagnoses or procedures using relevant ICD-9 codes, laboratory results, or filled outpatient prescriptions from health plan hospitalization discharge, ambulatory visit, laboratory, and pharmacy databases, as well as site-specific diabetes mellitus and cancer registries.
7
, 8
, 12
We collected baseline data on diagnoses of acute myocardial infarction, unstable angina, coronary artery revascularization, stroke or transient ischemic attack, cerebrovascular disease, other thromboembolism, atrial fibrillation or flutter, ventricular fibrillation or tachycardia, mitral or aortic valvular heart disease, peripheral arterial disease, rheumatic heart disease, receipt of a pacemaker, receipt of cardiac resynchronization therapy, receipt of an implantable cardioverter defibrillator, dyslipidemia, hypertension, diabetes mellitus, hospitalized bleed, diagnosed dementia, diagnosed depression, chronic lung disease, chronic liver disease, mechanical fall, and systemic cancer based on ICD-9 codes and Current Procedural Terminology procedure codes.We ascertained available ambulatory results for systolic and diastolic blood pressure, serum low-density lipoprotein and high-density lipoprotein cholesterol measurements, estimated glomerular filtration rate, and hemoglobin level on or before the index date from each site's Virtual Data Warehouse.
6
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Statistical Analysis
We compared baseline characteristics across groups of left ventricular systolic function using analysis of variance or relevant nonparametric tests for continuous variables and chi-square tests for categoric variables. Given the large sample size, we focused only on differences in baseline characteristics that may be clinically meaningful.
We constructed a logistic regression model to identify demographic and clinical correlates of incident heart failure with preserved left ventricular ejection fraction versus heart failure with reduced left ventricular ejection fraction. The model adjusted for age, sex, race, and any other variables that differed between groups with a P value≤.2. We also explored whether additional adjustment for clustering at the site level was necessary. All analyses were conducted using SAS statistical software, version 9.1 (SAS Institute Inc, Cary, NC).
Results
We identified 11,994 patients with incident heart failure over the period of study; the mean age of these patients was 72.4 years (standard deviation, 13.1), and 46.2% were female. Approximately half (48.3%) of all patients were aged 75 years or more (Table 1). A total of 6210 patients (51.8%) had heart failure with preserved left ventricular ejection fraction, and 3914 patients (32.6%) had heart failure with reduced left ventricular ejection fraction, with 1870 (15.6%) having borderline systolic dysfunction.
Table 1Baseline Characteristics of 11,994 Patients with Newly Diagnosed Heart Failure Identified Between 2005 and 2008
| Variable | Overall N=11,994 | Preserved EF N=6210 | Borderline EF N=1870 | Reduced EF N=3914 | P Value |
|---|---|---|---|---|---|
| Mean (SD) age (y) | 72.4 (13.1) | 74.7 (12.1) | 71.6 (12.9) | 69.1 (14.0) | <.001 |
| Age categories (y) | <.001 | ||||
| <45 | 404 (3.4) | 123 (2.0) | 60 (3.2) | 221 (5.6) | |
| 45-54 | 894 (7.5) | 312 (5.0) | 141 (7.5) | 441 (11.3) | |
| 55-64 | 1974 (16.5) | 827 (13.3) | 365 (19.5) | 782 (20.0) | |
| 65-74 | 2929 (24.4) | 1508 (24.3) | 457 (24.4) | 964 (24.6) | |
| 75-84 | 3815 (31.8) | 2218 (35.7) | 564 (30.2) | 1033 (26.4) | |
| ≥85 | 1978 (16.5) | 1222 (19.7) | 283 (15.1) | 473 (12.1) | |
| Female gender, n (%) | 5539 (46.2) | 3543 (57.1) | 719 (38.4) | 1277 (32.6) | <.001 |
| Race categories | <.001 | ||||
| White | 8922 (74.4) | 4759 (76.6) | 1421 (76.0) | 2742 (70.1) | |
| Black/African American | 972 (8.1) | 428 (6.9) | 157 (8.4) | 387 (9.9) | |
| Asian American | 711 (5.9) | 374 (6.0) | 104 (5.6) | 233 (6.0) | |
| Native Hawaiian or other Pacific Islander | 99 (0.8) | 52 (0.8) | 13 (0.7) | 34 (0.9) | |
| American Indian or Alaska Native | 33 (0.3) | 15 (0.2) | 4 (0.2) | 14 (0.4) | |
| Missing/unknown | 1257 (10.5) | 582 (9.4) | 171 (9.1) | 504 (12.9) | |
| Medical history, n (%) | |||||
| Acute myocardial Infraction | 858 (7.2) | 381 (6.1) | 198 (10.6) | 279 (7.1) | <.001 |
| Unstable angina | 473 (3.9) | 273 (4.4) | 93 (5.0) | 107 (2.7) | <.001 |
| Coronary artery bypass surgery | 475 (4.0) | 256 (4.1) | 116 (6.2) | 103 (2.6) | <.001 |
| Percutaneous coronary intervention | 875 (7.3) | 393 (6.3) | 198 (10.6) | 284 (7.3) | <.001 |
| Ischemic stroke or transient ischemic attack | 753 (6.3) | 438 (7.1) | 128 (6.8) | 187 (4.8) | <.001 |
| Cerebrovascular disease | 1803 (15.0) | 1027 (16.5) | 304 (16.3) | 472 (12.1) | <.001 |
| Other thromboembolic event | 68 (0.6) | 42 (0.7) | 13 (0.7) | 13 (0.3) | .06 |
| Atrial fibrillation or flutter | 3699 (30.8) | 2195 (35.3) | 586 (31.3) | 918 (23.5) | <.001 |
| Ventricular tachycardia or fibrillation | 207 (1.7) | 69 (1.1) | 40 (2.1) | 98 (2.5) | <.001 |
| Mitral or aortic valvular disease | 2038 (17.0) | 1315 (21.2) | 315 (16.8) | 408 (10.4) | <.001 |
| Peripheral arterial disease | 718 (6.0) | 398 (6.4) | 129 (6.9) | 191 (4.9) | .001 |
| Rheumatic heart disease | 224 (1.9) | 128 (2.1) | 32 (1.7) | 64 (1.6) | .26 |
| Implantable cardioverter defibrillator | 116 (1.0) | 22 (0.4) | 23 (1.2) | 71 (1.8) | <.001 |
| Pacemaker | 512 (4.3) | 282 (4.5) | 80 (4.3) | 150 (3.8) | .23 |
| Dyslipidemia | 7175 (59.8) | 3833 (61.7) | 1191 (63.7) | 2151 (55.0) | <.001 |
| Hypertension | 8994 (75.0) | 5114 (82.4) | 1402 (75.0) | 2478 (63.3) | <.001 |
| Diabetes mellitus | 2301 (19.2) | 1217 (19.6) | 383 (20.5) | 701 (17.9) | .03 |
| Hospitalized bleeds | 498 (4.2) | 306 (4.9) | 78 (4.2) | 114 (2.9) | <.001 |
| Diagnosed dementia | 803 (6.7) | 480 (7.7) | 128 (6.8) | 195 (5.0) | <.001 |
| Diagnosed depression | 1959 (16.3) | 1141 (18.4) | 294 (15.7) | 524 (13.4) | <.001 |
| Chronic lung disease | 4148 (34.6) | 2369 (38.1) | 629 (33.6) | 1150 (29.4) | <.001 |
| Chronic liver disease | 428 (3.6) | 242 (3.9) | 57 (3.0) | 129 (3.3) | .12 |
| Mechanical fall | 264 (2.2) | 178 (2.9) | 31 (1.7) | 55 (1.4) | <.001 |
| Systemic cancer | 862 (7.2) | 493 (7.9) | 120 (6.4) | 249 (6.4) | .004 |
| Baseline eGFR category (mL/min/1.73 m2), n (%) | <.001 | ||||
| ≥130 | 23 (0.2) | 9 (0.1) | 6 (0.3) | 8 (0.2) | |
| 90-130 | 1503 (12.5) | 690 (11.1) | 235 (12.6) | 578 (14.8) | |
| 60-89 | 4746 (39.6) | 2382 (38.4) | 758 (40.5) | 1606 (41.0) | |
| 45-59 | 2583 (21.5) | 1406 (22.6) | 386 (20.6) | 791 (20.2) | |
| 30-44 | 1614 (13.5) | 983 (15.8) | 239 (12.8) | 392 (10.0) | |
| 15-29 | 572 (4.8) | 376 (6.1) | 75 (4.0) | 121 (3.1) | |
| <15 | 99 (0.8) | 70 (1.1) | 15 (0.8) | 14 (0.4) | |
| Dialysis | 209 (1.7) | 117 (1.9) | 40 (2.1) | 52 (1.3) | |
| Missing | 645 (5.4) | 177 (2.9) | 116 (6.2) | 352 (9.0) | |
| Baseline hemoglobin category (g/L), n (%) | <.001 | ||||
| ≥16.0 | 804 (6.7) | 303 (4.9) | 131 (7.0) | 370 (9.5) | |
| 15.0-15.9 | 1225 (10.2) | 495 (8.0) | 202 (10.8) | 528 (13.5) | |
| 14.0-14.9 | 2101 (17.5) | 976 (15.7) | 341 (18.2) | 784 (20.0) | |
| 13.0-13.9 | 2338 (19.5) | 1295 (20.9) | 349 (18.7) | 694 (17.7) | |
| 12.0-12.9 | 1925 (16.0) | 1147 (18.5) | 304 (16.3) | 474 (12.1) | |
| 11.0-11.9 | 1285 (10.7) | 829 (13.3) | 185 (9.9) | 271 (6.9) | |
| 10.0-10.9 | 788 (6.6) | 508 (8.2) | 116 (6.2) | 164 (4.2) | |
| 9.0-9.9 | 343 (2.9) | 219 (3.5) | 51 (2.7) | 73 (1.9) | |
| <9.0 | 166 (1.4) | 101 (1.6) | 29 (1.6) | 36 (0.9) | |
| Missing | 1019 (8.5) | 337 (5.4) | 162 (8.7) | 520 (13.3) | |
| Systolic blood pressure category (mm Hg), n (%) | <.001 | ||||
| ≥180 | 383 (3.2) | 234 (3.8) | 56 (3.0) | 93 (2.4) | |
| 160-179 | 894 (7.5) | 533 (8.6) | 132 (7.1) | 229 (5.9) | |
| 140-159 | 2486 (20.7) | 1351 (21.8) | 412 (22.0) | 723 (18.5) | |
| 130-139 | 2416 (20.1) | 1283 (20.7) | 368 (19.7) | 765 (19.5) | |
| 121-129 | 1791 (14.9) | 899 (14.5) | 280 (15.0) | 612 (15.6) | |
| 110-120 | 2603 (21.7) | 1253 (20.2) | 417 (22.3) | 933 (23.8) | |
| 100-109 | 609 (5.1) | 290 (4.7) | 79 (4.2) | 240 (6.1) | |
| < 100 | 283 (2.4) | 120 (1.9) | 41 (2.2) | 122 (3.1) | |
| Missing | 529 (4.4) | 247 (4.0) | 85 (4.5) | 197 (5.0) | |
| Diastolic blood pressure category (mm Hg), n (%) | <.001 | ||||
| ≥110 | 153 (1.3) | 59 (1.0) | 22 (1.2) | 72 (1.8) | |
| 100-109 | 341 (2.8) | 129 (2.1) | 49 (2.6) | 163 (4.2) | |
| 90-99 | 853 (7.1) | 366 (5.9) | 146 (7.8) | 341 (8.7) | |
| 85-89 | 726 (6.1) | 311 (5.0) | 118 (6.3) | 297 (7.6) | |
| 81-84 | 951 (7.9) | 482 (7.8) | 153 (8.2) | 316 (8.1) | |
| ≤80 | 8440 (70.4) | 4616 (74.3) | 1297 (69.4) | 2527 (64.6) | |
| Missing | 530 (4.4) | 247 (4.0) | 85 (4.5) | 198 (5.1) | |
| HDL cholesterol category (g/dL), n (%) | <.001 | ||||
| ≥60 | 2110 (17.6) | 1229 (19.8) | 291 (15.6) | 590 (15.1) | |
| 50-50.9 | 2174 (18.1) | 1180 (19.0) | 306 (16.4) | 688 (17.6) | |
| 40-49.9 | 3147 (26.2) | 1663 (26.8) | 517 (27.6) | 967 (24.7) | |
| 35-39.9 | 1516 (12.6) | 784 (12.6) | 244 (13.0) | 488 (12.5) | |
| <35 | 1532 (12.8) | 730 (11.8) | 286 (15.3) | 516 (13.2) | |
| Missing | 1515 (12.6) | 624 (10.0) | 226 (12.1) | 665 (17.0) | |
| LDL cholesterol category (g/dL), n (%) | <.001 | ||||
| ≥200 | 118 (1.0) | 45 (0.7) | 20 (1.1) | 53 (1.4) | |
| 160-199.9 | 483 (4.0) | 234 (3.8) | 84 (4.5) | 165 (4.2) | |
| 130-159.9 | 1341 (11.2) | 668 (10.8) | 216 (11.6) | 457 (11.7) | |
| 100-129.9 | 2746 (22.9) | 1453 (23.4) | 417 (22.3) | 876 (22.4) | |
| 70-99.9 | 3837 (32.0) | 2114 (34.0) | 576 (30.8) | 1147 (29.3) | |
| <70 | 1837 (15.3) | 1016 (16.4) | 320 (17.1) | 501 (12.8) | |
| Missing | 1632 (13.6) | 680 (11.0) | 237 (12.7) | 715 (18.3) |
EF=ejection fraction; eGFR=estimated glomerular filtration rate; HDL=high-density lipoprotein; LDL=low-density lipoprotein; SD=standard deviation.
Among those with heart failure with preserved left ventricular ejection fraction, the mean age was 74.7 years and 55.4% were aged 75 years or more; 57.1% of these patients were women. For those with heart failure with reduced left ventricular ejection fraction, the mean age was 69.1 years and 38.5% were aged 75 years or more; 32.6% of these patients were women. For those with borderline systolic dysfunction, the mean age was 71.6 years and 45.2% were aged 75 years or more; 38.4% of these patients were women (Table 1).
Medication use in the 120 days before the diagnosis date is summarized in Table 2. Of note, approximately half of all patients were receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers during this time period; more than half were receiving beta-blockers, and approximately one third were receiving loop diuretics.
Table 2Baseline Medication Use in 11,994 Patients with Newly Diagnosed Heart Failure Identified Between 2005 and 2008
| Medication Category | Overall N=11,994 | Preserved EF N=6210 | Borderline EF N=1870 | Reduced EF N=3914 | P Value |
|---|---|---|---|---|---|
| ACE inhibitors/angiotensin II receptor blockers | 5688 (47.4) | 3080 (49.6) | 927 (49.6) | 1681 (42.9) | <.001 |
| Aldosterone receptor antagonist | 221 (1.8) | 93 (1.5) | 29 (1.6) | 99 (2.5) | .001 |
| Beta-blocker | 6416 (53.5) | 3877 (62.4) | 1000 (53.5) | 1539 (39.3) | <.001 |
| Calcium channel blocker | 3140 (26.2) | 2099 (33.8) | 442 (23.6) | 599 (15.3) | <.001 |
| Digoxin | 865 (7.2) | 498 (8.0) | 117 (6.3) | 250 (6.4) | .002 |
| Diuretic (loop) | 3571 (29.8) | 2085 (33.6) | 513 (27.4) | 973 (24.9) | <.001 |
| Diuretic (thiazide) | 2807 (23.4) | 1728 (27.8) | 401 (21.4) | 678 (17.3) | <.001 |
| Nitrate | 1403 (11.7) | 723 (11.6) | 272 (14.5) | 408 (10.4) | <.001 |
| Statin | 5463 (45.5) | 2980 (48.0) | 911 (48.7) | 1572 (40.2) | <.001 |
| Other lipid-lowering drug | 636 (5.3) | 366 (5.9) | 106 (5.7) | 164 (4.2) | .001 |
| Antiplatelet agent | 973 (8.1) | 484 (7.8) | 202 (10.8) | 287 (7.3) | <.001 |
| Anticoagulant | 2033 (17.0) | 1198 (19.3) | 322 (17.2) | 513 (13.1) | <.001 |
ACE=angiotensin-converting enzyme; EF=ejection fraction.
Those with incident heart failure with preserved left ventricular ejection fraction differed significantly from those with heart failure with reduced left ventricular ejection fraction across a range of demographic and clinical characteristics (Table 3). In multivariable analyses, older patients were more likely to be diagnosed with heart failure with preserved left ventricular ejection fraction. For example, the odds of having heart failure with preserved left ventricular ejection fraction for those aged 65 to 74 years were 14% higher than for those aged 55 to 64 years; the odds for those aged 75 to 84 years were 34% higher, and the odds for persons aged 85 years or more were 51% higher. Women were more than 2-fold more likely than men to have heart failure with preserved left ventricular ejection fraction (adjusted odds ratio [OR], 2.24; 95% confidence interval [CI], 2.06-2.44). Compared with white patients, black patients were less likely to have heart failure with preserved systolic function (adjusted OR, 0.69; 95% CI, 0.67-0.71).
Table 3Adjusted Odds Ratios for Preserved Left Ventricular Ejection Fraction in Adults with Newly Diagnosed Heart Failure (2005-2008)
| Variable | Adjusted OR for Preserved Systolic Function (95% CI) |
|---|---|
| Age group (y) | |
| <45 | 0.77 (0.70-0.85) |
| 45-54 | 0.79 (0.72-0.86) |
| 55-64 | Reference |
| 65-74 | 1.14 (1.08-1.20) |
| 75-84 | 1.34 (1.31-1.37) |
| ≥85 | 1.51 (1.41-1.61) |
| Female gender, n (%) | 2.24 (2.06-2.44) |
| Race categories | |
| White | Reference |
| Black/African American | 0.69 (0.67-0.71) |
| Asian American | 1.02 (0.94-1.12) |
| Native Hawaiian or other Pacific Islander | 1.09 (0.89-1.33) |
| American Indian or Alaska Native | 0.53 (0.46-0.62) |
| Missing/unknown | 0.79 (0.70-0.89) |
| Medical history, n (%) | |
| Acute myocardial Infarction | 0.78 (0.65-0.95) |
| Coronary artery bypass surgery | 1.79 (1.39-2.33) |
| Percutaneous coronary intervention | 0.95 (0.80-1.13) |
| Ischemic stroke or transient ischemic attack | 1.05 (0.95-1.17) |
| Other thromboembolic event | 1.05 (0.83-1.34) |
| Atrial fibrillation or atrial flutter | 1.66 (1.57-1.76) |
| Ventricular tachycardia or fibrillation | 0.53 (0.49-0.58) |
| Mitral or aortic valvular disease | 1.99 (1.64-2.40) |
| Peripheral arterial disease | 0.98 (0.87-1.09) |
| Rheumatic heart disease | 0.86 (0.74-1.01) |
| Implantable cardioverter defibrillator | 0.29 (0.24-0.35) |
| Pacemaker | 0.89 (0.78-1.01) |
| Dyslipidemia | 1.09 (0.98-1.22) |
| Hypertension | 1.75 (1.62-1.88) |
| Diabetes mellitus | 1.06 (0.99-1.14) |
| Hospitalized bleeds | 1.31 (1.11-1.54) |
| Diagnosed dementia | 1.10 (1.01-1.20) |
| Diagnosed depression | 1.20 (1.16-1.24) |
| Chronic lung disease | 1.38 (1.22-1.55) |
| Chronic liver disease | 1.27 (1.07-1.49) |
| Mechanical fall | 1.38 (1.07-1.78) |
| Systemic cancer | 1.02 (0.87-1.21) |
| eGFR (mL/min/1.73 m2) | |
| ≥130 | 1.36 (0.86-2.16) |
| 90-130 | 1.02 (0.96-1.10) |
| 60-89 | Reference |
| 45-59 | 0.95 (0.90-1.00) |
| 30-44 | 1.07 (0.98-1.18) |
| 15-29 | 1.31 (0.99-1.73) |
| <15 | 2.12 (1.77-2.54) |
| Dialysis | 1.47 (1.26-1.71) |
| Missing | 0.84 (0.61-1.17) |
| Hemoglobin (g/L) | |
| ≥16.0 | 0.72 (0.62-0.82) |
| 15.0-15.9 | 0.70 (0.65-0.74) |
| 14.0-14.9 | 0.76 (0.75-0.78) |
| 13.0-13.9 | Reference |
| 12.0-12.9 | 1.15 (1.01-1.31) |
| 11.0-11.9 | 1.42 (1.35-1.50) |
| 10.0-10.9 | 1.36 (1.10-1.67) |
| 9.0-9.9 | 1.37 (1.17-1.60) |
| <9.0 | 1.34 (1.03-1.75) |
| Missing | 0.65 (0.53-0.80) |
| Systolic blood pressure (mm Hg) | |
| ≥180 | 2.04 (1.59-2.60) |
| 160-179 | 1.60 (1.41-1.80) |
| 140-159 | 1.28 (1.13-1.45) |
| 130-139 | 1.13 (1.06-1.21) |
| 121-129 | 1.00 (0.95-1.04) |
| 110-120 | Reference |
| 100-109 | 0.80 (0.66-0.97) |
| <100 | 0.68 (0.62-0.75) |
| Missing | 1.67 (1.30-2.14) |
| HDL cholesterol (g/dL) | |
| ≥60 | 0.87 (0.79-0.97) |
| 50-50.9 | 0.83 (0.79-0.88) |
| 40-49.9 | Reference |
| 35-39.9 | 1.01 (0.91-1.13) |
| <35 | 0.90 (0.81-1.01) |
| Missing | 0.96 (0.75-1.23) |
| LDL cholesterol (g/dL) | |
| ≥200 | 0.56 (0.42-0.73) |
| 160-199.9 | 0.98 (0.83-1.16) |
| 130-159.9 | Reference |
| 100-129.9 | 1.08 (0.96-1.21) |
| 70-99.9 | 1.14 (1.04-1.25) |
| <70 | 1.22 (1.09-1.36) |
| Missing | 0.84 (0.71-0.98) |
CI=confidence interval; eGFR=estimated glomerular filtration rate; HDL=high-density lipoprotein; LDL=low-density lipoprotein; OR=odds ratio.
Individuals with a history of coronary artery bypass surgery, mitral or aortic valvular disease, atrial fibrillation or flutter, or a diagnosis of hypertension were more likely to have heart failure with preserved left ventricular ejection fraction, as were those with a diverse range of noncardiac comorbid conditions, including chronic lung disease, chronic liver disease, a history of a hospitalized bleed, a history of a mechanical fall, a diagnosis of depression, and a diagnosis of dementia. Patients with a history of acute myocardial infarction and a history of ventricular fibrillation or ventricular tachycardia were less likely to have heart failure with preserved left ventricular ejection fraction (Table 3).
Patients with higher systolic blood pressures at baseline were more likely to have heart failure with preserved left ventricular ejection fraction (Table 3). Compared with a baseline systolic blood pressure of 110 to 120 mm Hg, the odds for those patients with systolic blood pressures of 130 to 139 mm Hg were 13% higher; the odds for patients with systolic blood pressures of 140 to 159 and 160 to 170 mm Hg were 28% and 60% higher, respectively. For those patients with systolic blood pressures of≥180 mm Hg, the adjusted OR was 2.04 (95% CI, 1.59-2.60). Lower low-density lipoprotein levels, lower hemoglobin levels, and very low estimated glomerular filtration rates (<15 mL/min/1.73 m2) were more likely in those presenting with heart failure with preserved left ventricular ejection fraction.
Discussion
In this large, contemporary, multicenter cohort composed of patients with newly diagnosed heart failure, more than 50% had heart failure with preserved left ventricular ejection fraction. These findings are sobering in that of the 2011 American College of Cardiology Foundation/American Heart Association/American Medical Association-Physician Consortium for Performance Improvement performance measures for adults with heart failure,
13
all of the measures associated with therapeutic interventions focus solely on patients with heart failure with reduced left ventricular ejection fraction. Such patients comprise less than one third of those with incident heart failure, according to the findings of our study.- Bonow R.O.
- Ganiats T.G.
- Beam C.T.
- et al.
ACCF/AHA/AMA-PCPI 2011 performance measures for adults with heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures and the American Medical Association-Physician Consortium for Performance Improvement.
Circulation. 2012; 125: 2382-2401
The nomenclature regarding the classification of heart failure has been a subject of some controversy.
5
The most recently revised 2011 American College of Cardiology Foundation/American Heart Association guidelines for the diagnosis and management of heart failure use the term “heart failure with normal left ventricular ejection fraction.”14
In the present study, we took a somewhat less stringent approach to characterizing patients, because we used both quantitative and qualitative assessments of left ventricular systolic function, which represents how patients are frequently evaluated and classified in clinical practice, especially given the known challenges in the accuracy of the calculation of left ventricular ejection fraction.- Hunt S.A.
- Abraham W.T.
- Chin M.H.
- et al.
2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation.
Circulation. 2009; 119 (Review. No abstract available. Erratum in: Circulation. 2010;121:e258): e391-e479
As has been reported in previous studies, older age, female sex, hypertension, presence of atrial fibrillation, and lower hemoglobin levels were more likely to be present in patients with heart failure with preserved left ventricular ejection fraction.
5
, 15
Our study findings also serve to emphasize the complexity of the patient population with heart failure; a variety of noncardiac conditions, such as chronic lung disease, chronic liver disease, depression, and dementia, were more likely to be present in patients diagnosed with heart failure with preserved left ventricular ejection fraction. The implications of noncardiac comorbidities and how they relate to clinical decision-making and clinical outcomes in the patient population with heart failure have been increasingly appreciated.16
, 17
, 18
, 19
Study Limitations
Our study has some limitations. Insured populations in our participating health plans may not be fully representative of the general population. Nevertheless, this limitation is counterbalanced by the breadth of geographic and demographic diversity represented across 4 geographically diverse health plans, as well as the community-based nature of health care delivery, suggesting that findings from our study are likely to be highly generalizable to patients with heart failure in “real-world” practice settings. In our study, heart failure diagnoses were not adjudicated through medical record abstraction and expert review. However, prior studies have shown a high positive predictive value for the approach we used to identify patients with heart failure.
Our findings confirm that a majority of patients who present with heart failure have heart failure with preserved left ventricular ejection fraction, and it is likely that the numbers of patients affected by this form of the heart failure syndrome will increase with the aging of the US population over the coming decades. Yet, there remains a dearth of evidence to guide the management of these complex patients who have adverse outcomes, including hospitalization and mortality at high rates.
Conclusions
Few studies have been undertaken that have specifically focused on patients with heart failure with preserved left ventricular ejection fraction, and clinical trials regarding heart failure have tended to exclude the types of patients most commonly presenting with this condition, including the elderly, women, and those with high burdens of comorbidity.
1
, 20
, 21
The imperative to address this situation has never been more apparent and urgent.Acknowledgments
The authors thank all of the project managers, data programmers, and analysts for the critical technical contributions and support that made this study possible.
References
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- 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation.Circulation. 2009; 119 (Review. No abstract available. Erratum in: Circulation. 2010;121:e258): e391-e479
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Article info
Publication history
Published online: March 15, 2013
Footnotes
Funding: The study was supported by 1RC1HL099395 and U19 HL91179 from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH). Support for Dr McManus was also provided by NIH Grant KL2RR031981, and Dr Saczynski received additional support from NIH Grant K01AG33643. The sponsors had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the manuscript.
Conflict of Interest: Larry Allen, MD, MHS, has served as a consultant for Amgen and J&J/Janssen. The other authors have no conflicts of interest associated with the work presented in this manuscript.
Authorship: All authors had access to the data and played a role in writing this manuscript.
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© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
