Female sex-specific and -predominant cardiovascular risk factors and heart failure practice guidelines.

Heart failure (HF) etiology, presentation and prognosis differ by sex, with female sex-specific and -predominant risk factors playing important roles. We systematically reviewed the studies cited by the 2017 American College of Cardiology/ American Heart Association/ Heart Failure Society of America Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Female cardiovascular risk factors were broadly categorized as female sex-specific (reproductive, pregnancy, menopausal) and female sex-predominant (depression, anthracycline exposure, autoimmune disease) risk factors. Of the 205 cited articles, only 3 studies (1.6%) reported any female sex-specific cardiovascular risk factor in the data analysis or results sections. Oral contraceptive use (n = 1), menopausal status (n = 2) and hormone replacement therapy (n = 2) were the only female sex-specific cardiovascular risk factors reported. No other female sex-specific or -predominant cardiovascular risk factor was reported by any of the eligible studies. Our work highlights that in addition to the need for proportional representation of women in heart failure clinical studies, inclusion of female sex-specific and -predominant risk factors in data collection and analysis is of paramount importance to guide heart failure care in the female population.

Impact of Current Versus Previous Cardiac Resynchronization Therapy Guidelines on the Proportion of Patients With Heart Failure Eligible for Therapy.

OBJECTIVES: This study sought to ascertain the impact of heart failure (HF) guideline change on the number of patients eligible to undergo cardiac resynchronization therapy (CRT). BACKGROUND: The 2013 HF guideline of the American College of Cardiology Foundation and American Heart Association (ACCF/AHA) narrowed the recommendations for CRT. The impact of this guideline change on the number of eligible patients for CRT has not been described. METHODS: Using data from Get With The Guidelines-Heart Failure between 2012 and 2015, this study evaluated the proportion of hospitalized patients with HF who were eligible for CRT on the basis of historical and current guideline recommendations. The authors identified 25,102 hospitalizations for HF that included patients with a left ventricular ejection fraction (LVEF) ≤35% from 283 hospitals. Patients with a medical, system-related, or patient-related reason for not undergoing CRT were excluded. RESULTS: Overall, 49.1% (n = 12,336) of patients with HF, an LVEF ≤35%, and no documented contraindication were eligible for CRT on the basis of historical guidelines, and 33.1% (n = 8,299) of patients were eligible for CRT on the basis of current guidelines, a 16.1% absolute reduction in eligibility (p < 0.0001). Patients eligible for CRT on the basis of current guidelines were more likely to have CRT with an implantable cardioverter-defibrillator or CRT with pacing only placed or prescribed at discharge (57.8% vs. 54.9%; p < 0.0001) compared with patients eligible for CRT on the basis of historical guidelines. CONCLUSIONS: In this population of patients with HF, an LVEF ≤35%, and no documented contraindication for CRT, the current ACCF/AHA HF guidelines reduce the proportion of patients eligible for CRT by approximately 15%.

Noninvasive Bioelectrical Impedance for Predicting Clinical Outcomes in Outpatients With Heart Failure.

BACKGROUND: Noninvasive bioelectrical impedance analysis (BIA) has shown promise in acute heart failure (HF) management. To our knowledge, its use in predicting outcomes in outpatients with chronic HF patients has not been well described. METHODS AND RESULTS: BIA assessment of edema index was performed in 359 outpatients with HF using the InBody 520 scale. Edema index was calculated by dividing extracellular by total body water. Patients were stratified into those with low (≤0.39) and high (>0.39) edema indices. The outcome of interest was death, urgent transplant, or ventricular assist device over 2-year follow up. Patients with a high edema index were older, had higher B-type natriuretic peptide values and New York Heart Association Class. Patients with a high edema index had poorer outcomes (unadjusted hazard ratio 1.90, 95% confidence intervals 1.05-3.56). However, in multivariate analyses, a high edema index was not an independent predictor of outcomes (adjusted hazard ratio 1.21, 95% confidence interval 0.51-2.90). CONCLUSIONS: A high edema index using a bioimpedance scale in a HF clinic correlated with patient outcomes in unadjusted analyses, but was not a predictor of outcomes once other measures of HF severity are accounted for. As a noninvasive measure of volume status, use of BIA in a HF clinic may be beneficial in determining patient prognosis and treatment when other outcome predictors are not immediately available.

Rates and reasons for device-based guideline eligibility in patients with heart failure.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) are recommended by guidelines for patients with heart failure (HF) meeting specific criteria. Uncertainty exists regarding estimates of device eligibility, related in part to the method of assessing for guideline nonadherence. OBJECTIVE: The aim of this study was to identify the rates of guideline eligibility and device utilization after accounting for reasons for not receiving an ICD or CRT. METHODS: Patients were identified from 2006 to 2011 in a tertiary Heart Function Clinic in Canada. The chart-level data were collected that would indicate guideline eligibility and nonadherence. RESULTS: A total of 762 patients with HF were included (mean age 66 years; 527 (69%) were males; median left ventricular ejection fraction 33%). Over follow-up, 331 patients (43%) were never guideline eligible whereas 431 (57%) were guideline eligible for a device. Yearly rates for ICD and CRT adherence in "guideline-eligible" patients ranged from 59% to 68% and from 66% to 81%, respectively. "Patient preference" was the most commonly documented reason for guideline nonadherence in eligible patients. After removal of patients with reasons for nonadherence, rates of ICD and CRT adherence in the "truly eligible" patients were found to be higher (70%-81% and 71%-88%, respectively) than those in guideline-eligible patients. Independent predictors of device nonadherence in truly eligible patients were age >75 years, QRS duration <120 ms, left ventricular ejection fraction <30%, and female sex. CONCLUSION: Based on chart-level data, utilization rates of device-based therapies in patients with HF appear much higher than those of prior registry-based estimates. Given the importance of patient preferences for lack of device use, future quality-of-care metrics based on guideline adherence should capture detailed chart-level data and patient preferences.

Mortality outcomes among status Aboriginals and whites with heart failure.

BACKGROUND: Aboriginals have more cardiovascular risk factors than do non-Aboriginals that predispose them to the development of heart failure (HF). Whether long-term mortality outcomes and health care use differ between Aboriginals and whites with HF is unknown. METHODS: The population consisted of all Albertans aged ≥ 20 years with an incident HF hospitalization between 2000 and 2008. Aboriginal status is recorded in the Alberta Health Care Insurance Registry and white ethnicity was determined using previously validated surname analysis algorithms. Cox and logistic regression was used to examine mortality outcomes after adjustment for key variables. RESULTS: Compared with whites (n = 42,288), status aboriginal patients with HF (n = 1158) were significantly younger (mean age, 62.6 vs 75.4 years; P < 0.0001) and had higher rates of diabetes (45% vs 29%; P < 0.0001) and chronic obstructive pulmonary disease (40% vs 36%; P < 0.0001) but lower rates of most other comorbidities. Although crude mortality rates were lower in status Aboriginals than in whites at 1 year (22% vs 31%; P < 0.0001) and at 5 years (48% vs 59%; P < 0.0001), after adjustment, status Aboriginals exhibited increased mortality at 1 year (adjusted odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01-1.38) and 5 years (adjusted OR, 1.39; 95% CI, 1.16-1.67). Compared with whites, status Aboriginals used more health care resources in the years before and after an incident HF hospitalization but less specialist care. CONCLUSIONS: Although status Aboriginals hospitalized for the first time with HF are > 10 years younger, they use more health care resources and have increased short- and long-term mortality compared with their white counterparts.

The unrecognized burden of osteoporosis-related vertebral fractures in patients with heart failure.

BACKGROUND: Heart failure (HF) is associated with several factors that contribute to both reduced bone mineral density and increased risk of osteoporosis-related fractures. Our objectives were to describe the prevalence and predictors of the most common osteoporotic fracture, vertebral compression fractures (VCF), in patients with HF. METHODS AND RESULTS: We conducted a cross-sectional study in a random sample of patients attending a tertiary care HF Clinic in Edmonton, Alberta, Canada. We collected sociodemographic, clinical, medication, and chest radiograph information. Primary outcome was board-certified radiologist-documented VCF on chest radiographs. Multivariable logistic regression was used to determine independent correlates of VCF. Overall, 623 patients with HF were included; 32% were over 75 years of age, 31% were women, 65% had ischemic cardiomyopathy, and 38% had atrial fibrillation. Prevalence of VCF was 77 of 623 (12%; 95% confidence interval, 10% to 15%), and 42 of 77 (55%) patients had multiple fractures. Only 15% of those with VCF were treated for osteoporosis. In multivariable analyses adjusted for age, female sex, weight, and medications, the only remaining predictors independently associated with fracture were atrial fibrillation (present in 42 of 77 [55%] of those with VCF versus 197 of 540 [36%] of those without; adjusted odds ratio, 2.1; 95% confidence interval, 1.2 to 3.6; P=0.009) and lipid-lowering drugs (used by 36 of 77 [47%] of those with VCF versus 342 of 540 [63%] of those without; adjusted odds ratio, 0.2; 95% confidence interval, 0.1 to 0.9; P=0.03). CONCLUSIONS: About one-tenth of HF patients had a chest radiograph-documented VCF, and half of those with VCF had multiple fractures; most (85%) were not receiving an osteoporosis-specific therapy. A previously unrecognized risk factor-atrial fibrillation-was found to be independently associated with VCF. Chest radiograph reports may represent an important case-finding tool for osteoporosis-specific VCF, particularly in HF patients with atrial fibrillation.

Prevalence and predictors of vertebral fracture in patients with chronic obstructive pulmonary disease.

OBJECTIVES: Patients with COPD are at risk for osteoporosis-related vertebral compression fractures (VCF) which predispose to more fractures and worsening pulmonary function. Our objectives were to: 1 document VCF prevalence in COPD patients; and 2 determine the independent correlates of VCF. METHODS: From 2004-2006, we prospectively recruited consecutive consenting COPD patients presenting with acute exacerbation at three Canadian Emergency Departments (ED). We collected clinical and pulmonary function data. Primary outcome was radiologist documented VCF on chest radiograph. Multivariable logistic regression was used for all adjusted analyses. RESULTS: Overall, 245 patients were studied; 37% were >or=75 years and 44% were women. Prevalence of VCF documented by chest radiograph was 22 of 245 (9%; 95%CI 6-13%). Almost half (10 of 22 [43%]) of VCF patients were not treated for osteoporosis and all 10 received oral steroids. Compared to patients without fractures, those with VCF were older (p=0.014), had COPD of longer duration (p=0.09) and greater severity (mean FEV(1) 0.9 vs 1.1L; p=0.05), and had lower body mass index [BMI] (median 26 vs 28; p=0.01). Across BMI quartiles (from heaviest [median 37] to lightest [median 21]) the prevalence of VCF progressively increased (2%, 8%, 10%, 21%; p<0.001). In analyses adjusted for age, sex, and COPD duration, the only independent correlate of VCF was BMI: VCF increased as BMI decreased from heaviest (OR=1) to lightest (OR=11.0) quartiles (p=0.025). CONCLUSIONS: Almost one-tenth of COPD patients presenting with acute exacerbation have chest radiographs documenting VCF. About half of patients with VCF were not treated for osteoporosis, but all were started on oral steroids. Our findings suggest chest radiograph reports may represent an important case-finding tool for VCF, particularly in underweight patients with COPD.

Different in vivo repopulating activities of purified hematopoietic stem cells before and after being stimulated to divide in vitro with the same kinetics.

OBJECTIVE: The Hoechst 33342-effluxing side population (SP) of adult mouse bone marrow (BM) contains most of the hematopoietic stem cells (HSCs). Here we measured the HSC content of specific subsets of SP cells and then used a highly HSC-enriched fraction to investigate the effect of different growth factors on the initial rate of HSC proliferation in vitro and the accompanying maintenance (or loss) of HSCs in the first-division progeny. MATERIALS AND METHODS: Staining with Rhodamine-123 (Rho) was used to subfractionate lineage marker-negative (lin-) SP cells. Cells were assayed for HSCs by examining their ability to generate sustained (>4 months) multi-lineage lympho-myeloid clones in irradiated hosts. Cultures of single lin- Rho- SP cells were used to monitor growth factor effects on HSC proliferation and function. RESULTS: More than 40% of mice injected with single lin- Rho- SP cells showed long-term lympho-myeloid reconstitution. Some clones peaked within 8 weeks but others developed more slowly apparently unrelated to the pattern of lineage representation. 3/3 clones tested repopulated secondary mice. Either Steel factor+interleukin-11 (+/- flt3-ligand) or Steel factor+thrombopoietin stimulated at least 75% of single lin- Rho- SP cells to divide in vitro with the same synchronous kinetics. However, in the first cocktail, the frequency of HSCs among the first-division doublets was preserved but in the latter it was greatly diminished. CONCLUSION: Exogenous growth factors can differentially affect the ability of HSCs to execute a self-renewal division within a single cell cycle even when the kinetics of proliferation are the same.