Predictor Of Mortality In Heart Failure Research Articles

Abstract 10608: Genome-Wide Association Study Identifies Polymorphisms Associated with Heart Failure Mortality in a Diverse Patient Population

Introduction: Few genome-wide association studies (GWAS) of heart failure (HF) mortality have been published, with most focused on incidence or surrogate endpoints. Our aim was to identify genomic predictors of HF mortality in a racially diverse population. Hypothesis: Both ancestry-specific and trans-ancestry variants are associated with survival in HF patients. Methods: HF patients with preserved or reduced ejection fraction from the University of Illinois Chicago cardiology clinics were prospectively enrolled and followed until 11/2015. Whole blood was collected. Clinical data were retrospectively acquired through medical records. Genotyping was performed via Affymetrix Axiom Pan-African Array and imputed via TOPMed Imputation Server. Genetic ancestry (African/non-African) was assigned by principal component (PC) analysis. Within each ancestral population, associations between genetic variants and all-cause mortality were assessed by Cox regression model, adjusted for age, sex, NYHA class, HF medication regimen, and PCs. A trans-ancestry fixed-effect meta-analysis was then conducted. P < 5.0 x 10 -8 was considered statistically significant. Results: The cohort included 319 HF patients (age 63 ± 13 yrs, 51% men, median follow-up 33 mos), comprised of 237 African ancestry (AA) (134 deaths) and 82 non-AA subjects (41 deaths). In the AA GWAS, 5 loci reached genome-wide significance. The top single nucleotide polymorphism (SNP), rs142008984 on chromosome 1 ( P = 5.21 x 10 -10 , HR = 8.55, 95%CI 4.34 - 16.82), resides in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene. No SNPs in the non-AA GWAS reached the defined significance level, and the AA-associated NOS1AP SNPs were not present in non-AA. Meta-analysis revealed 2 additional significant loci, among which was the top SNP on chromosome 6, rs79027708 ( P = 1.43 x 10 -9 , HR = 0.15, 95% CI 0.08 - 0.28), in the phosphodiesterase 10A ( PDE10A) gene. Conclusions: This study identified novel loci associated with all-cause mortality in a racially diverse HF population. NOS1AP and PDE10A have previously been associated with sudden cardiac death, cardiac hypertrophy, and fibrosis risk. Risk variants specific to AA were also identified, which may contribute to the lower survival in this population.

Prognostic role of albumin level in heart failure: A systematic review and meta-analysis.

Background:Hypoalbuminemia (HA) is common in HF, however, its pathophysiology and clinical implications are poorly understood. While multiple studies have been published in the past decade investigating the role of serum albumin in HF, there is still no consensus on the prognostic value of this widely available measure. The objective of this study is to assess the prognostic role of albumin in heart failure (HF) patientMethods:Unrestricted searches of MEDLINE, EMBASE, Cochrane databases were performed. The results were screened for relevance and eligibility criteria. Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The Begg and Mazumdar rank correlation test was utilized to evaluate for publication bias.Results:A total of 48 studies examining 44,048 patients with HF were analyzed. HA was found in 32% (95% confidence interval [CI] 28.4%–37.4%) HF patients with marked heterogeneity (I2 = 98%). In 10 studies evaluating acute HF, in-hospital mortality was almost 4 times more likely in HA with an odds ratios (OR) of 3.77 (95% CI 1.96–7.23). HA was also associated with a significant increase in long-term mortality (OR: 1.5; 95% CI: 1.36–1.64) especially at 1-year post-discharge (OR: 2.44; 95% CI: 2.05–2.91; I2 = 11%). Pooled area under the curve (AUC 0.73; 95% CI 0.67–0.78) was comparable to serum brain natriuretic peptide (BNP) in predicting mortality in HF patients.Conclusion:Our results suggest that HA is associated with significantly higher in-hospital mortality as well as long-term mortality with a predictive accuracy comparable to that reported for serum BNP. These findings suggest that serum albumin may be useful in determining high-risk patients.

Factors Affecting Mortality in Heart Failure Patients

Introduction Globally, heart failure (HF) is a leading cause of morbidity and mortality as well as healthcare expenditure in people older than 65 years of age. Worldwide, the prevalence of HF ranges from 1-7% depending on the country and after its diagnosis, survival rates are 50% at 5 years and 10% at 10 years. This study aims to determine which factors in HF can predict mortality, to inform methods of reducing HF mortality for future research. Study Method A retrospective analysis of patients admitted with HF to South Western Sydney Local Health District from 2012 to 2015 was conducted. The mean follow-up period was 3 years. Univariate analysis was performed on factors previously correlated to mortality in HF, including age (separated into groups =70 years old), left ventricular ejection fraction (LVEF), electrolytes, atrial fibrillation (AF), anaemia (defined by WHO criteria as Results On univariate analysis, significant variables included CKD (p = 0.001; OR = 2.1; CI [1.5-2.9]); anaemia (p = 0.002; OR = 1.6; CI [1.2-2.2]); CNCI (p = 0.001; OR = 0.6; CI [0.4-0.8]); age (p = 0.043; OR =1.5; CI [1.0-2.3]) and ACEIs (p = 0.049; OR = 0.7; CI [0.6-1.0]. Other factors such as LVEF, electrolytes, AF, betablockers, spironolactone, diuretics and ARBs were not statistically significant. Logistic regression analysis of significant factors showed CKD was the most important factor (p = 0.001; OR = 2.0; CI [1.5-2.8]) followed by CNCI (p = 0.001; OR = 0.6; CI [0.4-0.8]) and anaemia (p = 0.018; OR = 1.4; CI [1.1-2.0]). Age (p = 0.073) and ACEI (p = 0.127) were not significant when accounting for confounding factors. Conclusion The most important predictor of mortality in HF was chronic renal impairment. CNC intervention was previously viewed considered to alleviate morbidity, but when examined, was shown to decrease mortality as well in HF patients. Anaemia, which is an easily treatable condition, was a significant factor contributing to death, and should be a point of further investigation. Even though ACEI and age were significant on univariate analysis, when corrected for other factors, they had no influence on outcome.

Nur77 protects against adverse cardiac remodelling by limiting neuropeptide Y signalling in the sympathoadrenal-cardiac axis.

Cardiac remodelling and heart failure are promoted by persistent sympathetic activity. We recently reported that nuclear receptor Nur77 may protect against sympathetic agonist-induced cardiac remodelling in mice. The sympathetic co-transmitter neuropeptide Y (NPY) is co-released with catecholamines and is a known cardiac modulator and predictor of heart failure mortality. Recently, transcriptome analyses revealed NPY as a putative target of Nur77. In this study, we assess whether Nur77 modulates adverse cardiac remodelling via NPY signalling. Nur77 represses NPY expression in the PC12 adrenal chromaffin cell line. Accordingly, NPY levels are higher in adrenal gland, plasma, and heart from Nur77-KO compared to wild-type mice. Conditioned medium from Nur77-silenced chromaffin cells and serum from Nur77-KO mice induce marked hypertrophy in cultured neonatal rat cardiomyocytes, which is inhibited by the NPY type 1 receptor (NPY1R) antagonist BIBO3304. In cardiomyocytes from Nur77-KO mice, intracellular Ca2+ is increased partially via the NPY1R. This is independent from elevated circulating NPY since cardiomyocyte-specific Nur77-deficient mice (CM-KO) do not have elevated circulating NPY, but do exhibit BIBO3304-sensitive, increased cardiomyocyte intracellular Ca2+. In vivo, this translates to NPY1R antagonism attenuating cardiac calcineurin activity and isoproterenol-induced cardiomyocyte hypertrophy and fibrosis in full-body Nur77-KO mice, but not in CM-KO mice. The cardioprotective action of Nur77 can be ascribed to both inhibition of circulating NPY levels and to cardiomyocyte-specific modulation of NPY-NPY1R signalling. These results reveal the underlying mechanism of Nur77 as a promising modifier gene in heart failure.

Evaluation of Predictors of Mortality Associated With Childhood Heart Failure in Nigeria: A 2-Center Study.

The aim of this study was to evaluate the predictors of mortality in childhood heart failure (HF) in 2 tertiary hospitals. A 51-month retrospective review of case notes of children with HF admitted into children's emergency rooms of 2 tertiary centers in Southern Nigeria was done. Bio-data and certain sociodemographic variables including mortality were abstracted. Bivariate and multivariate analyses were done to evaluate the predictors of mortality in HF. The case notes of 289 children were analyzed, consisting of 153 males (52.9%) and 142 infants (49.1%). Lower respiratory tract infections, 121 (41.9%), were the commonest causes of HF. Twenty-eight children (9.7%) died. In multivariate analyses, only late presentation (P < 0.0001) was an independent predictor of mortality in HF. Education of the populace about early presentation to hospital is imperative to prevent unnecessary deaths associated with HF.

Soluble ST2 correlates with some indicators of right ventricular function in hypertensive heart failure.

PurposeST2 receptor, which is a member of the Toll-like/interleukin-1 (IL-1) receptor family, has been found to be increased in the serum of patients 1 day after myocardial infarction. Several other studies have shown that soluble ST2 levels correlate with severity of heart failure (HF), left ventricular ejection fraction, creatinine clearance, B-type natriuretic peptide and C-reactive protein, and are predictors of mortality in HF. Most of these studies were not only limited to ischemic heart disease but also concentrated on left-sided HF. We therefore decided to study the relationship between soluble ST2 and some markers of right ventricular (RV) function in a cohort of hypertensive HF subjects.Patients and methodsThis is a prospective cohort study of hypertensive HF patients presenting to the University of Abuja Teaching Hospital, Abuja, over a 12-month period. ST2 was measured in plasma sample by the enzyme-linked immunosorbent assay (ELISA) method. Right ventricular diameters in diastole (RVDD) and right atrial area (RAA) were obtained on echocardiography, while right ventricular systolic pressure (RVSP) was estimated from echocardiography by the addition of the pressure gradient between the right ventricle and right atrium (RA) to the pressure in the RA.ResultsThere was a significant correlation between RVSP and soluble ST2 (t=0.75, p<0.0001), RVDD (t=0.28, p=0.004) and RAA (t=0.46, p=0.002).ConclusionIn a cohort of hypertensive HF subjects, soluble ST2 correlates significantly with RVSP, RVDD and RAA.

Clinical characteristics and prognosis of patients admitted for heart failure: A 5-year retrospective study of African patients

BackgroundMortality associated with heart failure (HF) remains high. There are limited clinical data on mortality among HF patients from African populations. We examined the clinical characteristics, long-term outcomes, and prognostic factors of African HF patients with preserved, mid-range or reduced left ventricular ejection fraction (LVEF). Methods and resultsWe conducted a retrospective longitudinal cohort study of individuals aged ≥18years discharged from first HF admission between January 1, 2009 and December 31, 2013 from the Cardiac Clinic, Directorate of Medicine of the Komfo Anokye Teaching Hospital, Ghana. A total of 1488 patients diagnosed of HF were included in the analysis. Of these, 345 patients (23.2%) had reduced LVEF (LVEF<40%) [HFrEF], 265(17.8%) with mid-range LVEF (40%≥LVEF<50%) [HFmEF] and 878 (59.0%) had preserved LVEF (LVEF≥50%) [HFpEF]. Kaplan–Meier curves and log-rank test demonstrated better prognosis for HFpEF compared to HFrEF and HFmEF patients. An adjusted Cox analysis showed a significantly lower risk of mortality for HFpEF (hazard ratio (HR); 0.74; 95% confidence interval (CI) 0.57–0.94) p=0.015). Multivariate analyses showed that age, higher New York Heart Association (NYHA) functional class, lower LVEF, chronic kidney disease, atrial fibrillation, anemia, diabetes mellitus and absence of statin and aldosterone antagonist treatment were independent predictors of mortality in HF. Although, prognostic factors varied across the three groups, age was a common predictor of mortality in HFpEF and HFmEF. ConclusionsThis study identified the clinical characteristics, long-term mortality and prognostic factors of African HF patients with reduced, mid-range and preserved ejection fractions in a clinical setting.

PS 14-16 PREDOMINANCE OF HYPERTENSION IN CONTEMPORARY AETIOLOGIES, TRENDS AND MORTALITY OF PATIENTS WITH ACUTE HEART FAILURE AS SEEN FROM TWO CARDIAC REFERRAL CENTRES IN DOUALA, CAMEROON

Objective: Heart failure (HF) continues to be a global health problem. Due to limited epidemiological data in Africa, there is need to explore and better understand its aetiology and outcome to improve its management. Design and Method: We analysed clinical and echocardiographic data of patients with acute HF at the cardiology units of Douala General Hospital and Douala Cardiovascular Center, among which 290 retrospective and 122 prospective cases during a period of 5 years (2009–2013). Chi square and student t-tests (where appropriate) were used for group comparisons while logistic regression models were used to investigate the predictors of mortality in HF and survival estimated using Kaplan Meier curves. Results: In all, 412 patients (214 men (mean age 58.1 ± 14.8 years) and 198 women (mean age 62.7 ± 17.4 years)) were included. The aetiologies of HF were predominantly non-ischemic: hypertensive cardiomyopathy (HTCM) (54.5%), dilated cardiomyopathy (20.5%), valvular heart disease (VHD) (11.7%) and ischemic heart disease (4.9%). The trend in incidence of HTCM and IHD was constant over 5 years while VHD had a declining trend (p < 0.01). A low use of beta-blockers was noticeable. Mortality rates were 14.3% for in hospital, 29.6% at 6 months to 38.2% at one year. Conclusions: Contemporary aetiologies of HF in Cameroon are similar to previous reports from other African registries; with dominance of HTCM and declining but persisting VHD. Mortality rates of HF are high, huge efforts are needed to improve management of HF in low-resourced settings.

Review of nutritional screening and assessment tools and clinical outcomes in heart failure.

Recent studies have suggested that undernutrition as defined using multidimensional nutritional evaluation tools may affect clinical outcomes in heart failure (HF). The evidence supporting this correlation is unclear. Therefore, we conducted this systematic review to critically appraise the use of multidimensional evaluation tools in the prediction of clinical outcomes in HF. We performed descriptive analyses of all identified articles involving qualitative analyses. We used STATA to conduct meta-analyses when at least three studies that tested the same type of nutritional assessment or screening tools and used the same outcome were identified. Sensitivity analyses were conducted to validate our positive results. We identified 17 articles with qualitative analyses and 11 with quantitative analysis after comprehensive literature searching and screening. We determined that the prevalence of malnutrition is high in HF (range 16-90%), particularly in advanced and acute decompensated HF (approximate range 75-90%). Undernutrition as identified by multidimensional evaluation tools may be significantly associated with hospitalization, length of stay and complications and is particularly strongly associated with high mortality. The meta-analysis revealed that compared with other tools, Mini Nutritional Assessment (MNA) scores were the strongest predictors of mortality in HF [HR (4.32, 95% CI 2.30-8.11)]. Our results remained reliable after conducting sensitivity analyses. The prevalence of malnutrition is high in HF, particularly in advanced and acute decompensated HF. Moreover, undernutrition as identified by multidimensional evaluation tools is significantly associated with unfavourable prognoses and high mortality in HF.

Right Ventricular Function in Cardiovascular Disease, Part II

Right ventricular (RV) function may be impaired in pulmonary hypertension (PH), congenital heart disease (CHD), and coronary artery disease and in patients with left-sided heart failure (HF) or valvular heart disease. In recent years, many studies have demonstrated the prognostic value of RV function in cardiovascular disease. In the past, however, the importance of RV function has been underestimated. This perception originated from studies on open-pericardium dog models and from the observation that patients may survive without a functional subpulmonary RV (Fontan procedure). In the 1940s, studies using open-pericardium dog models showed that cauterization of the RV lateral wall did not result in a decrease in cardiac output or an increase in systemic venous pressure.1–3 As was later demonstrated, the open-pericardium model did not take into account the complex nature of ventricular interaction. In 1982, Goldstein and colleagues2 showed that RV myocardial infarction (RVMI) in a closed-chest dog model led to significant hemodynamic compromise. These findings were further supported by clinical studies demonstrating an increased risk of death, arrhythmia, and shock in patients with RVMI.4 The study of the RV is a relatively young field. In 2006, the National Heart, Lung, and Blood Institute identified RV physiology as a priority in cardiovascular research.5 The goal of this review is to present a clinical perspective on RV physiology and pathobiology. In the first article of the series, the anatomy, physiology, embryology, and assessment of the RV were discussed. In this second part, we discuss the pathophysiology, clinical importance, and management of RV failure. RV failure is a complex clinical syndrome that can result from any structural or functional cardiovascular disorder that impairs the ability of the RV to fill or to eject blood. The cardinal clinical manifestations of RV failure are (1) fluid retention, which may lead …

Diabetic Cardiomyopathy and Anesthesia

Diabetic Cardiomyopathy and Anesthesia

Abstract 3276: Assessment of Predictive Accuracy of Centers for Medicare and Medicaid Services’ Method to Risk Adjust Patients for Interhospital Comparison of 30-day Mortality Rates

Introduction : The Centers for Medicare and Medicaid Services (CMS) will initiate public reporting of 30 day death rates for hospitals caring for patients with heart failure (HF). While hospital specific rates will be adjusted for medical comorbidities, it is not known if this method is adequate to allow direct hospital comparisons. Hypothesis : More accurate risk adjustment of patients can be accomplished by including variables that have previously been described to be predictors of mortality in HF. Methods : We assessed the CMS HF risk adjustment model in a population of 3639 patients studied in the Guidelines Applied in Practice (GAP) - HF study. Probabilties for 30 day mortality were calculated for the CMS model. Multivariable logistic regression analysis was then performed with other models including variables (no mVO 2 ) from the Heart Failure Survival Score (HFSS), ADHERE Registry model (ARM), body mass index categories (BMI), pre-admission origin of patient (PAO), and admission in the previous 6 months (AP6). Probabilities of mortality were tabulated. Backward selection was then used to derive the best model from all candidate variables from a derivation data subset, followed by testing of the model on a validation data subset. Area under the curve (AUC) was then compared for each model. Results : The AUCs and 95% CI are shown in the table below. Calculated AUCs for the CMS model and separate models were similar. The best model was defined by the following variables: admission in the previous 6 months, BUN &gt; 43, systolic blood pressure &gt; 115, 35 ≤ BMI &lt; 40, BMI ≥ 40, mean arterial pressure, serum sodium, and PAO as well as the CMS model variables. The AUCs for the derivation and validation sets were both significantly greater than that provided by the CMS model alone. Conclusions : Risk adjustment for the purpose of interhospital comparison of 30-day mortality rates is best performed with models that include clinical admission variables in addition to the medical comorbidites. Comparison of AUCs for 30 day mortality prediction