Ambulatory Heart Failure Patients Research Articles

Risk Prediction Models for Mortality in Ambulatory Heart Failure Patients: A Systematic Review

Purpose Optimal management of heart faikure (HF) requires accurate assessment of prognosis. Many prognostic models are available. The aim was to identify studies evaluating the use of risk prediction models for mortality in ambulatory HF patients, describe their performance and clinical applicability. Methods and Materials We searched for studies in MEDLINE, EMBASE and CINAHL in May 2012 and scanned references of included studies. Two reviewers selected citations including HF patients and reporting on model performance in derivation and/or validation cohorts. We abstracted data related to population, outcomes, study quality and model discrimination and calibration. Results Of the 9952 reviewed, we included 32 studies testing 18 models. Only 4 models were validated in independent cohorts: the Heart Failure Survival Score (HFSS), the Seattle Heart Failure Model (SHFM), the PACE risk score and a model by Frankenstein et al. The HFSS was validated in 8 cohorts (2240 patients) showing poor to modest discrimination (c-statistic 0.56-0.79), being lower in more recent cohorts. The SHFM was validated in 14 cohorts (16057 patients) describing poor to acceptable discrimination (0.63-0.81), remaining relatively stable over time. Both models reported adequate calibration, though overestimating survival in specific populations. The other two models were validated in one cohort each, reporting poor discrimination (0.66-0.69). Among the remaining 14 models, six were validated by bootstrapping (c-statistic 0.74-0.85); the rest were not validated. Conclusions Externally validated HF models showed inconsistent performance. The HFSS and SHFM demonstrated modest discrimination and questionable calibration. A new model derived from contemporary patient cohorts may be required for improved prognostic performance.

CRT before Transplant or VAD? The Role of CRT in Stage D Heart Failure

Purpose Cardiac resynchronization therapy (CRT) improves outcomes in ambulatory heart failure (HF) patients with New York Heart Association (NYHA) class II-IV symptoms. However, its role in stage D patients, particularly those eligible for heart transplant (HTx) or ventricular assist device (VAD), has not been well characterized. This study investigates the clinical outcomes of patients who were stage D at time of CRT implant, and the potential factors associated with CRT response. Methods and Materials In this retrospective study, medical records of patients referred to the CRT clinic from Jan 2010 to Dec 2011 were reviewed. Patients were included if they met criteria for stage D HF: 1) inotrope-dependent, and/or listed for HTx, 2) peak oxygen consumption (VO2max) 35% or QRS duration Results Fifty-five patients (mean age 63±11yrs, 75% male) met stage D criteria, of whom 50 had successful CRT implant and were followed for an average of 12±8 months. At last follow-up, 42% (21/50) improved by one NYHA class, or had 10% increase in VO2max or absolute EF; 36% (18/50) were unchanged; 22% (11/50) worsened by one NYHA class or died. CRT response was established by 6 months and did not change over time. Left bundle-branch block and paced QRS morphology at baseline were associated with clinical improvement (91vs.61%, p Conclusions Stage D patients appear to have a lower response rate to CRT than the general HF population. QRS morphology may predict CRT response in these patients. The decision to implant CRT in HTx/VAD eligible stage D patients should include careful consideration of the potential limited benefits.

Using Heart Failure Instruments To Determine When To Refer Heart Failure Patients to Palliative Care

Purpose Assessing the need for palliative care in heart failure (HF) is difficult because of the fluctuating disease course. The Palliative Performance Scale (PPS) and the Edmonton Symptom Assessment Score (ESAS) are instruments used by palliative care programs to determine disease severity and the need for palliative care services. These tools were developed and evaluated in a cancer population and there is limited evidence on their applicability to the HF population. The purpose of our study was to determine if scores on the cancer scales (ESAS and PPS) correlated with the scores on heart failure scales (MLHFQ, VAS and SHFM) in order to determine if heart failure scores can be used to trigger a referral to palliative care. Methods and Materials We administered the ESAS, MLHFQ, VAS, PPS and SHFM in a shuffled manner to 78 NYHA FC III-IV ambulatory HF patients followed at a tertiary care HF clinic. We used Pearson’s Correlation to determine if the ESAS and the PPS correlated with the MLHFQ, Overall Health VAS and 1-year SHFM predicted survival. Results The population was predominately male (62.8%), mean age 60.1 ± 13 years and a diagnosis of idiopathic cardiomyopathy (45%). There were moderate correlations between the ESAS and the MLHFQ (r = 0.483, p Conclusions The relapsing/remitting nature of heart failure makes it difficult to estimate when patients are nearing end-of-life. This study shows a significant relationship between palliative care scales and heart failure instruments suggesting that patients with multiple symptoms or individual symptom scores > 7, MLHFQ scores > 60 and/or overall health VAS scores

Changes in Circulating Progenitor Cells Are Associated with Functional Capacity in Heart Failure Patients: A Longitudinal Study

Purpose Circulating progenitor cells (CPCs) are involved in the process of endothelial repair and are a prognostic factor in cardiovascular diseases. We aimed to evaluate the association between serial measurements of CPCs and functional capacity in heart failure (HF) patients. Methods and Materials We included 126 consecutive consenting ambulatory HF patients with reduced left ventricular ejection fraction (LVEF 2 ). We used mixed-effect models to analyze the independent association between CPCs and peak VO 2 . Results The mean age was 55±12 years; 29 (23%) patients were female. Forty (35%) patients had ischemic cardiomyopathy. During follow up, a decrease in CD34+VEGFR2+cells was independently associated with increased functional capacity; a 10-cell decrease in CD34+VEGFR2+cells was associated with an increase of 0.2 ml/kg/min in peak VO 2 (p 2 of 0.28 ml/kg/min (p=0.01), and in diabetics a decrease, rather than an increase in EO-CFUs, was associated with an increased peak VO 2 (p Conclusions Higher EO-CFU and lower circulating CD34+VEGFR2+cells are associated with improvements in functional capacity in non-diabetic HF patients. Improved vascular angiogenic capacity could be associated with better functional capacity in HF patients. In diabetics, lower EO-CFUs were associated with improved functional capacity suggesting a differential behaviour.

CIRCULITE® SYNERGY® System for the Treatment of Intermacs ≥4 Heart Failure

Purpose The CircuLite® Synergy® System, a micro-pump based assist device, has been optimized to improve performance in an EU clinical trial for chronic ambulatory heart failure patients. We report the results from the last 24 consecutive patients. Methods and Materials 24 non-inotrope dependent (INTERMACS ≥4; 20 males, 61±15yrs, EF 20±5%) patients were implanted in a minimally invasive off pump procedure. Blood is drawn through the inflow cannula from the left atrium to the micro-pump (placed in a right subclavicular pocket) and discharged through an outflow graft to the right subclavian artery. Results Mean duration of support is 7 months (range 5-713d). Follow up at 2 months showed improved mean PA pressure (38±12 vs 28.4±7), cardiac output (3.9±1 vs 4.9±1), pulmonary capillary wedge pressure (27.2±9 vs 17.3±6), peak VO2 (11.3±3 vs 12.9±3), 6 minute walk (299±143 vs 420±118) and Minnesota Living with Heart Failure Questionnaire (63.5±20.4 vs 49.2±24.3). Four devices have been explanted: 1 following full recovery of LV function; 1 following significant decrease in heart size causing suction events; 1 following reoccurring bleeding 72 days post-implant; 1 following epistaxis and anticoagulation changes that resulted in pump thrombosis. The most significant adverse event has been bleeding (4.5 events/patient year) with 3 perioperative deaths due to complications of bleeding, that has been addressed with additional training. No perioperative neurological or infection events were observed. Conclusions Synergy improves hemodynamics and functional status with low adverse event rates in chronic ambulatory heart failure patients (INTERMACS ≥4). The Synergy System has the potential for broad application in this population of patients not sick enough to justify the risks associated with more surgically invasive assist devices.

Population of Polish patients participating in the Heart Failure Pilot Survey (ESC-HF Pilot)

Heart failure (HF) is currently one of the main causes of cardiovascular mortality. In order to collect current epidemiological data on patients with HF, the Heart Failure Pilot Survey (ESC-HF Pilot) registry was initiated. Primary objective of the study was to compare clinical epidemiology of outpatients and inpatients with HF and investigate currently used diagnostic and therapeutic modalities in Poland and 11 other European countries. The ESC-HF Pilot Survey study was a prospective multicentre observational registry conducted in 2009-2011 in 136 cardiology centres in 12 European countries selected to represent different health systems and care attitudes across Europe. All outpatients with HF and patients admitted due to acute decompensated HF were included into the registry during the enrolment period (1 day per week for 8 consecutive months). Researchers completed detailed medical data questionnaires for all HF patients recruited to the study. In all participating centres across Europe, 6108 patients were recruited, including 1159 patients from Poland (19% of the survey population). The majority of Polish participants were admitted due to acute HF (73%), while ambulatory chronic HF patients predominated in the remaining European centres (69%). Polish patients develop HF at a younger age compared to other European countries (proportion of patients above 65 years: 54 vs. 65%, respectively) and they are more severely ill (NYHA class III: 44 vs. 34%, respectively; NYHA class IV: 18 vs. 11%; mean BNP level 910 vs. 773 pg/mL). Angiographically documented coronary artery disease was the major aetiology of HF in Poland (39 vs. 33%) which explains a higher rate of invasive revascularisation procedures in the Polish population (13 vs. 7%). In Poland, therapy with implantable cardioverter- -defibrillators was used more frequently during the initial hospitalisation (7 vs. 4%), but the rate of cardiac resynchronisation therapy device implantation was smaller than in other European countries (4 vs. 7%). Drug therapy used in our country was comparable to the rest of Europe, except for more frequent use of aldosterone antagonists. Despite significant differences in the clinical characteristics seen between Polish and other European patients participating in the ESC-HF Pilot study, mortality at 3 months did not differ between Polish and other European centres (2.5 vs. 3%). The ESC-HF Pilot Survey findings indicate a very high standard of inpatient HF treatment but at the same time unsatisfactory current ambulatory HF therapy in Poland.

Association between adrenergic receptor genotypes and beta‐blocker dose in heart failure patients: analysis from the HF‐ACTION DNA substudy

Beta-blockers reduce morbidity and mortality in chronic heart failure (HF) patients with reduced ejection fraction. However, there is heterogeneity in the response to these drugs, perhaps due to genetic variations in the β1-adrenergic receptor (ADRβ1). We examined whether the Arg389Gly polymorphism in ADRβ1 interacts with the dose requirements of beta-blockers in patients with systolic HF. HF-ACTION was a randomized, multicentre trial of ambulatory HF patients with systolic dysfunction who were randomized to exercise training or usual care. A subset of patients provided DNA. The relationships among beta-blocker dose, ADRβ1-389 genotype, and outcomes were assessed using the Cox proportional hazards regression model. The interaction between beta-blocker dose and the ADRβ1-389 genotype was tested. DNA information was available for 957 patients. The alleles did not deviate from Hardy-Weinberg equilibrium. Patients with the ADRβ1-389 Arg/Arg genotype receiving low-dose beta-blockers had a two-fold increase in the risk of death compared with those receiving a high dose (hazard ratio 2.09; P = 0.015); this was not conferred in Gly carriers. There was also an interaction between improvements in Kansas City Cardiomyopathy Questionnaire score and beta-blocker dose by genotype, suggesting that higher doses of beta-blockade might be needed to achieve benefit in Arg/Arg genotype patients. There was a gene-dose interaction with the ADRβ1-389 Arg/Arg vs. Gly carrier genotype and beta-blocker dose, suggesting that patients with the Arg/Arg genotype might require a higher dose of beta-blockade to achieve a treatment response similar to that of Gly carriers.

Risk stratification of ambulatory patients with advanced heart failure undergoing evaluation for heart transplantation

Risk stratification of ambulatory heart failure (HF) patients has relied on peak VO(2)<14 ml/kg/min. We investigated whether additional clinical variables might further specify risk of death, ventricular assist device (VAD) implantation (INTERMACS <4) or heart transplantation (HTx, Status 1A or 1B) within 1 year after HTx evaluation. We hypothesized that right ventricular stroke work index (RVSWI), pulmonary capillary wedge pressure (PCWP) and the model for end-stage liver disease-albumin score (MELD-A) would be additive prognostic predictors. We retrospectively collected data on 151 ambulatory patients undergoing HTx evaluation. Primary outcomes were defined as HTx, LVAD or death within 1 year after evaluation. Average age in our cohort was 55 ± 11.1 years, 79.1% were male and 39% had an ischemic etiology (LVEF 21 ± 10.5% and peak VO(2) 12.6 ± 3.5 ml/kg/min). Fifty outcomes (33.1%) were observed (27 HTxs, 15 VADs and 8 deaths). Univariate logistic regression showed a significant association of RVSWI (OR 0.47, p = 0.036), PCWP (OR 2.65, p = 0.007) and MELD-A (OR 2.73, p = 0.006) with 1-year events. Stepwise regression showed an independent correlation of RVSWI<5gm-m(2)/beat (OR 6.70, p < 0.01), PCWP>20 mm Hg (OR 5.48, p < 0.01), MELD-A>14 (OR 3.72, p< 0.01) and peak VO(2)<14 ml/kg/min (OR 3.36, p = 0.024) with 1-year events. A scoring system was developed: MELD-A>14 and peak VO(2)<14-1 point each; and PCWP>20 and RVSWI<5-2 points each. A cut-off at≥4 demonstrated a 54% sensitivity and 88% specificity for 1-year events. Ambulatory HF patients have significant 1-year event rates. Risk stratification based on exercise performance, left-sided congestion, right ventricular dysfunction and liver congestion allows prediction of 1-year prognosis. Our findings support early and timely referral for VAD and/or transplant.

Haemodynamic effects of different basic heart rates in ambulatory heart failure patients treated with cardiac resynchronization therapy

The impact of different basic paced heart rates (pHRs) in patients receiving cardiac resynchronization therapy (CRT) remains largely unknown. The aim of the present study was to investigate the haemodynamic effects of different pHRs (60 or 80 b.p.m.), using an implanted haemodynamic monitor (IHM), during a 2-week period in ambulatory CRT patients. Ten CRT patients received an IHM (Chronicle(®), Medtronic Inc.) to continuously record right ventricular systolic (RVSP) and diastolic (RVDP) pressure, as well as estimated pulmonary artery diastolic pressure (ePAD) during a 2-week period at two basic pHR programming (60 and 80 b.p.m.). Cardiac output (CO) was calculated using a validated IHM algorithm. At the end of each period, 6 min walk test (6MWT), quality of life (QoL), and plasma levels of brain natriuretic peptide (BNP) were also assessed. Pacing at 80 b.p.m. significantly reduced the 2-week average of ePAD compared with 60 b.p.m. (23.4 ± 6.2 vs. 25.1 ± 6.5 mmHg, P = 0.03), whereas CO was increased (4.5 ± 1.3 vs. 4.2 ± 1.4 L/min; P = 0.01). Similarly ePAD, RVSP, and RVDP were significantly lower with a pHR of 80 b.p.m. (P < 0.05). The 6MWT, QoL score, and BNP were not affected by the pHR. In CRT patients, a basic pHR of 80 b.p.m. compared with 60 b.p.m. reduces filling pressures and increases CO during a 2-week period of ambulatory living. This suggests that increasing the basic pHR may be considered to achieve short-term haemodynamic improvement. The long-term effects of differential pHR programming remain to be established.

Serum Phosphate and Long-Term Outcome Among Patients With Stable Heart Failure

BackgroundElevated serum phosphate levels are associated with excess risk for cardiovascular mortality in patients with and without chronic kidney disease and with increased risk for incident heart failure. We determined the association of serum phosphate concentrations with disease severity and long-term outcome in patients with overt heart failure. Methods and ResultsClinical and laboratory parameters of 974 ambulatory heart failure patients were evaluated. Prevalence of elevated phosphate levels (>4.5 mg/dL) was 5.8% in men and 6.0% in women. Phosphate was significantly correlated with disease severity as assessed by New York Heart Association class, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide (P < .01, respectively). Multivariate sex-stratified Cox regression analysis adjusted for various clinically relevant covariates revealed baseline phosphate to be independently associated with death from any cause or heart transplantation (HR 1.26 [95% CI 1.04–1.52]; P < .001). This relation was maintained in patients with and without chronic kidney disease. After categorization based on quartiles of phosphate levels, a graded, independent relation between phosphate and outcome was observed (P for trend <.001). ConclusionsWe found a graded, independent relation between serum phosphate and adverse outcome in patients with stable heart failure. Also, serum phosphate was related to disease severity. These findings further highlight the clinical importance of serum phosphate in cardiovascular disease.

Abstract 19365: Serial Changes in ST2 are Superior to Other Biomarkers in the Prediction of Adverse Events in a Cohort of Ambulatory Chronic Heart Failure Patients

Background: Disease progression in heart failure (HF) reflects multiple neurohormonal derangements resulting in adverse prognosis in the absence of overt clinical events. ST2 is up-regulated in response to cardiac injury/hemodynamic stress while modulating cardiac remodeling via inflammatory and apoptotic pathways. Accordingly, we evaluated changes in ST2 over time in conjunction with troponin T (cTnT) and BNP in ambulatory patients with chronic HF. Methods: A cohort of 191 NYHA class III-IV HF patients was prospectively evaluated with serial specimens collected every 3 months over a 2-year period. Primary end points were death or cardiac transplantation; secondary end points were combined death/transplantation and HF-related hospitalization. Plasma ST2 (Critical Diagnostics) was evaluated against contemporary cTnT (Roche 4th generation) and BNP (Shinogi) assays. Gender specific cut-points (&gt;49.3 and &gt;33.5 ng/mL for males and females, respectively) and a clinically defined optimal cut-point for ST2 (&gt;35 ng/mL) were evaluated. Results: Time-dependent analyses (dichotomous and continuous variable) demonstrated ST2 gender specific cut-points were superior to a single ST2 cut-point and associated with an increased risk of death or transplantation (HR 4.8, 95% CI 2.8 to 8.3, p&lt;0.0001) and combined death/transplantation/HF-hospitalization (HR 2.1, 95% CI 1.7 to 2.5, p&lt;0.0001). Although cTnT remained the strongest predictor of death/transplantation (HR 3.2, 95% CI 1.6 to 5.4, p&lt;0.0001) in multivariate analyses adjusted for cTnT and BNP, ST2 (HR 3.0, 95% CI 1.6 to 5.4, p=0.0003) added significantly to predictive accuracy. Furthermore, elevated ST2 was the only independent predictor of HF-hospitalization (HR 1.7, 95% CI 1.4 to 2.1, p&lt;0.0001). In these models BNP was no longer significantly predictive (HR 1.2, 95% CI 0.7 to 2.2, p=0.58). Conclusions: Serial monitoring of changes in ST2 using gender specific cut-points adds to the diagnostic ability of cTnT in predicting mortality and/or transplantation in outpatients with chronic HF. ST2 uniquely predicts HF-hospitalization/death/transplantation, suggesting a serial monitoring strategy with cTnT and ST2 will optimize identification of HF patients at increased risk for events.

Circulating Proangiogenic Progenitor Cells Independently Predict Functional Capacity in Heart Failure Patients

BackgroundEndothelial dysfunction is an important underlying mechanism in the pathophysiology of heart failure (HF). Circulating proangiogenic progenitor cells (CPCs) are endothelial and hematopoietic progenitor cells involved in the process of vasculogenesis repairing damaged and dysfunctional endothelium. Our aim was to evaluate whether an independent association exists between CPCs and functional capacity in HF patients. MethodsThis cross-sectional study included 121 ambulatory HF patients with reduced left ventricular ejection fraction seen at a single institution. We analyzed the association between CPCs, measured as circulating CD34+VEGFR2+ cells and early outgrowth colony forming units (EO-CFUs), and patients’ functional capacity measured as peak oxygen consumption (V˙o2). ResultsThe mean age was 55 ± 11 years; 96 patients (79%) were male. Forty-three patients (36%) had ischemic cardiomyopathy. Patients were taking optimal HF therapy (96% taking β-blockers, 91% taking renin-angiotensin inhibitors, and 60% had an implanted internal cardiac defibrillator). In univariate analyses, CD34+VEGFR2+ cells were inversely associated with peak V˙o2 (P = 0.02) while EO-CFUs showed a positive association with peak V˙o2 (P < 0.01). These associations persisted after adjusting for sex, New York Heart Association class, body mass index, diabetes, cardiac resynchronization therapy, ischemic cardiomyopathy and b-type natriuretic peptide levels. ConclusionsCultured EO-CFUs may represent a measure of functional capacity and vasculogenesis potential while CD34+VEGFR2+ cells represent the mobilized cells in response to endothelial damage. Our study suggests that lower EO-CFUs (worse cell function) and higher CD34+VEGFR2+ cells are associated with poorer functional capacity.

Important Differences in Mode of Death Between Men and Women With Heart Failure Who Would Qualify for a Primary Prevention Implantable Cardioverter-Defibrillator

Whether sex differences in implantable cardioverter-defibrillator (ICD) benefit exist remains unanswered. We evaluated sex differences in mode of death among a large cohort of ambulatory heart failure patients who meet criteria for a primary prevention ICD. Patients from 5 trials or registries were included if they met American College of Cardiology/American Heart Association/Heart Rhythm Society guideline criteria for implantation of a primary prevention ICD. We investigated the potential sex differences in total deaths and total deaths by mode of death. The relationship between the estimated total mortality and mode of death by percentage of total mortality was also analyzed by sex. The Seattle Heart Failure Model was used to estimate total mortality in this analysis. A total of 8337 patients (1685 [20%] women) met inclusion criteria. One-year mortality was 10.8±0.3%. In women, the age-adjusted all-cause mortality was 24% lower (hazard ratio [HR], 0.76; confidence interval [CI], 0.68-0.85; P<0.0001), the risk of sudden death was 31% lower (HR, 0.69; CI, 0.58-0.83; P<0.0001), but no significant difference in pump failure death was observed. Throughout a range of total mortality risk, women had a 20% lower all-cause mortality (HR, 0.80; CI, 0.71-0.89; P<0.001) and 29% fewer deaths that were sudden (HR, 0.71; CI, 0.59-0.86;P<0.001) compared with men. Women with heart failure have a lower mortality than men, and fewer of those deaths are sudden throughout a spectrum of all-cause mortality risk. These data provide a plausible reason for and thus support the possibility that sex differences in ICD benefit may exist.

Contemporary outcomes of optimally treated heart failure patients with sleep apnea. Case for urgency in evaluation of newer interventions? From The Atlanta Cardiomyopathy Consortium

The incidence and prevalence of heart failure (HF) continues to rise in the United States. Over fivemillion Americans carry the diagnosis of HF that leads to 12–15 million office visits and 6.5 million hospital days per year; 550,000 new cases are diagnosed annually [1]. Besides morbidity andmortality, the economic burden of HF is substantial, the direct and indirect cost of HF in 2008 was $34.8 billion and is on pace to triple by 2030 [2]. Sleep disorder breathing, or sleep apnea (SA), is a highly prevalent co-morbid condition occurring in 40–75% of HF patients [3–6]. Evenwith the current advances in medical therapy, the prevalence of SA has remained unchanged [7]. SA is known to induce hypoxia, increase sympathetic stimulation, inflammatory and oxidative stress, and has been associated with adverse outcomes in HF [8–11]. When diagnosed early, effective treatment of SA improves left ventricular ejection fraction, sympathetic activity, quality of life, and yet reports on improvement of clinical outcomes have been conflicting [12–19]. In this study, we assessed the outcomes in a contemporary cohort of HF patients with clinically diagnosed SA on optimal medical therapy followed in a tertiary care specialty clinic. We examined the association of history of SAwith outcomes in 313 ambulatory HF patients enrolled in the Atlanta Cardiomyopathy Consortium, a prospective cohort study enrolling HF patients from three university-affiliated teaching hospitals from July 2007. Inclusion criteria included age N18 years and a diagnosis of HF with either reduced or preserved ejection fraction. Exclusion criteria included congenital heart disease, previous heart transplantation or currently awaiting transplant, known cardiac infiltrative disease (e.g., amyloidosis), previous other solid organ transplantation, and endstage HF requiring outpatient continuous inotrope infusion. All patients underwent past history surveys, physical examination, electrocardiogram, 6-minute walk test, psychosocial questionnaires, and collection of blood and urine samples at baseline. Every six months, the patients are contacted to assess medication changes, procedures, new diagnoses, and hospitalizations. Mortality data are collected through medical record review, information obtained from family members, and Social Security Death Index query. Hospitalization data are obtained from regular electronic health record review, all outpatient notes from any specialty encounter for any reported admission to an outside hospital, and direct patient inquiry during follow-up. Primary outcome was defined as the composite of death, cardiac transplantation, left ventricular assist device (LVAD) use, or HF related hospitalization. The secondary outcome incorporated the primary outcome and all-cause admissions. Values are expressed as mean±standard deviation (SD) for continuous and count (%) for categorical variables. Outcomes were described with Kaplan–Meier estimates and compared with the logrank statistic between groups. Categorical variables were compared using the chi-square test, and other continuous, non-time dependent variables in these groups were compared with t-test. Multivariable Cox proportional hazards analysis was then performed adjusting for known predictors of outcomes. Statistical analysis was done with SAS 9.2 (SAS Institute Inc., Cary, NC, USA). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. Mean age of patients was 57±12 years, 65% were male and 50% were white. Sixty seven (22%) patients had history of SA. Other comorbidities included diabetes (34%), coronary artery disease (40%), hypertension (67%), dyslipidemia (52%) and active tobacco abuse (13%). Beta-blocker use was 93% and ACE inhibitors or angiotensin II receptor blocker was 79%, respectively. Mean ejection fraction was 30±15%. Table 1 compares the baseline characteristics of patients with and without SA. Prevalence of chronic kidney disease, diabetes, and depressionwas significantly higher in patients with SA. Therewas

490 Change in Renal Function and Association With Acute Hospitalization in Chronic Ambulatory Heart Failure Patients

Acute deteriorations in renal function are common in hospitalized heart failure patients and associated with a worse prognosis. The relationship between small, serial fluctuations in renal function and prognosis in ambulatory heart failure patients remains unclear. Cardiorenal syndrome is a new and emerging classification for dual organ dysfunction occurring in the heart failure population and there is significance in identifying prognostic factors for its onset and progression. We set out to evaluate the rates of change in three measures of renal function: cystatin C (a serine protease inhibitor that appears to be a more sensitive approximation of renal GFR) , creatinine and estimated glomerular filtration rate (eGFR) and their association with acute hospitalization in an ambulatory cohort of heart failure patients. A total of 140 patients (83% male, mean EF 24.8±7.0%) were prospectively followed for up to 24 months (median 333 days (IQR 192-457) in a tertiary care heart failure clinic. Laboratory values and clinical outcomes were measured every 3 months. eGFR was calculated by the MDRD equation. Mixed and ordinary linear regression models were employed to determine the association of rates of renal function change and hospitalization. During the study period there were a total of 84 (range 0-9; 60%) hospitalizations in the study population. In general, renal function decreased in the population over the study period (eGFR 0.28mls/min/m2 per month (95% CI -0.43 to -0.14, p<0.0001); creatinine 0.62 μmol/L per month (95% CI 0.27-0.96, p<0.0001). The rates of change of serum creatinine and eGFR were highly associated with acute hospitalizations; eGFR -1.07 (95% CI -1.83 to -0.32, p=0.005), creatinine 0.56 (95% CI 0.23-0.89, p=0.001). Changes in cystatin C were not associated with hospitalizations (0.003 95% CI -0.004 to 0.010, p=0.4). Serial changes in serum creatinine and eGFR, but not cystatin C, are associated with an increased risk of hospitalization in chronic stable ambulatory heart failure patients.

492 Urinary NGAL is not Associated With Renal Function Changes or Hospitalization in Ambulatory Heart Failure Patients

Urinary neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be an early predictive biomarker for acute kidney injury and serves as a surrogate for injury to renal tubules. Renal function deteriorations are common in CHF yet it remains unclear whether renal tubular injury is involved. Further if renal tubular injury occurs it is unclear whether declines in GFR lead to tubular injury or vice versa. We set out to investigate changes in urinary NGAL and the temporal relationship with GFR changes and hospitalization. Patients with an LVEF < 40% were prospectively followed in a tertiary care heart failure clinic for up to 24 months (median 333 days (IQR 192-457). Laboratory values and clinical outcomes were measured every 3 months. Mixed linear and ordinary linear regression models with sandwich estimators were employed to determine the relationship between changes in urinary NGAL and changes in renal function change and hospitalization. Urinary NGAL was measured by ELISA. A total of 140 patients (83% male, mean EF 24.8±7.0%) were enrolled during the study period. Changes in urinary NGAL were not associated with hospitalization (p=0.2). Increases in NGAL were not associated with a subsequent decline in eGFR (p=0.1) nor vice versa, declines in eGFR associated with increases in subsequent urinary NGAL (p=0.5). Urinary NGAL, a promising biomarker of renal tubular injury in acute kidney injury, is not associated with changes in eGFR or hospitalization in an ambulatory heart failure population.

488 Serial Measures of the Fractional Excretion of Urea(FEurea), Fractional Excretion of Sodium(FEna) and the Urea/Creatinine Ratio(UCr) for Predicting Changes in Renal Function in Ambulatory Heart Failure Patients

Worsening renal function often follows changes in renal perfusion and solute clearance. In patients with chronic compensated heart failure, subtle changes in renal perfusion could alter the fractional excretion of urea (FEurea) and give insight into subtle states of renal hypoperfusion. FEurea is a simple, quick and inexpensive surrogate measure of diminishing renal perfusion and renal vasoconstriction in response to the neurohormonal perturbations and functional decline in cardiac function. Furthermore, the FEurea is not affected by diuretics.

Quantifying Circadian Variation of Multiple Physiologic Signals in Ambulatory Heart Failure Patients

Quantifying Circadian Variation of Multiple Physiologic Signals in Ambulatory Heart Failure Patients

Predicting All-Cause Death and Medical Hospitalization in Ambulatory Heart Failure Patients With Electronic Medical Record Data

Predicting All-Cause Death and Medical Hospitalization in Ambulatory Heart Failure Patients With Electronic Medical Record Data

Can the Seattle Proportional Risk Model Identify Patients With a Greater ICD Benefit in HF-ACTION?

Meta-analysis of primary prevention ICD trials suggests that ICDs decrease sudden death by 60%. Prediction of which heart failure patients are most likely to die of sudden death vs. non sudden death is important to determine who will benefit from an ICD. We developed the Seattle Proportional Risk Model (SPRM) to estimate the percent of deaths that are sudden (AHA 2011). We applied this model to HF-ACTION, a trial designed to evaluate exercise training in ambulatory heart failure (NYHA II-IV, EF35%) patients.