Outcomes In Chronic Heart Failure Research Articles

High Serum Concentrations of Uric Acid: Clinical and Prognostic Significance in Chronic Heart Failure

The article is devoted to the value of asymptomatic hyperuricemia in patients with chronic heart failure (CHF). The review summarizes results of a number of epidemiological reports that have increasingly linked elevated serum uric acid with an increased risk of incident CHF and adverse outcomes in CHF patients. Pharmacological and non-pharmacological approaches to influencing disturbances of uric acid metabolism are discussed.

Prognostic significance of endogenous erythropoietin in long-term outcome of patients with acute decompensated heart failure.

Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear. We examined 539 consecutive ADHF patients with EPO measurement on admission from our registry. During a median follow-up period of 329 days, a higher EPO level on admission was independently associated with worse clinical outcomes [hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.06-1.48, P = 0.008], and haemoglobin level was the strongest determinant of EPO level (P < 0.001), whereas estimated glomerular filtration rate (eGFR) was not significant in multivariate regression analysis. In the anaemic subgroup of 318 patients, a higher EPO level than expected on the basis of their haemoglobin level was related to increased adverse events (HR 1.63, 95% CI 1.05-2.49, P = 0.028). Moreover, estimated plasma volume excess rate was positively associated with EPO level (P = 0.003), and anaemic patients with a higher than expected EPO level tended to have a higher estimated plasma volume excess rate and plasma lactate level, and lower systemic oxygen saturation level with the preservation of the reticulocyte production index than those with a lower than expected EPO level. A high EPO level predicts long-term worse clinical outcomes in ADHF patients, independent of anaemia and impaired renal function. Anaemia and hypoxia due to severe congestion may synergistically contribute to a high EPO level in high-risk HF patients.

PROGNOSTIC VALUE OF RIGHT-SIDED VOLUME OVERLOAD IN PATIENTS PRESENTING WITH ACUTE HEART FAILURE: INSIGHTS FROM ASCEND-HF

Elevated jugular venous pressure (JVP) and peripheral edema predict worse outcomes in chronic heart failure (HF) patients. We studied these findings in acute HF in the ASCEND-HF trial of nesiritide vs. placebo. Of 7,141 ASCEND-HF patients, 7,135 patients had complete data on baseline JVP and

Chronic heart failure in heart transplant recipients: Presenting features and outcome

The ageing graft frequently shows coronary lesions and a restrictive physiology. To determine the presenting features and outcome of chronic heart failure in heart transplant recipients. In this cohort study, we compared 44 consecutive heart transplant recipients who developed chronic heart failure more than 1 year after heart transplantation with 44 control heart transplant recipients who did not develop heart failure. We found that patients who developed heart failure had more frequently a history of hypertension or diabetes before transplantation. During the 12 months after transplantation, significantly more patients had moderate-to-severe acute rejections (≥ grade 2R) in the heart failure group than in the control group. At the time of heart failure diagnosis, systolic left ventricular function was preserved in 50% of patients and coronary angiography was normal or near normal in 36% of patients. Half of the 44 patients in the heart failure group died within 2 years of heart failure diagnosis. Ascites and end-stage renal failure requiring dialysis were significantly more frequent during follow-up in the heart failure group than in the control group (respectively, 10/44 vs 0/44 [P=0.001] and 18/44 vs 5/44 [P=0.003]). In heart transplant recipients presenting with heart failure, systolic left ventricular function is frequently preserved and coronary angiography is frequently abnormal, but may be normal or near normal. During follow-up, the main features of these patients are a high mortality rate after heart failure diagnosis, a frequent need for renal dialysis and frequent ascites.

Non-adherence to ivabradine and placebo and outcomes in chronic heart failure: an analysis from SHIFT.

In heart failure, non-adherence increases events; in turn, the effect of hospitalization on adherence is incompletely understood. We explored the relationship of non-adherence to outcomes, hospitalizations with non-adherence, and the influence of non-adherence on treatment effects of heart rate lowering with ivabradine. In the randomized, controlled Systolic Heart failure treatment with the If-inhibitor ivabradine Trial (SHIFT), we studied the effect of non-adherence (n = 1287) compared with adherence (n = 5204) on cardiovascular outcomes. After adjustment, non-adherence was associated with the primary composite endpoint of cardiovascular death and heart failure hospitalization (hazard ratio 3.47, 95% confidence interval 2.91-4.13, P < 0.0001). No interaction with the treatment groups of placebo or ivabradine (P for interaction 0.54) occurred. Similar results for cardiovascular death and heart failure hospitalization, as well as for cardiovascular hospitalization, heart failure death, and total death were observed. The effect of ivabradine was maintained in patients being adherent or becoming non-adherent during the trial (P for interaction = 0.54). Patients with a previous hospitalization were more likely to become non-adherent thereafter. Non-adherence identifies a group at particularly high cardiovascular event risk independent of treatment allocation. Non-adherent patients in the ivabradine group maintain a treatment benefit. Patients with previous hospitalizations are more likely to become non-adherent and represent a group of particularly high-risk patients in whom special attention to stimulate adherence may be valuable. ISRCTN70429960.

Impact of SERVE-HF on management of sleep disordered breathing in heart failure: a call for further studies.

Sleep disordered breathing (SDB) (obstructive sleep apnea, central sleep apnea/Cheyne-Stokes respiration or the combination of both) is highly prevalent in patients with a wide variety of cardiovascular diseases including hypertension, arrhythmia, coronary artery disease, myocardial infarction and stroke (reviewed previously in the September issue of this journal). Its close association with outcomes in chronic heart failure with reduced ejection fraction (HF-REF) suggests that it may be a potential treatment target. Herein, we provide an update on SDB and its treatment in HF-REF.

Pathophysiological mechanism and therapeutic role of S100 proteins in cardiac failure: a systematic review.

S100 proteins are a family of highly acidic calcium-binding proteins involved in calcium handling in many tissues and organs. Some of these proteins are highly expressed in cardiac tissue, and an impairment of some specific S100 proteins has been related to heart failure. To check this hypothesis, we decided to review the literature since 2008 until May 2015. According to the studies collected, recovering S100A1 levels may enhance contractile/relaxing performance in heart failure, reverse negative force-frequency relationship, improve contractile reserve, reverse diastolic dysfunction and protect against pro-arrhythmic reductions of sarcoplasmic reticulum calcium. The safety profile of gene therapy was also confirmed. Increased S100B protein levels were related to a worse outcome in chronic heart failure. S100A8/A9 complex plasma levels, as well as other inflammatory biomarkers, were significantly higher in chronic heart failure patients. S100A2 seems to increase both contractile and relaxation performance in animal cardiomyocytes. Otherwise, S100A6 cardiac expression seems to have no effects on contractility. S100A4 KO mice showed reduced cardiac interstitial fibrosis. Data collected encourage a potential prospective application in human. These proteins could be exploited as biomarkers in stadiation and prognosis of chronic heart failure, as well as therapeutic target to rescue failing heart. Registration details The study protocol has been registered in PROSPERO ( http://www.crd.york.ac.uk/PROSPERO/ ) under registration number CRD42015027932.

Self-care and Its Predictors in Patients With Chronic Heart Failure in Western Iran.

Chronic heart failure (CHF) is an increasing and costly health problem worldwide. Effective self-care behaviors reduce the cost and improve CHF outcomes. Interventions targeting improvement of self-care need to identify the baseline status of patients and factors associated with self-care to tailor the programs to patients' needs. The aim of this study was to describe self-care and its predictors in patients with CHF in western Iran. In a cross-sectional study, 255 patients with CHF in Kermanshah were recruited and 231 (mean [SD] age, 66 [13] years; 51.5% women) completed the interviews. Self-care maintenance, self-care management, and self-care confidence were evaluated using a Persian heart failure self-care index. Each of these 3 measures had a total possible score of 100, with 22 indicators. The mean (SD) self-care scores were low: maintenance, 33.8 (10.7); management, 32.2 (12.0); and confidence, 43.6 (15.6). Self-care maintenance was significantly and positively associated with education, disease duration, and living conditions. Self-care management was significantly and positively associated with education and number of hospital admissions. However, the parameter estimates in all those relationships were small. Self-care in patients with CHF in Iran needs major improvement, and many determinants of self-care identified by other studies were not consistently associated with poor self-care scores in Iran. Further research considering a wide range of factors associated with self-care (eg, socioeconomic and health system-related factors) and application of culturally relevant interventional strategies is recommended.

Prognostic Value of Galectin-3 for Adverse Outcomes in Chronic Heart Failure

BackgroundClinical studies have suggested the prognostic value of galectin-3, a marker of fibrosis, in chronic heart failure. However, the specific role of galectin-3, compared with established biomarkers, remains uncertain. Methods and ResultsThe Penn Heart Failure Study was an ambulatory heart failure cohort that included 1385 participants with reduced (1141), preserved (106), and recovered (138) left ventricular ejection fraction (LVEF). Cox regression models determined the association between galectin-3 and risk of all-cause mortality, cardiac transplantation, or placement of a ventricular assist device. Receiver operating characteristic curves compared the prognostic accuracy of galectin-3, high-sensitivity soluble Toll-like receptor 2 (ST2), troponin I, and B-type natriuretic peptide (BNP) at 1 and 5 years. Higher galectin-3 levels were associated with an increased risk of adverse events (adjusted hazard ratio of 1.96 for each doubling in galectin-3; P < .001). This association was most pronounced among participants with preserved LVEF (adjusted hazard ratio 3.30; P < .001). At 5 years, galectin-3 was the most accurate discriminator of risk among participants with preserved LVEF (area under the curve 0.782; P = .81 vs high-sensitivity ST2; P = .029 vs troponin I; P = .35 vs BNP). BNP was most accurate among participants with reduced and recovered LVEF (areas under the curves 0.716 and 0.728, respectively). ConclusionsGalectin-3 could have prognostic value for long-term events among patients with heart failure and preserved ejection fraction.

Plasma kidney injury molecule-1 in heart failure: renal mechanisms and clinical outcome.

Urinary kidney injury molecule-1 (KIM-1) is a marker of tubular damage and associated with worse outcome in heart failure (HF). Plasma KIM-1 has not been described in HF. In a renal mechanistic cohort of 120 chronic HF patients, we established the association between plasma KIM-1, renal invasive haemodynamic parameters {renal blood flow ([(131) I]hippuran clearance) and measured glomerular filtration rate (GFR; [(125) I]iothalamate)} and urinary tubular damage markers. The association between plasma KIM-1, plasma creatinine, and clinical outcome was further explored in a cohort of 2033 acute HF patients. Median plasma KIM-1 was 171.5 pg/mL (122.8-325.7) in chronic (n = 99) and 295.1 pg/mL (182.2-484.2) in acute HF (n = 1588). In chronic HF, plasma KIM-1 was associated with GFR (P < 0.001), creatinine, and cystatin C. Plasma KIM-1 was associated with urinary N-acetyl-β-d-glucosaminidase (NAG), but not with other urinary tubular damage markers. Log plasma KIM-1 predicted adverse clinical outcome after adjustment for age, gender, and GFR [hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.07-3.53, P = 0.030]. Statistical significance was lost after correction for NT-proBNP (HR 1.61, 95% CI 0.81-3.20, P = 0.175). In acute HF, higher plasma KIM-1 levels were associated with higher creatinine, lower albumin, and presence of diabetes. Log plasma KIM-1 predicted 60-day HF rehospitalization (HR 1.27, 95% CI 1.03-1.55, P = 0.024), but not 180-day mortality or 60-day death or renal or cardiovascular rehospitalization. Plasma KIM-1 is associated with glomerular filtration and urinary NAG, but not with other urinary tubular damage markers. Plasma KIM-1 does not predict outcome in chronic HF after correction for NT-proBNP. In acute HF, plasma KIM-1 predicts HF rehospitalization in multivariable analysis.

Risk stratification of patients with chronic heart failure using cardiac iodine-123 metaiodobenzylguanidine imaging: incremental prognostic value over right ventricular ejection fraction.

AimsRight ventricular (RV) systolic dysfunction has been shown to be an independent predictor of clinical outcome in patients with chronic heart failure (CHF), and cardiac metaiodobenzylguanidine (MIBG) imaging also provides prognostic information. We aimed to evaluate the long‐term predictive value of combining RV systolic dysfunction and abnormal findings of cardiac MIBG imaging on outcome in CHF patients.Methods and resultsWe enrolled 63 CHF outpatients with left ventricular ejection fraction (EF) <40% in a prospective cohort study. At entry, RVEF was measured by radionuclide angiography. Furthermore, cardiac MIBG imaging was performed, and the cardiac MIBG washout rate (WR) was calculated. Reduced RVEF was defined as ≤37%, and abnormal WR was defined as >27%. The study endpoint was unplanned hospitalization for worsening heart failure (WHF) and cardiac death. During a follow‐up period of 8.9 ± 4.3 years, 19 of 63 patients had unplanned hospitalization for WHF, and 19 of 63 patients had cardiac death. In multivariate analysis, both WR and RVEF were independent predictors of unplanned WHF hospitalization, while WR was also an independent predictor of cardiac death. A risk‐stratification model based on independent predictors of unplanned WHF hospitalization separated the patients into those with low (absence of the predictors), intermediate (one of the predictors), and high (two or more of the predictors) risk of unplanned WHF hospitalization (P < 0.0001) or cardiac death (P = 0.0113).ConclusionsCardiac MIBG imaging provides incremental value when it is used along with RV systolic dysfunction to predict clinical outcome in patients with CHF.

Free Triiodothyronine Levels and Short-Term Prognosis in Chronic Heart Failure Patients With Type 2 Diabetes

In chronic heart failure (CHF) patients with type 2 diabetes mellitus (T2DM), the role of thyroid hormone (TH) in predicting CHF severity and prognosis is unclear. The authors therefore investigated the role of TH in predicting CHF severity and prognosis in these specific patients. A total of 224 CHF patients (114 with T2DM) over a mean follow-up time of 6.56 ± 0.18 months were studied. TH, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were measured. Free triiodothyronine (FT3) levels were lower in the T2DM group compared with the nondiabetes group (P = 0.026) and higher in the New York Heart Association (NYHA) I group than in the NYHA III and IV groups (both P < 0.05). Compared with the low NT-proBNP group, the high NT-proBNP group had lower FT3 levels (P < 0.01). NT-proBNP correlated with NYHA classes (r = 0.541, P < 0.001), and inversely correlated with left ventricular ejection fraction (r = -0.431, P < 0.001) and FT3 levels (r = -0.335, P < 0.001). In multiple linear regression analysis, NT-proBNP was significantly correlated with NYHA classes (P < 0.001), left ventricular ejection fraction (P < 0.001) and FT3 (P = 0.004). Kaplan-Meier curves showed that the low FT3 group had an increased rate of short-term adverse outcomes of CHF (log rank, χ = 9.794, P = 0.002). FT3 levels are associated with the severity of CHF and seem to reflect short-term outcomes in CHF patients with T2DM.

Increased Serum Levels of the Notch Ligand DLL1 Are Associated With Diastolic Dysfunction, Reduced Exercise Capacity, and Adverse Outcome in Chronic Heart Failure

BackgroundNotch receptors and ligands have been demonstrated in myocardial tissue in experimental as well as clinical heart failure (HF), and a role for Notch signaling in myocardial remodeling and disease progression may be anticipated. We hypothesized that serum levels of the Notch ligand Delta-like-1 (DLL1) would be associated with clinical and hemodynamic variables in patients with HF. Methods and ResultsWe measured serum DLL1 in 183 patients with chronic HF and 50 age- and sex-matched healthy control subjects by means of enzyme immunoassay. Our main findings were that (i) HF patients had significantly higher serum DLL1 levels than healthy control subjects, (ii) DLL1 levels were significantly correlated with neurohormonal activation, systemic inflammation, and impaired kidney function, (iii) high DLL1 levels were associated with diastolic dysfunction and reduced exercise capacity, but not with impaired systolic function, and (iv) in univariate analysis, but not after multivariable adjustment, high levels of DDL1 were associated with adverse outcome. ConclusionsOur findings may imply that DLL1 and the Notch signaling pathways are involved in the pathophysiology of HF, potentially affecting diastolic function.

Glycosylated haemoglobin is associated with neurohormonal activation and poor outcome in chronic heart failure patients with mild left ventricular systolic dysfunction.

We aimed to evaluate the impact of glycometabolic imbalance as assessed by glycosylated haemoglobin [HbA(1c)] on neurohormonal activation and outcome in chronic heart failure (CHF). Nine hundred and twenty CHF patients (65 ± 12 years, left ventricular ejection fraction 33 ± 10%, 29% diabetic patients) underwent a thorough humoral and clinical characterization, including HbA(1c), and were then followed up for the endpoint of cardiac death. In the whole population, diagnosis of diabetes resulted in no difference in neurohormonal or echocardiographic data, or in outcome. Conversely, the diabetic patients with HbA(1c) above 7% showed, in comparison to both diabetic patients with HbA(1c) below 7% and non-diabetic individuals, higher plasma renin activity (1.81, 0.48-5.68 vs. 1.23, 0.43-2.8 and 1.29, 0.44-5 ng/ml/h, respectively; P < 0.01 for both), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (1602, 826-3498 vs. 1022, 500-3543 and 1134, 455-3545 ng/l, respectively; P < 0.01 for both) and worse symptoms with a higher rate of cardiac mortality vs. both diabetic patients with HbA1(c) below 7% and non-diabetic individuals (P < 0.05 for both). In the left ventricular ejection fraction 38-50% tertile (mild left ventricular dysfunction), elevated HbA(1c) was associated with higher NT-pro-BNP and PRA (P < 0.01), and, alongside NT-pro-BNP, resulted the only independent predictor of outcome beyond diagnosis of diabetes. HbA(1c) failed to show up differences in neuroendocrine activation or in outcome in moderate and severe left ventricular dysfunction tertiles. Glycometabolic imbalance, as represented by HbA(1c), is associated with neurohormonal activation and poor prognosis in CHF patients, beyond diabetes. The impact of metabolic derangement on prognosis appears greater at the early stages of CHF, when it might exacerbate neurohormonal activation.

0336 : Gender -related dissociation in outcomes in chronic heart failure in Moroccan woman: clinical, biological and echocardiographic features

Chronic heart failure (CHF) is a major cause of morbidity and mortality in the world. Few studies have examined the difference between the two gender and features in African woman. We conducted a retrospective study of patients with chronic heart failure followed between 2006- 2012 at the daily hospital Ibn Rochd in Casablanca. Of the 1613 patients, 603 were women. We studied the prevalence of cardiovascular risk factors, the severity of clinical symptoms and major cardiovascular events (acute coronary syndrom, stroke and acute heart failure). We also collected biological parameters (serum sodium, serum potassium, hemoglobin and creatinine) and echocardiographic criteria with poor prognosis (dilated left ventricular>60mm, ejection fraction<35%, pulmonary hypertension, severe mitral regurgitation). We compared our results with statistical analysis to the men of our population to identify prognostic markers in women with CHF. Mean age was 68,3 years. Woman is more likely to hypertension (49% vs 33%) and diabetes (39% vs 27%). Smoking is less common in women (with 3.4% vs 48%). Further, metabolic disorder dominates in the male population specially anemia. There is no significant difference in the severity of clinical symptoms. The etiology of CHF is dominated in women by valvulopathy, but man ischemic etiology dominates as in the developed countries. For echocardiographic features, half women has ejection fraction less than 35%. In addition, pulmonary arterial hypertension beyond 40 mmHg was significantly elevated in women. We find a higher acute cardiac decompensation rate at 9.9% vs. 7.7% (p = 0.01). Otherwise, the occurrence of major cardiovascular events is lower in women such as myocardial infraction (29% vs 40.3%) and stroke (5.9% vs 19%) p<0,001. Moroccan woman with chronic heart failure is more predisposed to cardiovascular risk factors and acute heart decompensation. Nevertheless, she has fewer major cardiovascular events.

(465) - BAG3 Variant Is Associated With Ventricular Remodeling But Not Clinical Outcomes in Chronic Heart Failure

Common genetic variants at 1p36 (rs1739843), 6p21 (rs9262636) and 10q26 (rs2234962) show replicated associations with heart failure (HF) risk. We hypothesized that these variants would associate with HF severity and clinical outcomes in chronic HF.

Increased visit-to-visit blood pressure variability is associated with worse cardiovascular outcomes in low ejection fraction heart failure patients: Insights from the HEAAL study

BackgroundRecent data have highlighted shortcomings of the usual blood pressure (BP) hypothesis in several populations, and emphasized the importance of visit-to-visit variability of BP in predicting cardiovascular events. Herein, we aimed at assessing the association between visit-to-visit BP variability and outcomes in chronic heart failure (CHF) patients enrolled in the Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan (HEAAL). Methods and resultsThe HEAAL study randomized 3834 patients with HF and reduced ejection fraction administered 150mg or 50mg losartan daily in a double blind, randomized, controlled trial. The patients were followed up for up to 6.8years after randomization, and BP was measured at 3 time points in the first year and at semi-annual visits in the years thereafter. Three measures of visit-to-visit BP variability were computed for each subject: the standard deviation, the coefficient of variation and the average absolute visit-to-visit variation. Cox proportional hazard models were used to investigate the relationship between variations in systolic blood pressure, baseline covariates and the time to death or heart failure hospitalization (i.e. primary outcome). In multivariate analyses stratified on baseline BP, the patients with higher visit-to visit BP variability exhibited poorer outcomes (average absolute difference in SBP in mmHg:hazard ratio: 1.023 [95% CI (1.013, 1.034), P<0.0001]), independent from high dose losartan (still beneficial). ConclusionsFor the first time, visit-to-visit BP variability was found elevated in CHF patients with reduced ejection fraction, and associated with poorer cardiovascular outcomes. Such assessments should be prioritized for testing prevention strategies in CHF. Clinical trial registrationThis study is registered with the ClinicalTrials.gov, number NCT00090259.

Elevated heart rate at 24–36 h after admission and in-hospital mortality in acute in non-arrhythmic heart failure

BackgroundElevated resting heart rate is associated with worse outcomes in chronic heart failure (HF) but little is known about its prognostic impact in acute setting. The main aim of the present study was to examine the relationship between resting heart rate obtained 24–36h after admission for acute non-arrhythmic HF and in-hospital mortality. Methods and resultsWe examined the association of heart rate with in-hospital mortality in a cohort of 712 patients admitted for acute HF. None of the patients had significant arrhythmias, required invasive ventilation, or presented with acute coronary syndrome or primary valvular disease. Forty patients (5.6%) died during the hospital stay. Those patients were significantly older (78±9 vs. 72±12years; p=0.0021), had higher heart rate (92±22 vs. 78±18bpm; p<0.0001), NT pro-BNP (p=0.0005), creatinine (p=0.023), were often diabetics (p=0.026) and had lower systolic and diastolic blood pressures (p<0.05). There was a significant graded relationship between the increase in mortality rate and tertile of heart rate (p<0.01). With multivariable analysis, age (p=0.037), heart rate (p<0.0001), diastolic blood pressure (p<0.001), prior ischemic heart disease (p=0.02) and creatinine (p=0.019) emerged as independent predictors of in-hospital mortality. After adjusting for predictors of poor prognosis, patients in the highest heart rate tertile had worst outcomes when compared with those in the lowest heart rate group (p=0.007). ConclusionsHigher heart rate 24–36h after admission for acute non-arrhythmic HF is associated with increased risk of in-hospital mortality. Early targeting of elevated heart rate might represent a complementary therapeutic challenge.

Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure.

Recent metabolomic, experimental and clinical studies have demonstrated that trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor of coronary artery disease (CAD). This finding suggests a link between the gut microbiota and atherosclerosis. The potential impact of TMAO in chronic heart failure (HF) is unknown. We hypothesized that TMAO levels would provide prognostic information about adverse outcomes in chronic HF. Prospective, observational study including 155 consecutive patients with chronic HF. In addition, 100 patients with stable CAD without HF and 33 matched healthy individuals were included as controls. Plasma levels of TMAO and its precursors choline and betaine were measured, and associations with symptoms, aetiology and transplant-free survival in the patients with HF were explored. Plasma levels of TMAO (P = 0.01), choline (P < 0.001) and betaine (P < 0.001) were elevated in patients with chronic HF compared to control subjects, with the highest levels in patients with New York Heart Association (NYHA) classes III and IV. Furthermore, TMAO levels were highest in individuals with ischaemic HF, followed by those with stable CAD and nonischaemic HF. TMAO, but not choline or betaine, was associated with reduced transplant-free survival: approximately 50% of patients in the upper tertile of TMAO levels died or received a heart transplant during 5.2 years of follow-up (unadjusted Cox-regression: hazard ratio 2.24, 95% confidence interval 1.28-3.92, P = 0.005). TMAO levels were elevated in patients with HF and associated with NYHA class, ischaemic aetiology and adverse outcomes. Future studies should focus on gut microbiota, dietary composition and intestinal dysfunction in relation to TMAO levels and clinical outcome in HF.

Abstract 17082: Carotid Body Denervation Improves Autonomic Balance and Prevents the Worsening of Heart Failure in Rats After Large Myocardial Infarction

Introduction: Carotid body denervation (CBD) abolishes the carotid body hypersensitivity induced sympathoexcitatory hypertension. Since the carotid body hypersensitivity is a salient feature and predicts poor outcome of chronic heart failure (CHF), we hypothesized that CBD restores normal autonomic balance, thus improves CHF in rats after large myocardial infarction (MI). Methods: We created MI in 8 weeks Sprague-Dawley rats. Surviving rats at 2 weeks after MI were randomized into CBD (n=11) and sham-operated (Sham; n=13) groups. We removed the tissues around the carotid bifurcation and established CBD. In some rats (Sham; n=5, CBD; n=5), we telemetrically recorded heart rate (HR). One month after CBD, we compared physiological, histological and immunochemical findings between CBD and Sham. Results: CBD significantly reduced HR (337±15 vs. 364±12 bpm, p&lt;0.05). CBD markedly increased the power spectral density of HR in the high frequency range (81.0±9.5 vs. 29.0±8.2 n.u., p&lt;0.05) and decreased that of the low frequency/high frequency ratio (0.6±0.2 vs. 1.8±0.5, p&lt;0.05) indicating the restoration of autonomic balance. CBD significantly reduced biventricular weight (3.1±0.3 vs. 3.7±0.3 g/kg, p&lt;0.05) and left ventricle (LV) end-diastolic pressure (22±5 vs. 33±5 mmHg, p&lt;0.01) and increased maximum LV dp/dt (5118±809 vs. 4217±472 mmHg/sec, p&lt;0.05). CBD reduced lung weight (a marker of pulmonary edema) (6.8±2.0 vs. 12.4±1.5 g/kg, p&lt;001). Furthermore, CBD reduced plasma brain natriuretic peptide (70±43 vs. 166±71 pg/ml, p&lt;0.01) and plasma norepinephrine as an index of sympathetic drive (384±202 vs. 1048±997 pg/ml, p&lt;0.05). CBD significantly reduced the number of inflammatory macrophages (345±45 vs. 474±73 counts/mm2, p&lt;0.05) in the LV and the plasma concentration of interleukin-1β (14.3±4.7 vs. 24.5±11.8 pg/ml, p&lt;0.05) indicating that CBD also suppressed the inflammatory response in CHF. Conclusions: CBD restores normal autonomic balance and prevents the worsening of heart failure in rats after large myocardial infarction. CBD may serve as a novel neuro-modulatory therapy for CHF patients.