Death In Chronic Heart Failure Research Articles

Prognostic Significance of Serum Chloride Level Reduction in Patients with Chronic Heart Failure with Different Ejection Fractions.

Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF) with different ejection fractions. We sought to determine the postdischarge outcomes associated with lower serum chloride between different CHF types.We reviewed the medical records of 1221 consecutive patients with CHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in-hospital death, missing follow-up data, missing serum chloride level data, or chronic dialysis therapy, 791 patients were included. Of these patients, 343 had heart failure with reduced ejection fraction (HFrEF; i.e., left ventricular ejection fraction (LVEF) < 40%), and 448 had heart failure with preserved ejection fraction (HFpEF) or heart failure with median ejection fraction (HFmrEF; HFpEF plus HFmrEF; i.e., LVEF ≥40%). Over a median follow-up of 750 days, 344 patients (43.5%) had all-cause mortality. In the univariate analysis, serum sodium and chloride were strongly associated with mortality in both HF subgroups (P < 0.0001). A multivariable model including both serum sodium and chloride showed the highly significant association between serum chloride and survival (P < 0.0001), whereas the association between serum sodium and mortality was not reported (HFpEF plus HFmrEF, hazard ratio (HR) 0.975, 95% confidence interval [CI] 0.942-1.010, P = 0.158; HFrEF, HR 1.007, 95% CI 0.966-1.051, P = 0.734). Kaplan-Meier survival curve analysis revealed a significant difference in mortality risk with decreasing chloride levels in all patients with CHF. The optimal cutoff value of chloride in predicting all-cause mortality was 102.95 mmol/L with area under the curve value of 0.76 [HR 0.760, 95% CI 0.727-0.793, P < 0.0001], sensitivity of 60.2%, and specificity of 78.3%.Lower serum chloride is an independent predictor of death in CHF, regardless of heart failure subtype.

PO-01-244 BMAL1 REGULATES THE CIRCADIAN RHYTHM OF RYR2 AND CONTRIBUTES TO CIRCADIAN VENTRICULAR ARRHYTHMIA IN CHRONIC HEART FAILURE AFTER MYOCARDIAL INFARCTION

Ventricular arrhythmia (VAs) is the major cause of sudden cardiac death in chronic heart failure (CHF) after myocardial infarction (MI), and previous studies have reported that VAs exist circadian oscillation in CHF. Peripheral circadian clock can regulate expression and function of ion channels in cardiomyocytes, which is associated with circadian rhythm of VAs in CHF. However, the regulation of peripheral circadian clock on Ryanodine Receptor 2 (RYR2), a calcium channel on cardiac sarcoplasmic reticulum, remain to be fully understood. We aimed to explore the regulation of peripheral circadian clock on RYR2 and VA events in CHF. CHF was induced by ligation of coronary artery of mice, and RT-PCR were performed to investigate the circadian rhythm of RYR2 in CHF myocardial tissue. Amplitude of calcium transient of ISO-induced cardiomyocytes at different time was measured to study the circadian rhythm of RYR2 function. To confirm the circadian oscillation of VAs, VAs incidences at different time of CHF wild type mice and cardiomyocyte-specific Bmal1 knockout (CKO) mice were investigated by programmed electrical stimulation. Infections of Ad-CLOCK and/or Ad-BMAL1 were applied to overexpress CLOCK, BMAL1 and CLOCK-BMAL1 in cardiomyocytes, and expression of RYR2 was measured by Western blot. Chromatin immunoprecipitation assay (ChIP) and luciferase (LUC) were applied to determine whether CLOCK-BMAL1 transcriptionally regulate RYR2 expression. CLOCK, BMAL1, and RYR2 exhibited notable circadian rhythm in CHF mice (Figure A, P<0.05). Amplitude of calcium transient at CT36 was lower than CT24 (Figure B, P<0.05). Compared to CT36, VAs had higher incidence at CT24(Figure C, P<0.05), and incidences of VAs had no significant difference between CT24 and CT36 in CKO Mice or using Dantrolene, an antagonist of RYR2. Ad-CLOCK and Ad-BMAL1 co-infection resulted in overexpression of RYR2 (Figure D, P<0.05), and BMAL1 bound to the enhancer of RYR2 gene and upregulated RYR2 expression transcriptionally (Figure E). In conclusion, BMAL1, as peripheral circadian clock, could contribute to circadian oscillation of VAs in CHF by regulating the circadian rhythm of RYR2.

The Causal Effects of Anxiety-Mediated Social Support on Death in Patients with Chronic Heart Failure: A Multicenter Cohort Study.

Chronic heart failure (CHF) affects more than 3.8 million people worldwide. There is a paucity of studies focusing on psychosocial issues in CHF patients. This study aimed to investigate the association of social support, mental adjustment and death to exploring whether mental adjustment could mediate the relationship. From May 2017 to June 2021, we conducted a multicenter clinical study to collect 1552 patients data. The Patient Report Outcome (PRO) scale were disseminated to collect information in the physical, psychological, social and therapeutic domains of patients. Marginal structural model was used to investigate the association of social support and CHF death, and the role of mental adjustment in their mediation. The direct effect of social support accounted for 44.76% of the total effect. High social support (≥14 points) reduced mortality by 46.3% (RR=0.537, P=0.027), medium social support (11-14 points) reduced mortality by 45.3% (RR=0.547, P=0.042). Anxiety (effect percentage: 24.63%) and appetite-sleep quality (effect percentage: 30.61%) played a mediating role between social support and death in CHF patients. In women, aged >75 years, divorced or widowed patients were most prone to anxiety due to inadequate support (RR=0.519, P=0.019; RR=0.403, P=0.002; RR=0.413, P=0.041). Family care and socioeconomic assistance significantly reduced the risk of death (RR=0.689, P=0.040; RR=0.584, P=0.012). Social support can reduce patient mortality, especially family care and social economic assistance. The elderly, female, divorced or widowed patients are more likely to cause mental illness due to inadequate social support.

Comorbid Hypertension Reduces the Risk of Ventricular Arrhythmia in Chronic Heart Failure Patients with Implantable Cardioverter-Defibrillators.

Aims: Low blood pressure (BP) has been shown to be associated with increased mortality in patients with chronic heart failure. This study was designed to evaluate the relationships between diagnosed hypertension and the risk of ventricular arrhythmia (VA) and all-cause death in chronic heart failure (CHF) patients with implantable cardioverter-defibrillators (ICD), including those with preserved left ventricular ejection fraction (HFpEF) and indication for ICD secondary prevention. We hypothesized that a stable hypertension status, along with an increasing BP level, is associated with a reduction in the risk of VA in this population, thereby limiting ICD efficacy. Methods: We retrospectively enrolled 964 CHF patients, with hypertension diagnosis and hospitalized BP measurements obtained before ICD implantation. The primary outcome measure was defined as the composite of SCD, appropriate ICD therapy, and sustained VT. The secondary endpoint was time to death or heart transplantation (HTx). We performed multivariable Cox proportional hazard regression and entropy balancing to calculate weights to control for baseline imbalances with or without hypertension. The Fine–Gray subdistribution hazard model was used to confirm the results. The effect of random BP measurements on the primary outcome was illustrated in the Cox model with inverse probability weighting. Results: The 964 patients had a mean (SD) age of 58.9 (13.1) years; 762 (79.0%) were men. During the interrogation follow-up [median 2.81 years (interquartile range: 1.32–5.27 years)], 380 patients (39.4%) reached the primary outcome. A total of 244 (45.2%) VA events in non-hypertension patients and 136 (32.1%) in hypertension patients were observed. A total of 202 (21.0%) patients died, and 31 (3.2%) patients underwent heart transplantation (incidence 5.89 per 100 person-years; 95% CI: 5.16–6.70 per 100 person-years) during a median survival follow-up of 4.5 (IQR 2.8–6.8) years. A lower cumulative incidence of VA events was observed in hypertension patients in the initial unadjusted Kaplan–Meier time-to-event analysis [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.53–0.80]. The protective effect was robust after entropy balancing (HR: 0.71, 95% CI: 0.56–0.89) and counting death as a competing risk (HR: 0.71, 95% CI: 0.51–1.00). Hypertension diagnosis did not associate with all-cause mortality in this population. Random systolic blood pressure was negatively associated with VA outcomes (p = 0.065). Conclusions: In hospitalized chronic heart failure patients with implantable cardioverter-defibrillators, the hypertension status and higher systolic blood pressure measurements are independently associated with a lower risk of combined endpoints of ventricular arrhythmia and sudden cardiac death but not with all-cause mortality. Randomized controlled trials are needed to confirm the protective effect of hypertension on ventricular arrhythmia in chronic heart failure patients.

Dynamic changes in cardiovascular and systemic parameters prior to sudden cardiac death in heart failure with reduced ejection fraction: a PARADIGM-HF analysis.

Prognostic models of sudden cardiac death (SCD) typically incorporate data at only a single time-point. We investigated independent predictors of SCD addressing the impact of integrating time-varying covariates to improve prediction assessment. We studied 8399 patients enrolled in the PARADIGM-HF trial and identified independent predictors of SCD (n=561, 36% of total deaths) using time-updated multivariable-adjusted Cox models, classification and regression tree (CART), and logistic regression analysis. Compared with patients who were alive or died from non-sudden cardiovascular deaths, patients who suffered a SCD displayed a distinct temporal profile of New York Heart Association (NYHA) class, heart rate and levels of three biomarkers (albumin, uric acid and total bilirubin), with significant differences observed more than 1year prior to the event (Pinteraction  < 0.001). In multivariable models adjusted for baseline covariates, seven time-updated variables independently contributed to SCD risk (incremental likelihood chi-square=46.2). CART analysis identified that baseline variables (implantable cardioverter-defibrillator use and N-terminal prohormone of B-type natriuretic peptide levels) and time-updated covariates (NYHA class, total bilirubin, and total cholesterol) improved risk stratification. CART-defined subgroup of highest risk had nearly an eightfold increment in SCD hazard (hazard ratio 7.7, 95% confidence interval 3.6-16.5; P < 0.001). Finally, changes over time in heart rate, NYHA class, blood urea nitrogen and albumin levels were associated with differential risk of sudden vs. non-sudden cardiovascular deaths (P < 0.05). Beyond single time-point assessments, distinct changes in multiple cardiac-specific and systemic variables improved SCD risk prediction and were helpful in differentiating mode of death in chronic heart failure.

Particle size and cholesterol content of circulating HDL correlate with cardiovascular death in chronic heart failure

Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0–8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p < 0.001). This change in size was due to a reduction in the percentage of small HDL-P (54.6% vs. 60% for CV-death vs. alive; p < 0.001). HDL-C/P ratio was higher in the CV-death group (51.0 vs. 48.3, p < 0.001). HDL-Sz and HDL-C/P ratio were significantly associated with CV death after multivariable regression analysis (HR 1.22 [95% CI 1.01–1.47], p = 0.041 and HR 1.04 [95% CI 1.01–1.07], p = 0.008 respectively). HDL-Sz and HDL-C/P ratio are independent predictors of CV death in chronic HF patients.

Exchange proteins directly activated by cAMP mediate cardiac repolarization and arrhythmogenesis during chronic heart failure.

Most sudden cardiac death in chronic heart failure (CHF) is caused by malignant ventricular arrhythmia (VA); however, the molecular mechanism remains unclear. This study aims to explore the effect of exchange proteins directly activated by cAMP (Epac) on VA in CHF and the potential molecular mechanism. Transaortic constriction was performed to prepare CHF guinea pigs. Epac activation model was obtained with 8-pCPT administration. Programmed electrical stimulation (PES) was performed to detect effective refractory period (ERP) or induce VA. Isolated adult cardiomyocytes were treated with 8-pCPT and (or) the Epac inhibitor. Cellular electrophysiology was examined by whole-cell patch clamp. With Epac activation, corrected QT duration was lengthened by 12.6%. The 8-pCPT increased action potential duration (APD) (APD50: 236.9 ± 18.07 ms vs. 328.8 ± 11.27 ms, p < 0.05; APD90: 264.6 ± 18.22 ms vs. 388.6 ± 6.47 ms, p < 0.05) and decreased rapid delayed rectifier potassium (IKr) current (tail current density: 1.1 ± 0.08 pA/pF vs. 0.7 ± 0.03 pA/pF, p < 0.05). PES induced more malignant arrhythmias in the 8-pCPT group than in the control group (3/4 vs. 0/8, p < 0.05). The selective Epac1 inhibitor CE3F4 rescued the drop in IKr after 8-pCPT stimulation (tail current density: 0.5 ± 0.02 pA/pF vs. 0.6 ± 0.03 pA/pF, p < 0.05). In conclusion, Epac1 regulates IKr, APD, and ERP in guinea pigs, which could contribute to the proarrhythmic effect of Epac1 in CHF.

Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI-HF trial.

AimsCeramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention.Methods and resultsIn a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure (GISSI‐HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow‐up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high‐risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P < 0.05 or less) higher levels of plasma Cer(d18:1/16:0) and Cer(d18:1/24:1), but lower levels of plasma Cer(d18:1/22:0) and Cer(d18:1/24:0) than had those who did not. All plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly higher in patients who died due to cardiovascular causes. In Cox regression analyses, all five plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly associated with a greater risk of cardiovascular mortality (with unadjusted hazard ratios ranging from 1.23 to 1.59; P < 0.001 or less). These significant associations were attenuated after adjustment for multiple established risk factors, New York Heart Association functional class, left ventricular ejection fraction, use of medications, plasma pentraxin‐3 levels, and, especially, plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels. When we applied a Bonferroni correction for multiple comparisons (using a P‐threshold 0.05/5 ceramide ratios = 0.01), none of the five plasma ratios of each ceramide with Cer(d18:1/24:0) remained statistically associated with the risk of cardiovascular mortality (with adjusted hazard ratios ranging from 1.10 to 1.23).ConclusionsHigher levels of specific plasma ceramides [especially when used in ratios with Cer(d18:1/24:0)] are associated with increased cardiovascular mortality in ambulatory patients with chronic HF. However, these associations are weakened after adjustment for established cardiovascular risk factors, medication use, and plasma NT‐proBNP concentrations.

Rapamycin regulates the balance betweencardiomyocyte apoptosis and autophagy in chronic heart failure by inhibiting mTOR signaling.

The progressive loss of cardiomyocytes caused by cell death leads to cardiac dysfunction and heart failure (HF). Rapamycin has been shown to be cardioprotective in pressure-overloaded and ischemic heart diseases by regulating the mechanistic target of rapamycin (mTOR) signaling network. However, the impact of rapamycin on cardiomyocyte death in chronic HF remains undetermined. Therefore, in the current study we addressed this issue using a rat myocardial infarction (MI)-induced chronic HF model induced by ligating the coronary artery. Following surgery, rats were randomly divided into six groups, including the sham-, vehicle- and rapamycin-operated groups, at 8 or 12 weeks post-MI. A period of 4 weeks after MI induction, the rats were treated with rapamycin (1.4 mg-kg-day) or vehicle for 4 weeks. Cardiac function was determined using echocardiography, the rats were subsequently euthanized and myocardial tissues were harvested for histological and biochemical analyses. In the cell culture experiments with H9c2 rat cardiomyocytes, apoptosis was induced using angiotensin II (100 nM; 24 h). Cardiomyocyte apoptosis and autophagy were assessed via measuring apoptosis- and autophagy-associated proteins. The activities of mTOR complex 1 (mTORC1) and mTORC2 were evaluated using the phosphorylation states of ribosomal S6 protein and Akt, respectively. The activity of the endoplasmic reticulum (ER) stress pathway was determined using the levels of GRP78, caspase-12, phospho-JNK and DDIT3. Echocardiographic and histological measurements indicated that rapamycin treatment improved cardiac function and inhibited cardiac remodeling at 8 weeks post-MI. Additionally, rapamycin prevented cardiomyocyte apoptosis and promoted autophagy at 8 weeks post-MI. Rapamycin treatment for 4 weeks inhibited the mTOR and ER stress pathways. Furthermore, rapamycin prevented angiotensin II-induced H9c2 cell apoptosis and promoted autophagy by inhibiting the mTORC1 and ER stress pathways. These results demonstrated that rapamycin reduced cardiomyocyte apoptosis and promoted cardiomyocyte autophagy, by regulating the crosstalk between the mTOR and ER stress pathways in chronic HF.

Abstract 12975: Cardiac I-123 Metaiodobenzylguanidine Imaging Predicts the Risk of Cardiac Death in Patients With Chronic Heart Failure, Irrespective of Blood Urea Nitrogen to Creatinine Ratio: A Long-Term Follow Up Study

Background: Cardiac I-123 metaiodobenzylguanidine (MIBG) imaging, which reflects cardiac sympathetic activity, provides prognostic information in patients with chronic heart failure (CHF). On the other hand, elevated blood urea nitrogen to creatinine ratio (BUN/Cr), a surrogate for renal neurohumoral activation, is associated with poor outcome in patients with heart failure. However, there is no information available on the prognostic value of cardiac MIBG imaging in patients with CHF, relating to BUN/Cr. Methods: We studied 109 CHF outpatients (NYHA class:2.1±0.6, ischemic origin:52%) with left ventricular ejection fraction &lt;40% (30±8%) in our prospective cohort study. At the enrollment, we measured serum level of BUN and Cr, and performed cardiac MIBG scintigraphy. Elevated BUN/Cr was defined as &gt;20. The cardiac MIBG washout rate (WR) was calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Abnormal WR was defined as &gt;27%. Results: Forty patients had elevated BUN/Cr, and 55 patients had abnormal WR. During a follow up period of 7.5±4.2 yrs, 36 of 109 patients had cardiac death. At multivariate Cox analysis, WR was significantly independently associated with cardiac death in group with both elevated BUN/Cr (p=0.02) and normal BUN/Cr (p=0.004). Kaplan-Meier analysis showed that patients with abnormal WR had a higher risk of cardiac death than those with normal WR, in group with both elevated BUN/Cr (48%[11/23] vs 6%[1/17], p=0.02, adjusted hazard ratio 11.8[95%CI 1.5-92.2]) and normal BUN/Cr (55%[18/33] vs 17%[6/36], p=0.001, adjusted hazard ratio 4.6[95%CI 1.8-11.6]). Conclusion: The cardiac MIBG imaging could predict the risk of cardiac death in CHF, irrespective of BUN/Cr.

1,25-Dihydroxyvitamin D to PTH(1-84) Ratios Strongly Predict Cardiovascular Death in Heart Failure.

ObjectivesVitamin D deficiency and hyperparathyroidism are common in patients with heart failure (HF). There is a growing body of evidence supporting the role of vitamin D and parathyroid hormone (PTH) in cardiac remodeling and worsening of HF. Lack of reliable automated testing of 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active metabolite of vitamin D, has limited its contribution to the prognostic assessment of HF. Here, the association of 1,25(OH)2D and PTH(1–84) levels was evaluated for prediction of cardiovascular death in chronic HF patients.MethodsWe conducted a single center prospective cohort including 170 chronic HF patients (females n = 36; males n = 134; NYHA II-IV; mean age: 67 years; etiology: ischemic n = 119, dilated cardiomyopathy n = 51; mean LVEF: 23%). The primary outcome was cardiovascular death.ResultsSerum levels of 1,25(OH)2D decreased markedly with increased HF severity. Medians were 33.3 pg/mL for NYHA-II patients, 23.4 pg/mL for NYHA-III, and 14.0 pg/mL for NYHA-IV patients (p<0.001). Most patients had levels of 25(OH)D below 30ng/mL, and stratification by NYHA functional class did not show significant differences (p = 0.249). The 1,25(OH)2D to PTH(1–84) ratio and the (1,25(OH)2D)2 to PTH(1–84) ratio were found to be the most significantly related to HF severity. After a median follow-up of 4.1 years, 106 out of 170 patients reached the primary endpoint. Cox proportional hazard modeling revealed 1,25(OH)2D and the 1,25(OH)2D to PTH(1–84) ratios to be strongly predictive of outcomes.Conclusions1,25(OH)2D and its ratios to PTH(1–84) strongly and independently predict cardiovascular mortality in chronic HF.

Blood pressure variability analysis enhances risk stratification in chronic heart failure

Introduction Outcomes related to chronic heart failure (CHF) remains very poor: mortality is related to its severity ranging from 5 to 10% in patients with mild to 30-40% in severe cases [1,2]. The main cause of death in CHF is related to arrhythmic events and these patients are also at risk

Even Slightly Elevated Plasma Uric Acid Levels Could be a Predictor of Cardiovascular Death in Chronic Heart Failure

Even Slightly Elevated Plasma Uric Acid Levels Could be a Predictor of Cardiovascular Death in Chronic Heart Failure

Expansion of the red cell distribution width and evolving iron deficiency as predictors of poor outcome in chronic heart failure

An elevated red cell distribution width (RDW) and iron deficiency (ID) at baseline predict enhanced mortality in chronic heart failure (CHF), but little is known about the prognostic implications of their temporal trends. We sought to determine the survival implications of temporal changes in RDW and evolving ID in patients with CHF. The relation between red cell indices on first consultation and over time with mortality in 274 stable patients with systolic CHF was analysed. The combination of a rising RDW with a falling mean cell volume (MCV) over time defined evolving ID. Over a median 12 month period, 51% and 23% of patients had a rise in RDW and evolving ID, respectively. After a median follow-up of 27 months, 60 (22%) patients died. A rising RDW predicted enhanced all-cause mortality (unadjusted HR for 1% per week rise 9.27, 95% CI 3.58 to 24.00, P<0.0001) independently and incrementally to baseline RDW, with an absolute increase >0.02% per week optimally predictive. Evolving ID also related to higher rates of mortality (HR 2.78, 95% CI 1.64 to 4.73, P<0.001) and was prognostically worse than a rising RDW alone (P<0.005). Patients with evolving ID who maintained their Hb levels over time had a 2-fold greater risk of death than those whose Hb levels declined without evolving ID. An expanding RDW and evolving iron deficiency over time predict an amplified risk of death in CHF and should be utilised for risk stratification and/or therapeutically targeted to potentially improve outcomes.

Lipopolysaccharide Responsiveness is an Independent Predictor of Death in Chronic Heart Failure

Lipopolysaccharide Responsiveness is an Independent Predictor of Death in Chronic Heart Failure

Renal Function in Relation to Cardiac 123I-MIBG Scintigraphy in Patients with Chronic Heart Failure

The aim of this study was to explore if estimates of renal function could explain variability of 123I-metaiodobenzylguanidine (123I-MIBG) assessed myocardial sympathetic activity. Furthermore estimates of renal function were compared to 123I-MIBG as predictors of cardiac death in chronic heart failure (CHF). Semi-quantitative parameters of 123I-MIBG myocardial uptake and washout were calculated using early heart/mediastinum ratio (H/M), late H/M and washout. Renal function was calculated as estimated Creatinine Clearance (e-CC) and as estimated Glomerular Filtration Rate (e-GFR). Thirty-nine patients with CHF (24 males; age: 64.4 ± 10.5 years; NYHA II/III/IV: 17/20/2; LVEF: 24.0 ± 11.5%) were studied. Variability in any of the semi-quantitative 123I-MIBG myocardial parameters could not be explained by e-CC or e-GFR. During follow-up (60 ± 37 months) there were 6 cardiac deaths. Cox proportional hazard regression analysis showed that late H/M was the only independent predictor for cardiac death (Chi-square 3.2, regression coefficient: −4.095; standard error: 2.063; hazard ratio: 0.17 [95% CI: 0.000–0.950]). Addition of estimates of renal function did not significantly change the Chi-square of the model. Semi-quantitative 123I-MIBG myocardial parameters are independent of estimates of renal function. In addition, cardiac sympathetic innervation assessed by 123I-MIBG scintigraphy seems to be superior to renal function in the prediction of cardiac death in CHF patients.

Abstract 17950: Prediction of Sudden Cardiac Death in Chronic Heart Failure Patients with Mild to Moderate Systolic Dysfunction a Prospective Comparative Study of Cardiac I-123 Metaiodobenzylguanidine Imaging and Heart Rate Turbulence

Background: Although it is shown that ICD therapy could prevent sudden cardiac death (SCD) in chronic heart failure (CHF) patients with severely reduced LV systolic function (LV ejection fraction &lt;35%), it remains unclear which CHF patients with LVEF&gt;35% would have the risk of SCD. Therefore, we sought to prospectively compare the prognostic values for SCD of cardiac metaiodobenzylguanidine (MIBG) imaging and heart rate turbulence (HRT) analysis ,which are expected to provide prognostic information , in CHF patients with LVEF&gt;35% in the gray zone for the ICD therapy. Methods and Results: We enrolled 55 CHF outpatients (NYHA 2±0.2) with radionuclide LV ejection fraction from 35% to 50% (38.5±0.8%). We performed the cardiac MIBG imaging and 24-hour Holter monitoring at the entry. The cardiac MIBG wash out rate (WR) was calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Abnormal WR was defined as WR &gt;27%. Furthermore, we also performed HRT analysis from Holter monitoring. Turbulance onset (TO) and turbulence slope (TS) were calculated as HRT parameters. Abnormal values of HRT analysis were defined as TO≥0% and TS≤2.5ms/beat. Result: During the follow up period of 6.0±0.8 years, 7 of 55 patients had SCD. At multivariate Cox analysis, WR was significantly (p=0.015) and independently associated with SCD, while TO and TS had no association with SCD. SCD was significantly more frequently observed in patients with than without abnormal WR (30% vs 3%, p=0.002), although there was no significant difference in the incidence of SCD between patients with and without abnormal HRT results. The hazard ratio of abnormal WR for SCD was 13 .7( 95%CI 1.6 to 114.7). Conclusion: Cardiac MIBG imaging, but not HRT analysis, would be useful to predict the risk of sudden cardiac death in CHF patients with mildly to moderately reduced LV systolic function.

Abstract 18126: Attenuations in Serum Albumin Over Time Powerfully Predict an Amplified Risk of Death in Chronic Heart Failure

Background: Worsening heart failure is typically accompanied by diffuse inflammation, plasma volume expansion, diminished nutritional status and blunted liver biosynthetic function due to hepatic congestion. Because attenuations in serum albumin over time reliably reflects these derangements, we hypothesized that it would be predictive of death in patients (pts) with chronic heart failure (CHF) and that its prognostic power would supercede that of static single measures of albumin at baseline. Methods: We analysed the relation of serum albumin on first consultation and over time with mortality in 246 outpatients with CHF (mean [±SD] age 68±12y, LVEF 29±8%, albumin 42±5 g/L, 48% NYHA class &gt;2, 55% ischemic). Results: On initial consultation, 12 (5%) pts had an albumin &lt; 35g/L. Over a median (±IQR) follow-up of 13±18 months, 51 (21%) pts died, 132 (54%) pts had a fall in albumin, and 46 (19%) pts harboured attenuations &gt; 6g/L. On Cox proportional hazards analyses, a lower albumin at baseline predicted increased mortality (HR 0.89, CI 0.84 - 0.94, χ 2 :18, P&lt;0.0001) independently of all covariates. However, a falling albumin over time (unadjusted HR 0.89, CI 0.84 - 0.92, χ 2 53, P&lt;0.0001) was even more predictive (Difference in ROC AUC for baseline vs Δalbumin 0.16, P&lt;0.001) and did so independently of baseline albumin, NYHA class and changes in urea and hemoglobin (Δalbumin adjusted HR 0.84, CI 0.81 - 0.88, χ 2 54, P&lt;0.0001). A reduction in albumin &gt; 6 g/L optimally predicted death (ROC AUC 0.82, CI 0.76 - 0.86, P&lt;0.0001, Fig A) and conferred a 6-fold escalated risk of mortality (HR 6.42, CI: 3.67 - 11.22, P&lt;0.0001, Fig B). In incremental prognostic analyses, the addition of Δalbumin to the strongest 4 variable model dramatically augmented the χ 2 value (Fig C). Conclusions: Attenuations in serum albumin over time strongly correlate to an enhanced risk of death in chronic heart failure and could be utilised to further refine risk stratification.

107 Expansion of the red cell distribution width and evolving iron deficiency as predictors of poor outcome in chronic heart failure

BackgroundRed cell distribution width (RDW) is a surrogate of many aberrations (inflammation, malnutrition, iron deficiency (ID)) that may drive chronic heart failure (CHF) progression. While an elevated RDW and iron...

Onset of heart failure determines the hepatic cell death pattern

Background and rationale. Acute and chronic heart failure (HF) may affect the liver, but the underlying mechanisms that lead to progressive liver damage are poorly understood. The hepatic cytokeratin-18 (CK18) epitopes M65 and M30 have been reported to distinguish between overall (necrotic) and apoptotic cell death, respectively. We aimed to evaluate the predominant hepatic cell death pattern in acute vs. chronic heart failure and examined if these assays predict the course of the disease.Main results. In a prospective study comprising 21 patients with acute HF (AHF) and 18 patients with chronic HF (CHF) serum levels of M65 and M30 were assessed. Compared with CHF, M65 levels were significantly increased in patients with AHF (CHF: 1,283 ± 591.6U/l vs. AHF: 20,912 ± 15,132U/l, p > 0.001). In addition, M30 levels were significantly increased in AHF (CHF: 642.2 ± 177.4U/l vs. AHF: 3,844 ± 5,293U/l, p < 0.05), but the M30/M65 ratio was significantly higher in CHF (CHF: 0.54 ± 0.15 vs. AHF: 0.20 ± 0.19, p < 0.001), indicating a greater contribution of apoptotic cell death in CHF. AHF patients with higher M30 values had a worse prognosis.Conclusions. The ratio of CK18 M30/M65 is a potential marker to discriminate AHF from CHF induced LF and M30 might be a prognostic marker for survival in AHF induced liver injury.