Increased ratio of sST2/LVMI predicted cardiovascular mortality and heart failure rehospitalization in heart failure with reduced ejection fraction patients: a prospective cohort study.

BACKGROUND: Inflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes. Soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, is assumed to play a significant role in the fibrotic response to inflammation. Left ventricular mass index (LVMI) is a parameter of the prefibrotic inflammatory phase of heart failure preceding remodeling. The present study aimed to investigate the prognostic value of the sST2/LVMI ratio in heart failure with reduced ejection fraction. METHODS: This was a prospective cohort study. A total of 45 consecutive patients with heart failure with reduced ejection fraction, treated between September 2015 and December 2016, were enrolled. The sST2/LVMI ratio was measured at baseline. The primary endpoint was a composite of cardiovascular mortality and readmission for heart failure. The prognostic impact of the sST2/LVMI ratio was evaluated using a multivariable Cox proportional hazards regression model. RESULTS: Forty-five patients were enrolled in this study. Their average age was 48 ± 14 years, and approximately 20% of them were men. Patients were followed for 9 months, during which the primary outcome occurred in 15 patients. Kaplan-Meier analysis showed that patients with a high sST2/LVMI ratio (≥ 0.39) had shorter event-free survival than those with intermediate (between 0.39 and 0.24) and low ratios (< 0.24) (log-rank, P = 0.022). The fully adjusted multivariable Cox regression analysis showed that the sST2/LVMI ratio was positively associated with the composite outcome in patients with heart failure with reduced ejection fraction after adjusting for confounders (hazard ratio 1.64, 95% confidence interval 1.06 to 2.54). By subgroup analysis, a stronger association was found with age between 40 and 55 years, systolic blood pressure < 115 or ≥ 129 mmHg, diastolic blood pressure < 74 mmHg, hematocrit < 44.5%, and interventricular septum thickness ≥ 8.5 mm. CONCLUSION: In patients with heart failure with reduced ejection fraction, the relationship between the sST2/LVMI ratio and the composite outcome was linear. A higher baseline ratio of sST2/LVMI was associated with an increased risk of cardiovascular mortality and heart failure rehospitalization in the short-term follow-up.

Reciprocal organ interactions during heart failure: a position paper from the ESC Working Group on Myocardial Function.

Heart failure-either with reduced or preserved ejection fraction (HFrEF/HFpEF)-is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs.

Prevalence of cardiac amyloidosis among elderly patients with systolic heart failure or conduction disorders.

Objective: Cardiac amyloid infiltration can lead to systolic heart failure (HF) or to conduction disorders (CD). Patients with transthyretin (ATTR) amyloidosis are particularly exposed. We sought to determine the prevalence of ATTR and AL among patients >60 years admitted with CD or unexplained systolic HF and increased wall thickness. Materials and Methods: We studied 143 patients (57% males, 79 ± 9 years) with HF (N = 28) or CD requiring pacemaker implantation (N = 115). In total, 139 (97%) patients (28 with HF and 111 with CD) underwent 99mTc-DPD scintigraphy to detect ATTR, and 105 (73%; 19 HF and 86 CD) underwent AL screening. Results: Five patients (4%; 95%CI:0-7%) exhibited wild-type ATTR (ATTRwt) amyloidosis, 2 (2%; 95%CI:0-4%) had CD and 3 (11%; 95%CI:0-23%) HF. No patient showed AL. The 2 ATTRwt patients with CD were previously asymptomatic, did not show classical ECG signs and exhibited mild LV hypertrophy with preserved LVEF. By contrast, all ATTRwt patients with HF had ECG and echocardiographic signs of amyloid. During a mean follow-up of 18 ± 11 months, 3(60%) patients with ATTRwt amyloidosis (1 CD and 2 HF) and 14(10.4%) without died. Conclusion: Prevalence of ATTRwt amyloidosis in patients with CD requiring pacemaker is low. Although, additional studies are needed, prevalence seems to be higher in elderly patients with systolic HF.

Prognostic value of real-time three-dimensional echocardiography compared to two-dimensional echocardiography in patients with systolic heart failure.

Heart failure (HF) is associated with morbidity and mortality. Real-time three-dimensional echocardiography (RT3DE) may offer additional prognostic data in patients with HF. The study aimed to evaluate the prognostic value of real-time three-dimensional echocardiography (RT3DE). This is a prospective study that included 89 patients with HF and left ventricular ejection fraction (LVEF) < 0.50 who were followed for 48 months. Left atrium and ventricular volumes and functions were evaluated by RT3DE. TDI and two-dimensional echocardiography parameters were also obtained. The endpoint was a composite of death, heart transplantation and hospitalization for acute decompensated HF. The mean age was 55 ± 11 years, and the LVEF was 0.32 ± 0.10. The composite endpoint occurred in 49 patients (18 deaths, 30 hospitalizations, one heart transplant). Patients with outcomes had greater left atrial volume (40 ± 16 vs. 32 ± 12 mL/m2; p < 0.01) and right ventricle diameter (41 ± 9 vs. 37 ± 8 mm, p = 0.01), worse total emptying fraction of the left atrium (36 ± 13% vs. 41 ± 11%; p = 0.03), LVEF (0.30 ± 0.09 vs. 0.34 ± 0.11; p = 0.02), right ventricle fractional area change (34.8 ± 12.1% vs. 39.2 ± 11.3%; p = 0.04), and greater E/e' ratio (19 ± 9 vs. 16 ± 8; p = 0.04) and systolic pulmonary artery pressure (SPAP) (50 ± 15 vs. 36 ± 11 mmHg; p < 0.01). In multivariate analysis, LVEF (OR 4.6; CI 95% 1.2-17.6; p < 0.01) and SPAP (OR 12.5; CI 95% 1.8-86.9; p < 0.01) were independent predictors of patient outcomes. LVEF and the SPAP were independent predictors of outcomes in patients with HF.

Mortality prediction using CHADS2/CHA2DS2-VASc/R2CHADS2 scores in systolic heart failure patients with or without atrial fibrillation.

The CHADS2, CHA2DS2-VASc, and R2CHADS2 scores are well-known predictors of stroke caused by atrial fibrillation (AF), but no studies have evaluated their use for stratifying all-cause mortality risk in patients discharged for systolic heart failure (SHF) with or without AF.This study analyzed data in the Taiwan Society of Cardiology-heart failure with reduced ejection fraction (TSOC-HFrEF) registry. These data were obtained by a prospective, multicenter, observational survey of patients treated at 21 medical centers in Taiwan after hospitalization for acute, pre-existing or new onset SHF from May, 2013 to October, 2014. During 1 year follow-up, 198 patients were lost follow-up, and final 1311 (86.8%) patients were included for further analysis. During the follow-up period, 250 (19%) patients died. Multivariate analysis revealed that body mass index, thyroid disorder, valvular surgery history, chronic kidney disease (CKD), and scores for CHADS2, CHA2DS2-VASc, and R2CHADS2 were significant independent predictors of mortality in the overall population of SHF patients (all P < .05) The c-indexes showed that CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were significantly associated with mortality in SHF patients with or without AF (all P < 005). However, R2CHADS2 had significantly higher accuracy in predicting mortality in all SHF patients compared with CHADS2 and CHA2DS2-VASc (DeLong test, P < .0001), especially in SHF without AF (DeLong test, P = .0003).Scores for CHADS2, CHA2DS2-VASc, and R2CHADS2 can be used to predict 1-year all-cause mortality in SHF patients with or without AF. For predicting all-cause mortality in SHF patients, R2CHADS2 is more accurate than CHADS2 and CHA2DS2-VASc.

Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis is an infiltrative cardiomyopathy that is challenging to diagnose. We hypothesized that the novel biomarkers hepatocyte growth factor (HGF), galectin-3 (GAL-3), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) would be elevated in cardiac amyloidosis and may be able to discriminate from non-cardiac systemic amyloidosis or other cardiomyopathies with similar clinical or morphologic characteristics. METHODS: Patients were selected from the Vanderbilt Main Heart Registry according to the following groups: (1) amyloid light-chain (AL) cardiac amyloidosis (n = 26); (2) transthyretin (ATTR) cardiac amyloidosis (n = 7); (3) left ventricular hypertrophy (LVH) (n = 45); (4) systolic heart failure (n = 42); and (5) non-cardiac systemic amyloidosis (n = 7). Biomarkers were measured in stored plasma samples. Biomarkers' discrimination performance in predicting AL cardiac amyloidosis (i.e., Concordance index) was reported. A survival analysis was used to explore the relationship between HGF levels and mortality among AL cardiac amyloidosis patients. RESULTS: HGF levels were markedly elevated in patients with AL cardiac amyloidosis (median = 622, interquartile range (IQR): 299-1228 pg/mL) compared with the other groups, including those with non-cardiac systemic amyloidosis (median = 134, IQR: 94-163 pg/mL, p < 0.001). HGF was not a specific marker for ATTR amyloidosis. Gal-3 was elevated in all groups with amyloidosis but could not differentiate between those with and without cardiac involvement. There was no difference in IL-6 or VEGF between those with AL cardiac amyloidosis compared to other groups (p = 0.13 and 0.057, respectively). CONCLUSIONS: HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.

Hypothermia is an independent predictor of short and intermediate term mortality in acute systolic heart failure: Insights from the ESCAPE trial.

INTRODUCTION: Admission hypothermia is associated with increased mortality in patients hospitalized with sepsis, trauma or stroke. We hypothesized that hypothermia on admission in patients with acute systolic heart failure (HF) would be associated with worse survival. METHODS: Using ESCAPE trial data, we compared patients hospitalized with acute systolic HF with admission temperature ≤35.5°C or >35.5°C. The study endpoints were 30-day and 6-month all-cause mortality. RESULTS: Among the 398 patients (mean age 56years, 74% men) who had body temperature recorded on hospital admission, 23 had a temperature ≤35.5°C (hypothermia) and 375 patients had a temperature >35.5°C. By univariate comparison, hypothermic patients had a higher blood urea nitrogen (BUN) level (46.6versus 34.6mg/dL, P=0.04) and creatinine level (1.85 versus 1.49mg/dL, P=0.035) and higher frequency of malignancy (26.1% versus 6.1%, P=0.001). There was a significant correlation between admission temperature and body mass index (r=0.201, P<0.0001). Patients with temperature≤35.5°C had a higher 30-day (17.4% versus 4.3%, univariate OR 4.724, 95% CI 1.439-15.509, P=0.01) and 6-month (43.5% versus 18.1%, univariate OR 3.473, 95% CI 1.462-8.25, P=0.005) all-cause mortality. Cox proportional hazard analysis revealed that admission temperature ≤35.5°C is an independent predictor of mortality (hazard ratio 2.222, 95% CI 1.117-4.420, P=0.023). Kaplan-Meier analysis comparing survival in patients with admission temperature ≤35.5°C or >35.5°C showed a significant inter-group difference in survival (log-rank P value=0.001). CONCLUSION: Admission body temperature ≤35.5°C is an independent predictor of short and intermediate term mortality in patients hospitalized with acute systolic HF.

Melanoma cell adhesion molecule as an emerging biomarker with prognostic significance in systolic heart failure.

BACKGROUND: Melanoma cell adhesion molecule (MCAM) is a marker of endothelial damage. MCAM diagnostic and prognostic value was assessed in chronic heart failure (CHF). MATERIALS & METHODS: 130 CHF patients and 32 controls were included in the study. Telephone follow-up lasted one year. End points were: death from all causes, and hospitalization with CHF exacerbation. RESULTS: MCAM was higher in patients than in controls (p = 0.01). Receiver operator curve analysis revealed that MCAM may serve as a predictor of death (area under the curve: 0.8404; p < 0.002). Patients with MCAM above 500 ng/ml had worse prognosis (p = 0.03). NT-proBNP and age were independent predictors of death in multivariate analysis. CONCLUSION: The increased MCAM indicates endothelial damage in CHF and may serve as a marker of worse prognosis in these patients.

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure / Valor Prognóstico da Resistência Vascular Pulmonar através de Ressonância Magnética em Insuficiência Cardíaca

Abstract Background: Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective: We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods: Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. Results: 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). Conclusions: In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF.

Resumo Fundamento: A hipertensão pulmonar está associada a mau prognóstico em insuficiência cardíaca. No entanto, o diagnóstico não-invasivo é desafiador na prática clínica. Objetivo: Avaliar a utilidade prognóstica da estimativa não-invasiva das resistências vasculares pulmonares (RVP) medidas através de ressonância magnética cardiovascular na previsão de desfechos cardiovasculares adversos em insuficiência cardíaca com fração de ejeção reduzida (ICFEr). Métodos: Registro prospectivo de pacientes com fração de ejeção do ventrículo esquerdo (FEVE) < 40% internados recentemente por insuficiência cardíaca descompensada, durante três anos. As RVP foram calculadas com base na fração de ejeção do ventrículo esquerdo e velocidade média do fluxo na artéria pulmonar estimada por ressonância magnética cardíaca. Durante a evolução, reinternação por insuficiência cardíaca e mortalidade por todas as causas foram consideradas eventos adversos. Resultados: Foram incluídos 105 pacientes (FEVE média de 26,0 ± 7,7%, etiologia isquêmica em 43%). Os valores de RVP nos pacientes que apresentaram eventos adversos durante o seguimento em longo prazo foram mais altos (6,93 ± 1,9 versus 4,6 ± 1,7 unidades Wood estimadas (uWe), p < 0,001). Na análise de regressão multivariada de Cox, RVP ≥ 5 eWu (valor de corte segundo a curva ROC) mostrou-se independentemente associada a um maior risco de eventos adversos aos 9 meses de seguimento (RR = 2,98; IC 95% = 1,12-7,88; p < 0,03). Conclusões: Em pacientes com ICFEr, a presença de RVP ≥ 5,0 uW está associada a uma evolução clínica significativamente pior. A estimativa não-invasiva da RVP através de ressonância magnética cardíaca pode ser útil na estratificação de risco em ICFEr, independentemente da etiologia, presença de realce tardio pelo gadolínio ou FEVE.

Variables Measured During Cardiopulmonary Exercise Testing as Predictors of Mortality in Chronic Systolic Heart Failure.

BACKGROUND: Data from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables. OBJECTIVES: The study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER). METHODS: Among patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [Vo2], exercise duration, percent predicted peak Vo2 [%ppVo2], ventilatory efficiency) were examined. RESULTS: Over a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both %ppVo2 and exercise duration were equally able to predict (Wald chi-square: ∼141) and discriminate (c-index: 0.69) mortality. Peak Vo2 (ml·kg(-1)·min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppVo2, exercise duration, and peak Vo2 (ml·kg(-1)·min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak Vo2 of 10.9 ml·kg(-1)·min(-1) versus 5.3 ml·kg(-1)·min(-1) in women. CONCLUSIONS: Peak Vo2, exercise duration, and % ppVo2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak Vo2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

Iron deficiency: Prevalence and relation to cardiovascular biomarkers in heart failure outpatients.

BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES: To identify the prevalence of ID in a HF clinic and evaluate whether ID is associated with increased plasma concentrations of different cardiovascular biomarkers that carry a poor prognosis. METHODS: We prospectively included 149 patients with systolic HF referred to an outpatients HF clinic. ID was defined as ferritin<100 µg/L or ferritin 100-300 µg/L and Tranferin-saturation<0.20. Five different cardiovascular biomarkers were analyzed on frozen plasma. RESULTS: The patients had a median age of 70 (Interquartile range: 64-75) years, 25% were females, 29% were in functional class III-IV and LVEF was 32 (27-39) %. The prevalence of ID was 45% (95%-confidence interval (CI): 37-53%). In multivariate analyses, ID was not associated with plasma concentrations of troponin I, NT-proBNP, MR-proANP, chromogranin A or copeptin (P>0.05 for all) but with plasma concentrations of hs-CRP (odds ratio: 2.03, 95%-CI: 1.02-4.02, P=0.043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF patients.

Detection of subtle left ventricular systolic dysfunction in patients with significant aortic regurgitation and preserved left ventricular ejection fraction: speckle tracking echocardiographic analysis.

AIMS: The aim of this study was to characterize left ventricular (LV) mechanics in symptomatic and asymptomatic patients with moderate-to-severe or severe aortic regurgitation (AR) and preserved ejection fraction (left ventricular ejection fraction) using two-dimensional speckle tracking echocardiography (2D-STE). The association between baseline LV strain and development of indications for surgery in asymptomatic patients was also evaluated. METHODS AND RESULTS: A total of 129 patients with moderate-to-severe or severe AR and LVEF >50% (age 55 ± 17 years, 64% male, 53% asymptomatic at baseline) were included. Standard echocardiography and 2D-STE were performed at baseline. Compared with asymptomatic patients, symptomatic patients had significantly impaired LV longitudinal (-14.9 ± 3.0 vs. -16.8 ± 2.5%, P < 0.001), circumferential (-17.5 ± 2.9 vs. -19.3 ± 2.8%, P = 0.001), and radial (35.7 ± 12.2 vs. 43.1 ± 14.7%, P = 0.004) strains. Among 49 asymptomatic patients who were followed up, 26 developed indications for surgery (symptoms onset or LVEF ≤50%). These patients had comparable LV volumes, LVEF, and colour Doppler assessments of AR jet at baseline, but more impaired LV longitudinal (P = 0.009) and circumferential (P = 0.017) strains compared with patients who remained asymptomatic. Impaired baseline LV longitudinal (per 1% decrease, HR = 1.21, P = 0.04) or circumferential (per 1% decrease, HR = 1.22, P = 0.04) strain was independently associated with the need for surgery. CONCLUSION: Multidirectional LV strain was more impaired in symptomatic than in asymptomatic patients with moderate-to-severe or severe AR, despite preserved LVEF. In asymptomatic AR patients, longitudinal and circumferential strains identified patients who would require surgery during follow-up.

Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study).

Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensity-matched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m(2), those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73 m(2) and with neutral effect in those with GFR <30 ml/min/1.73 m(2).

[Carriage of A Allele of Polymorphic Marker G(-238)A of TNF Gene Is Associated With Unfavorable Prognosis in Patients With Chronic Systolic Heart Failure].

AIM: to elucidate association between polymorphic markers of interleukin-6 (Il-6) and tumor necrosis factor (TNF) genes and unfavorable outcomes in patients with chronic heart failure (CHF). MATERIAL AND METHODS: We determined levels of TNF and Il-6 and genotypes of polymorphic markers G(-238)A of TNF gene (rs361525) and G(--174)C of IL-6 gene (rs1800795) in 151 patients (mean age 64.5 years) hospitalized because of decompensation of systolic CHF (left ventricular ejection fraction ≤ 40%) after stabilization of their state. Unfavorable outcomes were registered during follow-up for 2 years. RESULTS: Mean levels of NT-proBNP, Il-6, and TNF were 2481.1 ± 199.86 fmol/ml, 21.8 7.46 rg/ml, and 10.07 ± 0.65 rg/ml, respectively. 138 (94.4%), 13 (8.6%) and 0 patients were carriers of genotypes GG, AG, and AA of polymorphic marker G(-238)A of TNF gene, respectively; 54 (35.8%), 69 (45.7%), and 28 (18.5%) patients carried genotypes GG, GC, and CC of polymorphic marker G(-174)C gene IL-6, respectively. There was no association between Il-6, TNF levels and carriage of either of genotypes as well as unfavorable clinical course of CHF. Mean survival time before repetitive episode of CHF decompensation (including lethal one) was significantly shorter among carriers of A allele compared with carriers of G allele of polymorphic marker G(-238)A of TNF gene (243 ± 97.7 and 947 ± 78 days, respectively, p = 0.018). Mean time before all cause death was also shorter in carriers of A compared with carriers of G allele (289 ± 122.9 and 1039 ± 73.3 days, respectively, p = 0.03). The studied polymorphism of IL-6 gene had no prognostic value. CONCLUSION: We obtained data on association between carriage of A allele of polymorphic marker G(-238)A of TNF gene and unfavorable prognosis in patients with CHF and inpraired left ventricular systolic function.

Parâmetros Ecocardiográficos e Sobrevida na Cardiopatia Chagásica com Disfunção Sistólica Importante / Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction

Fundamento: O ecocardiograma fornece dados importantes na avaliação cardiológica de pacientes em insuficiência cardíaca. A identificação de parâmetros ecocardiográficos na cardiopatia chagásica grave auxiliaria na implementação terapêutica e na avaliação prognóstica. Objetivo: Correlacionar parâmetros ecocardiográficos com desfecho mortalidade cardiovascular em pacientes com fração de ejeção < 35%. Métodos: Estudo de análise retrospectiva de parâmetros ecocardiográficos coletados prospectivamente e pré-especificados em 60 pacientes incluídos no Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias - braço cardiopatia chagásica. Os parâmetros foram: diâmetros e volumes diastólico e sistólico do ventrículo esquerdo, fração de ejeção, diâmetro do átrio esquerdo, volume do átrio esquerdo, volume indexado do átrio esquerdo, pressão sistólica da artéria pulmonar, integral da velocidade do fluxo aórtico, índice de performance miocárdica, taxa de aumento da pressão do ventrículo esquerdo, tempo de relaxamento isovolumétrico, velocidade das ondas E, A, Em, Am e Sm, tempo de desaceleração da onda E, relação E/A , E/Em e insuficiência mitral. Resultados: No seguimento médio de 24,18 meses, 27 pacientes faleceram. a fração de ejeção média era de 26,6 ± 5,34%. Na análise multivariada, foram incluídos os parâmetros de fração de ejeção (HR = 1,114; p = 0,3704), volume indexado do átrio esquerdo (HR = 1,033; p < 0,0001) e relação E/Em (HR = 0,95; p = 0,1261). O volume indexado do átrio esquerdo foi um fator de predição independente em ...

Background: Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. Objective: To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%. Methods: Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. Results: In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m2 were associated with a significant increase in mortality (log rank p < 0.0001). Conclusion: The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction. .

Relationships between right ventricular function, body composition, and prognosis in advanced heart failure.

OBJECTIVES: This study sought to examine the relationships between right ventricular (RV) function, body composition, and prognosis in patients with advanced heart failure (HF). BACKGROUND: Previous studies investigating HF-related cachexia have not examined the impact of RV function on body composition. We hypothesized that RV dysfunction is linked to weight loss, abnormal body composition, and worsened prognosis in advanced HF. METHODS: Subjects with advanced HF (n = 408) underwent prospective assessment of body composition (skinfold thickness, dual-energy X-ray absorptiometry), comprehensive echocardiography, and blood testing. Subjects were followed up for adverse events (defined as death, transplantation, or circulatory assist device). RESULTS: Subjects with RV dysfunction (51%) had lower body mass index, lower fat mass index, and were more likely to display cachexia (19%). The extent of RV dysfunction correlated with greater antecedent weight loss and a lower fat/lean body mass ratio. Over a median follow-up of 541 days, there were 150 events (37%). Risk of event was greater in subjects with RV dysfunction (hazard ratio: 3.09 [95% confidence interval (CI): 2.18 to 4.45]) and cachexia (hazard ratio: 2.90 [95% CI: 2.00 to 4.12]) in univariate and multivariate analyses. Increased body mass index was associated with a lower event rate (HR per kg/m(2): 0.92 [95% CI: 0.88 to 0.96]), and this protection was mediated by a higher fat mass (0.91 [95% CI: 0.87 to 0.96]) but not a fat-free mass index (0.97 [95% CI: 0.92 to 1.03]). CONCLUSIONS: RV dysfunction and cardiac cachexia often coexist, have additive adverse impact, and might be mechanistically interrelated. Wasting of fat but not of lean mass was predictive of adverse outcome, suggesting that fat loss is either a surrogate of enhanced catabolism or adipose tissue is cardioprotective in the context of HF.

The impact of eplerenone at different levels of risk in patients with systolic heart failure and mild symptoms: insight from a novel risk score for prognosis derived from the EMPHASIS-HF trial.

AIMS: Our objective was to create a simple prognostic risk score for patients with systolic heart failure and mild symptoms. We then assessed the efficacy of eplerenone across different categories of risk. METHODS AND RESULTS: The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF) was an international randomized trial, comparing eplerenone with placebo in 2737 patients with systolic heart failure and mild symptoms. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure, over a median 2.1 years follow-up. Using multivariable Cox modelling age, sex, systolic blood pressure, estimated glomerular filtration rate, diabetes, BMI, haemoglobin, prior heart failure (HF) hospitalization, prior myocardial infarction/coronary artery bypass surgery (CABG), and heart rate were identified as strong independent risk factors. Estimates from the model were converted into a simple integer risk score which was categorized into three groups of low-, medium-, and high risk. In placebo patients, the rates (per 100 patient-years) for the primary outcome were 7.6, 19.0, and 39.4 in the low-, medium-, and high-risk groups, respectively. On eplerenone, these rates were reduced to 5.6, 12.2, and 24.2, respectively. Eplerenone was beneficial across all risk categories and the hazard ratios were similar. The absolute treatment benefit was greatest among those at highest risk. Similar patterns emerged for all-cause mortality and for all HF hospitalizations. CONCLUSION: This easy-to-use integer risk score should be of value in quantifying individual patient risk in patients with systolic HF and mild symptoms. The relative benefits of eplerenone appeared consistent across the whole spectrum of risk, including those at lower risk.