P5447Prognostic significance of carboxy-terminal telopeptide (ICTP) and Caspase-3 in patients with non-ischemic dilated cardiomyopathy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Kazukauskiene ◽  
V Baltruniene ◽  
D Bironaite ◽  
S Cibiras ◽  
K Rucinskas ◽  
...  

Abstract Background Non-ischemic dilated cardiomyopathy (niDCM) is a common debilitating disease leading to heart failure and poor prognosis. Therefore, a reliable diagnosis of niDCM and search of prognostic biomarkers is a task of paramount importance preventing final destruction of myocardium and improving the outcomes of the disease. The aim of the study was to evaluate the prognostic value of carboxy-terminal telopeptide (ICTP), a marker of myocardial collagen I degradation, and Caspase-3, a marker of apoptosis, in serum and endomyocardium biopsies (EMBs) of patients with niDCM. Methods 34 consecutive patients (male 25 (78%); 43.83±12.17 years) with niDCM (average of left ventricle (LV) end-diastolic diameter 6.94±0.78 cm, LV ejection fraction 24.97±6.93%, mean pulmonary capillary wedge pressure 32.9±8.7 mmHg) were enrolled in the study. The levels of ICTP and Caspase-3 in patients' serum and EMBs were measured by ELISA. After a follow-up period of 5 years, 18 patients (53%) have reached the primary composite end-point of heart failure: 6 patients (17.6%) died, 6 patients (17.6%) had heart transplantation and 6 patients (17.6%) underwent left ventricle assist device implantation. Results Univariate Cox proportional hazard model and ROC curve analysis identified levels of ICTP and Caspase-3 in serum as predictors of composite end-point (Table 1). However, the levels of ICTP and Caspase-3 in EMBs had no prognostic value. The cut-off values of serum biomarkers for prediction of the outcome were 13.43 pg/mg protein (sensitivity 67%; specificity 81%) for ICTP and 10.21 pg/mg protein (sensitivity 53%; specificity 87%) for Caspase-3. Univariate Cox regression analysis revealed that patients with higher levels of ICTP and Caspase-3 than cut-off values in serum had higher risk of reaching the composite end-point compared to the patients with lower cut-off values (HR 4.4 (95% CI: 1.6–12.1) and 3.15 (95% CI: 1.2–8.29), respectively). Kaplan-Meier survival analysis demonstrated that patients with serum Caspase-3 and ICTP levels above cut-off values had significantly worse outcome (p=0.01 and p=0.002, respectively). Table 1 Biomarkers (pg/mg protein) Mean ± SD HR (95% CI) p-value AUC (95% CI) ICTP in serum 15.26±10.59 1.052 (1.013–1.093) 0.009 0.71 (0.53–0.89) ICTP in EMB 132±295 0.999 (0.998–1.001) 0.56 0.45 (0.28–0.61) Caspase-3 in serum 7.78±9.86 1.047 (1.002–1.093) 0.04 0.69 (0.51–0.87) Caspase-3 in EMB 283±282 1 (0.998–1.002) 0.92 0.50 (0.28–0.72) Conclusion The findings show that increased serum levels of Caspase-3 and ICTP are significantly associated with poor outcome in patients with niDCM. Acknowledgement/Funding the Research Council of Lithuania (Grants nos. MIP-086/2012 and MIP-011/2014), the European Union, EU-FP7, SARCOSI Project (no. 291834)

Medicina ◽  
2020 ◽  
Vol 56 (1) ◽  
pp. 27
Author(s):  
Vaida Baltrūnienė ◽  
Ieva Rinkūnaitė ◽  
Julius Bogomolovas ◽  
Daiva Bironaitė ◽  
Ieva Kažukauskienė ◽  
...  

Background and objectives: T-cadherin (T-cad) is one of the adiponectin receptors abundantly expressed in the heart and blood vessels. Experimental studies show that T-cad sequesters adiponectin in cardiovascular tissues and is critical for adiponectin-mediated cardio-protection. However, there are no data connecting cardiac T-cad levels with human chronic heart failure (HF). The aim of this study was to assess whether myocardial T-cad concentration is associated with chronic HF severity and whether the T-cad levels in human heart tissue might predict outcomes in patients with non-ischemic dilated cardiomyopathy (NI-DCM). Materials and Methods: 29 patients with chronic NI-DCM and advanced HF were enrolled. Patients underwent regular laboratory investigations, echocardiography, coronary angiography, and right heart catheterization. TNF-α and IL6 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, endomyocardial biopsies were obtained, and the levels of T-cad were assessed by ELISA and CD3, CD45Ro, CD68, and CD4- immunohistochemically. Mean pulmonary capillary wedge pressure (PCWP) was used as a marker of HF severity, subdividing patients into two groups: mean PCWP > 19 mmHg vs. mean PCWP < 19 mmHg. Patients were followed-up for 5 years. The study outcome was composite: left ventricular assist device implantation, heart transplantation, or death from cardiovascular causes. Results: T-cad shows an inverse correlation with the mean PCWP (rho = −0.397, p = 0.037). There is a tendency towards a lower T-cad concentration in patients with more severe HF, as indicated by the mean PCWP > 19 mmHg compared to those with mean PCWP ≤ 19 mmHg (p = 0.058). Cardiac T-cad levels correlate negatively with myocardial CD3 cell count (rho = −0.423, p = 0.028). Conclusions: Univariate Cox regression analysis did not prove T-cad to be an outcome predictor (HR = 1, p = 0.349). However, decreased T-cad levels in human myocardium can be an additional indicator of HF severity. T-cad in human myocardium has an anti-inflammatory role. More studies are needed to extend the role of T-cad in the outcome prediction of patients with NI-DCM.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Yamada ◽  
T Morita ◽  
Y Furukawa ◽  
S Tamaki ◽  
M Kawasaki ◽  
...  

Abstract Background Plasma volume (PV) expansion plays an essential role in heart failure and PV status provides prognostic information in patients (pts) with acute decompensated heart failure (ADHF). On the other hand, concomitant presence of pulmonary hypertension in heart failure is associated with increased adverse events and may be related to interventricular uncoupling and impaired cardiac efficiency. It has recently been shown that an increased mean pulmonary artery pressure to mean systemic arterial pressure ratio (MPS ratio), a marker of interventricular coupling and efficiency, is associated with worse clinical outcomes in patients with advanced heart failure. However, there is no information available on the long-term prognostic value of the combination of PV status and MPS ratio in pts admitted for ADHF. Methods We studied 248 pts admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. PV status and MPS ratio were obtained at the admission. PV status was calculated as the following: Actual PV = (1 − hematocrit) x [a + (b x body weight)] (a=1530 in males and a=864 in females, b=41 in males and b=47.9 in females), Ideal PV = c x body weight (c=39 in males and c=40 in females), and PV status = [(actual PV − ideal PV)/ideal PV] x 100(%). The study endpoint was cardiovascular death (CVD). Results During a mean follow-up period of 5.2±4.4 yrs, 62 pts had CVD. PV status (10.0±16.2 vs 5.0±15.3%, p=0.03) and MPS ratio (0.408±0.114 vs 0.347±0.102, p=0.0001) were significantly greater in patients with than without CVD. At multivariate Cox regression analysis, PV status and MPS ratio were significantly associated with CVD, independently of prior heart failure hospitalization, eGFR, and serum sodium level and anemia. Patients with greater PV status (> median value = 4.6%) and MPS ratio (> median value = 0.346) had a significantly higher CVD risk than those with either and none of them (44% vs 22% vs 14%, p<0.0001, respectively). Conclusions The combination of PV status and MPS ratio might be useful for stratifying patients at risk for CVD in patients with ADHF.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Yamada ◽  
T Watanabe ◽  
T Morita ◽  
Y Furukawa ◽  
S Tamaki ◽  
...  

Abstract Background Malnutrition is associated with increased mortality risk in patients (pts) with acute decompensated heart failure (ADHF). On the other hand, concomitant presence of pulmonary hypertension in heart failure is associated with increased adverse events and may be related to interventricular uncoupling and impaired cardiac efficiency. It has recently been shown that an increased mean pulmonary artery pressure to mean systemic arterial pressure ratio (MPS ratio), a marker of interventricular coupling and efficiency, is associated with worse clinical outcomes in patients with advanced heart failure. However, there is no information available on the long-term prognostic value of the combination of malnutrition and MPS ratio in pts admitted for ADHF. Methods and results We studied 248 pts admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. Malnutrition was assessed by geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI) and controlling nutritional status score (CONUT). During a mean follow-up period of 5.2±4.4 yrs, 62 pts had cardiovascular death (CVD). MPS ratio was significantly greater in pts with than without CVD (0.408±0.114 vs 0.347±0.102, p=0.0001). GNRI and PNI were significantly lower, CONUT was significantly greater in pts with than without CVD. At multivariate Cox regression analysis, GNRI and MPS ratio were significantly associated with CVD, independently of prior heart failure hospitalization, eGFR, and serum sodium level and anemia, although PNI and CONUT showed the association with CVD at unvariate analysis. Pts with malnutrition (GNRI≤median value=96.5) and greater MPS ratio (≥median value=0.346) had a significantly higher CVD risk than those with either and none of them (51% vs 20% vs 12%, p&lt;0.0001, respectively). Conclusions The combination of malnutrition and MPS ratio might be useful for stratifying pts at risk for CVD in patients with ADHF. Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Przewlocka-Kosmala ◽  
T H Marwick ◽  
E A Jankowska ◽  
P Ponikowski ◽  
W Kosmala

Abstract H2FPEF (obesity, atrial fibrillation, age >60 yrs, ≥2 antihypertensives, E/e' >9, and pulmonary artery systolic pressure by echo >35 mmHg) is a newly-developed score used for establishing the likelihood of heart failure with preserved ejection fraction (HFpEF). Given the clinical significance of its components, it is tempting to speculate that this algorithm might be useful for cardiovascular (CV) risk prediction. Aim To investigate the prognostic value of H2FPEF score in a well-characterized HFpEF population. Methods and results A group of 205 patients (64±8yrs) with symptomatic HFpEF, underwent clinical and echocardiographic evaluation. At a mean follow-up of 26.2 months, 64 patients (31%) experienced the composite of CV hospitalization or death, and 51 (25%) HF hospitalization. Cox regression analysis revealed that H2FPEF was significantly associated with both study endpoints (HR: 1.30; 95% CI: 1.10 to 1.54; p=0.002 for CV hospitalization or death, and 1.45; 95% CI: 1.21 to 1.75; p<0.001 for HF hospitalization). The prognostic value of H2FPEF was non-inferior to a traditional prognosticator in HF - MAGGIC (Meta-analysis Global Group in Chronic Heart Failure) risk score (area under ROC curve 0.62 for H2FPEF and 0.65 for MAGGIC, p=0.58, for the composite end-point, and 0.66 for both predictors, p=0.96, for HF hospitalization). Using an externally-derived cutpoint for H2FPEF of 5 (considered as the upper limit of the range corresponding to an intermediate probability of HFpEF), we demonstrated that the subset with the score equal to or above this threshold was characterized by a higher risk of both study end-points (Figure). Figure 1. Kaplan-Meier estimates of survival free of the study outcomes according to H2FPEF score. Conclusions H2FPEF score, originally dedicated to discrimination of HFpEF, is a potent prognosticator in this condition, with the ability to identify increased clinical risk comparable to MAGGIC score.


2010 ◽  
Vol 119 (10) ◽  
pp. 443-452 ◽  
Author(s):  
Julio Núñez ◽  
Marifina Chilet ◽  
Juan Sanchis ◽  
Vicent Bodí ◽  
Eduardo Núñez ◽  
...  

AHF (acute heart failure) causes significant morbidity and mortality. Recent studies have postulated that the expression of inflammatory mediators, such as cytokines and chemokines, plays an important role in the development and progression of heart failure. A pro-inflammatory state has been postulated as a key factor in triggering CMV (cytomegalovirus) reactivation. Therefore we sought to determine the prevalence of active CMV infection in immunocompetent patients admitted for AHF and to quantify the association with the risk of the combined end point of death or AHF readmission. A total of 132 consecutive patients admitted for AHF were enrolled in the present study. Plasma CMV DNAaemia was assessed by qRT-PCR (quantitative real-time PCR), and cytokine measurements in plasma were performed by ELISA. Clinical data were evaluated by personnel blinded to CMV results. The independent association between active CMV infection and the end point was determined by Cox regression analysis. During a median follow-up of 120 [IQR (interquartile range), 60–240] days, 23 (17.4%) deaths, 34 (24.2%) readmissions for AHF and 45 (34.1%) deaths/readmissions for AHF were identified. Plasma CMV DNAaemia occurred in 11 (8.3%) patients, albeit at a low level (<100 copies/ml). The cumulative rate of the composite end point was higher in patients with CMV DNAaemia (81.8 compared with 29.8%; P<0.001). After adjusting for established risk factors, the occurrence of CMV DNAaemia was strongly associated with the clinical end point [hazard ratio = 4.39 (95% confidence interval, 2.02–9.52); P<0.001]. In conclusion, active CMV infection occurs, although uncommonly, in patients with AHF, and may be a marker of disease severity.


2020 ◽  
Vol 9 (1) ◽  
pp. 137
Author(s):  
Ewa Romuk ◽  
Wojciech Jacheć ◽  
Ewa Zbrojkiewicz ◽  
Alina Mroczek ◽  
Jacek Niedziela ◽  
...  

We investigated whether the additional determination of ceruloplasmin (Cp) levels could improve the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients in a 1-year follow-up. Cp and NT-proBNP levels and clinical and laboratory parameters were assessed simultaneously at baseline in 741 HF patients considered as possible heart transplant recipients. The primary endpoint (EP) was a composite of all-cause death (non-transplant patients) or heart transplantation during one year of follow-up. Using a cut-off value of 35.9 mg/dL for Cp and 3155 pg/mL for NT-proBNP (top interquartile range), a univariate Cox regression analysis showed that Cp (hazard ratio (HR) = 2.086; 95% confidence interval (95% CI, 1.462–2.975)), NT-proBNP (HR = 3.221; 95% CI (2.277–4.556)), and the top quartile of both Cp and NT-proBNP (HR = 4.253; 95% CI (2.795–6.471)) were all risk factors of the primary EP. The prognostic value of these biomarkers was demonstrated in a multivariate Cox regression model using the top Cp and NT-proBNP concentration quartiles combined (HR = 2.120; 95% CI (1.233–3.646)). Lower left ventricular ejection fraction, VO2max, lack of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, and nonimplantation of an implantable cardioverter-defibrillator were also independent risk factors of a poor outcome. The combined evaluation of Cp and NT-proBNP had advantages over separate NT-proBNP and Cp assessment in selecting a group with a high 1-year risk. Thus multi-biomarker assessment can improve risk stratification in HF patients.


Author(s):  
Mustafa Umut Somuncu ◽  
Belma Kalayci ◽  
Ahmet Avci ◽  
Tunahan Akgun ◽  
Huseyin Karakurt ◽  
...  

AbstractBackgroundThe increase in soluble suppression of tumorigenicity 2 (sST2) both in the diagnosis and prognosis of heart failure is well established; however, existing data regarding sST2 values as the prognostic marker after myocardial infarction (MI) are limited and have been conflicting. This study aimed to assess the clinical significance of sST2 in predicting 1-year adverse cardiovascular (CV) events in MI patients.Materials and methodsIn this prospective study, 380 MI patients were included. Participants were grouped into low sST2 (n = 264, mean age: 60.0 ± 12.1 years) and high sST2 groups (n = 116, mean age: 60.5 ± 11.6 years), and all study populations were followed up for major adverse cardiovascular events (MACE) which are composed of CV mortality, target vessel revascularization (TVR), non-fatal reinfarction, stroke and heart failure.ResultsDuring a 12-month follow-up, 68 (17.8%) patients had MACE. CV mortality and heart failure were significantly higher in the high sST2 group compared to the low sST2 group (15.5% vs. 4.9%, p = 0.001 and 8.6% vs. 3.4% p = 0.032, respectively). Multivariate Cox regression analysis concluded that high serum sST2 independently predicted 1-year CV mortality [hazard ratio (HR) 2.263, 95% confidence interval (CI) 1.124–4.557, p = 0.022)]. Besides, older age, Killip class >1, left anterior descending (LAD) as the culprit artery and lower systolic blood pressure were the other independent risk factors for 1-year CV mortality.ConclusionsHigh sST2 levels are an important predictor of MACE, including CV mortality and heart failure in a 1-year follow-up period in MI patients.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Valzania ◽  
R Bonfiglioli ◽  
F Fallani ◽  
J Frisoni ◽  
M Biffi ◽  
...  

Abstract Background While the beneficial effects of cardiac resynchronization therapy (CRT) have been widely investigated soon after CRT implantation, relatively few data are available on long-term clinical outcomes of CRT recipients. Aim To investigate long-term outcomes of CRT patients with non-ischemic dilated cardiomyopathy stratified as responders and non-responders according to radionuclide angiography. Methods Consecutive heart failure patients with non-ischemic dilated cardiomyopathy undergoing CRT implantation at our University Hospital between 2007 and 2013 were enrolled. All patients were assessed with equilibrium Tc99 radionuclide angiography at baseline and after 3 months of CRT. Left ventricular (LV) ejection fraction was computed on the basis of relative end-diastolic and end-systolic counts, and intraventricular dyssynchrony was derived by Fourier phase analysis. Response to CRT was defined by an absolute increase in LV ejection fraction (LVEF) ≥5% at 3-month follow-up. Clinical outcome was assessed after 10 years through hospital records review. Results Forty-seven patients (83% men, 63±11 years) were included in the study. At 3 months, 25 (53%) patients were identified as CRT responders according to LVEF increase (from 26±8 to 38±12%, p&lt;0.001). In these patients, LV dyssynchrony decreased from 59±30° to 29±18° (p&lt;0.001). Twenty-two (47%) patients were defined as non-responders. No significant changes in LVEF and LV dyssynchrony (50±30° vs. 38±19°, p=0.07) were observed in non-responders. At long-term follow-up (11±2 years), all-cause and cardiac mortality rates were 24% and 12% in responders vs. 32% and 27% in non-responders, respectively (p=ns). Heart transplantation was performed in 3 patients. One (4%) patient among CRT responders compared with 6 (27%) patients among non-responders died of worsening heart failure (p=0.03). Conclusions Although late overall mortality of non-ischemic CRT recipients was not significantly different between mid-term responders and non-responders, CRT responders were at lower risk of worsening heart failure death. Funding Acknowledgement Type of funding source: None


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