Prognostic value and reversibility of liver stiffness in patients undergoing tricuspid annuloplasty

Abstract Background Hepatic dysfunction was previously suggested to be related to poor outcome in patients undergoing tricuspid annuloplasty (TA), the predictive value of liver stiffness (LS) for adverse events is nonetheless uncertain. Purpose The aim of this study was to evaluate the prognostic value and reversibility of LS in patients undergoing TA. Methods A total of 158 patients (age 63, male 35%) who underwent TA during left-sided valve surgery were prospectively evaluated. Transient elastography was used to assess LS. Patients were divided into three groups according to tertiles of LS. Adverse outcome was defined as heart failure requiring hospital admission or mortality. Results The median LS was 13.9 (8.1–22.3) kPa which independently correlates with tricuspid regurgitation severity (assessed by effective regurgitant orifice area), inferior vena cava diameter and tricuspid annular plane systolic excursion. During a median follow-up of 31 months, 49 adverse events occurred. Multivariable Cox regression analysis demonstrated that LS was an independent predictor of adverse events. Furthermore, a higher LS tertile was predictive for adverse events (Hazard Ratio 4.19, P<0.01) even after adjusting for the other prognosticators. Kaplan-Meier curve showed that patients in the third tertile LS group had the highest percentage of adverse events followed by patients in the second tertile. Significant improvement of LS at 1-year post-TA was noted only in patients who had no adverse events but not in those who experienced heart failure. Conclusions The present study demonstrates that LS is predictive of adverse outcome in patients undergoing TA. These findings suggested that assessing LS, an integrative assessment of right heart condition, may aid the management of patients undergoing TA. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Health and Medical Research Fund from the Food and Health Bureau, the Government of Hong Kong Special Administrative Region.

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Multimarker Approach in Risk Stratification of Patients with Decompensated Heart Failure

Kardiologiia ◽

10.18087/cardio.2637 ◽

2019 ◽

Vol 59 (1S) ◽

pp. 53-64

Author(s):

V. N. Protasov ◽

O. Yu. Narusov ◽

A. A. Skvortsov ◽

D. E. Protasova ◽

T. V. Kuznetsova ◽

...

Keyword(s):

Heart Failure ◽

Adverse Events ◽

Hospital Discharge ◽

Primary Endpoint ◽

Prognostic Value ◽

Successful Resuscitation ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Galectin 3

Purpose: to study prognostic value of various biomarkers and their combinations in patients who survived decompensation of chronic heart failure.Materials and methods.Patients (n=159) who were hospitalized with diagnosis of heart failure (HF) decompensation were included in a prospective single-center study. Examination on admission and the day of hospital discharge, included measurement of concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), copeptin, soluble suppression of tumorigenicity 2 (sST2), kopetin, neutrophil gelatinase-associated lipocalin (NGAL), and galectin-3. Te combined primary endpoint comprised cardiovascular (CV) death, frst hospitalization because of HF heart failure decompensation, episodes of HF deterioration which required additional i/v diuretics, and CV death with successful resuscitation.Results.During one-year follow-up 56 pts (35.2%) reached the combined primary endpoint. Tere were 78 (49.1%) cardiovascular events. During hospitalization, patients with the decompensation of heart failure experienced a decrease of sST2, NT-proBNP, galectin-3, kopetin, hsTnT and an insignifcant increase of NGAL. ROC analysis identifed signifcant relation between concentrations of NT-proBNP, sST2, copeptin and, to a lesser degree, hsTnT, determined at hospital discharge, and risk of combined primary endpoint during 1-year follow-up: area under the curve (AUC) was 0.733 [95% CI 0.645–0.820], p<0.0001, 0.772 [95% CI 0.688–0.856], p<0.0001, 0.735 [95% CI 0.640–0.830], p<0.0001, and 0.659 [95% CI 0.553–0.764], p=0.005, respectively. Patients who during hospitalization did not achieve cut-oﬀ values of NT-proBNP ≤1696 rg/ml, sST2≤37.8 hg/ml, copeptin≤28.31 rmol/L and hsTnT≤28.37 rg/ml, had higher risk of reaching adverse events during 1 year; OR and 95% CI were 2.96 [1.61, 5.42] p<0.0001, 4.31 [2.34, 7.93] p<0.0001, 3.06 [1.59, 5.89] and 2.19 [2.12, 4.27]), respectively. According to Cox regression analysis, risk of the combined primary end point was the highest in patients with 3 or more elevated markers (OR = 6.6 [3.584, 12.158], p<0.0001), average in patients with 2 elevated markers (OR = 1.123 [0.51, 2.48]), p=0.7), and the lowest in patients with no markers increase or increase of only one marker (OR = 0.11 [0.049, 0.241], p<0.0001). In the Kaplan-Mayer survival analysis all three groups were statistically diﬀerent. In order to identify the most prognostically strong model, a reclassifcation analysis was performed. According to this analysis, the combination of sST2 and NT-proBNP concentrations determined at hospital discharge, exceeded one NT-proBNP (reclassifcation = –8.1%). At the same time, predictive value of only sST2 just insignifcantly less than value of sST2 and NT-proBNP combination (reclassifcation = –1.9%).Conclusion.Patients with three and more elevated markers at hospital discharge have high risk of adverse events. Te biggest prognostic value has combination of sST2 and NT-proBNP concentrations. In order to determine the long-term prognosis of a patient with HF decompensation, it is sufcient to measure concentrations of sST2 and NT-proBNP at hospital discharge. Alternatively, it is possible to limit to sST2 only, which is just insignifcantly inferior to the sST2 and NT-proBNP combination. Patients with concentrations of sST2 ≥37.8 hg/ml and NT-proBNP ≥1696 rg/ml at hospital discharge have maximal 1year risk of death due to recurrent HF decompensation.

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Coronary sinus catalase and ceruloplasmin levels predict all-cause mortality in patients with end-stage heart failure awaiting heart transplantation

European Heart Journal ◽

10.1093/ehjci/ehaa946.1005 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

W Szczurek ◽

M Gasior ◽

M Skrzypek ◽

G Kubiak ◽

A Kuczaj ◽

...

Keyword(s):

Heart Failure ◽

Heart Transplantation ◽

Coronary Sinus ◽

Public Institution ◽

Funding Source ◽

Organ Shortage ◽

Number Of Patients ◽

End Stage ◽

Medical University

Abstract Background, As a consequence of the worldwide increase in life expectancy and due to significant progress in the pharmacological and interventional treatment of heart failure (HF), the proportion of patients that reach an advanced phase of disease is steadily growing. Hence, more and more numerous group of patients is qualified to the heart transplantation (HT), whereas the number of potential heart donors has remained invariable since years. It contributes to deepening in disproportion between the demand for organs which can possibly be transplanted and number of patients awaiting on the HT list. Therefore, accurate identification of patients who are most likely to benefit from HT is imperative due to an organ shortage and perioperative complications. Purpose The aim of this study was to identify the factors associated with reduced survival during a 1.5-year follow-up in patients with end-stage HF awating HT. Method We propectively analysed 85 adult patients with end-stage HF, who were accepted for HT at our institution between 2015 and 2016. During right heart catheterization, 10 ml of coronary sinus blood was additionally collected to determine the panel of oxidative stress markers. Oxidative-antioxidant balance markers included glutathione reductase (GR), glutathione peroxidase (GPx), glutathione transferase (GST), superoxide dismutase (SOD) and its mitochondrial isoenzyme (MnSOD) and cytoplasmic (Cu/ZnSOD), catalase (CAT), malondialdehyde (MDA), hydroperoxides lipid (LPH), lipofuscin (LPS), sulfhydryl groups (SH-), ceruloplasmin (CR). The study protocol was approved by the ethics committee of the Medical University of Silesia in Katowice. The endpoint of the study was mortality from any cause during a 1.5 years follow-up. Results The median age of the patients was 53.0 (43.0–56.0) years and 90.6% of them were male. All included patients were treated optimally in accordance with the guidelines of the European Society of Cardiology. Mortality rate during the follow-up period was 40%. Multivariate logistic regression analysis showed that ceruloplasmin (odds ratio [OR] = 0.745 [0.565–0.981], p=0.0363), catalase (OR = 0.950 [0.915–0.98], p=0.0076), as well as high creatinine levels (OR = 1.071 [1.002–1.144], p=0.0422) were risk factors for death during 1.5 year follow-up. Conclusions Coronary sinus lower ceruloplasmin and catalase levels, as well as higher creatinine level are independently associated with death during 1.5 year follow-up. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of SIlesia, Katowice, POland

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Prognostic value of D-dimer for adverse outcomes in patients with infective endocarditis: an observational study

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02078-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying-Wen Lin ◽

Mei Jiang ◽

Xue-biao Wei ◽

Jie-leng Huang ◽

Zedazhong Su ◽

...

Keyword(s):

Regression Analysis ◽

Infective Endocarditis ◽

Adverse Events ◽

Prognostic Value ◽

Multivariable Analysis ◽

Adverse Outcomes ◽

Hospital Death ◽

Large Sample Size ◽

Cox Regression Analysis ◽

D Dimer

Abstract Background Increased D-dimer levels have been shown to correlate with adverse outcomes in various clinical conditions. However, few studies with a large sample size have been performed thus far to evaluate the prognostic value of D-dimer in patients with infective endocarditis (IE). Methods 613 patients with IE were included in the study and categorized into two groups according to the cut-off of D-dimer determined by receiver operating characteristic (ROC) curve analysis for in-hospital death: > 3.5 mg/L (n = 89) and ≤ 3.5 mg/L (n = 524). Multivariable regression analysis was used to determine the association of D-dimer with in-hospital adverse events and six-month death. Results In-hospital death (22.5% vs. 7.3%), embolism (33.7% vs 18.2%), and stroke (29.2% vs 15.8%) were significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L. Multivariable analysis showed that D-dimer was an independent risk factor for in-hospital adverse events (odds ratio = 1.11, 95% CI 1.03–1.19, P = 0.005). In addition, the Kaplan–Meier curve showed that the cumulative 6-month mortality was significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L (log-rank test = 39.19, P < 0.0001). Multivariable Cox regression analysis showed that D-dimer remained a significant predictor for six-month death (HR 1.11, 95% CI 1.05–1.18, P < 0.001). Conclusions D-dimer is a reliable prognostic biomarker that independently associated with in-hospital adverse events and six-month mortality in patients with IE.

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Echocardiographic assessment of CRT candidates. Does it work equally well in intermediate QRS duration?

European Heart Journal ◽

10.1093/ehjci/ehaa946.0807 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Duchenne ◽

M Cvijic ◽

J.M Aalen ◽

C.K Larsen ◽

E Galli ◽

...

Keyword(s):

Heart Failure ◽

Mechanical Dyssynchrony ◽

Public Institution ◽

Cardiac Resynchronization ◽

Funding Source ◽

Entire Study ◽

Qrs Duration ◽

Echocardiographic Assessment ◽

Echocardiographic Images ◽

Crt Response

Abstract Background The presence of mechanical dyssynchrony – such as apical rocking (ApRock) and septal flash (SF) – on echocardiography is associated with favourable outcome after cardiac resynchronization therapy (CRT). Myocardial scar on the other hand, has a considerable negative impact on CRT response. There is growing evidence that a visual echocardiographic assessment of mechanical dyssynchrony by ApRock, SF and scar predicts CRT response. Little is known however if this works equally well in patients with intermediate QRS duration (120–150ms), where guideline recommendation for CRT is weaker. Methods A total of 400 unselected patients referred for CRT, who fulfil the contemporary guidelines, were enrolled in this multicentre study. Echocardiographic images were visually assessed before CRT implantation, focussing on the presence of ApRock, SF and location and extent of scar segments in the left ventricle (LV), resulting in a CRT response prediction (i.e. Reader Interpretation). Readers were blinded to all patient information other than ischaemic aetiology of heart failure. CRT response was defined as ≥15% reduction in LV end-systolic volume on echocardiography, on average 15 months after device implantation. Results Overall, 321 (80%) patients had a left bundle branch block (LBBB), with an average QRS duration of 166±25ms. Ischemic aetiology of heart failure was found in 131 (33%) patients. Before CRT, ApRock and SF were present in 254 (64%) and 244 (61%) patients, respectively. ApRock and SF alone predicted CRT response with an area under the curve (AUC) of 0.79 (95% CI: 0.74–0.84) and 0.78 (95% CI: 0.73–0.83) (Figure A), while the echocardiographic Reader Interpretation had an AUC of 0.85 (95% CI: 0.81–0.89), with a sensitivity of 89% and a specificity of 82% for the prediction of CRT response (Figure B) (p<0.0001 vs. ApRock and SF alone). A total of 92 patients had a QRS duration of 120–150ms, and 48 of them responded to CRT. In these patients, the AUC of Reader Interpretation was comparable to that of the entire study cohort [0.83 (95% CI: 0.75–0.92)], as was sensitivity and specificity (90% and 79%, respectively, p=0.717 vs. the AUC of the entire cohort) (Figure C). Conclusions A visual assessment of LV function, by means of mechanical dyssynchrony and scar, has an excellent predictive value for CRT response, and requires only apical echocardiographic images. Responders were identified equally well in the challenging subgroup of patients with a QRS duration of 120–150 ms. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): KU Leuven

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Prognostic value of global longitudinal layer specific strain for patients with heart failure with reduced ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0117 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Johnsen ◽

M Sengeloev ◽

P Joergensen ◽

N Bruun ◽

D Modin ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Prognostic Value ◽

Left Ventricular ◽

Volume Index ◽

Funding Source ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

All Cause Mortality ◽

Echocardiographic Parameters

Abstract Background Novel echocardiographic software allows for layer-specific evaluation of myocardial deformation by 2-dimensional speckle tracking echocardiography. Endocardial, epicardial- and whole wall global longitudinal strain (GLS) may be superior to conventional echocardiographic parameters in predicting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). Purpose The purpose of this study was to investigate the prognostic value of endocardial-, epicardial- and whole wall GLS in patients with HFrEF in relation to all-cause mortality. Methods We included and analyzed transthoracic echocardiographic examinations from 1,015 patients with HFrEF. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained. A p value in a 2-sided test <0.05 was considered statistically significant. Cox proportional hazards regression models were constructed, and both univariable and multivariable hazard ratios (HRs) were calculated. Results During a median follow-up time of 40 months, 171 patients (16.8%) died. A lower endocardial (HR 1.17; 95% CI (1.11–1.23), per 1% decrease, p<0.001), epicardial (HR 1.20; 95% CI (1.13–1.27), per 1% decrease, p<0.001), and whole wall (HR 1.20; 95% CI (1.14–1.27), per 1% decrease, p<0.001) GLS were all associated with higher risk of death (Figure 1). Both endocardial (HR 1.12; 95% CI (1.01–1.23), p=0.027), epicardial (HR 1.13; 95% CI (1.01–1.26), p=0.040) and whole wall (HR 1.13; 95% CI (1.01–1.27), p=0.030) GLS remained independent predictors of mortality in the multivariable models after adjusting for significant clinical parameters (age, sex, total cholesterol, mean arterial pressure, heart rate, ischemic cardiomyopathy, percutaneous transluminal coronary angioplasty and diabetes) and conventional echocardiographic parameters (left ventricular (LV) ejection fraction, LV mass index, left atrial volume index, deceleration time, E/e', E-velocity, E/A ratio and tricuspid annular plane systolic excursion). No other echocardiographic parameters remained an independent predictors after adjusting. Furthermore, endocardial, epicardial and whole wall GLS had the highest C-statistics of all the echocardiographic parameters. Conclusion Endocardial, epicardial and whole wall GLS are independent predictors of all-cause mortality in patients with HFrEF. Furthermore, endocardial, epicardial and whole wall GLS were superior prognosticators of all-cause mortality compared with all other echocardiographic parameters. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Herlev and Gentofte Hospital

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Prognostic role of sonographic decongestion in patients with acute heart failure with reduced and preserved ejection fraction: a multicentre study

European Heart Journal ◽

10.1093/ehjci/ehaa946.1219 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

N.R Pugliese ◽

M Mazzola ◽

G Bandini ◽

G Barbieri ◽

S Spinelli ◽

...

Keyword(s):

Heart Failure ◽

Adverse Events ◽

Ejection Fraction ◽

Acute Heart Failure ◽

Vena Cava ◽

Composite Endpoint ◽

Clinical Findings ◽

Preserved Ejection Fraction ◽

Net Reclassification Improvement ◽

B Lines

Abstract Aims Our aim was to assess the dynamic changes of pulmonary congestion (PC) through variations of sonographic B-lines, in addition to conventional clinical, biohumoral and echocardiographic findings, to improve prognostic stratification of patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). Methods In this multicenter, prospective, observational study, lung ultrasound was performed in all patients at admission and before discharge by trained investigators, blinded to clinical findings and outcomes. Results We enrolled 208 consecutive patients admitted for acute heart failure (125 HFrEF, 83 HFpEF, mean age 75.9±11.7 years, 36% females, mean ejection fraction 38%). After 180-day follow-up, 38 composite endpoint events occurred (cardiovascular deaths or HF re-hospitalisations). In a multivariate model, B-lines at discharge had independent prognostic value in the overall population together with NT-proBNP, moderate-to-severe mitral regurgitation (MR) and inferior vena cava diameter at admission. When dividing the population in HFrEF and HFpEF, B-lines at discharge was the only independent parameter to predict events in all subgroups. At ROC analysis, a cut-off of B-lines>15 at discharge displayed the highest accuracy in predicting adverse events (AUC=0.80, p<0.0001). The identification of patients unable to halve B-lines during hospitalization (ΔB-lines%), in addition to B-lines >15 at discharge, improved event classification (integrated discrimination improvement=4%, p=0.01; continuous net reclassification improvement=22.8%, p=0.04). Conclusions The presence of residual subclinical sonographic PC at discharge predicts adverse events in the whole spectrum of acute HF patients, independently of conventional biohumoral and echocardiographic parameters. The dynamic evaluation of pulmonary decongestion during hospital stay can further improve patient risk stratification. Funding Acknowledgement Type of funding source: None

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Optimal doses of heart failure medication in women and men: perspective from daily clinical care

European Heart Journal ◽

10.1093/ehjci/ehaa946.1030 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Bots ◽

N.C Onland-Moret ◽

I.I Tulevski ◽

G.A Somsen ◽

H.M Den Ruijter

Keyword(s):

Heart Failure ◽

Clinical Care ◽

Daily Practice ◽

Left Ventricular ◽

Cubic Splines ◽

Public Institution ◽

Angiotensin Ii Receptor Blocker ◽

Funding Source ◽

Target Dose ◽

Natural Cubic Splines

Abstract Background Heart failure (HF) guidelines recommend equal target doses for women and men. Recently, these recommendations have been challenged as research suggested that women with HF with reduced Ejection Fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended dose while men may require the full dose. However, it is unclear how often women and men reach guideline-recommended target doses in daily practice. Purpose To evaluate whether women and men with HF reach guideline-recommended target doses for Angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blocker (ARB), β-blockers (BB) and mineralocorticoid receptor antagonists (MRA) in daily practice. Methods We extracted data from 13 outpatient cardiology clinics for all individuals diagnosed with HF within 14 days leading up to their visit who were prescribed at least one guideline-recommended HF medication. HF was defined based on a combination of the cardiologist's diagnosis and left ventricular systolic or diastolic dysfunction determined during echocardiography. Guideline-recommended medication groups and target doses were taken from the 2016 ESC HF guidelines or from literature for medications not mentioned in the guidelines. To enable comparison between medications and medication groups, daily dose was converted to percentage of target dose. Mean change in percentage of target dose over consecutive medication prescriptions was modelled for men and women using natural cubic splines. Results We included 1254 patients with HF (48% women). Women were on average older at diagnosis (71 vs 67 years) and more often had hypertension (54.9 vs 44.3%), but less often had diabetes mellitus (13.5 vs 19.4%), a history of coronary heart disease (7.8 vs 19.6%,) or past cardiovascular interventions (8.7 vs 23.0%) than men. In total, 1069 patients were prescribed an ACEI/ARB (46% women), 920 a BB (48% women) and 243 an MRA (43% women). Women were more often prescribed only one medication than men (39.6 vs 33.2%, p=0.014). Approximately 14% of first prescriptions for all medications were at 100% of target dose or higher for both women and men, with the majority of prescriptions being either at 1–49% of target dose (47.2 vs 45.5%, respectively) or 50–99% of target dose (39.1 vs 40.8%, respectively). The natural cubic splines showed that this distribution did not change over consecutive drug prescriptions in either women or men. Only MRA prescriptions for men showed an upward trend and reached 100% of target dose. Conclusion In daily practice, both women and men were unlikely to reach guideline-recommended target doses for both ACEI/ARBs and BBs. For MRAs, women were less likely to reach target dose than men. Optimal dosing in HF is difficult for both sexes, but in light of recent evidence, the challenge in daily practice seems to lie more in undertreatment of men than overtreatment of women. Figure 1 (women in red, men in blue) Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): ZonMw

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

European Heart Journal ◽

10.1093/eurheartj/ehz746.0403 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

I Kazukauskiene ◽

V Baltruniene ◽

D Bironaite ◽

S Cibiras ◽

K Rucinskas ◽

...

Keyword(s):

Heart Failure ◽

Left Ventricle ◽

Dilated Cardiomyopathy ◽

Prognostic Value ◽

Caspase 3 ◽

Cox Regression ◽

Cox Regression Analysis ◽

End Point ◽

Non Ischemic Dilated Cardiomyopathy ◽

Carboxy Terminal

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)

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