Preoperative and mid-term right ventricular systolic function assessment, at rest and during exercise, with speckle-tracking echocardiography after left ventricular assist device implantation.

OBJECTIVES: The study aimed to compare pre- and postoperative resting as well as postprocedural resting and exertional right ventricular speckle-tracking echocardiographic parameters at a mid-term follow-up after left ventricular assist device (LVAD) implantation. METHODS: Patients with implanted third-generation LVADs with hydrodynamic bearings were prospectively enrolled (NCT05063006). Myocardial deformation was evaluated before pump implantation and at least three months after the procedure, both at rest and during exercise. RESULTS: We included 22 patients, 7.3 months (IQR, 4.7-10.2) after the surgery. The mean age was 58.4 ± 7 years, 95.5% were men, and 45.5% had dilated cardiomyopathy. The RV strain analysis was feasible in all subjects both at rest and during exercise. The RV free wall strain (RVFWS) worsened from -13% (IQR, -17.3 to -10.9) to -11.3% (IQR, -12.9 to -6; p = 0.033) after LVAD implantation with a particular decline in the apical RV segment [-11.3% (IQR, -16.4 to -6.2) vs -7.8% (IQR, -11.7 to -3.9; p = 0.012)]. The RV four-chamber longitudinal strain (RV4CSL) remained unchanged [-8.5% (IQR, -10.8 to -6.9) vs -7.3% (IQR, -9.8 to -4.7; p = 0.184)]. Neither RVFWS (-11.3% (IQR, -12.9 to -6) vs -9.9% (IQR, -13.5 to -7.5; p = 0.077) nor RV4CSL [-7.3% (IQR, -9.8 to -4.7) vs -7.9% (IQR, -9.8 to -6.3; p = 0.548)] changed during the exercise test. CONCLUSIONS: In patients who are pump-supported, the right ventricular free wall strain tends to worsen after LVAD implantation and remains unchanged during a cycle ergometer stress test.

Right ventricle to pulmonary artery coupling as a predictor of perioperative outcome in patients with secondary mitral valve insufficiency.

BACKGROUND: The aim of the study was to assess some parameters of right ventricle (RV) function as predictors of short-term mortality in patients with severe secondary mitral regurgitation (SMR) after mitral valve surgery. METHODS: We conducted a retrospective analysis of 112 consecutive patients with severe SMR who had undergone mitral valve repair or replacement with or without concomitant coronary artery bypass surgery. We assessed RV to pulmonary artery coupling by calculating the ratio of tricuspid annular plane systolic excursion (TAPSE) to non-invasively estimated RV systolic pressure (RVSP). The study endpoint was 30 days post-procedural mortality. RESULTS: Overall, the 30-day mortality was 6%. TAPSE/RVSP ratio < 0.42 mm/mmHg was a significant predictor of mortality and remained so after adjusting for age and sex. The Kaplan-Meier survival analysis showed that patients with RVSP > 55 mmHg and those with TAPSE/RVSP ratio < 0.42 mm/mmHg had a lower survival probability. CONCLUSIONS: TAPSE/RVSP < 0.42 mm/mmHg is a strong predictor of short-term mortality in patients with SMR when considered for valve surgery.

Hemodynamic parameters of aortic valve prostheses - KRAK-AS registry analysis.

Introduction: The treatment of choice for aortic stenosis is a valve replacement. Some patients have post-procedural increased pressure gradient on the implanted prosthesis because of patient-prosthesis mismatch (PPM), known to adversely influence prognosis. The PPM risk should be initially predicted and effort made to avoid this complication, specifically in large body size patients. Aim: To assess the frequency of PPM taking into account the valvular prosthesis type in a real-life population of consecutive patients included in the Krakow aortic stenosis registry. Material and methods: The KRAK-AS registry was conducted in July-October 2016. Patients were assessed before and after valve surgery and during the 3-year follow-up. Patients who underwent aortic valve intervention were clinically and echocardiographically evaluated within a month after surgery and divided into groups depending on the implanted prosthesis type. Analysis of patients with a smaller (< 23 mm) and larger than median (≥ 23 mm) valve diameter was performed. Results: The valve implantation was performed in 229 patients (42 mechanical, 139 biological, 48 transcatheter). No differences between patient groups compared by PPM occurrence was seen at baseline. Median age was 70 years; 55.5% were men. At least moderate PPM (iEOA ≤ 0.85 cm2/m2) was observed in 40% of mechanical valves, 33% of biological valves, and was significantly less frequent (10%) in patients after transcatheter valve implantation, p = 0.0001. Severe PPM (iEOA < 0.65 cm2/m2) was found in 17.6% of mechanical valve PPM patients, 4.3% of biological ones, and no patients after transcatheter procedure. Conclusions: PPM is a frequent phenomenon in the real-life population of patients undergoing surgical aortic valve replacement, being significantly less frequent in the case of a transcatheter procedure.

Computed tomography guided tailored approach to transfemoral access in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Transfemoral approach (TFA) is the most common access route for transcatheter aortic valve implantation (TAVI). Percutaneous femoral access (PA) is preferred over the surgical approach (SA), however, may be associated with a higher risk of access site complications. Thus, we aimed to assess outcomes of computed tomography-guided tailored approach to percutaneous and surgical TFA in patients undergoing TAVI. METHODS: We evaluated data of 158 patients, who underwent TAVI via femoral route between January 2017 and December 2018. In the PA group, vascular closure was performed with the use of two percutaneous suture devices and an additional mechanical seal device. We compared complications rate and outcomes. RESULTS: Of the 158 patients (92%; mean age 79.6 years, 60.8% female), in 92 (61%) patients PA was performed and in 66 (39%) patients SA was used. Median (interquartile range) radiation exposure as well as contrast volume dose was higher in the PA group compared to the SA group 614.0 (410.0; 1104.0) mGy vs. 405 (240.5; 658.0) mGy (p < 0.001) and 150.0 (120.0; 180.7) mL vs. 130.0 (100.0; 160.0) mL (p = 0.04), respectively. Bleeding complications were similar in the PA group 11 (12.2%) compared to 5 (8.62%) in the SA group (p = 0.48). Median length of hospital stay was also similar in the PA and the SA group 6.00 (5.00; 8.00) days vs. 6.00 (4.00; 8.00) days, respectively (p = 0.31). CONCLUSIONS: Computed tomography-guided PA in TAVI may provide comparable procedural outcomes compared to the SA, despite a higher radiation dose and the use of contrast dye, while being less invasive.

Relationships between circulating galectin-3, extracellular matrix fibrosis and outcomes in dilated cardiomyopathy.

BACKGROUND: Galectin-3 is an emerging biomarker in cardiovascular disease. Myocardial galectin-3 is involved in the pathology of cardiac fibrosis; however, the role of circulating galectin-3 is not yet established. OBJECTIVES: To assess the relationships between circulating galectin-3, fibrosis and outcomes in dilated cardiomyopathy (DCM). MATERIAL AND METHODS: We included 70 patients (age: 48 ±12.1 years, ejection fraction (EF) 24.4 ±7.4%) with new-onset DCM (n = 35, ≤6 months). Galectin-3 and procollagen type I and III (PICP, PINP, PIIICP, and PIIINP), transforming growth factor ß (TGF-ß), connective tissue growth factor (CTGF), osteopontin (OPN), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitor (TIMP-1) were determined in serum at baseline and after 3 and 12 months. Patients underwent endomyocardial biopsy. The endpoint was a combination of death and urgent hospitalization at 12 months. RESULTS: Galectin-3 did not correlate with biopsy-determined fibrosis. Baseline galectin-3 correlated with OPN,, TIMP-1, PIIICP, and MMP-2. In new-onset DCM, galectin-3 levels at baseline were higher than at 3 and 12 months, whereas in chronic DCM there was no difference. Galectin-3 was a predictor of the endpoint (hazard ratio (HR) = 1.115; 95% confidence interval (95% CI) = 1.009-1.231; p < 0.05). The best cut-off value was 14.54 ng/mL (area under the curve (AUC) = 0.67). Patients with galectin-3 ≥14.54 ng/mL had an increased risk of events (HR = 2.569; 95% CI = 1.098-6.009; p < 0.05). CONCLUSIONS: Circulating galectin-3 is unrelated to fibrosis. Serial measurements of galectin-3 correlated with markers of fibrosis, including markers of collagen synthesis and OPN. Circulating galectin-3 was independently associated with cardiovascular (CV) outcomes in DCM.

Expert opinion of the Heart Failure Working Group of the Polish Cardiac Society on the use of dapagliflozin in the treatment of heart failure with reduced ejection fraction.

Heart failure (HF) is a global health problem inherent in an aging population with coexisting cardiovascular diseases. Based on data from the Polish National Health Fund (Polish, Narodowy Fundusz Zdrowia), approximately 1.2 million people in Poland currently suffer from HF, and 140 000 of them die annually. Recently, Poland was ranked fifth among the European Union countries regarding the number of patients with diagnosed HF and first in terms of the number of HF hospitalizations (547 per 100 000 population) among 34 countries associated in the Organization for Economic Cooperation and Development. In recent years, a significant progress has been made in the diagnosis and treatment of HF with reduced left ventricular ejection fraction (HFrEF), which has resulted in a reduction in cardiovascular and total mortality. Despite these advantages, 5-year survival in the course of HF is still worse than that observed in some types of cancer, both in the populations of men and women. Hence, the search for drugs improving the prognosis in this group of patients is still ongoing. Sodium-glucose cotransporter 2 inhibitors represent a new group of drugs that will undoubtedly be a milestone in the treatment of patients with HFrEF. This expert opinion covers the history of dapagliflozin, which, from a drug dedicated to the treatment of type 2 diabetes, has become one of the most effective drugs improving prognosis and quality of life as well as reducing the number of hospitalizations in patients with HF. This document presents the opinion from the experts of the Heart Failure Working Group of the Polish Cardiac Society on the most relevant studies on dapagliflozin and indications for its use.

Safety and performance of a novel transventricular beating heart mitral valve repair system: 1-year outcomes.

OBJECTIVES: The objective of this study was to evaluate the safety and performance of a novel, beating heart procedure that enables echocardiographic-guided beating heart implantation of expanded polytetrafluoroethylene (ePTFE) artificial cords on the posterior mitral leaflet of patients with degenerative mitral regurgitation. METHODS: Two prospective multicentre studies enrolled 13 (first-in-human) and 52 subjects, respectively. Patients were treated with the HARPOON beating heart mitral valve repair system. The primary (30-day) end point was successful implantation of cord(s) with mitral regurgitation reduction to ≤moderate. An independent core laboratory analysed echocardiograms. RESULTS: Of 65 patients enrolled, 62 (95%) achieved technical success, 2 patients required conversion to open surgery and 1 procedure was terminated. The primary end point was met in 59/65 (91%) patients. Among the 62 treated patients, the mean procedural time was 2.1 ± 0.5 h. Through discharge, there were no deaths, strokes or renal failure events. At 1 year, 2 of the 62 patients died (3%) and 8 (13%) others required reoperations. At 1 year, 98% of the patients with HARPOON cords were in New York Heart Association class I or II, and mitral regurgitation was none/trace in 52% (n = 27), mild in 23% (n = 12), moderate in 23% (n = 12) and severe in 2% (n = 1). Favourable cardiac remodelling outcomes at 1 year included decreased end-diastolic left ventricular volume (153 ± 41 to 119 ± 28 ml) and diameter (53 ± 5 to 47 ± 6 mm), and the mean transmitral gradient was 1.4 ± 0.7 mmHg. CONCLUSIONS: This initial clinical experience with the HARPOON beating heart mitral valve repair system demonstrates encouraging early safety and performance. CLINICAL REGISTRATION NUMBERS: NCT02432196 and NCT02768870.

Impact of the mechanism of mitral regurgitation on clinical outcomes in patients after mitral valve surgery.

BACKGROUND: Mitral regurgitation (MR) is the second most frequent indication for valve surgery. There are few studies addressing mitral valve (MV) surgery in the context of etiology of MR. AIMS: We aimed to compare postoperative outcomes in the context of the etiological mechanism of MR in patients after MV surgery. METHODS: The study group included 337 consecutive patients with severe MR. Preoperative comorbidities, postoperative clinical course, and predictors of in­hospital mortality were assessed. RESULTS: Primary etiology of MR was observed in 72% of patients, and of secondary, in 28% (P <0.001). Among the primary MR group, the most common etiological factor was fibroelastic deficiency (79%), followed by Barlow disease (16%) and rheumatic disease (5%) (P <0.001). Secondary MR was seen in ischemic heart disease (67%) and dilated cardiomyopathy (33%) (P <0.001). The incidence of death and complications following surgery did not differ between the groups. Univariate analysis revealed that higher risk of death was associated with older age, severe heart failure symptoms, impaired left ventricular ejection fraction, previous percutaneous coronary interventions, cardiopulmonary bypass time, low cardiac output syndrome, and wound infections (P = 0.004, P <0.001, P = 0.005, P = 0.009, P = 0.002, P = 0.006, and P = 0.03, respectively). Also MV replacement with concomitant other valve surgery increased the risk of mortality (P = 0.049). CONCLUSIONS: This study indicates that the clinical outcomes and in­hospital mortality in patients with severe MR correlate with the type of procedure and concomitant perioperative comorbidities rather than the etiological mechanism of MR itself.

The relationship between myocardial fibrosis and myocardial microRNAs in dilated cardiomyopathy: A link between mir-133a and cardiovascular events.

It is unknown whether fibrosis-associated microRNAs: miR-21, miR-26, miR-29, miR-30 and miR-133a are linked to cardiovascular (CV) outcome. The study evaluated the levels of extracellular matrix (ECM) fibrosis and the prevalence of particular microRNAs in patients with dilated cardiomyopathy (DCM) to investigate any correlation with CV events. METHODS: Seventy DCM patients (48 ± 12 years, EF 24.4 ± 7.4%) underwent right ventricular biopsy. The control group was comprised of 7 patients with CAD who underwent CABG and intraoperative biopsy. MicroRNAs were measured in blood and myocardial tissue via qPCR. The end-point was a combination of CV death and urgent HF hospitalization at the end of 12 months. There were differential levels of circulating and myocardial miR-26 and miR-29 as well as myocardial miR-133a when the DCM and CABG groups were compared. Corresponding circulating and myocardial microRNAs did not correlate with one another. There was no correlation between microRNA and ECM fibrosis. By the end of the 12-month period of the study, CV death had occurred in 6 patients, and a further 19 patients required urgent HF hospitalization. None of the circulating microRNAs was a predictor of the combined end-point; however, myocardial miR-133a was an independent predictor in unadjusted models (HR 1.53; 95% CI 1.14-2.05; P < .004) and adjusted models (HR 1.57; 95% CI 1.14-2.17; P < .005). The best cut-off value for the miR-133a level for the prediction of the combined end-point was 0.74 ΔCq, with an AUC of 0.67. The absence of a correlation between the corresponding circulating and myocardial microRNAs calls into question their cellular source. This study sheds new light on the role of microRNAs in ECM fibrosis in DCM, which warrants further exploration.

Beating-Heart Mitral Valve Repair Using a Novel ePTFE Cordal Implantation Device: A Prospective Trial.

BACKGROUND: Conventional mitral valve (MV) operations allow direct anatomic assessment and repair on an arrested heart, but require cardiopulmonary bypass, aortic cross-clamping, sternotomy or thoracotomy, and cardioplegic cardiac arrest, and are associated with significant perioperative disability, and risks of morbidity and mortality. OBJECTIVES: This study evaluated safety and performance of a transesophageal echocardiographic-guided device designed to implant artificial expanded polytetrafluoroethylene (ePTFE) cords on mitral leaflets in the beating heart. METHODS: In a prospective multicenter study, 30 consecutive patients with severe degenerative mitral regurgitation (MR) were treated with a mitral valve repair system (MVRS) via small left thoracotomy. The primary (30-day) endpoint was successful implantation of cords with MR reduction to moderate or less. RESULTS: The primary endpoint was met in 27 of 30 patients (90%). Three patients required conversion to open mitral surgery. There were no deaths, strokes, or permanent pacemaker implantations. At 1 month, MR was mild or less in 89% (24 of 27) and was moderate in 11% (3 of 27). At 6 months, MR was mild or less in 85 % (22 of 26), moderate in 8% (2 of 26), and severe in 8% (2 of 26). Favorable cardiac remodeling at 6 months included decreases in end-diastolic (161 ± 36 ml to 122 ± 30 ml; p < 0.001) and left atrial volumes (106 ± 36 ml to 69 ± 24 ml; p < 0.001). The anterior-posterior mitral annular dimension decreased from 34.7 ± 5.8 mm to 28.2 ± 5.1 mm; p < 0.001 as did the mitral annular area (10.0 ± 2.7 cm2 vs. 6.9 ± 2.0 cm2; p < 0.0001). CONCLUSIONS: MVRS ePTFE cordal implantation can reduce the invasiveness and morbidity of conventional MV surgery. The device's safety profile is promising and prospective trials comparing the outcomes of the MVRS to conventional MV repair surgery are warranted. (CE Mark Study for the Harpoon Medical Device [TRACER]; NCT02768870).

Prevalence and clinical presentation of myocardial bridge on the basis of the National Polish Percutaneous Interventions Registry and the Classification of Rare Cardiovascular Diseases.

BACKGROUND A myocardial bridge (MB) is defined as a congenital anomaly, in which a segment of an epicardial coronary artery takes an intramuscular course. AIMS The aim of the study was to evaluate the prevalence of MB in coronary arteries among patients who were diagnosed using coronary angiography. METHODS Data were obtained from the National Polish Percutaneous Interventions Registry for patients hospitalized between January 1, 2014, and December 31, 2016, in invasive cardiology departments in Poland and divided into groups with and without MB. RESULTS The study included 298 558 patients. The non­MB group comprised 296 133 patients (99.19%; women, 38.01%), while the MB group included 2425 patients (0.81%; women, 39.98%). The most frequent location of MB was the left anterior descending artery (n = 2355; 97.11% of patients). The MB group less often had diabetes (14.68% vs 21.63%), previous stroke (1.61% vs 2.96%), previous myocardial infarction (10.97% vs 21.97%), kidney disease (2.8% vs 5.04%), previous coronary artery bypass graft (1.03% vs 5.64%), previous percutaneous coronary intervention (13.20% vs 25.86%) than the non­MB group (P <0.0001). The incidence of acute coronary syndromes was lower in the MB group (P <0.0001), while smoking was more common (18.76% vs 16.87%, P <0.01). CONCLUSIONS Patients with MB were younger and had fewer comorbidities and risk factors for atherosclerosis than patients without MB. The condition was more common among patients with stable coronary artery disease. Smoking and female sex appeared to be associated with a more clinically symptomatic presentation of MB.

Creatine kinase-MB and red cell distribution width as predictors of contrast-induced nephropathy after percutaneous coronary intervention in acute myocardial infarction.

INTRODUCTION: Contrast-induced nephropathy (CIN) is acute kidney injury (AKI), caused by administration of iodinated contrast media. The reported risk factors of CIN are: pre-existing renal dysfunction, admission anemia, diabetic nephropathy, old age, dehydration, high volume and osmolarity of administered contrast media. Patients with acute myocardial infarction (AMI) have threefold higher risk of developing CIN. The aim of the study was to identify risk factors of CIN among patients who underwent percutaneous coronary intervention (PCI) due to AMI. METHODS: This retrospective single-centre study included 257 patients (mean age, 69.19 ± 1.4 years; men 66.15%) undergoing PCI for AMI between January 2012 and January 2013. Demographic data, type and location of MI, co-morbidities and laboratory results were analysed. RESULTS: CIN was found in 50 out of 257 patients (19.5%). Patients who developed CIN were older (p = 0.001), more commonly had chronic kidney disease (p = 0.01) and lower LVEF (p = 0.01). Baseline Red Cell Distribution Width (RDW) was significantly higher in the CIN group (14.85 ± 4.6 vs. 13.62 ± 1.3, p = 0.001). CK-MB levels on admission were significantly higher in the CIN group compared to the non- CIN group (95.6 ± 129.9 vs. 47.03 ± 61.3, p = 0.001). Multivariate model including "classical" CIN risk actors revealed that only baseline CK-MB level (p = 0.001), age >75 years (p = 0.001) and baseline RDW (p = 0.03) were independent predictors for the development of CIN. CONCLUSION: In conclusion, increased CK-MB on admission as a surrogate of time of ischemia, and increased RDW levels on admission as a marker of chronic in ammation are independently associated with higher risk of CIN among patients treated with primary PCI.

Transapical Beating-Heart Mitral Valve Repair With an Expanded Polytetrafluoroethylene Cordal Implantation Device: Initial Clinical Experience.

BACKGROUND: Degenerative mitral valve (MV) disease is a common cause of severe mitral regurgitation (MR) and accounts for the majority of MV operations. Conventional MV surgery requires cardiopulmonary bypass, aortic cross-clamping, cardioplegia, and a thoracotomy or sternotomy and, therefore, is associated with significant disability, risks, and unpredictable rates of MV repair. Transesophageal echocardiography-guided beating-heart MV repair with expanded polytetrafluoroethylene cordal insertion has the potential to significantly reduce surgical morbidity. We report the first-in-human clinical experience with a novel preformed expanded polytetrafluoroethylene knot implantation device (Harpoon TSD-5) designed to treat degenerative MR. METHODS: Through a small left thoracotomy, the device was inserted into the heart and guided by transesophageal echocardiography to the ventricular surface of the prolapsed leaflet. Multiple expanded polytetrafluoroethylene cords were anchored in the leaflet and then adjusted to the correct length to restore MV leaflet coaptation and secured at the epicardium. RESULTS: Eleven patients with posterior leaflet prolapse and severe MR, with mean±SD age of 65±13 years and mean ejection fraction of 69±7%, were treated with 100% procedural success. Immediate postprocedural mean MR grade was trace. At 1 month, the mean MR grade was mild with significant decreases in end-diastolic volume (139 to 107 mL; P=0.03) and left atrial volume (118 to 85 mL; P=0.04). CONCLUSIONS: A novel device used for beating-heart image-guided MV repair demonstrates a significant reduction in MR with favorable left ventricular and left atrial reverse remodeling. This approach has the potential to decrease invasiveness and surgical morbidity. Further follow-up is necessary to assess long-term efficacy. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02432196.

Mitral and aortic annular calcifications and cerebrovascular ischemic episodes in patients with coronary artery disease.

INTRODUCTION:  Atherosclerosis is a systemic pathological process involving the whole arterial bed. Valvular calcifications are associated with cardiovascular risk factors. Significant carotid stenosis accounts for approximately 20% of cerebrovascular ischemic episodes.  OBJECTIVES:  The aim of the study was to assess the relationship between mitral and aortic annular calcifications, increased carotid intima-media thickness (CIMT), and incidence of cerebrovascular ischemic episodes. PATIENTS AND METHODS:  A total of 127 patients with angiographically confirmed coronary artery disease (68 men and 59 women; aged 74 (33-87) years) were divided into 4 groups: with aortic valve calcifications (AVCs), mitral annular calcifications (MACs), both aortic valve and mitral annular calcifications (AMVCs), and no valvular calcifications (no-VCs), based on the echocardiographic assessment of the mitral and aortic valves. CIMT and the presence of atherosclerotic plaques were evaluated by carotid ultrasonography. A history of cerebrovascular ischemic episodes was obtained.  RESULTS:  The combined prevalence of mitral or aortic valve calcifications in the study population was 59% (AVCs, 55%; MACs, 24%; and AMVCs, 21%). CIMT was significantly increased in the MAC and AMVC groups (P <0.05 for MACs; P <0.01 for AMVCs). Ischemic stroke was more common in the AVC group (P <0.05), while the MAC group had a higher incidence of carotid plaques (P <0.05), transient ischemic attacks (TIA; P <0.05), and strokes (P <0.05) as compared with the no-VC group. In multivariate analysis, only MACs remained independently associated with increased CIMT. CONCLUSIONS:  In patients with coronary artery disease, MACs are independently associated with increased CIMT but not with TIA or stroke. There is no relationship between the concomitant presence of mitral and aortic calcifications and carotid atherosclerosis.  

Serum biomarkers and clinical outcomes in heart failure patients treated de novo with carvedilol.

BACKGROUND: The role of inflammatory and hemodynamic stress biomarkers in heart failure (HF) patients treated de novo with beta-blockers has been poorly studied. METHODS: A total of 86 patients (age 56 ± 9 years, 81 men) with left ventricular ejection fraction (LVEF) < 40% and previously not treated with beta-blockers were initiated on carvedilol. At baseline and 12 months later we performed echocardiography, cardiopulmonary exercise testing, and determined serum levels of B-type natriuretic peptide (BNP), endothelin-1 (ET-1), C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha (TNF -a). Patients were followed up over a total period of 9 ± 3 years from baseline. RESULTS: Increased baseline CRP and its on-treatment decrease were associated with improvement of LVEF (est. coefficient per one SD: 1.6; 95% CI: -0.05,3.28; p = 0.056, and -1.80; -3.43, -0.18; p = 0.030, respectively) and diminishing of LV end-systolic volume index [mL/m2] (-6.83; -11.32; -2.34; p = 0.003, and 5.85; 1.23; -10.46; p = 0.014, respectively). Higher baseline ET-1 and on-treatment increase in TNF-a predicted frequent admissions (> 1) for cardiac complications (odds ratio per one SD: 1.98; 95% CI: 1.09-3.59; p = 0.025, and 2.07, 1.12-3.84, p = 0.021, respectively) whereas higher baseline BNP was associated with increased mortality (hazard ratio per one SD: 2.09, 95% CI: 1.26-3.45; p = 0.004). CONCLUSIONS: Serum biomarkers may have different roles in prediction of clinical outcomes among HF patients treated de novo with carvedilol.