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Competing Interests: None declared

Cardiac resynchronization therapy (CRT) for selected heart failure (HF) patients improves symptoms and reduces morbidity and mortality; however, the prognosis of HF is still poor. There is an emerging need for tools that might help in optimal patient selection and provide prognostic information for patients and their families. Several risk scores have been created in recent years; although, no literature review is available that would list the possible scores for the clinicians. We identified forty-eight risk scores in CRT and provided the calculation methods and formulas in a ready-to-use format. The reviewed score systems can predict the prognosis of CRT patients; some of them have even provided an online calculation tool. Significant heterogeneity is present between the various risk scores in terms of the variables incorporated and some variables are not yet used in daily clinical practice. The lack of cross-validation of the risk scores limits their routine use and objective selection. As the number of prognostic markers of CRT is overwhelming, further studies might be required to analyze and cross-validate the data., Competing Interests: GS reports personal fees from Abbott, Bayer, Boston Scientific, and Johnson and Johnson Medical outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Boros, Perge, Merkely and Széplaki.)

Introduction: Femoro-popliteal bypass with autologous vascular graft is a key revascularization method in chronic limb-threatening ischemia (CLTI). However, the lack of suitable autologous conduit may occur in 15-45% of the patients, necessitating the implantation of prosthetic or allogen grafts. Only little data is available on the outcome of allograft use in CLTI., Aims: Our objective were to evaluate the long term results of infrainguinal allograft bypass surgery in patients with chronic limb-threatening ischemia (CLTI) and compare the results of arterial and venous allografts., Methods: Single center, retrospective study analysing the outcomes of infrainguinal allograft bypass surgery in patients with CLTI between January 2007 and December 2017., Results: During a 11-year period, 134 infrainguinal allograft bypasses were performed for CLTI [91 males (67.9%)]. Great saphenous vein (GSV) was implanted in 100 cases, superficial femoral artery (SFA) was implanted in 34 cases. Early postoperative complications appeared in 16.4% of cases and perioperative mortality (<30 days) was 1.4%. Primary patency at one, three and five years was 59%, 44% and 41%, respectively, while secondary patency was 60%, 45% and 41%, respectively. Primary patency of the SFA allografts was significantly higher than GSV allografts (1 year: SFA: 84% vs. GSV: 51% p = 0,001; 3 years: SFA: 76% vs. GSV: 32% p = 0,001; 5 years: SFA: 71% vs. GSV: 30% p = 0.001). Both primary and secondary patency of SFA allograft implanted in below-knee position were significantly higher than GSV bypasses (p = 0.0006; p = 0.0005, respectively). Limb salvage at one, three and five years following surgery was 74%, 64% and 62%, respectively. Long-term survival was 53% at 5 years., Conclusion: Allograft implantation is a suitable method for limb salvage in CLTI. The patency of arterial allograft is better than venous allograft patency, especially in below-knee position during infrainguinal allograft bypass surgery., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Solid evidence is not available on the ideal technique of surgical repair (open or endovascular) of noninfrarenal abdominal aortic aneurysms. Objective: Our aim was to analyze the postoperative effect of mortality and the level of proximal cross-clamping of the patients who underwent open surgical aortic repair of non-infrarenal abdominal aortic aneurysms with intact wall. Method: This is a retrospective, single-centre study, which reviews the results of open surgical repair, performed for intact non-infrarenal abdominal aorta aneurysms between 2005 and 2017. Aneurysms were analyzed in two groups, based on the level of aortic cross-damping: juxta-pararenal aortic aneurysm group with inter- or suprarenal aortic cross-clamping and suprarenal aortic aneurysm group with supraceliac aortic cross-clamping. Primary endpoints were 30-day, 1-, 2- and 5-year mortality. Secondary endpoints were postoperative acute kidney injury, including hemodialysis, and major postoperative complications. Results: In our clinic, 94 patients underwent open surgical aortic repair with cross-clamping above at least one renal artery. The median follow-up was 3.14 (1.55-5.00) years. The overall 30-day, 1-, 2- and 5-year mortality were 9%, 20%, 27% and 48%, respectively. The mortality was significantly lower in the juxta/pararenal abdominal aortic aneurism group at 30 day and 1 year. The overall perioperative incidence of acute kidney injury was 54% and 30% at discharge. Significantly more in-hospital acute renal dysfunction was noticed in the patients with suprarenal aortic aneurysm than with juxta/pararenal aneurysm, however, the difference was not significant at discharge. Major postoperative complications were more frequent in the suprarenal aneurysm group. Conclusion: Open surgical repair of abdominal aortic aneurysms with supraceliac aortic cross-clamping is associated with significantly higher morbidity, early and mid-term mortality than the repair of juxta/pararenal aneurysms. Chronic kidney disease and major postoperative complications are independent factors of mid- and long-term mortality.

Background: We lack data on the effect of single premature ventricular contractions (PVCs) on the clinical and echocardiographic response after cardiac resynchronization therapy (CRT) device implantation. We aimed to assess the predictive value of PVCs at early, 1 month-follow up on echocardiographic response and all-cause mortality., Methods: In our prospective, single-center study, 125 heart failure patients underwent CRT implantation based on the current guidelines. Echocardiographic reverse remodeling was defined as a ≥ 15% improvement in left ventricular ejection fraction (LVEF), end-systolic volume (LVESV), or left atrial volume (LAV) measured 6 months after CRT implantation. All-cause mortality was investigated by Wilcoxon analysis., Results: The median number of PVCs was 11,401 in those 67 patients who attended the 1-month follow-up. Regarding echocardiographic endpoints, patients with less PVCs develop significantly larger LAV reverse remodeling compared to those with high number of PVCs. During the mean follow-up time of 2.1 years, 26 (21%) patients died. Patients with a higher number of PVCs than our median cut-off value showed a higher risk of early all-cause mortality (HR 0.97; 95% CI 0.38-2.48; P = 0.04). However, when patients were followed up to 9 years, its significance diminished (HR 0.78; 95% CI 0.42-1.46; P = 0.15)., Conclusions: In patients undergoing CRT implantation, lower number of PVCs predicted atrial remodeling and showed a trend for a better mortality outcome. Our results suggest the importance of the early assessment of PVCs in cardiac resynchronization therapy and warrant further investigations., (© 2022. The Author(s).)

Összefoglaló. Bevezetés: Az elmúlt évtizedekben számos országban jelentős mértékben változott a hasi aortaaneurysmák sebészi kezelése az eredményesebb ellátás céljából: endovascularis beavatkozások terjedése, nagy betegforgalmú aortacentrumok kialakítása. Célkitűzés: A Magyarországon, infrarenalis aortaaneurysmák miatt végzett beavatkozások rövid távú eredményeinek elemzése elsősorban műtéti technika (endovascularis vs. nyitott aortareconstructio), intézeti betegforgalom (kis vs. nagy betegforgalmú intézet) és időszak (2010-2014 vs. 2015-2019) alapján. Módszer: A Nemzeti Érsebészeti Regiszterben 2010. 01. 01. és 2019. 12. 31. között prospektíven rögzített multicentrikus adatok retrospektív feldolgozása. Eredmények: A regiszterben 3206 infrarenalis aortaaneurysma-műtétet rögzítettek. A második öt évben jelentősen nőtt az endovascularis aortareconstructio aránya a nyitotthoz képest (p<0,0001), illetve a nagy betegforgalmú intézetek szignifikánsan több rupturált aortaaneurysmát láttak el, mint a kis betegforgalmú intézetek (p<0,0001) az első öt évhez viszonyítva. A perioperatív mortalitás rupturált aortaaneurysma miatt a nagy betegforgalmú intézetekben végzett nyitott aortareconstructio esetén szignifikánsan alacsonyabb volt a kis betegforgalmú intézetekkel szemben az első öt évben (p = 0,0011), illetve a nagy betegforgalmú intézetekben végzett endovascularis aortareconstructio esetén szignifikánsan alacsonyabb volt a nyitottal szemben a második öt évben (p = 0,029). A nem rupturált aortaaneurysma-műtétek perioperatív mortalitása a nagy betegforgalmú intézetekben végzett nyitott aortareconstructio esetén szignifikánsan alacsonyabb volt a kis betegforgalmú intézetekhez képest az első és a második öt évben is (p = 0,0007; p = 0,004). Mind a nagy, mind a kis betegforgalmú intézetekben végzett endovascularis aortareconstructio esetén szignifikánsan alacsonyabb volt a perioperatív mortalitás a második öt évben (p<0,0001; p<0,0001). A rupturált és a nem rupturált aortaaneurysmák perioperatív mortalitásának független rizikófaktora az intézetek betegforgalma (p = 0,006; p = 0,004), a betegek életkora (p<0,0001; p = 0,001), a preoperatív renalis megbetegedés (p = 0,007; p = 0,007), a transzfúzióigény (p<0,0001; p<0,0001), illetve nem rupturált aortaaneurysmák esetében a műtéti technika (p<0,0001) is. Következtetés: Endovascularis aortareconstructio és nagy betegforgalmú intézetek esetében szignifikánsan alacsonyabb perioperatív mortalitás érhető el. Orv Hetil. 2021; 162(31): 1233-1243., Introduction: The organisation of aortic disease care has changed significantly in many countries over the last decade: centralized, high-volume centers were established., Objective: To analyse the perioperative mortality and the number of the infrarenal aortic aneurysm repairs according to the type of procedure (endovascular vs. open), patient volume (low vs. high) and time period (2010-2014 vs. 2015-2019)., Methods: The multicentric data registered prospectively in the Hungarian National Vascular Registry between 01. 01. 2010 and 31. 12. 2019 were analysed retrospectively., Results: 3206 infrarenal aortic aneurysms were recorded. The endovascular-open repair rate was significantly higher (p<0.0001) and the high-volume institutes managed significantly more ruptured aneurysms (p<0.0001) in the second period. The perioperative mortality of the open repair of ruptured aneurysms was significantly lower in the high-volume institutes than in the low-volume ones in the first period (p = 0.0011), and the mortality of endovascular repair was significantly lower compared with open repair in the high-volume institutes in the second period (p = 0.029). The perioperative mortality of the open repair of non-ruptured aneurysm was significantly lower in the high-volume institutes in both periods (p = 0.0007; p = 0.004). Furthermore, the mortality of endovascular repair was significantly lower compared with open repair both in the high- and the low-volume institutes in the second period (p<0.0001; p<0.0001). Patient volume (p = 0.006; p = 0.004), age (p<0.0001; p = 0.001), preoperative renal insufficiency (p = 0.007; p = 0.007) and the need of blood transfusion (p<0.0001; p<0.0001) were independent risk factors of the perioperative mortality of ruptured and non-ruptured aneurysms. Type of the procedure was also an independent risk factor in the case of non-ruptured aneurysms (p<0.0001)., Conclusion: Endovascular repair and aortic surgery in the high-volume institutes result in significantly lower perioperative mortality. Orv Hetil. 2021; 162(31): 1233-1243.

Background: Global right ventricular (RV) function is determined by the interplay of different motion components related to the myofiber architecture, and the relative importance of these components is still not thoroughly characterized. The aims of this study were to quantify the relative contributions of longitudinal, radial, and anteroposterior motion components to global RV function and to examine their determining factors in a large cohort of healthy volunteers using three-dimensional echocardiography., Methods: Three hundred healthy adults with a balanced age range and an equal sex distribution were investigated at two centers. A three-dimensional mesh model of the right ventricle was generated, and its motion was decomposed along the three anatomically relevant axes. Multiplicative relative contributions were measured by dividing the ejection fraction (EF) values generated by shortening in the longitudinal, radial, and anteroposterior directions by global RV EF (longitudinal EF index [LEFi], radial EF index [REFi], and anteroposterior EF index, respectively). The circumferential contribution was defined as shortening in the radial and anteroposterior directions, omitting only longitudinal shortening., Results: Circumferential EF index was markedly higher compared with LEFi (79 ± 7% vs 47 ± 9%, P < .001). LEFi (47 ± 9%) and anteroposterior EF index (49 ± 7%) were found to be similar in the pooled population, whereas REFi (44 ± 10%) was lower (P < .001). In younger individuals (20-39 years of age), the relative contribution of longitudinal shortening was significantly higher compared with the radial component; however, in the older age groups, LEFi and REFi were comparable. Age, body surface area, heart rate, and RV end-diastolic volume were independent predictors of LEFi and REFi, but all with opposite effects on the two motion directions., Conclusions: In contrast to the traditional viewpoint, the contributions of the radial and anteroposterior motion directions may be of comparable significance with that of longitudinal shortening in determining global RV function. Standard parameters referring only to longitudinal shortening of the right ventricle may be inadequate to characterize RV function thoroughly., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: Our aim was to develop a machine learning (ML)-based risk stratification system to predict 1-, 2-, 3-, 4-, and 5-year all-cause mortality from pre-implant parameters of patients undergoing cardiac resynchronization therapy (CRT)., Methods and Results: Multiple ML models were trained on a retrospective database of 1510 patients undergoing CRT implantation to predict 1- to 5-year all-cause mortality. Thirty-three pre-implant clinical features were selected to train the models. The best performing model [SEMMELWEIS-CRT score (perSonalizEd assessMent of estiMatEd risk of mortaLity With machinE learnIng in patientS undergoing CRT implantation)], along with pre-existing scores (Seattle Heart Failure Model, VALID-CRT, EAARN, ScREEN, and CRT-score), was tested on an independent cohort of 158 patients. There were 805 (53%) deaths in the training cohort and 80 (51%) deaths in the test cohort during the 5-year follow-up period. Among the trained classifiers, random forest demonstrated the best performance. For the prediction of 1-, 2-, 3-, 4-, and 5-year mortality, the areas under the receiver operating characteristic curves of the SEMMELWEIS-CRT score were 0.768 (95% CI: 0.674-0.861; P < 0.001), 0.793 (95% CI: 0.718-0.867; P < 0.001), 0.785 (95% CI: 0.711-0.859; P < 0.001), 0.776 (95% CI: 0.703-0.849; P < 0.001), and 0.803 (95% CI: 0.733-0.872; P < 0.001), respectively. The discriminative ability of our model was superior to other evaluated scores., Conclusion: The SEMMELWEIS-CRT score (available at semmelweiscrtscore.com) exhibited good discriminative capabilities for the prediction of all-cause death in CRT patients and outperformed the already existing risk scores. By capturing the non-linear association of predictors, the utilization of ML approaches may facilitate optimal candidate selection and prognostication of patients undergoing CRT implantation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Resynchronization therapy (CRT) improves mortality and induces reverse remodeling in heart failure (HF) patients with reduced ejection fraction and wide QRS. Nonetheless, some patients do not improve despite the optimal medical therapy and right indications for device implantation. Therefore, finding biomarkers suitable for identification of those patients is crucial. Vitamin D plays a classic hormonal role in the regulation of bone metabolism and also has physiological functions in wide range of nonskeletal tissues. Based on recent studies, low levels of vitamin D seem to directly contribute to pathogenesis and worsening of HF. We planned to assess the role of vitamin D levels on clinical outcomes of HF patients undergoing CRT., Methods and Results: We enrolled 136 HF patients undergoing CRT. Total plasma vitamin D levels were measured at baseline and 6 months later. Primary endpoint was 5-year all-cause mortality; secondary endpoint was lack of good clinical response, defined as less than 15% increase of left ventricular ejection fraction after six months. During follow-up, 58 patients reached the primary, and 45 patients reached the secondary endpoint. Vitamin D levels less than 24.13 ng/mL predicted 5-year mortality ( p = 0.045) and poor clinical response ( p = 0.03) after adjusting to all significant baseline predictors., Conclusion: Our study showed that vitamin D deficiency has a significant impact in heart failure patients; it is an independent predictor of lack of midterm clinical response and long-term mortality in patients undergoing CRT. Therefore, monitoring vitamin D status of heart failure patients could be of clinical significance., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 P. Perge et al.)

Introduction: Levels of cardiac necroenzymes, high-sensitive troponin (hsTnT) and creatine kinase muscle-brain (CKMB) increase as a result of a myocardial damage following catheter ablation., Aim: To analyze the mid-term alteration of hsTnT and CKMB levels following radiofrequency ablation (RFCA) for atrial fibrillation (AF), atrial flutter (AFlu), AV-nodal reentry tachycardia (AVNRT) and electrophysiological studies (EPS) without ablation., Method: Patients undergoing RFCA for various indications and EPS were consecutively enrolled in our prospective study. Concentrations of hsTnT and CKMB were measured from serial blood samples directly before and after the procedure, 4 and 20 hours later and at 3 months follow-up., Results: Forty-seven patients (10 EPS, 12 AVNRT, 13 AFlu, 12 AF) with mean age of 55 ± 13 were included. hsTnT levels increased significantly in all groups after the procedures, while CKMB changed only in the AF group. hsTnT exceeded the reference value in all patients with ablation and in 80% of patients with EPS 4 hours post-ablation. Peak average hsTnT levels for EPS, AVNRT, AFlu were 24 ± 11, 260 ± 218 and 541 ± 233 ng/L, respectively. The highest hsTnT level was measured in the AF group (799 ± 433 ng/L). We found a positive correlation between hsTnT levels and ablation time after RFCA., Conclusions: The hsTnT levels significantly change after EPS and RFCA, in all patients who underwent ablation, and in 80% of those with EPS had hsTnT positivity in the early post-procedural phase. hsTnT levels depended significantly on the type of the subgroups and correlated with the ablation time. Awareness of those observations is essential to correctly interpret elevated hsTnT levels following RFCA. Orv Hetil. 2019; 160(14): 540-548.

Introduction and Objectives: Cardiac resynchronization therapy (CRT) is beneficial for selected heart failure (HF) patients, although nonresponse to therapy is still prevalent. We investigated a set of novel biomarkers associated with various pathophysiological pathways of HF. Our purpose was to assess their ability to predict clinical outcomes after CRT., Methods: We studied 136 chronic HF patients undergoing CRT. We measured the plasma levels of fractalkine, pentraxin-3, hepatocyte growth factor (HGF), carbohydrate antigen-125, and matrix metalloproteinase-9 before and 6 months after CRT. The primary endpoint of the study was 5-year all-cause mortality, and we considered the absence of 6-month reverse remodelling (defined as at least a 15% decrease in end-systolic volume) as a secondary endpoint., Results: Fifty-eight patients died during the 5-year follow-up period and 66 patients were categorized as nonresponders. In multivariable models, only an increased HGF was an independent predictor of both mortality (HR, 1.35; 95%CI, 1.11-1.64; P=.003; per 1 standard deviation increase) and the absence of reverse remodelling (OR, 1.83; 95%CI, 1.10-3.04; P=.01; per 1 standard deviation increase). Applying HGF to the basic multivariable model of both mortality (net reclassification improvement=0.69; 95%CI, 0.39-0.99; P<.0001; integrated discrimination improvement=0.06; 95%CI, 0.02-0.11) and reverse remodelling (net reclassification improvement=0.39; 95%CI, 0.07-0.71; P=.01; integrated discrimination improvement=0.03; 95%CI, 0.00-0.06) resulted in a statistically significant reclassification and discrimination improvement., Conclusions: Of the investigated biomarkers, only HGF predicted clinical outcomes following CRT independently of other parameters. Reclassification analyses showed that HGF measurements could be useful in refining patient selection., (Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Changes in the levels of serum creatinine and N-terminal of prohormone brain natriuretic peptide (NT-proBNP) are useful risk markers after cardiac resynchronization therapy (CRT). The diagnostic value of changes in serum uric acid levels has been established in chronic heart failure, but no data are available on the prognostic value of hyperuricemia in a CRT population., Design: We measured markers of renal function [creatinine, blood urea nitrogen (BUN) and uric acid] and NT-proBNP levels of 129 heart failure patients undergoing CRT in a prospective, observational study. The 5-year all-cause mortality and the 6-month clinical response (≥ 15% increase in the left ventricular ejection fraction) were considered as study end points., Results: In multivariable analyses, the uric acid was found to be a statistically significant predictor of the outcome. Uric acid levels exceeding 386 mmol/L before CRT increased the chances of mortality [n = 55, hazard ratio = 2.39 (1.30-4.39), p < 0.01] and poor clinical response [n = 37, odds ratio = 2.89 (1.22-6.87), p = 0.01] independently of serum NT-proBNP and other factors., Conclusions: Elevated uric acid concentrations in patients with CRT are associated with an increased risk of mortality and poor clinical response independently of the NT-proBNP levels and other relevant clinical factors.

Aims: There are previous studies on quality of life (QoL) in cardiac resynchronization therapy (CRT) patients; however, there are no data with the short EuroQol-five dimensions (EQ-5D) questionnaire predicting outcomes. We aimed to assess the predictive role of baseline QoL and QoL change at 6 months after CRT with EQ-5D on 5-year mortality and response., Methods and Results: In our prospective follow-up study, 130 heart failure (HF) patients undergoing CRT were enrolled. Clinical evaluation, echocardiography, and EQ-5D were performed at baseline and at 6 months of follow-up, continued to 5 years. Primary endpoint was all-cause mortality at 5 years. Secondary endpoints were (i) clinical response with at least one class improvement in New York Heart Association without HF hospitalization and (ii) reverse remodelling with 15% reduction in left ventricular end-systolic volume at 6 months. Fifty-four (41.5%) patients died during 5 years, 85 (65.3%) clinical responders were identified, and 63 patients (48.5%) had reverse remodelling. Baseline issues with mobility were associated with lower response [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.16-0.84; P = 0.018]. Lack of reverse remodelling correlated with self-care issues at baseline (OR 0.10, 95% CI 0.01-0.94; P = 0.04). Furthermore, self-care difficulties [hazard ratio (HR) 2.39, 95% CI 1.17-4.86; P = 0.01) or more anxiety (HR 1.51, 95% CI 1.00-2.26; P = 0.04) predicted worse long-term survival. At 6 months, mobility (HR 3.95, 95% CI 1.89-8.20; P < 0.001), self-care (HR 7.69, 95% CI 2.23-25.9; P = 0.001), or ≥ 10% visual analogue scale (VAS) (HR 2.24, 95% CI 1.27-3.94; P = 0.005) improvement anticipated better survival at 5 years., Conclusion: EuroQol-five dimension is a simple method assessing QoL in CRT population. Mobility issues at baseline are associated with lower clinical response, whereas self-care issues predict lack of reverse remodelling. Problems with mobility or anxiety before CRT and persistent issues with mobility, self-care, and VAS scale at 6 months predict adverse outcome.

Cardiac resynchronisation therapy (CRT) has been shown to reduce all-cause mortality, heart failure events, and symptoms while improving exercise capacity and quality of life. Nevertheless, despite a large number of multicentre randomised trials and clear evidence confirming the above, there is still a higher number of patients who fail to develop reverse remodelling. In order to select the optimal patient population, the current European Society of Cardiology guidelines recommend a simultaneous evaluation of QRS morphology and width. However, based on recent data, QRS width itself is a less accurate parameter in the prediction of the outcome, as compared to QRS morphology. Furthermore, the baseline left ventricular (LV) ejection fraction (LVEF), which is also an known criterion for selecting CRT candidates (partly applied due to cost-benefit reasons), can be misleading. Data showed that patients with LVEF > 35% might also benefit from this type of treatment. Thus, LVEF should be evaluated less rigorously when screening patients for resynchronisation therapy. While the subsequent beneficial response to CRT is multifactorial, procedure-related parameters, such as LV lead position, are also crucial. The first data released recently confirmed the previous empiric clinical experience indicating that the LV lead should be implanted into the lateral or posterior coronary sinus side branch. This location was associated with a better long-term clinical outcome in terms of death and heart failure events. Some issues related to CRT are awaiting further clarification, such as the choice of the type of the implanted device (pacemaker or defibrillator) or the decision about CRT device upgrade. This review discusses the current evidence regarding the above, focusing on the questions that should be handled with caution or require clarification.

Aims: There is lack of conclusive evidence from randomized clinical trials on the efficacy and safety of upgrade to cardiac resynchronization therapy (CRT) in patients with implanted pacemakers (PM) or defibrillators (ICD) with reduced left ventricular ejection fraction (LVEF) and chronic heart failure (HF). The BUDAPEST-CRT Upgrade Study was designed to compare the efficacy and safety of CRT upgrade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular (RV) septal/apical pacing, reduced LVEF, and symptomatic HF., Methods and Results: The BUDAPEST-CRT study is a prospective, randomized, multicentre, investigator-sponsored clinical trial. A total of 360 subjects will be enrolled with LVEF ≤ 35%, NYHA functional classes II-IVa, paced QRS ≥ 150 ms, and a RV pacing ≥ 20%. Patients will be followed for 12 months. Randomization is performed in a 3:2 ratio (CRT-D vs. ICD). The primary composite endpoint is all-cause mortality, a first HF event, or less than 15% reduction in left ventricular (LV) end-systolic volume at 12 months. Secondary endpoints are all-cause mortality, all-cause mortality or HF event, and LV volume reduction at 12 months. Tertiary endpoints include changes in quality of life, NYHA functional class, 6 min walk test, natriuretic peptides, and safety outcomes., Conclusion: The results of our prospective, randomized, multicentre clinical trial will provide important information on the role of cardiac resynchronization therapy with defibrillator (CRT-D) upgrade in patients with symptomatic HF, reduced LVEF, and wide-paced QRS with intermittent or permanent RV pacing., Clinical Trials.gov Identifier: NCT02270840., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardiac resynchronization therapy (CRT) in chronic heart failure has been shown to improve mortality and morbidity. However, comprehensive data are not available as concerns how circulating biomarkers reflecting different organ functions, such as serum uric acid, blood urea nitrogen (BUN), albumin, cholesterol, or various liver enzymes, change over time as a consequence of CRT. The aim of this prospective study was to overview these possible changes., Methods: A total of 20 routine laboratory parameters were measured in 122 control subjects and in 129 patients with chronic heart failure before CRT, 6 months, and 2 years later., Results: The levels of serum uric acid [before: 432 (331-516) mmol/L, 6-month: 372 (304-452) mmol/L, 2-year: 340 (290-433) mmol/L; p  < 0.001] and BUN [8.3 (6.4-11.5) mmol/L, 8.0 (6.3-11.1) mmol/L, 6.8 (5.0-9.7) mmol/L; p  < 0.001) reduced statistically significant. Total bilirubin underwent reduction [16 (11-23) μmol/L, 11 (7-14) μmol/L, 8 (7-13) μmol/L; p  < 0.001], while albumin increased [45 (43-48) g/L, 46 (44-48) g/L, 46 (43-48) g/L; p  = 0.04]. Cholesterol concentrations elevated [4.3 (3.6-5.0) mmol/L, 4.5 (3.8-5.1) mmol/L, 4.6 (3.8-5.4) mmol/L; p  < 0.001] and glucose decreased [6.2 (5.6-7.2) mmol/L, 5.9 (5.1-6.7) mmol/L, 5.7 (5.1-6.8) mmol/L; p  < 0.001]., Conclusions: CRT influences the levels of routinely used biomarkers suggesting improvements in renal function, liver capacity, and metabolic changes. These changes could mirror the multiorgan improvement after CRT.

Background: The chronic inflammation plays an important role in heart failure and complement components might be useful markers of the prognosis. We set out to evaluate their predictive value in the clinical outcomes of patients with cardiac resynchronization therapy (CRT)., Methods: We determined the complement levels C3, C3a, sC5b-9 and also the N-terminus of the prohormone brain natriuretic peptide (NT-proBNP) of 126 heart failure patients in a prospective, single-center observational study before and 6 months after CRT implantation., Results: CRT reduced the C3a [212.5 (148.2-283.6) vs. 153 (119.8-218.3) ng/mL, p < 0.0001] and the sC5b-9 levels [296.9 (234.2-358.8) vs. 255.1 (210.1-319.0) ng/mL, p = 0.0006], but not the total C3 levels [1.43 (1.26-1.61) vs. 1.38 (1.23-1.57) g/L, p = 0.57]. C3a predicted the 5-year mortality of the patients [C3a > 165 ng/mL hazard ratio = 4.21 (1.65-10.72), p = 0.003] independent of the NT-proBNP and other factors. After reclassification, we observed a significant net reclassification improvement [NRI = 0.71 (0.43-0.98), p < 0.0001] and integrated discrimination improvement [IDI = 0.08 (0.03-0.12), p = 0.0002]., Conclusions: In patients with CRT, elevated C3a levels increase the risk of mortality independent of the NT-proBNP levels or other factors. CRT exerts anti-inflammatory effect by reducing the complement activation.

Aims: The low lymphocyte counts and high neutrophil leucocyte fractions have been associated with poor prognosis in chronic heart failure. We hypothesized that the baseline ratio of the neutrophil leucocytes to the lymphocytes (NL ratio) would predict the outcome of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT)., Methods and Results: The qualitative blood counts and the serum levels of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) of 122 chronic heart failure patients and 122 healthy controls were analysed prospectively in this observational study. The 2-year mortality was considered as primary endpoint and the 6-month reverse remodelling (≥15% decrease in the end-systolic volume) as secondary endpoint. Multivariable regression analyses were applied and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. The NL ratio was elevated in chronic heart failure patients when compared with the healthy controls [2.93 (2.12-4.05) vs. 2.21 (1.64-2.81), P < 0.0001]. The baseline NL ratio exceeding 2.95 predicted the lack of the 6-month reverse remodelling [n = 63, odds ratio = 0.38 (0.17-0.85), P = 0.01; NRI = 0.49 (0.14-0.83), P = 0.005; IDI = 0.04 (0.00-0.07), P = 0.02] and the 2-year mortality [n = 29, hazard ratio = 2.44 (1.04-5.71), P = 0.03; NRI = 0.63 (0.24-1.01), P = 0.001; IDI = 0.04 (0.00-0.08), P = 0.02] independently of the NT-proBNP levels or other factors., Conclusion: The NL ratio is elevated in chronic heart failure and predicts outcome after CRT. According to the reclassification analysis, 4% of the patients would have been better categorized in the prediction models by combining the NT-proBNP with the NL ratio. Thus, a single blood count measurement could facilitate the optimal patient selection for the CRT., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction., Design: The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed., Results: After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n = 57). In the final model including all variables, the RDW [HR = 2.49 (1.27-4.86); p = 0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93-3.51); p = 0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model., Conclusions: Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT.

Background: Right ventricular (RV) dysfunction has been associated with poor prognosis in chronic heart failure (HF). However, less data is available about the role of RV dysfunction in patients with cardiac resynchronization therapy (CRT). We aimed to investigate if RV dysfunction would predict outcome in CRT., Design: We enrolled prospectively ninety-three consecutive HF patients in this single center observational study. All patients underwent clinical evaluation and echocardiography before CRT and 6 months after implantation. We assessed RV geometry and function by using speckle tracking imaging and calculated strain parameters. We performed multivariable Cox regression models to test mortality at 6 months and at 24 months., Results: RV dysfunction, characterized by decreased RVGLS (RV global longitudinal strain) [10.2 (7.0-12.8) vs. 19.5 (15.0-23.9) %, p<0.0001] and RVFWS (RV free wall strain) [15.6 (10.0-19.3) vs. 17.4 (10.5-22.2) %, p = 0.04], improved 6 months after CRT implantation. Increasing baseline RVGLS and RVFWS predicted survival independent of other parameters at 6 months [hazard ratio (HR) = 0.37 (0.15-0.90), p = 0.02 and HR = 0.42 (0.19-0.89), p = 0.02; per 1 standard deviation increase, respectively]. RVGLS proved to be a significant independent predictor of mortality at 24 months [HR = 0.53 (0.32-0.86), p = 0.01], and RVFWS showed a strong tendency [HR = 0.64 (0.40-1.00), p = 0.05]. The 24-month survival was significantly impaired in patients with RVGLS below 10.04% before CRT implantation [area under the curve = 0.72 (0.60-0.84), p = 0.002, log-rank p = 0.0008; HR = 5.23 (1.76-15.48), p = 0.003]., Conclusions: Our findings indicate that baseline RV dysfunction is associated with poor short-term and long-term prognosis after CRT implantation.