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Aims: Recommendations on cardiac resynchronization therapy (CRT) in patients with atrial fibrillation or flutter (AF) are based on less robust evidence than those in sinus rhythm (SR). We aimed to assess the efficacy of CRT upgrade in the BUDAPEST-CRT Upgrade trial population by their baseline rhythm., Methods and Results: Heart failure patients with reduced ejection fraction (HFrEF) and previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and ≥20% right ventricular (RV) pacing burden were randomized to CRT with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145). Primary [HF hospitalization (HFH), all-cause mortality, or <15% reduction of left ventricular end-systolic volume] and secondary outcomes were investigated. At enrolment, 131 (36%) patients had AF, who had an increased risk for HFH as compared with those with SR [adjusted hazard ratio (aHR) 2.99; 95% confidence interval (CI) 1.26-7.13; P = 0.013]. The effect of CRT-D upgrade was similar in patients with AF as in those with SR [AF adjusted odds ratio (aOR) 0.06; 95% CI 0.02-0.17; P < 0.001; SR aOR 0.13; 95% CI 0.07-0.27; P < 0.001; interaction P = 0.29] during the mean follow-up time of 12.4 months. Also, it decreased the risk of HFH or all-cause mortality (aHR 0.33; 95% CI 0.16-0.70; P = 0.003; interaction P = 0.17) and improved the echocardiographic response (left ventricular end-diastolic volume difference -49.21 mL; 95% CI -69.10 to -29.32; P < 0.001; interaction P = 0.21)., Conclusion: In HFrEF patients with AF and PM/ICD with high RV pacing burden, CRT-D upgrade decreased the risk of HFH and improved reverse remodelling when compared with ICD, similar to that seen in patients in SR., Competing Interests: Conflict of interest: B.M. reports grants from Boston Scientific, NRDIF Hungary, and National Heart Program during the conduct of the study; personal fees from Biotronik, Abbott, AstraZeneca, Novartis, and Boehringer Ingelheim; and grants from Medtronic outside the submitted work. I.O. reports lecture and advisory fees from Abbott, Biotronik, Boston Scientific, Medtronic, and Vitatron and travel grants from Abbott, Biotronik, Boston Scientific, and Medtronic. Attila K. reports grants from Bolyai Research Scholarship and FK ‘OTKA’ Research Grant from NKFIH outside the submitted work, stock from CardioSight, Inc. and stock option from Argus Cognitive, Inc. outside the submitted work, and personal fees from Argus Cognitive, Inc. and CardioSight Hungary LLC outside the submitted work. G.D. reports research grants to institution from Medtronic and Biotronik and lecture and advisory fees from Medtronic, Biotronik, and Abbott. C.F. reports support from the Semmelweis University, grants from Medtronic, consulting fees from Medtronic and Biotronik Hungary, and payment or honoraria for lectureures from Johnson and Johnson Co., Abbott Laboratories and Boehringer Ingelheim RCV GmbH and Co. L.G. reports support for the present manuscript from Vitatron Medical, Boston Scientific, Abbott Laboratories, Medtronic Hungary, and Biotronik Hungary; consulting fees from Medtronic Hungary and Abbott Hungary; honoraria; travel grants; participation on a data safety monitoring board or advisory board; and role in other board and committee (FESC, FEHRA, President of the Scientific Committee of the Hungarian Society of Cardiology, Past President of the Working Group on Cardiac Arrhythmias and Pacing, and EHRA Scientific Programme Board). Annamária K. reports grants from Bolyai Research Scholarship outside the submitted work; consulting fees from Medtronic; honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Biotronik, and Novartis; payment for expert testimony from Boehringer Ingelheim and Boston Scientific; travel grants from AstraZeneca and Novartis; participation on a data safety monitoring board or advisory board for Boehringer Ingelheim and Boston Scientific; and role in other board and committee (committee member of Hungarian Society of Cardiology and secretary of the Working Group on Cardiac Arrhythmias and Pacing, Hungarian Society of Cardiology). S.D.S. reports grants to institution from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, NeuroTronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI and consulting fees outside the scope of the current work from Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GSK, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProthera, Moderna, American Regent, Sarepta, Lexicon, AnaCardio, Akros, and Valo. R.H. reports institutional grants from Abbott, Biotronik, and Slovak Research and Development Agency; honoraria from Abbott and Medtronic; and travel grants from the European Society of Cardiology and Pfizer. He is also the president of the Slovak Heart Rhythm Association. E.M. reports grants from Novartis, Boehringer Ingelheim, and Biotronik Hungary. V.K. reports grants from Boston Scientific, ZOLL, Biotronik, Spire Inc., and NIH, consulting fees from Biotronik and Zoll, and payment or honoraria for lectures from Abbott Medical and Medtronic. The other authors declare no conflict of interest for this contribution., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Frailty is a complex clinical syndrome associated with aging and comorbidities, which correlates with unfavorable outcomes. However, in heart failure patients, frailty is very common, data is scarce about those, who are eligible for Cardiac Resynchronization Therapy (CRT) implantation. We investigated the incidence of frailty and the association of Frailty Index (FI) with the outcome. Thirty baseline clinical parameters were used by the Rockwood cumulative deficit method to determine patients' FI in our single-center cohort. Based on previous studies, patients with FI ≤ 0.210 were considered as non-frail, those with FI 0.10-0.210 were classified in Frail-1, with FI > 0.10 in Frail-2 groups, respectively. Echocardiographic response after 12 months and all-cause mortality were investigated by frailty groups. Among 1004 included patients, 75 (7%) were considered Non-frail, 271 (27%) grouped in Frail-1, and 658 (66%) in Frail-2 with a median FI of 0.36 (0.28-0.43). Patients in Frail-2 group were older, with more comorbidities compared with non-frail patients or those in Group Frail-1. During the median follow-up time of 4.8 years, 29 (39%) patients died in the Non-frail, 140 (52%) in Frail-1, and 471 (72%) in the Frail-2 groups (log-rank p < 0.001). Group Frail-2 showed an unfavorable outcome compared to the non-frail (HR 2.49, 95%CI 1.92-3.22; p < 0.001) and the Frail-1 group (1.83, 95%CI 1.55-2.16; p < 0.001). In our HFrEF patients eligible for CRT implantation, patients were exceedingly vulnerable with a high prevalence of frailty. The calculated frailty index was associated with outcome and proved to be prevalent in individual risk stratification., (© 2023. The Author(s).)

Choosing the optimal device during cardiac resynchronization therapy (CRT) upgrade can be challenging. Therefore, we sought to provide a solution for identifying patients in whom upgrading to a CRT-defibrillator (CRT-D) is associated with better long-term survival than upgrading to a CRT-pacemaker (CRT-P). To this end, we first applied topological data analysis to create a patient similarity network using 16 clinical features of 326 patients without prior ventricular arrhythmias who underwent CRT upgrade. Then, in the generated circular network, we delineated three phenogroups exhibiting significant differences in clinical characteristics and risk of all-cause mortality. Importantly, only in the high-risk phenogroup was upgrading to a CRT-D associated with better survival than upgrading to a CRT-P (hazard ratio: 0.454 (0.228-0.907), p = 0.025). Finally, we assigned each patient to one of the three phenogroups based on their location in the network and used this labeled data to train multi-class classifiers to enable the risk stratification of new patients. During internal validation, an ensemble of 5 multi-layer perceptrons exhibited the best performance with a balanced accuracy of 0.898 (0.854-0.942) and a micro-averaged area under the receiver operating characteristic curve of 0.983 (0.980-0.986). To allow further validation, we made the proposed model publicly available ( https://github.com/tokmarton/crt-upgrade-risk-stratification )., (© 2023. The Author(s).)

Aims: This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades., Methods and Results: PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76-0.94; P < 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80-0.87; P < 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79-1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96-1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients' characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time., Conclusion: The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates., Competing Interests: Conflict of interest: Béla Merkely reports grants from Boston Scientific, NRDIF Hungary, National Heart Program; personal fees from Biotronik, Abbott, Astra Zeneca, Novartis, and Boehringer-Ingelheim; and grants from Medtronic outside the submitted work. Annamária Kosztin reports grants from Bolyai Research Scholarship, consulting fees from Medtronic, personal fees from Biotronic, Boehringer-Ingelheim, Boston Scientific, AstraZeneca, Bayer, and Novartis outside the submitted work, and travel fees from AstraZeneca and Novartis outside the submitted work and reports participation on a Data Safety Monitoring Board or Advisory Board with Boehringer Ingelheim and Boston Scientific outside the submitted work. She is a committee member of the Hungarian Society of Cardiology and the secretary of the Working Group on Cardiac Arrhythmias and Pacing, Hungarian Society of Cardiology outside the submitted work. All other authors declare no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Heart failure (HF) is a leading cause of mortality and hospitalization in the elderly. However, data are scarce about their response to device treatment such as cardiac resynchronization therapy (CRT). We aimed to evaluate the age-related differences in the effectiveness of CRT, procedure-related complications, and long-term outcome. Between 2000 and 2020, 2656 patients undergoing CRT implantation were registered and analyzed retrospectively. Patients were divided into 3 groups according to their age: group I, < 65; group II, 65-75; and group III, > 75 years. The primary endpoint was the echocardiographic response defined as a relative increase > 15% in left ventricular ejection fraction (LVEF) within 6 months, and the secondary endpoint was the composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Procedure-related complications were also assessed. After implantation, LVEF showed significant improvement both in the total cohort [28% (IQR 24/33) vs. 35% (IQR 28/40); p < 0.01)] and in each subgroup (27% vs. 34%; p < 0.01, 29% vs. 35%; p < 0.01, 30% vs. 35%; p < 0.01). Response rate was similar in the 3 groups (64% vs. 62% vs. 56%; p = 0.41). During the follow-up, 1574 (59%) patients died. Kaplan-Meier curves revealed a significantly lower survival rate in the older groups (log-rank p < 0.001). The cumulative complication rates were similar among the three age groups (27% vs. 28% vs. 24%; p = 0.15). Our results demonstrate that CRT is as effective and safe therapy in the elderly as for young ones. The present data suggest that patients with appropriate indications benefit from CRT in the long term, regardless of age., (© 2023. The Author(s).)

Aims: The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies., Methods and Results: This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II-IVa), wide paced QRS (&gt;150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (2231 pg/ml [25th-75th percentile 1254-4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%)., Conclusion: When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT-proBNP, and frequent previous HF events., Clinical Trial Registration: ClinicalTrials.gov NCT02270840., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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).)

Aims: Patients with a pacemaker or implantable cardioverter-defibrillator are often considered for cardiac resynchronization therapy (CRT). However, limited comprehensive data are available regarding their long-term outcomes., Methods and Results: Our retrospective registry included 2524 patients [1977 (78%) de novo, 547 (22%) upgrade patients] with mild to severe symptoms, left ventricular ejection fraction ≤35%, and QRS ≥ 130ms. The primary outcome was the composite of all-cause mortality, heart transplantation (HTX), or left ventricular assist device (LVAD) implantation; secondary endpoints were death from any cause and post-procedural complications. In our cohort, upgrade patients were older [71 (65-77) vs. 67 (59-73) years; P < 0.001], were less frequently females (20% vs. 27%; P = 0.002) and had more comorbidities than de novo patients. During the median follow-up time of 3.7 years, 1091 (55%) de novo and 342 (63%) upgrade patients reached the primary endpoint. In univariable analysis, upgrade patients exhibited a higher risk of mortality/HTX/LVAD than the de novo group [hazard ratio (HR): 1.41; 95% confidence interval (CI): 1.23-1.61; P < 0.001]. However, this difference disappeared after adjusting for covariates (adjusted HR: 1.12; 95% CI: 0.86-1.48; P = 0.402), or propensity score matching (propensity score-matched HR: 1.10; 95% CI: 0.95-1.29; P = 0.215). From device-related complications, lead dysfunction (3.1% vs. 1%; P < 0.001) and pocket infections (3.7% vs. 1.8%; P = 0.014) were more frequent in the upgrade group compared to de novo patients., Conclusion: In our retrospective analysis, upgrade patients had a higher risk of all-cause mortality than de novo patients, which might be attributable to their more significant comorbidity burden. The occurrence of lead dysfunction and pocket infections was more frequent in the upgrade group., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.)

Aims: We aimed to assess the effect of cardiac resynchronization on left ventricular (LV) function, volumes, geometry, and mechanics in order to demonstrate reverse remodelling using cardiac magnetic resonance (CMR) with resynchronization on., Methods and Results: New York Heart Association (NYHA) Class II-III patients on optimal medical therapy with LV ejection fraction (LVEF) ≤35%, and complete LBBB with broad QRS (>150 ms) were prospectively recruited. Cardiac magnetic resonance examination was performed at baseline and at 6-month follow-up, applying both biventricular and AOO pacing. The following data were measured: conventional CMR parameters, remodelling indices, global longitudinal, circumferential, radial strain, global dyssynchrony [mechanical dispersion (MD) defined as the standard deviation of time to peak longitudinal/circumferential strain in 16 LV segments], and regional dyssynchrony (maximum differences in time between peak septal and lateral transversal displacement). Thirteen patients (64 ± 7 years, 38% male) were enrolled. Comparing the baseline and follow-up CMR parameters measured during biventricular pacing, significant increase in LVEF, and decrease in LV end-diastolic volume index (LVEDVi) and LV end-systolic volume index (LVESVi) were found. Left ventricular remodelling indices, global longitudinal, circumferential, and radial strain values showed significant improvement. Circumferential MD decreased (20.5 ± 5.5 vs. 13.4 ± 3.4, P < 0.001), while longitudinal MD did not change. Regional dyssynchrony drastically improved (362 ± 96 vs. 104 ± 66 ms, P < 0.001). Applying AOO pacing resulted in an immediate deterioration in LVEF, LVESVi, circumferential strain, global and regional dyssynchrony., Conclusion: Cardiac magnetic resonance imaging during biventricular pacing is feasible and enables a more precise quantification of LV function, morphology, and mechanics. As a result, it may contribute to a better understanding of the effects of resynchronization therapy and might improve responder rate in the future., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: While improvement in quality of life (QoL) has been widely reported in cardiac resynchronization therapy (CRT) patients, its predictive value is not well-understood. We aimed to assess the predictive role of baseline QoL on long-term heart failure (HF) or death events in mild HF patients enrolled in Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT)., Methods and Results: A total of 1791 of 1820 patients had their QoL evaluated at baseline, using the EuroQol-5 dimensions (EQ-5D) and the Kansas City Cardiomyopathy Questionnaires (KCCQ). Kaplan-Meier survival analyses and multivariate Cox models were utilized. Issues within any of the domains of the baseline EQ-5D questionnaire (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) were associated with long-term mortality (median follow-up 5.6 years) (all P < 0.05). Heart failure or death events were predicted by issues in baseline mobility [hazard ratio (HR) = 1.41, P < 0.001], usual activities (HR = 1.41, P < 0.001), and anxiety/depression (HR = 1.21, P = 0.035). The risk of HF events alone was significantly higher in patients with baseline mobility issues (HR = 1.42, P < 0.001) or usual activity (HR = 1.35, P = 0.003). Every 10% increase in the visual analogue scale (0-100) was associated with an 8% lower risk of all-cause mortality (P = 0.006), and a 6% lower risk of HF/death (P = 0.002). Mobility issues also predicted echocardiographic reverse remodelling (-33.08 mL vs. -31.17 mL, P = 0.043). Using the KCCQ, patients in the lower tertile of the clinical summary or physical limitations score had a significantly higher risk of long-term HF or death (P < 0.05)., Conclusion: In mild HF patients enrolled in MADIT-CRT, multiple baseline QoL questionnaire domains were predictors of echocardiographic remodelling, long-term all-cause mortality, and HF events., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The aim of our study was to investigate the long-term efficacy and safety of transseptal endocardial left ventricular lead implantation (TELVLI)., Methods and Results: Transseptal endocardial left ventricular lead implantation was performed in 54 patients (44 men, median age 69, New York Heart Association III-IV stage) between 2007 and 2017 in a single centre. In 36 cases, the transseptal puncture (TP) was performed via the femoral vein, and in 18 cases, the TP and also the left ventricular (LV) lead placement were performed via the subclavian vein. An electrophysiological deflectable catheter was used to reach the LV wall through the dilated TP hole. The LV lead implantation was successful in all patients. A total of 54 patients were followed up for a median of 29 months [interquartile range (IQR) 8-40 months], the maximum follow-up time was 94 months. Significant improvement in the LV ejection fraction was observed at the 3-month visit, from the median of 27% (IQR 25-34%) to 33% (IQR 32-44%), P < 0.05. Early lead dislocation was observed in three cases (5%), reposition was performed using the original puncture site in all. The patients were maintained on anticoagulation therapy with a target international normalized ratio between 2.5 and 3.5. Four thromboembolic events were noticed during follow-up. A total of 27 patients died, with a median survival of 15 months (IQR 6-40)., Conclusion: The TELVLI is an effective approach for cardiac resynchronization therapy (CRT) however it is associated with a substantial thromboembolic risk (7%)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: The authors aimed to evaluate the association of left ventricular (LV) lead location and long-term outcomes in MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy)., Background: There is limited data on the association of lead location with long-term clinical outcomes in patients with cardiac resynchronization therapy with defibrillator (CRT-D)., Methods: The LV lead location was classified in 797 patients with CRT-D, in 569 patients with left bundle branch block (LBBB), in 228 patients with non-LBBB, and in 505 patients with an implantable cardioverter-defibrillator (ICD) only. Leads were classified into apical (n = 83) and non-apical (n = 486); with the non-apical LV leads further categorized into anterior (n = 99) and posterior/lateral (n = 387) within LBBB. All-cause mortality and heart failure (HF) events were assessed using Kaplan-Meier and Cox analyses., Results: In CRT-D patients with LBBB and posterior/lateral LV lead location, there was an association with a significant reduction in long-term all-cause mortality (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.37 to 0.79; p = 0.001), and HF events (HR: 0.44, 95% CI: 0.33 to 0.60; p < 0.001) compared to an ICD only, accompanied with better LV reverse remodeling. CRT-D patients with LBBB and an anterior LV lead location were shown to be associated with a significant reduction in HF events compared to an ICD only (anterior HR: 0.50, 95% CI: 0.30 to 0.82; p = 0.006); however, no association with mortality reduction was observed from CRT-D versus an ICD only. CRT-D was not associated with improved outcomes in non-LBBB patients, regardless of LV lead location., Conclusions: In mild HF patients with LBBB and an implanted CRT-D, lateral/posterior, and anterior LV lead locations are similarly associated with reduction in the risk of HF or death events compared to ICD alone. Mortality benefit derived from CRT-D is associated only with patients with lateral/posterior LV lead location. An apical LV lead location should be avoided due to the early risk of death whenever possible. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT], NCT00180271; Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Post Approval Registry [MADIT-CRT-PAR], NCT01294449; and MADIT-CRT Long-Term International Follow-Up Registry - Europe, NCT02060110)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Patients with conventional pacemakers or implanted defibrillators are often considered for cardiac resynchronization therapy (CRT). Our aim was to summarize the available evidences regarding the clinical benefits of upgrade procedures. A systematic literature search was performed from studies published between 2006 and 2017 in order to compare the outcome of CRT upgrade vs. de novo implantations. Outcome data on all-cause mortality, heart failure events, New York Heart Association (NYHA) Class, QRS narrowing and echocardiographic parameters were analysed. A total of 16 reports were analysed comprising 489,568 CRT recipients, of whom 468,205 patients underwent de novo and 21,363 upgrade procedures. All-cause mortality was similar after CRT upgrade compared to de novo implantations (RR 1.19, 95% CI 0.88-1.60, p = 0.27). The risk of heart failure was also similar in both groups (RR 0.96, 95% CI 0.70-1.32, p = 0.81). There was no significant difference in clinical response after CRT upgrade compared to de novo implantations in terms of improvement in left ventricular ejection fraction (ΔEF de novo - 6.85% vs. upgrade - 9.35%; p = 0.235), NYHA class (ΔNYHA de novo - 0.74 vs. upgrade - 0.70; p = 0.737) and QRS narrowing (ΔQRS de novo - 9.6 ms vs. upgrade - 29.5 ms; p = 0.485). Our systematic review and meta-analysis of currently available studies reports that CRT upgrade is associated with similar risk for all-cause mortality compared to de novo resynchronization therapy. Benefits on reverse remodelling and functional capacity improved similarly in both groups suggesting that CRT upgrade may be safely and effectively offered in routine practice., Clinical Trial Registration: Prospero Database-CRD42016043747.

Aims: There are limited data on whether clinical presentation at first heart failure (HF) hospitalization predicts recurrent HF events. We aimed to assess predictors of recurrent HF hospitalizations in mild HF patients with an implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator., Methods and Results: Data on HF hospitalizations were prospectively collected for patients enrolled in MADIT-CRT. Predictors of recurrent HF hospitalization (HF2) after the first HF hospitalization were assessed using Cox proportional hazards regression models including baseline covariates and clinical presentation or management at first HF hospitalization. There were 193 patients with first HF hospitalization, and 156 patients with recurrent HF events. Recurrent HF rate after the first HF hospitalization was 43% at 1 year, 52% at 2 years, and 55% at 2.5 years. Clinical signs and symptoms, medical treatment, or clinical management of HF at first HF admission was not predictive for HF2. Baseline covariates predicting recurrent HF hospitalization included prior HF hospitalization (HR = 1.59, 95% CI: 1.15-2.20, P = 0.005), digitalis therapy (HR = 1.58, 95% CI: 1.13-2.20, P = 0.008), and left ventricular end-diastolic volume >240 mL (HR = 1.62, 95% CI: 1.17-2.25, P = 0.004)., Conclusions: Recurrent HF events are frequent following the first HF hospitalization in patients with implanted implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Neither clinical presentation nor clinical management during first HF admission was predictive of recurrent HF. Prior HF hospitalization, digitalis therapy, and left ventricular end-diastolic volume at enrolment predicted recurrent HF hospitalization, and these covariates could be used as surrogate markers for identifying a high-risk cohort., (© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

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.)

Context: Assessment of response to cardiac resynchronization therapy (CRT) is essential., Objective: To assess the predictive value of CT-apelin together with NT-proBNP in patients undergoing CRT., Methods: Serum CT-apelin and NT-proBNP were measured by ELISA before, and six months after CRT. Primary endpoint was non-response (<4% increase in LVEF) after six months., Results: From 81 patients, 15 proved to be non-responders. Six-month CT-apelin was superior compared to NT-proBNP in identifying non-responders by multivariate ROC (CT-apelin: p = 0.01, NT-proBNP: p = 0.13) and by logistic regression (CT-apelin: p = 0.01, NT-proBNP: p = 0.41) analyses., Conclusion: Six-month CT-apelin might be a valuable novel biomarker in identifying non-responders to CRT that was superior to NT-proBNP.

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: Data on longer right to left ventricular activation delay (RV-LV AD) predicting clinical outcome after cardiac resynchronization therapy (CRT) by left bundle branch block (LBBB) are limited. We aimed to evaluate the impact of RV-LV AD on N-terminal pro-B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and clinical outcome in patients implanted with CRT, stratified by LBBB at baseline., Methods and Results: Heart failure (HF) patients undergoing CRT implantation with EF ≤ 35% and QRS ≥ 120 ms were evaluated based on their RV-LV AD at implantation. Baseline and 6-month clinical parameters, EF, and NT-proBNP values were assessed. The primary endpoint was HF or death, the secondary endpoint was all-cause mortality. A total of 125 patients with CRT were studied, 62% had LBBB. During the median follow-up of 2.2 years, 44 (35%) patients had HF/death, 36 (29%) patients died. Patients with RV-LV AD ≥ 86 ms (lower quartile) had significantly lower risk of HF/death [hazard ratio (HR): 0.44; 95% confidence interval (95% CI): 0.23-0.82; P = 0.001] and all-cause mortality (HR: 0.48; 95% CI: 0.23-1.00; P = 0.05), compared with those with RV-LV AD < 86 ms. Patients with RV-LV AD ≥ 86 ms and LBBB showed the greatest improvement in EF (28-36%; P<0.001), NT-proBNP (2771-1216 ng/mL; P < 0.001), and they had better HF-free survival (HR: 0.23, 95% CI: 0.11-0.49, P < 0.001) and overall survival (HR: 0.35, 95% CI: 0.16-0.75; P = 0.007). There was no difference in outcome by RV-LV AD in non-LBBB patients., Conclusion: Left bundle branch block patients with longer RV-LV activation delay at CRT implantation had greater improvement in NT-proBNP, EF, and significantly better clinical outcome., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.

Aims: There are limited and contradictory data on the effects of CRT with implantable cardioverter defibrillator (CRT-D) on mortality as compared with CRT with pacemaker (CRT-P)., Methods and Results: We evaluated the long-term outcome of patients implanted with a CRT-D or CRT-P device in our high-volume single-centre experience. Data on all-cause mortality were derived from clinic visits and the Hungarian National Healthcare Fund Death Registry. Kaplan-Meier survival analyses and multivariate Cox regression models were used to evaluate all-cause mortality in patients with CRT-D vs. CRT-P, stratified by the aetiology of cardiomyopathy. From 2000 to 2011, 1122 CRT devices, 693 CRT-P (LVEF 28.2 ± 7.4%) and 429 CRT-D (LVEF 27.6 ± 6.4%), were implanted at our centre. During the median follow-up of 28 months, 379 patients died from any cause, 250 patients (36%) with an implanted CRT-P and 129 patients (30%) with an implanted CRT-D. There was no evidence of mortality benefit in patients implanted with a CRT-D compared with a CRT-P in the total cohort [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.73-1.32, P = 0.884]. In patients with ischaemic cardiomyopathy, CRT-D treatment was associated with a significant 30% risk reduction in all-cause mortality compared with an implanted CRT-P (HR 0.70, 95% CI 0.51-0.97, P = 0.03). In non-ischaemic patients, there was no mortality benefit of CRT-D over CRT-P (HR 0.98, 95% CI 0.73-1.32, P = 0.894, interaction P-value = 0.15)., Conclusions: In heart failure patients with ischaemic cardiomyopathy, CRT-D was associated with a mortality benefit compared with CRT-P, but no benefit of CRT-D over CRT-P in mortality was observed in non-ischaemic cardiomyopathy., (© 2014 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Abstract 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.

AimsPrimary prevention of sudden cardiac death (SCD) in non-ischemic heart failure (HF) patients remains a topic of debate at cardiac resynchronization therapy (CRT) implantation requiring individual risk assessment. Using the Goldenberg SCD risk score, we aimed to predict, which non-ischemic HF patients will benefit from the addition of an implantable cardioverter defibrillator (ICD) to CRT at long-term.MethodsBetween 2000 and 2018 non-ischemic HF patients undergoing CRT implantation were collected into our retrospective registry. The Goldenberg risk score (GRS) was calculated by the presence of atrial fibrillation, New York Heat Association (NYHA) class > 2, age > 70 years, blood urea nitrogen > 26 mg/dl and QRS > 120 ms. The primary endpoint was all-cause mortality, heart transplantation or left ventricular assist device implantation.ResultsFrom 667 patients, 347 (52%) underwent cardiac resynchronization therapy-pacemaker (CRT-P), 320 (48%) cardiac resynchronization therapy-defibrillator (CRT-D) implantations. During the median follow up time of 4.3 years, 306 (46%) patients reached the primary endpoint (CRT-D 37% vs. CRT-P 63%; p < 0.001). CRT-D patients were younger (64 vs. 69 years; p < 0.001), infrequently females (26 vs. 39%; p < 0.001), and had a lower ejection fraction (27 vs. 29%; p < 0.01) compared to CRT-P patients. After GRS calculation, patients were dichotomized by low (< 3) and high (≥ 3) scores. CRT-D patients with low GRS showed a mortality benefit compared to CRT-P (HR 0.68; 95% CI 0.48–0.96; p = 0.03), high-risk patients did not (HR 0.84; 95% CI 0.62–1.13; p = 0.26).ConclusionIn our non-ischemic cohort, patients with low GRS showed a clear long-term mortality benefit by adding ICD to CRT, however, in high-risk patients no further benefit could be observed.

Aims Recommendations on cardiac resynchronization therapy (CRT) in patients with atrial fibrillation or flutter (AF) are based on less robust evidence than those in sinus rhythm (SR). We aimed to assess the efficacy of CRT upgrade in the BUDAPEST-CRT Upgrade trial population by their baseline rhythm. Methods and results Heart failure patients with reduced ejection fraction (HFrEF) and previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and ≥20% right ventricular (RV) pacing burden were randomized to CRT with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145). Primary [HF hospitalization (HFH), all-cause mortality, or <15% reduction of left ventricular end-systolic volume] and secondary outcomes were investigated. At enrolment, 131 (36%) patients had AF, who had an increased risk for HFH as compared with those with SR [adjusted hazard ratio (aHR) 2.99; 95% confidence interval (CI) 1.26–7.13; P = 0.013]. The effect of CRT-D upgrade was similar in patients with AF as in those with SR [AF adjusted odds ratio (aOR) 0.06; 95% CI 0.02–0.17; P < 0.001; SR aOR 0.13; 95% CI 0.07–0.27; P < 0.001; interaction P = 0.29] during the mean follow-up time of 12.4 months. Also, it decreased the risk of HFH or all-cause mortality (aHR 0.33; 95% CI 0.16–0.70; P = 0.003; interaction P = 0.17) and improved the echocardiographic response (left ventricular end-diastolic volume difference −49.21 mL; 95% CI −69.10 to −29.32; P < 0.001; interaction P = 0.21). Conclusion In HFrEF patients with AF and PM/ICD with high RV pacing burden, CRT-D upgrade decreased the risk of HFH and improved reverse remodelling when compared with ICD, similar to that seen in patients in SR. [ABSTRACT FROM AUTHOR]

Background: The relative importance of variables explaining sex-related differences in outcomes is scarcely explored in patients undergoing cardiac resynchronization therapy (CRT). We sought to implement and evaluate machine learning (ML) algorithms for the prediction of 1- and 3-year all-cause mortality in CRT patients. We also aimed to assess the sex-specific differences in predictors of mortality utilizing ML.Methods: Using a retrospective registry of 2,191 CRT patients, ML models were implemented in 6 partially overlapping patient subsets (all patients, females, or males with 1- or 3-year follow-up). Each cohort was randomly split into training (80%) and test sets (20%). After hyperparameter tuning in the training sets, the best performing algorithm was evaluated in the test sets. Model discrimination was quantified using the area under the receiver-operating characteristic curves (AUC). The most important predictors were identified using the permutation feature importances method.Results: Conditional inference random forest exhibited the best performance with AUCs of 0.728 (0.645–0.802) and 0.732 (0.681–0.784) for the prediction of 1- and 3-year mortality, respectively. Etiology of heart failure, NYHA class, left ventricular ejection fraction, and QRS morphology had higher predictive power, whereas hemoglobin was less important in females compared to males. The importance of atrial fibrillation and age increased, while the importance of serum creatinine decreased from 1- to 3-year follow-up in both sexes.Conclusions: Using ML techniques in combination with easily obtainable clinical features, our models effectively predicted 1- and 3-year all-cause mortality in CRT patients. Sex-specific patterns of predictors were identified, showing a dynamic variation over time.

Aims This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades. Methods and results PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76–0.94; P < 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80–0.87; P < 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79–1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96–1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients' characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time. Conclusion The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates. [ABSTRACT FROM AUTHOR]