Frailty and heart failure (HF) both have become increasingly prevalent and each adversely affects prognosis. Data regarding the potential frailty-modifying effect of cardiac resynchronization therapy (CRT) upgrade remain scarce. This study aimed to evaluate the impact of frailty on clinical outcomes in the Budapest-CRT Upgrade trial population. Patients with heart failure and reduced ejection fraction (HFrEF), an implanted pacemaker or implantable cardioverter-defibrillator (ICD) and ≥ 20

Aims We aimed to externally validate the SEMMELWEIS-CRT score for predicting 1-year all-cause mortality in the European Cardiac Resynchronization Therapy (CRT) Survey I dataset-a large multi-centre cohort of patients undergoing CRT implantation. Methods and results The SEMMELWEIS-CRT score is a machine learning-based tool trained for predicting all-cause mortality in patients undergoing CRT implantation. This tool demonstrated impressive performance during internal validation but has not yet been validated externally. To this end, we applied it to the data of 1367 patients from the European CRT Survey I dataset. The SEMMELWEIS-CRT predicted 1-year mortality with an area under the receiver operating characteristic curve (AUC) of 0.729 (0.682-0.776), which concurred with the performance measured during internal validation [AUC: 0.768 (0.674-0.861), P = 0.466]. Moreover, the SEMMELWEIS-CRT score outperformed multiple conventional statistics-based risk scores, and we demonstrated that a higher predicted probability is not only associated with a higher risk of death [odds ratio (OR): 1.081 (1.061-1.101), P < 0.001] but also with an increased risk of hospitalizations for any cause [OR: 1.013 (1.002-1.025), P = 0.020] or for heart failure [OR: 1.033 (1.015-1.052), P < 0.001], a less than 5% improvement in left ventricular ejection fraction [OR: 1.033 (1.021-1.047), P < 0.001], and lack of improvement in New York Heart Association functional class compared with baseline [OR: 1.018 (1.006-1.029), P = 0.003]. Conclusion In the European CRT Survey I dataset, the SEMMELWEIS-CRT score predicted 1-year all-cause mortality with good discriminatory power, which confirms the generalizability and demonstrates the potential clinical utility of this machine learning-based risk stratification tool.

Abstract Background Utilizing remote monitoring (RM) in patients with heart failure (HF) who have cardiac implantable electronic devices (CIED) proves to be a dependable method for closely adhering to device-specific and heart failure-related parameters. While there is some favorable outcome data, the results remain incomplete. Aims We aimed to evaluate the advantages of continuous RM compared to the standard of care (SoC) in reducing all-cause mortality, cardiovascular-related death (CV), sudden cardiac death, and ICD shocks. Methods A systematic review and meta-analysis of randomized controlled trials (RCT) testing RM vs. SoC for the management of HF patients were performed. Endpoints were all-cause mortality, CV mortality, sudden cardiac death, ICD shocks. Odds ratios (ORs), Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. CENTRAL, EMBASE and MEDLINE were searched up, and only randomized controlled studies were included. Results Sixteen RCTs that enrolled a total of 11,140 patients were identified to evaluate all-cause mortality, resulting in an HR 0.83 (95% CI 0.72 to 0.96). When CV mortality was assessed, there was a significant difference between the RM group and SoC group, and the HR was 0.81 (95% CI 0.67 to 0.97) Moreover RM did not have an effect on the rate of sudden cardiac death and ICD shocks. Conclusions RM proved to be superior in reducing all-cause mortality and CV mortality compared to SoC despite of the heterogeneous study cohorts and unstandardized alert actions. However, the use of RM did not influence the occurrence of sudden cardiac death and ICD shocks.

AIMS:Patients with obesity have an overall higher cardiovascular risk, at the same time obesity could be associated with a better outcome in a certain subgroup of patients, a phenomenon known as the obesity paradox. Data are scarce in candidates for cardiac resynchronization therapy (CRT). We aimed to investigate the association between body mass index (BMI) and all-cause mortality in patients eligible for CRT. METHODS:Altogether 1,585 patients underwent cardiac resynchronization therapy between 2000-2020 and were categorized based on their BMI, 459 (29%) patients with normal weight (BMI < 25 kg/m2), 641 (40%) patients with overweight (BMI 25- < 30 kg/m2) and 485 (31%) with obesity (BMI ≥ 30 kg/m2). The primary endpoint was all-cause mortality, heart transplantation, and left ventricular assist device implantation. We assessed periprocedural complications and 6-month echocardiographic response. RESULTS:Normal-weight patients were older compared to patients with overweight or obesity (70 years vs. 69 years vs. 68 years; P ‹0.001), respectively. Sex distribution, ischaemic aetiology, and CRT-D implantation rates were similar in the three patient groups. Diabetes mellitus (BMI < 25 kg/m2 26% vs. BMI 25- < 30 kg/m2 37% vs. BMI ≥ 30 kg/m2 48%; P ‹0.001) and hypertension (BMI < 25 kg/m2 71% vs. BMI 25- < 30 kg/m2 74% vs. BMI ≥ 30 kg/m2 82%; P ‹0.001) were more frequent in patients with overweight and obesity. During the mean follow-up time of 5.1 years, 973 (61%) reached the primary endpoint, 66% in the BMI < 25 kg/m2 group, 61% in the BMI 25- < 30 kg/m2 group and 58% in the BMI ≥ 30 kg/m2 group (log-rank P‹0.05). Patients with obesity showed mortality benefit over normal-weight patients (HR 0.78; 95%CI 0.66-0.92; P = 0.003). The obesity paradox was present in patients free from diabetes, atrial fibrillation, and ischemic events. Periprocedural complication rates did not differ in the three groups (BMI < 25 kg/m2 25% vs. BMI 25- < 30 kg/m2 28% vs. BMI ≥ 30 kg/m2 26%; P = 0.48). Left ventricular ejection fraction improved significantly in all patient groups (BMI < 25 kg/m2 median ∆ -LVEF 7% vs. BMI 25- < 30 kg/m2 median ∆ -LVEF 7.5% vs. BMI ≥ 30 kg/m2 median ∆ -LVEF 6%; P < 0.0001) with a similar proportion of developing reverse remodeling (BMI < 25 kg/m2 58% vs. BMI 25- < 30 kg/m2 61% vs. BMI ≥ 30 kg/m2 57%; P = 0.48); P = 0.75). CONCLUSIONS:The obesity paradox was present in our HF cohort at long-term, patients underwent CRT implantation with obesity and free of comorbidities showed mortality benefit compared to normal weight patients. Patients with obesity showed similar echocardiographic response and safety outcomes compared to normal weight patients.

Abstract Introduction Approximately one-third of patients undergoing cardiac resynchronization therapy (CRT) implantation fail to show echocardiographic improvement and are categorized as non-responders, despite of probable beneficial clinical response. Purpose We aimed to evaluate the long-term outcome of CRT patients by their echocardiographic response outsorting those with unchanged parameters. Methods Altogether 1019 patients undergoing CRT implantation between 2000-2020 in our center were analyzed retrospectively. Patients were grouped by their echocardiographic response defined as LVEF change upto12 months: super-responders ≥20% (n=113), responders 6-19% (n=448), non-progressors 0-5% (n=244), and progressors <0% (n=214). The primary endpoint was the composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results During the median follow-up time of 4.7 years 547 (54%) patients died, 35 (31%) super-responders, 223 (50%) responders, 133 (55%) non-progressors, and 156 (73%) progressors. The mean change in LVEF occurred as follows: super-responders 24.5% ± 4.1%, responders 11.5% ± 3.8%, non-progressors 2.8% ± 1.8%, and progressors -6.6% ± 4.5% (p<0.001). Univariate Cox regression analysis revealed that non-progressors had a similar outcome to responders (HR 1.17; 95%CI 0.94-1.45; p=0.15) and a superior outcome to progressors (HR 0.60; 95%CI 0.48-0.76; p<0.001), which was also confirmed by multivariate analysis: non-progressors vs. responders (HR 1.25; 95%CI 0.98-1.58; p=0.07) and non-progressors vs. progressors (HR 0.62; 95%CI 0.47-0.80; p<0.001). Conclusion In our current analysis, non-progressors had a superior outcome to progressors suggesting that CRT moderates the remodeling process. These findings indicate their selection and the re-classification of CRT response by echocardiographic changes.Survival by responseMean change in LVEF by response

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.

Abstract Background Based on the results of the BUDAPEST-CRT Upgrade trial, in patients with intermittent or permanent right ventricular (RV) pacing and reduced left ventricular ejection fraction (HFrEF) upgrade to cardiac resynchronization therapy (CRT) reduces morbidity and mortality. Purpose Whether the substantial treatment effect of the CRT upgrade could also be detected in a better functional and exercise capacity is scarcely investigated. We examined the changes of the prespecified tertiary endpoints such as symptoms, quality of life (QoL), exercise capacity and natriuretic peptide measurement from baseline to 12 months. Methods In the BUDAPEST CRT Upgrade trial 360 HFrEF patients with a priorly implanted PM or ICD and >20% of RV pacing burden were randomly assigned to CRT-D upgrade (n=215) or ICD (n=145) in a 3:2 ratio. The prespecified tertiary endpoints were changes in quality of life measured by EQ-5D-3L, New York Heart Association (NYHA) functional class, 6-minute walk test (6-MWT), and NT-proBNP. When data of trial patients were unavailable due to death at 12 months, imputed values were used as 0 (6MWT) and 0 score (EQ-5D-3L) or a 5th grade (NYHA class). Responders were defined as >15% change of left ventricular end-systolic volume at 12 months. Results From baseline to 12 months, NYHA functional class improved in the CRT-D upgrade arm compared with the ICD only group [adjusted odds ratio (OR) 0.50; 95% CI 0.32-0.80; P=0.003]. According to the adjusted model there was a statistically significant decrease in the NT-proBNP [adjusted difference -1257 pg/mL; 95% CI -2287 – (-228); P=0.017]. In responders, the changes in NT-proBNP levels were significantly greater than in non-responders [adjusted difference -1635 pg/mL; 95% CI -2811 - (-459); P=0.007]. The progression of worsening of QoL attributed to ageing was moderated only by CRT-D upgrade [EQ-5D-3L difference by age -0.01; 95% CI -0.02 - (-0.003); P=0.004; interaction P=0.003]. 6MWT did not improve significantly in either group. Conclusions Patients receiving CRT upgrade showed a substantial improvement in symptoms and a significant decrease in natriuretic peptide levels, as compared to ICD alone, which was more pronounced in responders. Moreover, CRT-D upgrade could moderate the progression of worsening of quality of life attributed to ageing in this vulnerable, older patient population.

Abstract Introduction Left ventricular (LV) lead position is strongly associated with the long-term outcome of patients undergoing de novo cardiac resynchronization therapy (CRT) implantation. However, data is scarce about patients who undergo upgrade CRT from right ventricular (RV) pacing. Aims To investigate the impact of the LV lead location on the primary outcome of heart failure (HF) hospitalization, all-cause mortality, or echocardiographic reverse remodelling in the BUDAPEST CRT Upgrade trial cohort. Methods Heart failure patients with reduced ejection fraction (HFrEF), with previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and intermittent or permanent RV pacing, who were randomly assigned to the CRT-D arm (n=215) and those who were cross-overs from the ICD arm (n=27) were investigated. Short-axis position (anterior / posterior / lateral) of the LV lead was assessed. Primary endpoint encompassed HF hospitalization, all-cause mortality, and the end-systolic volume (ESV) decrease less than 15% from baseline to 12 months follow-up. Echocardiographic response was evaluated by percent change of ESV and LVEF. Results LV lead location was available for 223 patients (age 72.8 ± 8 years, 14% female, 38% diabetic, 49% with prior myocardial infarction, 30% with prior ICD) with a median follow-up time of 12.4 months. There was no difference in the occurrence of the primary endpoint by the lead positions (anterior vs. lateral OR 0.33; 95%CI 0.09-1.22, p=0.10, anterior vs. posterior OR 0.58; 95%CI 0.14-2.50, p=0.47). However, LVEF change was more pronounced in those with lateral LV lead location compared with anterior position (adjusted LVEF difference 7.43%, 95%CI 1.25 – 13.62; p=0.02), while those with posterior leads did not differ from the anterior ones (adjusted LVEF difference 3.00%, 95%CI -3.92 – 9.93; p=0.39). Decrease in ESV was also more remarkable with a lateral position as compared to the other locations (lateral vs. anterior adjusted ESV difference -0.17 mL, 95%CI -0.32 – (-0.01); p=0.03, posterior vs. anterior adjusted ESV difference -0.09 mL, 95%CI -0.26– 0.08; p=0.31). Conclusion Upgrade CRT results in better outcomes as compared to ICD alone; however, lateral LV lead position is associated with the most beneficial mid-term echocardiographic response as compared to other short-axis locations. This finding may translate into better clinical outcomes in the long term.

BACKGROUND:In the BUDAPEST (Biventricular Upgrade on left ventricular reverse remodeling and clinical outcomes in patients with left ventricular Dysfunction and intermittent or permanent APical/SepTal right ventricular pacing)-CRT Upgrade randomized trial, the authors have demonstrated improved mortality and morbidity after cardiac resynchronization therapy (CRT) upgrade in patients with heart failure with reduced ejection fraction (HFrEF) with high right ventricular (RV) pacing burden. OBJECTIVES:This substudy sought to examine the impact of CRT upgrade on symptoms, functional outcome, and exercise capacity. METHODS:In the BUDAPEST-CRT Upgrade trial, 360 HFrEF patients with pacemaker or implantable cardioverter-defibrillator (ICD) and ≥20% RV pacing burden were randomly assigned (3:2) to cardiac resynchronization therapy with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145). The prespecified tertiary endpoints were changes in quality of life (QoL) (EQ-5D-3L), NYHA functional class, 6-minute walk test, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. RESULTS:Up to 12 months, NYHA functional class improved in the CRT-D upgrade arm compared with ICD only (adjusted OR: 0.50 [95% CI: 0.32-0.80]; P = 0.003). A remarkable decrease was observed in NT-proBNP levels in the CRT-D arm (adjusted difference: -1,257 pg/mL [95% CI: -2,287 to -228 pg/mL]; P = 0.017). The progression of age-related worsening of QoL was moderated by CRT-D upgrade (EQ-5D-3L difference by each year: 0.015 [95% CI: 0.005-0.025]; P interaction = 0.003). However, exercise tolerance (6-minute walk test) remained unchanged in both groups. CONCLUSIONS:HFrEF patients with pacemaker/ICD and ≥20% RV pacing burden receiving CRT upgrade showed a substantial improvement in NYHA functional class and decrease in natriuretic peptide levels, as compared with ICD alone. Moreover, CRT-D upgrade could moderate the progression of worsening of QoL attributed to ageing in this vulnerable, elderly patient population. (Biventricular Upgrade on left ventricular reverse remodeling and clinical outcomes in patients with left ventricular Dysfunction and intermittent or permanent APical/SepTal right ventricular pacing [BUDAPEST]-CRT Upgrade trial; NCT02270840).

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.

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 ).

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union. Background Overweight and obese people have a higher risk of acquiring heart failure, however these patients tend to have more favorable outcome, a phenomenon known as the obesity paradox. Purpose We aimed to investigate the risk of obesity and the association of body mass index (BMI) on all-cause mortality in heart failure CRT patients at long-term. Methods We examined retrospectively 1585 patients undergoing CRT implantation at our clinic between 2000-2020 with their BMI available at baseline. Patients were sorted into three groups: normal weight (BMI ‹25), overweight (BMI 25-29.9) and obese (BMI≥30). The composite primary endpoint was all-cause mortality, heart transplantation or implantation of a left ventricular assist device. Time-to-event data was studied by log-rank and multivariate Cox regression analysis. We studied peri-procedural complication rates, and reverse remodeling, defined as a ≥15% relative increase in left ventricular ejection fraction (LVEF) within 6 months after CRT implantation. Results During our mean follow-up time of 5.1 years, 973 (61%) reached our primary endpoint, 302 (66%) in the BMI ‹25 group, 389 (61%) in the BMI 25-29.9 group and 282 (58%) in the BMI≥30 group. Obese patients showed mortality benefit over normal-weighed patients (HR 0.78; 95%CI 0.66-0.92; p=0.003), with only a trend in overweight patients over normal-weighed patients (HR 0.86; 95%CI 0.74-1.00; p=0.05). At multivariate analysis, BMI ‹25 patients showed a 19% higher risk of all-cause mortality compared to overweight and obese patients (HR 1.19; 95%CI 1.03-1.38; p=0.02) after adjusting for age, sex, NYHA class, diabetes, hypertension, myocardial infarction and atrial fibrillation. Obese and overweight patients were younger than normal-weighed patients (68yrs. vs. 69yrs. vs. 70 yrs.; p‹0.0001), similar sex distribution can be seen. Diabetes (BMI ‹25 48% vs. BMI 25-29.9 37% vs. BMI≥30 26%; p‹0.0001) and hypertension (BMI ‹25 82% vs. BMI 25-29.9 74% vs. BMI≥30 71%; p‹0.001) occurred more frequently in obese and overweight patients. Obese and overweight patients had a higher LVEF than in the normal weight group (30% vs. 28% vs. 27%; p‹0.001), respectively. Peri-procedural complication rates did not differ in the three groups. In all patient groups, a significant improvement in LVEF at 6 months was seen (BMI ‹25 ∆-EF 7%, BMI 25-29.9 ∆-EF 7.5%, and BMI ≥30 ∆-EF 6; p<0.001). No difference was seen in the proportion of developing reverse remodeling (BMI ‹25 58% vs. BMI 25-29.9 61% vs. BMI≥30 57%; p=0.75). Conclusions Despite having more co-morbidities like diabetes or hypertension, obese patients showed mortality benefit over normal-weighed patients proving, that the obesity paradox was present in our CRT patient cohort at long-term. Peri-procedural complications did not occur more frequently in obese or overweight patients. Echocardiographic response did not vary, similar reverse remodeling was observed across the patient groups.

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.

Abstract Introduction Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in selected patients with symptomatic heart failure with reduced ejection fraction (HFrEF) and prolonged QRS. However, approximately one-third of the implanted patients fail to show clinical improvement or reverse remodeling. The criteria by response have been recently changed, those patients with a minimal improvement in left ventricular ejection fraction (LVEF) are defined as "non-progressors" rather than as "non-responders", selecting from those patients in whom the progression could not be modified. Data are scarce regarding the long-term outcome of this patient population. Purpose We aimed to evaluate the long-term outcome of CRT patients by their response, comparing non-progressors with responders and progressors. Methods Altogether 1019 patients undergoing CRT implantation between 2000-2020 in our center were registered and analyzed retrospectively. Patients were divided into 4 groups according to their response status, which was defined on the basis of LVEF change in 12 months after CRT implantation as follows: super-responders ≥20% (n=113), responders 6-19% (n=448), non-progressors 0-5% (n=244), and progressors <0% (n=214). The primary endpoint was the composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results During the median follow-up time of 4.7 years 547 (54%) patients died, 35 (31%) super-responder, 223 (50%) responder, 133 (55%) non-progressor, and 156 (73%) progressor. The mean change in LVEF occurred as follows: super-responders 24.5% ± 4.1%, responders 11.5% ± 3.8%, non-progressors 2.8% ± 1.8%, and progressors -6.6% ± 4.5% (p<0.0001). Non-progressors were more commonly male, had worse NYHA functional status, worse renal function, higher baseline LVEF and serum creatinine levels, and more frequently had an ischemic etiology. Univariate Cox regression analysis revealed that non-progressors had similar outcome to responders (HR 1.17; 95%CI 0.94-1.45; p=0.15) and superior outcome to progressors (HR 0.60; 95%CI 0.48-0.76; p<0.0001), which was also confirmed by multivariate analysis after adjustment for age, gender, ischemic etiology, LVEF, and serum creatinine levels: nonprogressors vs. responders (HR 1.25; 95%CI 0.98-1.58; p=0.07) and nonprogressors vs. progressors (HR 0.62; 95%CI 0.47-0.80; p<0.0001). Conclusions In our current study, non-progressors to CRT had a similar long-term outcome to responders and superior outcome to progressors. These findings suggest that non-progressor patients would have continued to adversely remodel without CRT and CRT is beneficial for these patients by moderating the remodeling process rather than improving it. Our results support the fact that categorizing patients as "responders" or "non-responders" is inappropriate and patients could be grouped as super-responders, responders, non-progressors, and progressors.Probability of survival by CRT responseMultivariate analysis by response status

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Project no. RRF-2.3.1-21-2022-00004 (MILAB) has been implemented with the support provided by the European Union. Background Remote monitoring (RM) in heart failure (HF) patients with cardiac implantable electronic devices (CIED) is a reliable approach to strictly following the device-specific and heart failure-related parameters. Despite a few positive outcome data, results are incomprehensive. Aims We aimed to assess the benefit of continuous RM vs. standard of care (SoC) in the reduction of all-cause mortality, heart failure hospitalization (HF), and cardiovascular-related hospitalization (CV), and inappropriate therapy. Methods A systematic review and meta-analysis of randomized controlled trials (RCT) testing RM vs. SoC for the management of HF patients were performed. Endpoints were all-cause mortality, CV- and HF hospitalizations and inappropriate therapy. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated. CENTRAL, EMBASE and MEDLINE were searched up to 21th of December 2021. Only randomized controlled studies were included. Results Fourteen RCTs that enrolled a total of 8370 patients were identified to evaluate all-cause mortality, resulting in an OR 0.88 (95% CI 0.75 to 1.03). When CV - and HF hospitalizations were assessed, there were no differences between the RM group and SoC group, and the OR was 0.93 (95% CI 0.82 to 1.05) and 0.95 (95% CI 0.75 to 1.19), respectively.Moreover RM did not have an effect on the rate of inappropriate therapy, OR was 0.73. (95% CI 0.30 to 1.81). Conclusions RM proved to be non-inferior in reducing all-cause mortality, CV- and HF hospitalization and rate of inappropriate therapy when compared to standard of care despite of the heterogeneous study cohorts and unstandardized alert actions. All cause mortality Inappropriate shock

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Nemzeti Kardiovaszkuláris Laboratórium RRF-2.3.1-21-2022-00003. Background Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of ‘health deficits’ across a range of domains. Aims We assessed the frequency of, and outcomes related to frailty in patients with heart failure and reduced ejection fraction who previously underwent cardiac resynchronization therapy (CRT) implantation. Methods We used a cumulative deficits approach to construct a 30-item frailty index (FI) and applied it to identify frail patients enrolled in our CRT registry. The 30 items were derived from medical history, other patient characteristics and laboratory results, covering a range of body systems. In keeping with previous studies, patients with FI ≤0.210 were classified as non-frail and those with higher scores were divided into two categories using score increments of 0.100. Our primary endpoint was all-cause mortality. Results Among 1004 included patients, 75 (7%) were considered Non-frail, while 271 (27%) and 658 (66%) participants were categorized as Frail in groups 1- and 2. Patients in Frail group 2 were older, had a less favorable renal function, and generally had more comorbidities (i.e. atrial fibrillation, hypertension, ischemic cardiovascular disease) than patients categorized in the Non-frail or Frail group 1. During the median follow-up time of 4.4 (2.3-6.9) years, 17 (22%) patients in the Non-frail group, 103 (38%) in Frail group 1, and 479 (73%) in the Frail group 2 reached the primary endpoint. Non-frail patient group showed the most beneficial survival with a 70% (HR 0.31; 95% CI: 0.23-0.41; p<0.001) lower all-cause mortality risk compared to Frail group 2. Adjusting for relevant covariates, NYHA class, creatinine, and TAPSE were identified as independent predictors for all-cause mortality. Conclusion Based on our results, CRT candidates are exceedingly vulnerable with a high prevalence of frailty. The calculated frailty index was associated with the primary outcome of death from any cause. FI proved to be prevalent in individual risk stratification and can predict the outcome.