Cardiac Resynchronization Therapy Implantation Research Articles

Association between socioeconomic position and discontinuation of pharmacotherapy for heart failure after cardiac resynchronization therapy.

Pharmacological therapy remains a cornerstone in heart failure (HF) treatment despite implantation of a cardiac resynchronization therapy (CRT) device. The aim of this study was to investigate the association between 1) drug discontinuation, and 2) long-term adherence to HF pharmacotherapy after CRT implantation and socioeconomic position and multimorbidity. We conducted a registry-based cohort study including all patients who underwent a first-time CRT implantation at Aarhus University Hospital from 2000-2017. HF pharmacotherapy included beta blockers (BBs), renin angiotensin system inhibitors (ACEI/ARB), and mineralocorticoid receptor antagonists (MRAs). Patients were identified using the Danish Pacemaker and ICD Registry, and information about medication and comorbidities was obtained through linkage to the Danish health registries. We identified 2,007 patients of whom 1,880 (94%) were eligible for inclusion. The cumulative incidence of drug discontinuation at 10 years was 6% (95% confidence interval [CI] 5-8%) for BB, 10% (95% CI 9-12%) for ACEI/ARB, and 24% (95% CI 20-27%) for MRAs. Living alone was associated with higher BB discontinuation rates (hazard ratio [HR] 1.83, 95%CI 1.20-2.79), whereas patients with multimorbidity were more likely to discontinue ACEI/ARB- (HR 1.92, 95%CI 1.33-2.80) and MRA therapy (HR 1.51, 95% CI 1.10-2.09). Income- and educational level did not influence drug discontinuation rates, and similar adherence patterns were observed across all strata of socioeconomic position and multimorbidity. In patients with CRTs, drug discontinuation rates were low, and adherence to HF pharmacotherapy was comparable regardless of socioeconomic position. Living alone and multimorbidity were associated with discontinuation of specific HF drugs.

Re-classification of response to cardiac resynchronization therapy: the long-term effect of echocardiographic non-progression

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

The impact of clinical audits on patient radiation exposure for device procedures

Abstract Background Clinical audits aim to ensure ideal use of ionizing radiation in clinical practice. Since it became mandatory by Swiss law in 2018, such an audit also took place in our Cardiac Pacing and Electrophysiology Division at the University Heart Center. Purpose To establish local diagnostic reference levels (DRLs) for specific procedures and to examine if patient radiation exposure was reduced after the clinical audit. Methods Retrospective cohort study including patients from October 2018 to October 2020 who underwent device implantation, including pacemakers, implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy (CRT), or lead extraction / device explantation. Main measures to reduce radiation exposure after the audit were lower pulsed fluoroscopy frame rates and dose characteristics at baseline. Patient radiation exposure was evaluated with the dose-area product (DAP), cumulative dose, fluoroscopy time, and the number of cine acquisitions. Secondary endpoints included the effective dose, the acute procedural success rate and 30-day complications. Data were collected from a dose management system and cross-checked for accuracy with the patient information system. The third quartiles were set as local DRLs. Data before and after the clinical audit were compared. Results A total of 541 patients (45.7 % before the audit, 54.3% after the audit) were included. 28.3% had a conventional pacemaker, 22.0% a leadless pacemaker, 21.1% an ICD, and 17.2% a CRT implantation. Lead extraction / device explantation was undergone by 11.5% of patients. The local DRLs (including all procedures before and after the audit) for the DAP were significantly lower as compared to national DRLs (6.2 dGy.cm2 versus 300 dGy.cm2 for conventional pacemakers; 7.6 dGy.cm2 versus 200 dGy.cm2 for ICDs, 203 dGy.cm2 versus 570 dGy.cm2 for CRTs). After the audit, DAP (Figure 1), cumulative dose, effective dose and the number of cine acquisition significantly decreased for conventional pacemakers (p-value ≤ 0.04), whereas no significant differences were observed for the other procedures. The acute procedural success rate (98.4 vs 98.9%) and the 30-day complications (4.0 vs 7.8%) were not significantly different before and after the audit. Conclusions The clinical audit in our institution led to a significant reduction of radiation exposure for patients during pacemaker implantations. Regarding DRLs, local values were far below national DRLs, which suggests that national DRLs need to be updated more regularly. Our study highlights the importance of clinical audits and the need for more research in this field.

Ventricular arrhythmia events in patients with implantable cardioverter-defibrillator before and after the treatment with sodium-glucose co-transporter 2 inhibitors

Abstract Background The role of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in the treatment of chronic heart failure is expanding. However, the timing of implantable cardioverter-defibrillator (ICD) implantation for primary prevention in relation to the use of SGLT2i remains unclear. A small case series has described appropriate shocks from ICD in two patients following the initiation of SGLT2i, but a comprehensive analysis is lacking in the literature. Methods This study aimed to investigate the rate of ventricular arrhythmic burden and appropriate anti-tachycardia therapy from ICD before and after the initiation of SGLT2i therapy. We conducted a retrospective single-center analysis, comparing ventricular events from home monitoring reports three months before and three months after SGLT2i therapy initiation. Results Seventeen patients were enrolled in the study. At baseline, clinical characteristics were as follows: 13 (76%) were male, 9 (53%) had ischemic, 2 (12%) had valvular, and 6 (35%) had idiopathic cardiomyopathy. The mean end-diastolic volume (EDV) was 203 ± 90 ml, and the mean left ventricular ejection fraction was 0.36 ± 0.09. All patients were treated with beta-blockers, 14 (82%) with sacubitril-valsartan, 13 (76%) with aldosterone antagonists, 16 (94%) with furosemide, and 5 (29%) with amiodarone. SGLT2i started with dapagliflozin for 13 patients (76%), empagliflozin for 3 patients (18%), and canagliflozin for 1 patient (6%). Ten patients (59%) had single-chamber or dual-chamber ICDs, and 7 had implantable cardiac resynchronization therapy (CRT) defibrillators. In the three months before SGLT2i treatment, 4/17 patients had non-sustained ventricular tachycardia (NSVT), compared to 8/17 (23% vs. 47%, p-value 0.23) patients with NSVT after treatment. Seven patients (41%) experienced an increase in the rate of NSVT events, with one patient having 28 NSVT events after treatment versus none before treatment. No patients had anti-tachycardia therapy in the three months before treatment, while in the three months after SGLT2i treatment, 1 patient had ventricular tachycardia treated with anti-tachycardia pacing (110 days after the beginning of the treatment), and 2 patients had ventricular tachycardia treated with appropriate shocks (2 and 25 days after the initiation of SGLT2i treatment). Conclusion This small retrospective analysis revealed an increase in ventricular arrhythmic events in the three months following the initiation of SGLT2i. These findings highlight the need for a more extensive analysis to establish a stronger statistical correlation.

Impact of taurolidine use during cardiac electronic implantable device implantation in heart failure patients

Abstract Background Cardiac Implantable Electronic Device (CIED) infections represent a critical health threat with potentially fatal consequences. The TauroPace™ is an innovative solution that contains taurolidine specifically formulated to eradicate environmental microbial contamination on the surface of CIEDs. To date, scarce data are available in literature about Taurolidine’s effect on preventing CIED infections. Aims To investigate the ability of the TauroPace™ to reduce major CIED infections through 12 months follow-up in fragile patients such as heart failure (HF) patients. Methods This prospective cohort study included patients with HF and an ejection fraction ≤ 35%, who were referred for de novo implantation, upgrading or battery replacement of Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy with defibrillator (CRT-D), to the EP labs of two tertiary care hospitals. Patients with previous CIED infections were excluded. During the procedures, the catheters were submerged in the TauroPace™ solution and the pocket was irrigated with taurolidine. Starting from the main risk factors for the development of CIED-related infections as identified in the literature (including individuals with heart failure, diabetes, chronic kidney disease, and those undergoing defibrillators implantation, especially upgrades or revisions procedure), we conducted a meta-analysis and meta-regression to evaluate the relationship between the treatment effect's magnitude and various predictors. To estimate the incidence of CIED infections in high-risk subgroups, we utilized the percentage of patients with diabetes, chronic renal failure, or those undergoing replacement, upgrade, or revision procedures, along with other risk factors for CIED infections, as continuous variables and we were able to modify our comparison parameters based on the real percentage of risk factors that we obtained. Results The study included 69 consecutive patients (53 male [76.8 %], 34 ischemic [49,3 %], median [IQR] age 68 [59-73] years, 19 diabetic [27.5 %] and 34 [49.2 %] with chronic renal failure), of whom 39 (56.5 %) received ICD and 30 (43.5 %) CRT-D, with 28 (40.6 %) replacement procedures, 2 (2.9 %) upgrades, and 39 (57%) de novo implantations. During the one-year follow-up period, 1 [1.45 (Standard Error, SE 0.014) %] patient undergoing a CRT replacement developed an infection. The available data from the literature estimate an incidence rate of 6% (SE 0.0106) when considering a selected patient population with a very high risk of infection similar to our population. This is significantly higher than our cohort (z-score -2.5447, p value = 0.011). Conclusions Taurolidine has yielded promising results, demonstrating a low incidence rate of infections within our cohort of high-risk patients, which is below that reported in the literature. Further data will be necessary to validate and confirm these initial findings.

Comparative analysis of clinical outcomes in patients undergoing primary CRT implantation versus CRT upgrade: single center experience

Abstract Background As heart failure (HF) management evolves, cardiac resynchronization therapy (CRT) has emerged as a cornerstone intervention, improving left ventricular (LV) function and reducing morbidity and mortality. The Budapest trial specifically addressed upgrading from permanent pacemaker (PPM) to CRT, emphasizing the potential for improved clinical outcomes and quality of life in this population. The findings highlighted the impact of CRT upgrade and contribute valuable insights to the cardiac device strategies for HF patients. This study aims to compare clinical outcomes between patients undergoing primary CRT implantation and those undergoing CRT upgrade. Methods A retrospective analysis was conducted on a cohort of heart failure patients who received CRT devices between 2015 and 2019. Patients were categorized into two groups: those undergoing primary CRT implantation and those undergoing CRT upgrade. Clinical outcomes, including mortality rate, hospitalization for HF exacerbation, and improvements in left ventricular ejection fraction (LVEF), were assessed and compared between the two groups. Results A total of 847 patients were included in the study, with 74,5% (n=631) undergoing primary CRT implantation and 13,5% (n=114) receiving CRT upgrades. The mean age was 72±10 years-old and 57% (n=485) were women, and a mean follow-up time of 23±8 months. 33.7% (n=285) of the total were of ischemic etiology. The primary CRT implantation group demonstrated a mortality of 34% (n=215) and 13% (n=84) of hospitalization due to HF; NYHA functional class improvement in 58% (n=369), and 35,7% (n=225) were CRT responders with a mean LV ejection fraction (EF) improvement of ±10%, while the CRT upgrade group had a 31% (n=36) mortality and 19% (n=22) of hospitalization due to HF; NYHA functional class improvement in 60% (n=68), and 27% (n=31) were CRT responders with a mean LV EF improvement of 8,7%. There were no statistically significant differences regarding each endpoint, namely mortality, HF hospitalizations, NYHA functional class improvement, CRT responders and mean LVEF improvement. Conclusion A clear benefit from implantation of a primary CRT device implantation has already been demonstrated. However, recent trials revealed there was also benefit in upgrading from PPM to CRT patients with decrease LVEF, comparing with PPM. This study showed that the benefits from primary CRT were similar to the benefits from upgrading CRT, in terms of mortality reduction, HF hospitalizations, NYHA functional class improvement, CRT responders and mean LVEF improvement. Once again, just like in the most recent trials, this study demonstrates the clear benefit of upgrading from a PPM to CRT in patients with decreased LVEF.

Impact of non-typical LBBB on CRT response

Abstract Introduction Cardiac resynchronization therapy (CRT) benefits have been established in patients with heart failure and reduced left ventricular ejection fraction (HFrEF) who have a broad QRS and remain symptomatic despite optimized medical therapy. Responders typically are female, with LBBB and broader QRS. It remains uncertain to what extent do patients with non-LBBB QRS complex morphology respond to CRT and also if there are differences among various types of intraventricular conduction delays. Purpose To evaluate the impact of non-typical left bundle branch block (LBBB) on reverser remodeling and clinical events. Methods Single center, observational, retrospective study including patients (pts) who implanted CRT in the context of HFrEF, from 2015 to 2020. Evaluation of QRS morphology analysis was conducted. CRT response was defined by a reduction of LVESV≥15% or an increase in LVEF≥10%. Predictors of CRT response were evaluated with Chi-square and Mann- Whitney analysis. Impact on reverse remodeling and clinical outcomes was performed with Kaplan-Meyer analysis. Results A total of 361 pts were included for analysis, of which 184 had non-typical LBBB. Pts had a mean age of 71±9years old, the majority of pts were female (61%), and almost half were ischemic (47.8%). EGC evaluation prior to CRT implantation, revealed an atypical LBBB in 83 (45.1%) pts, typical RBBB in 23 (12.5%) pts, atypical RBBB 94.(9%) pts and nonspecific intraventricular conduction delay in 69 (37.5%) pts. During a mean time of follow-up of 2.9 ±2.4years, 33 pts (18%) had hospitalizations due to HF and 68 (37%) died. In this cohort, 78 pts (42.4%) were deemed as responders, who presented a better clinical outcome when compared to non-responders (p < 0.001, HR 2.629 [95% CI 1.635-4.225]. There was no difference among the four types of intraventricular conduction analyzed in respect to degree of CRT response – figure 1. Regarding clinical events during follow-up, there was once again no significant difference among the different patterns of non-typical LBBB– figure 2. In this subset population we found no independent predictors of CRT response, although non-responders were significantly older than responders (72±8 vs 69±10 years-old (p=0.016). Conclusion Although pts with non-typical LBBB morphology display a lower therapy response to CRT than reported for LBBB pts, the rate of response is not negligible and represents a protective factor for clinical outcomes. Different types of intraventricular conduction delay present no difference regarding long- term prognosis or reverse remodeling.Survival according to CRT response

Strauss criteria for left bundle branch block in cardiac resynchronization therapy: improved response with lower ventricular arrhythmic burden

Abstract Objectives The study sought to evaluate the impact of the stricter Strauss criteria for left bundle branch block (St-LBBB) on cardiac resynchronization therapy (CRT) response, hospitalizations, ventricular arrhythmia (VA) events and mortality. Background Although left bundle branch block (LBBB) is a strong predictor of response to CRT, a significant number of patients remain non-responders. Methods This is a retrospective analysis of prospectively collected data on heart failure (HF) patients with LBBB admitted for CRT implantation. Patients were divided in two groups according to the fulfillment or not of St-LBBB criteria. Results 82 patients with ischemic (ICM) and non-ischemic (NICM) HF [46 (56%) with St-LBBB and 36 (44%) with non-St-LBBB] were included. CRT response was more likely to occur in patients with St-LBBB (p<0.01), with the group of NICM exhibiting the greatest benefit (p<0.01). St-LBBB CRT responders displayed significantly lower rates of HF hospitalization (p<0.0001) compared to non-St-LBBB group. This was mostly evident in patients with NICM (p<0.0001) according to Kaplan-Meier time curves. CRT responders displayed significantly fewer VA events (p<0.001) and lower mortality rates (p<0.0001) than non-responders. Kaplan-Meier estimates demonstrated a significantly lower incidence of VAs in NICM patients with St-LBBB (p:0.049) in comparison to ICM patients with St-LBBB (p:0.25). Lower mortality rates were observed in CRT responders than non-responders (p<0.0001) with the group of NICM with St-LBBB criteria exhibiting the greatest benefit (p:0.0238). Conclusions Patients with NICM and St-LBBB present the greatest benefit with respect to CRT response, HF hospitalizations, VA events, and mortality. St-LBBB criteria may improve patient selection for CRT.

QRS INDEX TO PREDICT CARDIAC RESYNCHRONIZATION THERAPY RESPONSE: A TRICENTRIC STUDY

Abstract Background Several studies have evaluated the role of QRS duration (QRSd) or QRS narrowing as a predictor of response to cardiac resynchronization therapy (CRT) to reduce non–responders. Purpose The aim of our study was to determine the correlation between the relative change in QRS narrowing index (QI) compared to clinical outcome and prognosis in patients who underwent CRT implantation. Methods A three–center study involving 398 patients with a CRT device was conducted. Clinical variables, echocardiographic parameters and drug therapies, QRS duration before and after CRT implantation, and QRS index (QI) were measured. Results In a six–month follow–up, a significant improvement in left ventricle ejection fraction (EF), left ventricle end–diastolic and systolic volumes (LVEDV and LVESV) were observed. QI was significantly related to reverse remodelling (r = +0.22; 95% CI: 0.11 to 0.32, p= 0.001) and the cut–off value that best predicted LV reverse remodelling was 12.25% (AUC 0.7, p=0.001). At 24 months, a statistically significant difference was found between patients with a QI < 12.25% and those with a QI > 12.25%, regarding NYHA class worsening (p= 0,04). The mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes (p=0,0179). A correlation between pre–CRT QRSd/LVEDV and QI was observed (r = +0.20; 95% CI: 0.09 to 0.30, p=0.0003). A higher QRSd/LVEDV ratio was associated with an improved LVEF, LVEDV, LVESV (p <0.0001) at follow–up. Conclusions QI narrowing after CRT was related to greater echocardiographic reverse remodelling and lower rate of adverse events. The QI can improve adverse events’ prediction in a population with CRT regardless of comorbidities according to the Charlson Comorbidity index. QI could be used to predict CRT response.

VENTRICULAR ARRHYTHMIA EVENTS IN PATIENTS WITH IMPLANTABLE CARDIOVERTER–DEFIBRILLATOR BEFORE AND AFTER THE TREATMENT WITH SODIUM–GLUCOSE CO–TRANSPORTER 2 INHIBITORS

Abstract Background Role of sodium–glucose co–transporter 2 inhibitors (SGLT2i) in the treatment of chronic heart failure is increasing. However, some case series described appropriate shocks from ICD in patients following the initiations of SGLT2i and a larger analysis is not present in the literature. Methods The aim of this study is to investigate the rate of ventricular arrhythmic burden and appropriate anti–tachycardia therapy from ICD before and after the initiation of SGLT2i therapy. A retrospective single–center analysis was performed, comparing ventricular events from home monitoring reports 3 months before and 3 months after SGLT2i therapy treatment. Results Seventeen patients were enrolled in the study. The baseline clinical e therapy characteristics of patients are shown in the table. Ten patients (59%) had mono cameral or dual cameral ICD and 7 had implantable cardiac resynchronization therapy (CRT) defibrillators.During the 3 months before SGLT2i treatment, 4/17 patients had nun–sustained ventricular tachycardia (NSVT) vs 8/17 (23% vs 47%, P value 0.23) patients with NSTV after the treatment. Seven patients (41%) had an increase in the rate of NSVT events (with a patient with 28 NSVT after treatment vs 0 before treatment). No patients had anti–tachycardia therapy in the 3 months before treatment, while during the 3 months after the SGLT2i treatment, 1 patient had a ventricular tachycardia treated with anti–tachycardia pacing (110 days after the beginning of the treatment) and 2 patients had a ventricular tachycardia treated with appropriate shock (2 and 25 days after the beginning of SGLT2i treatment). Conclusion This small retrospective analysis showed an increase in ventricular arrhythmic events in the 3 months after the initiation of SGLT2i. These data prospect the need for a larger analysis for a stronger statistical correlation.

Comparative Analysis of Response to Cardiac Resynchronisation Therapy Upgrades in Patients with Implantable Cardioverter-Defibrillators and Pacemakers.

Introduction: The efficacy of de novo cardiac resynchronisation therapy (CRT) in patients with heart failure (HF), left ventricular systolic dysfunction (LVSD), and a broad QRS morphology is well established. However, the optimal stage for upgrading patients with existing pacemakers (PPMs) or implantable cardioverter-defibrillators (ICDs) and HF with high-burden right ventricular (RV) pacing remains uncertain. Thus, this multicentre retrospective analysis compared patients with pre-existing PPMs or ICDs who underwent CRT upgrades to investigate the appropriate stage for CRT implantation in these patients and to assess the validity of treating both PPM and ICD recipients under the same recommendation level in the current guidelines. Materials and Methods: A total of 151 participants underwent analysis in this study, comprising 93 upgrades to cardiac resynchronisation therapy with pacemaker (CRT-P) and 58 upgrades to cardiac resynchronisation therapy with defibrillator (CRT-D) across three centres in the UK. The aim of the study was to investigate the safety and efficacy of upgrading to CRT from an existing conventional pacemaker or an ICD in the context of high-burden RV pacing. The analysis was conducted separately for each group, assessing changes in echocardiographic parameters, functional New York Heart Association (NYHA) class, and procedure-related complications. Results: The PPM group had a higher percentage RVP burden compared to the ICD group. Post-upgrade, NYHA functional class and EF and LV volumes improved in both groups; however, the response to an upgrade from a pacemaker was greater compared to an upgrade from an ICD. Post-procedural complication risks were similar across the two subgroups but significantly higher compared to de novo implantation. Conclusions: Within the CRT-P subgroup, participants exhibited better responses than their CRT-D counterparts, evident both in echocardiographic improvements and clinical outcomes. Furthermore, patients with non-ischemic cardiomyopathy (NICM) were better responders than those with ischaemic cardiomyopathy. These findings suggest that international guidelines should consider approaching each subgroup separately in the future.

Cardiac resynchronization therapy in inotrope-dependent heart failure: a meta-analysis.

The viability of cardiac resynchronization therapy (CRT) in inotrope-dependent heart failure (HF) has been a matter of debate. We searched Medline, EMBASE, Scopus, and the Cochrane Library until 31 December 2022. Studies were included if (i) HF patients required inotropic support at CRT implantation; (ii) patients were ≥18years old; and (iii) they provided a clear definition of 'inotrope dependence' or 'inability to wean'. A meta-analysis was performed in R (Version 3.5.1). Nineteen studies comprising 386 inotrope-dependent HF patients who received CRT (mean age 64.4years, 76.9% male) were included. A large majority survived until discharge at 91.1% [95% confidence interval (CI): 81.2% to 97.6%], 89.3% were weaned off inotropes (95% CI: 77.6% to 97.0%), and mean discharge time post-CRT was 7.8days (95% CI: 3.9 to 11.7). After 1year of follow-up, 69.7% survived (95% CI: 58.4% to 79.8%). During follow-up, the mean number of HF hospitalizations was reduced by 1.87 (95% CI: 1.04 to 2.70, P<0.00001). Post-CRT mean QRS duration was reduced by 29.0ms (95% CI: -41.3 to 16.7, P<0.00001), and mean left ventricular ejection fraction increased by 4.8% (95% CI: 3.1% to 6.6%, P<0.00001). The mean New York Heart Association (NYHA) class post-CRT was 2.7 (95% CI: 2.5 to 3.0), with a pronounced reduction of individuals in NYHA IV (risk ratio=0.27, 95% CI: 0.18 to 0.41, P<0.00001). On univariate analysis, there was a higher prevalence of males (85.7% vs. 40%), a history of left bundle branch block (71.4% vs. 30%), and more pronounced left ventricular end-diastolic dilation (274.3±7.2 vs. 225.9±6.1mL). CRT appears to be a viable option for inotrope-dependent HF, with some of these patients seeming more likely to respond.

Mortality after cardiac resynchronization therapy or right ventricular pacing in transcatheter aortic valve replacement recipients.

Permanent pacemaker implantation (PMI) is associated with increased morbidity after transcatheter aortic valve replacement (TAVR). Cardiac resynchronization-therapy (CRT) is recommended for patients if left ventricular ejection fraction (LVEF) is ≤ 40% and ventricular pacing is expected in favor to sole right ventricular (RV) pacing. Meanwhile, LVEF may recover after TAVR in patients with aortic valve disease and the benefit of CRT is unknown. To analyze the impact of CRT implantation as compared to RV pacing after TAVR. Between 2012 and 2022, 4385 patients (53.1% female, mean age 81 ± 6years) without prior PMI undergoing TAVR were retrospectively identified in our institutional registry. After stratification of patients in LVEF ≤ 40%, 41-49% and ≥ 50%, Kaplan-Meier analysis revealed significantly different survival rates in each subgroup at 5years (37.0% vs. 43.5% vs. 55.1%; P ≤ 0.021). At multivariate regression, LVEF and new PMI after TAVR were not relevant for survival. A total of 105 patients with LVEF ≤ 40% received PMI after TAVR (86 patients with RV pacing and 19 with CRT). At 5years, all-cause mortality was significantly lower in patients with CRT-device as compared to patients without CRT-device (Kaplan Meier estimate of 21.1% vs. 48.8%; HR 0.48, CI 0.204 - 1.128; log rank p = 0.045). In multivariate analysis CRT remained a significant factor for 5-year survival in these patients (HR 0.3, CI 0.095-0.951, p = 0.041). In patients undergoing TAVR, PMI did not influence 5-year survival. In patients with LVEF ≤ 40%, CRT-device implantation was associated with improved survival compared to non-CRT-device implantation.

Implication of geriatric nutritional risk index on treatment response and long-term prognosis in patients with cardiac resynchronization therapy

PurposeGeriatric Nutritional Risk Index (GNRI) is a simple tool for assessing the nutritional status of the aging population. This study aims to explore the clinical implication of GNRI on treatment response and long-term clinical outcomes in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). MethodsPatients who underwent CRT implantation or upgrade at our hospital were retrospectively included. The association of GNRI and its tertiles with the echocardiographic response, all-cause mortality or heart transplantation, and the first hospitalization due to HF were investigated. ResultsTotally, 647 patients were enrolled, with a median age of 60 [Interquartile Range (IQR): 52–67] years and mean score of GNRI at 107.9 ± 23.7. Super-response rates increased significantly among the GNRI T1, T2, and T3 groups (25.1%, 29.8% vs. 41.1%, P = 0.002). Patients with higher GNRI were more likely to have better LVEF improvement after multiple adjustments (OR = 1.13, 95% CI: 1.04–1.23, P = 0.010). Higher GNRI was independently associated with a lower risk of all-cause mortality or heart implantation (HR = 0.95, 95% CI: 0.93–0.96, P < 0.001) and HF hospitalization (HR = 0.96, 95% CI: 0.95–0.98, P < 0.001). The inclusion of GNRI enhanced the predictability of all-cause mortality based on traditional model, including sex, New York Heart Association functional class, left bundle branch block, QRS reduction, and N-terminal pro-B-type natriuretic peptide level (C statistics improved from 0.785 to 0.813, P = 0.007). ConclusionHigher GNRI was associated with better treatment response and long-term prognosis in HF patients with CRT. Evaluation of nutritional status among CRT population is necessary for individualized choice of potential responders.

The effect of sodium-glucose co-transporter 2 inhibitors on outcomes after cardiac resynchronization therapy.

The trials upon which recommendations for the use of cardiac resynchronization therapy (CRT) in heart failure used optimal medical therapy (OMT) before sodium-glucose co-transporter 2 inhibitors (SGLT2i). Moreover, the SGLT2i heart failure trials included only a small proportion of participants with CRT, and therefore, it remains uncertain whether SGLT2i should be considered part of OMT prior to CRT. We compared electrocardiogram (ECG) and echocardiographic responses to CRT as well as hospitalization and mortality rates in consecutive patients undergoing implantation at a large tertiary centre between January 2019 to June 2022 with and without SGLT2i treatment. Three hundred seventy-four participants were included aged 74.0±11.5years (mean±standard deviation), with a left ventricular ejection fraction (LVEF) of 31.8±9.9% and QRS duration of 161±29ms. The majority had non-ischaemic cardiomyopathy (58%) and were in NYHA Class II/III (83.6%). These characteristics were similar between patients with (n=66) and without (n=308) prior SGLT2i treatment. Both groups demonstrated similar evidence of response to CRT in terms of QRS duration shortening, and improvements in LVEF, left ventricular end-diastolic inner-dimension (LVIDd) and diastolic function (E/A and e/e'). While there was no difference in rates of hospitalization (for heart failure or overall), mortality was significantly lower in patients treated with SGLT2i compared with those who were not (6.5 vs. 16.6%, P=0.049). We observed an improvement in mortality in patients undergoing CRT prescribed SGLT2i compared with those not prescribed SGLT2i, despite similar degrees of reverse remodelling. The authors recommend starting SGLT2i prior to CRT implantation, where it does not delay implantation.

Influence of multimorbidity and socioeconomic position on long-term health care utilization and prognosis in patients after cardiac resynchronization therapy implantation

Influence of multimorbidity and socioeconomic position on long-term health care utilization and prognosis in patients after cardiac resynchronization therapy implantation

Blood groups and Rhesus status as potential predictors of outcomes in patients with cardiac resynchronisation therapy

Cardiac resynchronisation therapy (CRT) improves prognosis in patients with heart failure (HF) however the role of ABO blood groups and Rhesus factor are poorly understood. We hypothesise that blood groups may influence clinical and survival outcomes in HF patients undergoing CRT. A total of 499 patients with HF who fulfilled the criteria for CRT implantation were included. Primary outcome of all-cause mortality and/or heart transplant/left ventricular assist device was assessed over a median follow-up of 4.6 years (IQR 2.3–7.5). Online repositories were searched to provide biological context to the identified associations. Patients were divided into blood (O, A, B, and AB) and Rhesus factor (Rh-positive and Rh-negative) groups. Mean patient age was 66.4 ± 12.8 years with a left ventricular ejection fraction of 29 ± 11%. There were no baseline differences in age, gender, and cardioprotective medication. In a Cox proportional hazard multivariate model, only Rh-negative blood group was associated with a significant survival benefit (HR 0.68 [0.47–0.98], p = 0.040). No association was observed for the ABO blood group (HR 0.97 [0.76–1.23], p = 0.778). No significant interaction was observed with prevention, disease aetiology, and presence of defibrillator. Rhesus-related genes were associated with erythrocyte and platelet function, and cholesterol and glycated haemoglobin levels. Four drugs under development targeting RHD were identified (Rozrolimupab, Roledumab, Atorolimumab, and Morolimumab). Rhesus blood type was associated with better survival in HF patients with CRT. Further research into Rhesus-associated pathways and related drugs, namely whether there is a cardiac signal, is required.

Evaluating the predictive value of late gadolinium enhancement assessed by cardiac magnetic resonance on sudden cardiac death in patients selected for implantable cardioverter defibrillator and cardiac resynchronization therapy implantation: a systematic review and meta-analysis.

Late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance (CMR) can evaluate myocardial scar associated with a higher risk of sudden cardiac death (SCD), which can guide the selection between cardiac resynchronization therapy with or without a defibrillator (CRT-P/CRT-D). Our aim was to investigate the association between LGE and SCD risk in patients with CRT using the LGE-CMR technique. We performed a systematic literature search using four databases. The target population was CRT candidates. The primary endpoint was SCD. The risk of bias was assessed using the QUIPS tool. Fifteen eligible articles were included with a total of 2494 patients, of whom 27%, 56%, and 19% had an implantable cardioverter defibrillator (ICD), CRT-D, and CRT-P, respectively. Altogether, 54.71% of the cohort was LGE positive, who had a 72% higher risk for SCD (HR 1.72; 95% CI 1.18-2.50) compared to LGE negatives. In non-ischemic patients, the proportion of LGE positivity was 46.6%, with a significantly higher risk for SCD as compared to LGE negatives (HR 2.42; 95% CI 1.99-2.94). The subgroup of CRT-only patients showed no difference between the LGE-positive vs. negative candidates (HR 1.17; 95% CI 0.82-1.68). Comparable SCD risk was observed between articles with short- (OR 7.47; 95% CI 0.54-103.12) vs. long-term (OR 6.15; 95% CI 0.96-39.45) follow-up time. LGE-CMR positivity was associated with an increased SCD risk; however, in CRT candidates, the difference in risk reduction between LGE positive vs. negative patients was statistically not significant, suggesting a role of reverse remodeling. LGE-CMR before device implantation could be crucial in identifying high-risk patients even in non-ischemic etiology.

Immediate pharmacotherapy intensification after cardiac resynchronization therapy: incidence, characteristics, and impact.

Cardiac resynchronization therapy (CRT) is an established treatment for drug-refractory heart failure (HF) in patients with left bundle branch block (LBBB). Acute haemodynamic improvement after CRT implantation may enable the intensification of HF medication soon thereafter. Immediate pharmacotherapy intensification (IPI) after CRT implantation achieves a synergetic effect, possibly leading to a better prognosis. This study aimed to explore the incidence, characteristics, and impact of IPI on real-world outcomes among CRT recipients with a history of hospitalization for acute HF. This multicentre retrospective study enrolled CRT recipients with LBBB morphology, a QRS width ≥120ms, a left ventricular ejection fraction ≤35%, and New York Heart Association II-IV HF symptoms. All patients had previous HF hospitalizations within the previous year and received guideline-directed medical therapy before CRT implantation. Patient baseline characteristics, including HF medication, were collected. IPI was defined as the intensification of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists within 30days of CRT implantation. The primary endpoint was all-cause death or first hospitalization for HF; the secondary endpoint was all-cause death. We enrolled 194 patients (75% male; mean age, 65±13years; 78% with non-ischaemic cardiomyopathy). One hundred five (54%) patients received IPI. Patients who received IPI exhibited a significantly shorter QRS duration (159±26 vs. 171±32ms; P=0.004), higher estimated glomerular filtration rate (55.2±20.0 vs. 47.8±24.7mL/min/1.73m2 ; P=0.022), and more dilated cardiomyopathy. During a median follow-up period of 29months, 70 (36%) patients reached the primary endpoint and 42 (22%) patients died. Patients with IPI showed significantly better outcomes for the primary and secondary endpoints than patients without IPI. The volumetric responder ratio at 6months after implantation was not significantly different between patients with and without IPI; however, patients who received IPI had reduced mortality even at 6months after implantation. In the multivariate analysis, IPI was an independent predictor of the primary endpoint (hazard ratio, 0.51; 95% confidence interval, 0.27-0.97; P=0.043). Immediate intensification of HF medication was achieved in 54% of CRT recipients and was significantly higher in patients without excessive QRS prolongation, preserved renal function, and dilated cardiomyopathy than others. In patients with LBBB morphology and QRS≥120ms, IPI was associated with a significantly better prognosis and fewer HF hospitalizations after CRT implantation than others.

History of cardiac resynchronization therapy : 30years of electrotherapeutic management for heart failure

The first permanent biventricular pacing system was implanted more than 30years ago. In this article, the historical development of cardiac resynchronization therapy (CRT), starting with the pathophysiological concept, followed by the initial "proof of concept" studies and finally the large prospective-randomized studies that led to the implementation of CRT in heart failure guidelines, is outlined. Since the establishment of CRT, both an expansion of indications, e.g., for patients with mild heart failure and atrial fibrillation, but also the return to patients with broad QRS complex and left bundle branch block who benefit most of CRT has evolved. New techniques such as conduction system pacing will have major influence on pacemaker therapy in heart failure, both as an alternative or adjunct to CRT.