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.

Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study.

BACKGROUND: A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot. METHODS: Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation. RESULTS: A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%-44%] at baseline to 42% [32%-50%] at early follow-up (P<0.001) and remained improved from baseline thereafter (P≤0.002). The QRS duration decreased from 180 [160-205] ms at baseline to 152 [133-182] ms at early follow-up (P<0.001) and remained decreased at intermediate and late follow-up (P≤0.001). Patients with upgraded CRT had consistent improvement in left ventricular ejection fraction and QRS duration at each time point (P≤0.004). Patients had a significantly improved New York Heart Association functional class after CRT implantation at each time point compared with baseline (P≤0.002). The transplant-free survival rates at 3, 5, and 8 years after CRT implantation were 85%, 79%, and 73%. CONCLUSIONS: In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population.

Efficacy and safety of novel left ventricular pacing leads: 1-year analysis of the NAVIGATOR trial.

OBJECTIVES: Assess safety and performance of novel quadripolar preshaped left ventricular (LV) leads: NAVIGO 4LV 2D ('S shaped') and NAVIGO 4LV ARC ('U shaped'). METHODS: Patients indicated for cardiac resynchronisation therapy were enrolled in a multicentre, prospective, controlled study (NAVIGATOR, NCT03279484). Patients were implanted with either a NAVIGO 4LV 2D or ARC lead, and assessed at 10 weeks, 6, 12 and 24 months post-implant. Co-primary safety and performance endpoints were assessed at 10 weeks. Safety endpoint was the patients' rate free from lead-related complications. Performance endpoint was the rate of patients with successful lead performance, defined as LV pacing threshold ≤2.5 V at 0.5 ms on at least one pacing vector, and the absence of phrenic nerve stimulation at the final programmed configuration. Lead-related complications and electrical parameters were monitored throughout study. RESULTS: A NAVIGO 4LV lead was successfully implanted in 211 out of 217 patients (97.2%). The safety endpoint was met, with 100% and 96.1% of patients free from complications for NAVIGO 4LV 2D and ARC, respectively. The performance endpoint was met with 98.1% and 98.9% of patients with a successful lead performance for NAVIGO 4LV 2D and ARC, respectively. Over 12 months, the global complication-free rate for both leads was 97.1% (95% CI: 93.71% to 98.70%), with a mean pacing capture threshold of 1.23 V±0.73 V and a mean impedance of 951 Ω±300.1 Ω. CONCLUSION: A high implantation success rate and low complication rate was reported for the novel NAVIGO 4LV 2D and ARC leads, along with successful performance up to 12 months.

Implantable cardioverter defibrillator and cardiac resynchronization treatment in people with type 2 diabetes: a comparison with age- and sex matched controls from the general population.

BACKGROUND: Increased risk of severe tachyarrhythmias is reported in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to explore if treatment with cardiac implantable electronic device (CIED) such as implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy- pacemaker and -defibrillator (CRT-P/CRT-D) differed in patients with vs. without T2DM. A secondary aim was to identify patient characteristics indicating an increased CIED treatment. METHOD: 416 162 adult patients with T2DM from the Swedish National Diabetes Registry and 2 081 087 controls from the Swedish population, matched for age, sex and living area, were included between 1/1/1998 and 31/12/2012 and followed until 31/12/2013. They were compared regarding prevalence of ventricular tachycardia (VT) at baseline and the risk of receiving a CIED during follow-up. Multivariable Cox regression analysis was performed to estimate the risk of CIED-treatment and factors identifying patients with such risk. RESULTS: Ventricular fibrillation (VF) (0.1% vs 0.0004%) and (VT) (0.2% vs. 0.1%) were more frequent among patients with T2DM compared to controls. CIED-treatment was significantly increased in patients with T2DM both in unadjusted and adjusted analyses. HR and 95% CI, after adjustment for sex, age, marital status, income, education, country of birth, coronary artery disease and congestive heart failure, were 1.32 [1.21-1.45] for ICD, 1.74 [1.55-1.95] for CRT-P and 1.69 [1.43-1.99] for CRT-D. Blood-pressure and lipid lowering therapies were independent risk factors associated to receiving CIED, while female sex was protective. CONCLUSIONS: Although the proportion of VT/VF was low, patients with T2DM had a higher prevalence of these conditions and increased risk for treatment with CIED compared to controls. This underlines the importance of recognizing that T2DM patients have an increased need of CIED.

Truncal Plane Blocks for Implantation of Cardiac Resynchronization Devices: A Systematic Review.

Patients undergoing subcutaneous implantable cardioverter-defibrillator (S-ICD) placement can experience significant perioperative pain. General anesthesia is traditionally used for S-ICD placement and is associated with increased risk. Truncal plane blocks (TPBs) and sedation offer an alternative for adequate analgesia while avoiding hemodynamic compromise related to general anesthesia. A comprehensive evidence search utilized PubMed, CINAHL, Google Scholar, EBSCOhost, US National Library of Medicine Clinical Trials, and Medline Complete databases and the evidence examined the efficacy of TPBs in S-ICD placement. The quality of evidence was assessed using the guidelines described in the Johns Hopkins Nursing Evidence-Based Practice Model. Three randomized-controlled trials, four nonrandomized experimental studies, two nonexperimental studies, and three case studies totaling 379 patients were reviewed. Ultrasound-guided TPBs with sedation demonstrated superior analgesic efficacy for S-ICD procedures. Hemodynamics marginally deviated from baseline values and were well tolerated by patients. The evidence suggests that TPBs provide adequate analgesia during intraoperative and postoperative periods. TPBs are effective in reducing pain scores and opioid consumption postoperatively. Although there were no significant changes in hemodynamic values, more research should be conducted to evaluate the effects on intraoperative hemodynamics.

How to assess and treat right ventricular electromechanical dyssynchrony in post-repair tetralogy of Fallot: insights from imaging, invasive studies, and computational modelling.

BACKGROUND AND AIMS: Right bundle branch block (RBBB) and resulting right ventricular (RV) electromechanical discoordination are thought to play a role in the disease process of subpulmonary RV dysfunction that frequently occur post-repair tetralogy of Fallot (ToF). We sought to describe this disease entity, the role of pulmonary re-valvulation, and the potential added value of RV cardiac resynchronization therapy (RV-CRT). METHODS: Two patients with repaired ToF, complete RBBB, pulmonary regurgitation, and significantly decreased RV function underwent echocardiography, cardiac magnetic resonance, and an invasive study to evaluate the potential for RV-CRT as part of the management strategy. The data were used to personalize the CircAdapt model of the human heart and circulation. Resulting Digital Twins were analysed to quantify the relative effects of RV pressure and volume overload and to predict the effect of RV-CRT. RESULTS: Echocardiography showed components of a classic RV dyssynchrony pattern which could be reversed by RV-CRT during invasive study and resulted in acute improvement in RV systolic function. The Digital Twins confirmed a contribution of electromechanical RV dyssynchrony to RV dysfunction and suggested improvement of RV contraction efficiency after RV-CRT. The one patient who underwent successful permanent RV-CRT as part of the pulmonary re-valvulation procedure carried improvements that were in line with the predictions based on his Digital Twin. CONCLUSION: An integrative diagnostic approach to RV dysfunction, including the construction of Digital Twins may help to identify candidates for RV-CRT as part of the lifetime management of ToF and similar congenital heart lesions.

Cardiac resynchronization using fusion pacing during exercise.

INTRODUCTION: Fusion pacing requires correct timing of left ventricular pacing to right ventricular activation, although it is unclear whether this is maintained when atrioventricular (AV) conduction changes during exercise. We used cardiopulmonary exercise testing (CPET) to compare cardiac resynchronization therapy (CRT) using fusion pacing or fixed AV delays (AVD). METHODS: Patients 6 months post-CRT implant with PR intervals < 250 ms performed two CPET tests, using either the SyncAV™ algorithm or fixed AVD of 120 ms in a double-blinded, randomized, crossover study. All other programming was optimized to produce the narrowest QRS duration (QRSd) possible. RESULTS: Twenty patients (11 male, age 71 [65-77] years) were recruited. Fixed AVD and fusion programming resulted in similar narrowing of QRSd from intrinsic rhythm at rest (p = .85). Overall, there was no difference in peak oxygen consumption (V̇O2 PEAK , p = .19), oxygen consumption at anaerobic threshold (VT1, p = .42), or in the time to reach either V̇O2 PEAK (p = .81) or VT1 (p = .39). The BORG rating of perceived exertion was similar between groups. CPET performance was also analyzed comparing whichever programming gave the narrowest QRSd at rest (119 [96-136] vs. 134 [119-142] ms, p < .01). QRSd during exercise (p = .03), peak O2 pulse (mL/beat, a surrogate of stroke volume, p = .03), and cardiac efficiency (watts/mL/kg/min, p = .04) were significantly improved. CONCLUSION: Fusion pacing is maintained during exercise without impairing exercise capacity compared with fixed AVD. However, using whichever algorithm gives the narrowest QRSd at rest is associated with a narrower QRSd during exercise, higher peak stroke volume, and improved cardiac efficiency.

QRS Morphology and the Risk of Ventricular Tachyarrhythmia in Cardiac Resynchronization Therapy Recipients.

BACKGROUND: There are conflicting data on the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the risk of life-threatening ventricular tachyarrhythmia in heart failure patients. OBJECTIVES: The authors aimed to assess whether QRS morphology is associated with risk of ventricular arrhythmias in CRT recipients. METHODS: The study population comprised 2,862 patients implanted with implantable cardioverter defibrillator (ICD)/CRT-D for primary prevention who were enrolled in 5 landmark primary prevention ICD trials (MADIT-II [Multicenter Automated Defibrillator Implantation Trial], MADIT-CRT [Multicenter Automated Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], MADIT-RIT [Multicenter Automated Defibrillator Implantation Trial-Reduction in Inappropriate Therapy], MADIT-RISK [Multicenter Automated Defibrillator Implantation Trial-RISK], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter Defibrillators]). Patients with QRS duration ≥130 ms were divided into 2 groups: those implanted with an ICD only vs CRT-D. The primary endpoint was fast ventricular tachycardia (VT)/ventricular fibrillation (VF) (defined as VT ≥200 beats/min or VF), accounting for the competing risk of death. Secondary endpoints included appropriate shocks, any sustained VT or VF, and the burden of fast VT/VF, assessed in a recurrent event analysis. RESULTS: Among patients with left bundle branch block (n = 1,792), those with CRT-D (n = 1,112) experienced a significant 44% (P < 0.001) reduction in the risk of fast VT/VF compared with ICD-only patients (n = 680), a significantly lower burden of fast VT/VF (HR: 0.55; P = 0.001), with a reduced burden of appropriate shocks (HR: 0.44; P < 0.001). In contrast, among patients with non-left bundle branch block (NLBBB) (N = 1,070), CRT-D was not associated with reduction in fast VT/VF (HR: 1.33; P = 0.195). Furthermore, NLBBB patients with CRT-D experienced a statistically significant increase in the burden of fast VT/VF events compared with ICD-only patients (HR: 1.90; P = 0.013). CONCLUSIONS: Our data suggest a potential proarrhythmic effect of CRT among patients with NLBBB. These data should be considered in patient selection for treatment with CRT.

Arrhythmic Risk in Biventricular Pacing Compared With Left Bundle Branch Area Pacing: Results From the I-CLAS Study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP. METHODS: The I-CLAS study (International Collaborative LBBAP Study) included patients with left ventricular ejection fraction ≤35% who underwent BVP or LBBAP for cardiac resynchronization therapy between January 2018 and June 2022 at 15 centers. We performed propensity score-matched analysis of LBBAP and BVP in a 1:1 ratio. We assessed the incidence of VT/VF and new-onset AF among patients with no history of AF. Time to sustained VT/VF and time to new-onset AF was analyzed using the Cox proportional hazards survival model. RESULTS: Among 1778 patients undergoing cardiac resynchronization therapy (BVP, 981; LBBAP, 797), there were 1414 propensity score-matched patients (propensity score-matched BVP, 707; propensity score-matched LBBAP, 707). The occurrence of VT/VF was significantly lower with LBBAP compared with BVP (4.2% versus 9.3%; hazard ratio, 0.46 [95% CI, 0.29-0.74]; P<0.001). The incidence of VT storm (>3 episodes in 24 hours) was also significantly lower with LBBAP compared with BVP (0.8% versus 2.5%; P=0.013). Among 299 patients with cardiac resynchronization therapy pacemakers (BVP, 111; LBBAP, 188), VT/VF occurred in 8 patients in the BVP group versus none in the LBBAP group (7.2% versus 0%; P<0.001). In 1194 patients with no history of VT/VF or antiarrhythmic therapy (BVP, 591; LBBAP, 603), the occurrence of VT/VF was significantly lower with LBBAP than with BVP (3.2% versus 7.3%; hazard ratio, 0.46 [95% CI, 0.26-0.81]; P=0.007). Among patients with no history of AF (n=890), the occurrence of new-onset AF >30 s was significantly lower with LBBAP than with BVP (2.8% versus 6.6%; hazard ratio, 0.34 [95% CI, 0.16-0.73]; P=0.008). The incidence of AF lasting >24 hours was also significantly lower with LBBAP than with BVP (0.7% versus 2.9%; P=0.015). CONCLUSIONS: LBBAP was associated with a lower incidence of sustained VT/VF and new-onset AF compared with BVP. This difference remained significant after adjustment for differences in baseline characteristics between patients with BVP and LBBAP. Physiological resynchronization by LBBAP may be associated with lower risk of arrhythmias compared with BVP.

Persistence of significant secondary mitral regurgitation post-cardiac resynchronization therapy and survival: a systematic review and meta-analysis : Mitral regurgitation and mortality post-CRT.

Cardiac resynchronization therapy (CRT) significantly reduces secondary mitral regurgitation (MR) in patients with severe left ventricular systolic dysfunction. However, uncertainty remains as to whether improvement in secondary MR correlates with improvement with mortality seen in CRT. We conducted a meta-analysis to determine the association of persistent unimproved significant secondary MR (defined as moderate or moderate-to-severe or severe MR) compared to improved MR (no MR or mild MR) post-CRT with all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A systematic search of PubMed, EMBASE, and Cochrane Library databases till July 31, 2022 identified studies reporting clinical outcomes by post-CRT secondary MR status. In 12 prospective studies of 4954 patients (weighted mean age 66.8 years, men 77.8%), the median duration of follow-up post-CRT at which patients were re-evaluated for significant secondary MR was 6 months and showed significant relative risk reduction of 30% compared to pre-CRT. The median duration of follow-up post-CRT for ascertainment of main clinical outcomes was 38 months. The random effects pooled hazard ratio (95% confidence interval) of all-cause mortality in patients with unimproved secondary MR compared to improved secondary MR was 2.00 (1.57-2.55); p < 0.001). There was insufficient data to evaluate secondary outcomes in a meta-analysis, but limited data that examined the relationship showed significant association of unimproved secondary MR with increased cardiovascular mortality and heart failure hospitalization. The findings of this meta-analysis suggest that lack of improvement in secondary MR post-CRT is associated with significantly elevated risk of all-cause mortality and possibly cardiovascular mortality and heart failure hospitalization. Future studies may investigate approaches to address persistent secondary MR post-CRT to help improved outcome in this population.

Artificial intelligence models in prediction of response to cardiac resynchronization therapy: a systematic review.

The aim of the presented review is to summarize the literature data on the accuracy and clinical applicability of artificial intelligence (AI) models as a valuable alternative to the current guidelines in predicting cardiac resynchronization therapy (CRT) response and phenotyping of patients eligible for CRT implantation. This systematic review was performed according to the PRISMA guidelines. After a search of Scopus, PubMed, Cochrane Library, and Embase databases, 675 records were identified. Twenty supervised (prediction of CRT response) and 9 unsupervised (clustering and phenotyping) AI models were analyzed qualitatively (22 studies, 14,258 patients). Fifty-five percent of AI models were based on retrospective studies. Unsupervised AI models were able to identify clusters of patients with significantly different rates of primary outcome events (death, heart failure event). In comparison to the guideline-based CRT response prediction accuracy of 70%, supervised AI models trained on cohorts with > 100 patients achieved up to 85% accuracy and an AUC of 0.86 in their prediction of response to CRT for echocardiographic and clinical outcomes, respectively. AI models seem to be an accurate and clinically applicable tool in phenotyping of patients eligible for CRT implantation and predicting potential responders. In the future, AI may help to increase CRT response rates to over 80% and improve clinical decision-making and prognosis of the patients, including reduction of mortality rates. However, these findings must be validated in randomized controlled trials.

Pacing-induced cardiomyopathy in patients with preserved ejection fraction undergoing permanent cardiac pacemaker placement.

BACKGROUND: Chronic right-ventricular (RV) pacing can worsen heart failure in patients with a low ejection fraction (EF), but little is known about pacing-induced cardiomyopathy (PICM) in patients with preserved EF. We aimed to investigate risk factors of PICM in these patients during long-term follow-up. METHODS: The prospective registry at Chosun University Hospital, South Korea, included de novo patients with preserved EF undergoing transvenous permanent pacemaker (PPM) implantation for atrioventricular blockage from 2017 to 2021. Patients with EF ≥ 50% and expected ventricular pacing ≥ 40% were included. Composite outcomes were cardiac death (pump failure), hospitalization because of heart failure, PICM, and biventricular pacing (BVP) upgrade. RESULTS: A total of 168 patients (69 men, 76.3 ± 10.4 years) were included. During three years of follow-up, one patient died, 14 were hospitalized, 16 suffered PICM, and two underwent BVP upgrade. PICM were associated with reduced global longitudinal strain (GLS), prolonged paced QRS duration (pQRSd) and diastolic variables (E/e', LAVI). Cox regression analysis identified pQRSd (hazard ratio [HR], 1.111; 95% confidence interval [CI], 1.011-1.222; P = 0.03) and reduced GLS (HR, 1.569; 95% CI, 1.163-2.118; P = 0.003) as independent predictors of PICM. GLS showed high predictive accuracy for PICM, with an area under the curve of 0.84 (95% CI 0.779-0.894; P < 0.001) [GLS -12.0, 62.5% sensitivity, and 86.1% specificity]. CONCLUSION: RV pacing increased the risk of PICM in patients with preserved EF. Reduced GLS and prolonged pQRSd could help identify individuals at high risk of PICM even with preserved EF.

Implications of ventricular arrhythmia after cardiac resynchronization therapy.

BACKGROUND: Conflicting data are available on whether ventricular arrhythmia (VA) or shock therapy increases mortality. Although cardiac resynchronization therapy (CRT) reduces the risk of VA, little is known about the prognostic value of VA among patients with CRT devices. OBJECTIVES: The purpose of this study was to evaluate the implications of VA as a prognostic marker for CRT. METHODS: We investigated 330 CRT patients within 1 year after CRT device implantation. The primary endpoint was the composite endpoint of all-cause death or hospitalization for heart failure. RESULTS: Forty-three patients had VA events. These patients had a significantly higher risk of the primary endpoint, even among CRT responders (P = .009). Fast VA compared to slow VA was associated with an increased risk of the primary endpoint (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.06-4.34; P = .035). Shock therapy was not associated with a primary endpoint (shock therapy vs antitachycardia pacing: HR 1.49; 95% CI 0.73-3.03; P = .269). The patients with VA had a lower prevalence of response to CRT (23 [53%] vs 202 [70%]; P = .031) and longer left ventricular paced conduction time (174 ± 23 ms vs 143 ± 36 ms; P = .003) than the patients without VA. CONCLUSION: VA occurrence within 1 year was related to paced electrical delay and poor response to CRT. VA could be associated with poor prognosis among CRT patients.

Echocardiographic mechanical dyssynchrony predicts long-term mortality in patients with cardiac resynchronisation therapy.

Cardiac resynchronisation therapy (CRT) is an established treatment for patients with symptomatic heart failure with reduced left ventricular ejection fraction (LVEF ≤ 35%; HFrEF) and conduction disturbances (QRS duration ≥ 130 ms). The presence of mechanical dyssynchrony (MD) on echocardiography has been hypothesised to be of predictive value in determining indication for CRT. This study investigated the impact of MD (apical rocking [AR] and septal flash [SF]) on long-term survival in CRT recipients. HFrEF patients (n = 425; mean age 63.0 ± 10.6 years, 72.3% male, 60.7% non-ischaemic aetiology) with a guideline-derived indication for CRT underwent device implantation. MD markers were determined at baseline and after a mean follow-up of 11.5 ± 8.0 months; long-term survival was also determined. AR and/or SF were present in 307 (72.2%) participants at baseline. During post-CRT follow-up, AR and/or SF disappeared in 256 (83.4%) patients. Overall mean survival was 95.9 ± 52.9 months, longer in women than in men (109.1 ± 52.4 vs. 90.9 ± 52.4 months; p < 0.001) and in younger (< 60 years) versus older patients (110.6 ± 53.7 vs. 88.6 ± 51.1 months; p < 0.001). Patients with versus without MD markers at baseline generally survived for longer (106.2 ± 52.0 vs. 68.9 ± 45.4 months; p < 0.001), and survival was best in patients with resolved versus persisting MD (111.6 ± 51.2 vs. 79.7 ± 47.6 months p < 0.001). Age and MD at baseline were strong predictors of long-term survival in HFrEF patients undergoing CRT on multivariate analysis. Novel echocardiography MD parameters in HFrEF CRT recipients predicted long-term mediated better outcome, and survival improved further when AR and/or SF disappear after CRT implantation.

Outcomes of cardiac resynchronization therapy in congenital heart disease: A meta-analysis and systematic review.

INTRODUCTION: Cardiac resynchronization therapy (CRT) is a standard treatment for patients with heart failure with reduced ejection fraction. However, there is still a gap of evidence in congenital heart disease (CHD) patients regarding resynchronization therapy. METHODS: We performed a meta-analysis and systematic review of CHD patients who received CRT implantation. We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to June 2023. Studies that reported response rate to CRT, total mortality rate, change in QRS duration, change in left ventricular ejection fraction, and change in New York Heart Association functional class were included. RESULTS: A total of 14 studies were included in the study. There were 10 studies that reported response rates after implantation. The overall response rate to CRT in CHD patients was 68% (95% confidence interval [CI] 61%-75%, I2 32%). The response rates in patients with systemic right ventricle (RV), systemic left ventricle (LV), and single ventricle were 58% (95% CI 46%-70%, I2 0%), 80% (95% CI 74%-86% I2 14%), and 67% (95% CI 49%-80% I2 0%). Response to CRT in systemic RV was inferior to systemic LV with an odds ratio of 0.38 (95% CI 0.15-0.95, I2 38%). The total mortality rate from seven studies was 12% (95% CI 8%-18%, I2 55%). The parameters which represented ventricular dyssynchrony improved after CRT implantation. CONCLUSION: The overall response rate to CRT in CHD was 68%. Patients with systemic RV had a lower response rate to CRT when compared to patients with systemic LV. The total mortality rate after CRT implantation was 12%.

Left bundle branch pacing lead for sensing ventricular arrhythmias in implantable cardioverter-defibrillator: A pilot study (LBBP-ICD study).

BACKGROUND: Left bundle branch pacing (LBBP) has been suggested as an alternative modality for biventricular pacing in cardiac resynchronization therapy (CRT)-eligible patients. As it provides stable R-wave sensing, LBBP has been recently used to provide sensing of ventricular arrhythmia in patients receiving implantable cardioverter-defibrillator (ICD) with CRT. OBJECTIVE: The aim of this study was to analyze the long-term safety and efficacy of the LBBP lead for appropriate detection of ventricular arrhythmia and delivery of antitachycardia pacing (ATP) in patients requiring defibrillator therapy with CRT. METHODS: CRT-eligible patients who underwent successful LBBP-optimized ICD and LBBP-optimized CRT with defibrillator were enrolled. The LBBP lead was connected to the right ventricular-P/S port after capping the IS-1 connector plug of the DF-1-ICD lead. LBBP-optimized ICD or LBBP-optimized CRT with defibrillator was decided on the basis of correction of conduction system disease. Documented arrhythmic episodes and therapy delivered were analyzed. RESULTS: Thirty patients were enrolled. The mean age was 59.7 ± 10.5 years. LBBP resulted in an increase in left ventricular ejection fraction from 29.9% ± 4.6% to 43.9% ± 11.2% (P < .0001). During a mean follow-up of 22.9 ± 12.5 months, 254 ventricular arrhythmic events were documented. Appropriate events (n = 225 [89%]) included nonsustained ventricular tachycardia (VT) (n = 212 episodes [94%]), VT (n = 8 [3.5%]), and ventricular fibrillation (n = 5 [2.5%]). ATP efficacy in terminating VT was 75%. Eleven percent of episodes (n = 29) were inappropriately detected because of T-wave oversensing. Inappropriate therapy (ATP) was delivered for 14 episodes (5.5%). Three patients (10%) had worsening of tricuspid regurgitation. CONCLUSION: Sensing from the LBBP lead for arrhythmia detection is safe as ∼90% of the episodes were detected appropriately. Future studies with a dedicated LBBP-defibrillator lead along with algorithms to avoid oversensing can help in combining defibrillation with conduction system pacing.

Left Bundle Branch Pacing vs Left Ventricular Septal Pacing vs Biventricular Pacing for Cardiac Resynchronization Therapy.

BACKGROUND: Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are considered to be acceptable as LBBAP strategies. Differences in clinical outcomes between LBBP and LVSP are yet to be determined. OBJECTIVES: The purpose of this study was to compare the outcomes of LBBP vs LVSP vs BIVP for CRT. METHODS: In this prospective multicenter observational study, LBBP was compared with LVSP and BIVP in patients undergoing CRT. The primary composite outcome was freedom from heart failure (HF)-related hospitalization and all-cause mortality. Secondary outcomes included individual components of the primary outcome, postprocedural NYHA functional class, and electrocardiographic and echocardiographic parameters. RESULTS: A total of 415 patients were included (LBBP: n = 141; LVSP: n = 31; BIVP: n = 243), with a median follow-up of 399 days (Q1-Q3: 249.5-554.8 days). Freedom from the primary composite outcomes was 76.6% in the LBBP group and 48.4% in the LVSP group (HR: 1.37; 95% CI: 1.143-1.649; P = 0.001), driven by a 31.4% absolute increase in freedom from HF-related hospitalizations (83% vs 51.6%; HR: 3.55; 95% CI: 1.856-6.791; P < 0.001) without differences in all-cause mortality. LBBP was also associated with a higher freedom from the primary composite outcome compared with BIVP (HR: 1.43; 95% CI: 1.175-1.730; P < 0.001), with no difference between LVSP and BIVP. CONCLUSIONS: In patients undergoing CRT, LBBP was associated with improved outcomes compared with LVSP and BIVP, while outcomes between BIVP and LVSP are similar.

Conventional biventricular pacing is still preferred to conduction system pacing for atrioventricular block in patients with reduced ejection fraction and narrow QRS.

It is well established that right ventricular pacing is detrimental in patients with reduced cardiac function who require ventricular pacing (VP), and alternatives nowadays are comprised of biventricular pacing (BiVP) and conduction system pacing (CSP). The latter modality is of particular interest in patients with a narrow baseline QRS as it completely avoids, or minimizes, ventricular desynchronization associated with VP. In this article, experts debate whether BiVP or CSP should be used to treat these patients.

Role of monocytes and dendritic cells in cardiac reverse remodelling after cardiac resynchronization therapy.

BACKGROUND AND AIMS: Monocytes and dendritic cells (DC) are both key inflammatory cells, with recognized effects on cardiac repair. However, there are distinct subsets of monocytes with potential for beneficial or detrimental effects on heart failure (HF) pathogenesis. The connection between reverse cardiac remodelling, the potential anti-inflammatory effect of cardiac resynchronization therapy (CRT) and monocytes and DC homeostasis in HF is far from being understood. We hypothesized that monocytes and DC play an important role in cardiac reverse remodelling and CRT response. Therefore, we aimed to assess the potential role of baseline peripheral levels of blood monocytes and DC subsets and their phenotypic and functional activity for CRT response, in HF patients. As a secondary objective, we aimed to evaluate the impact of CRT on peripheral blood monocytes and DC subsets, by comparing baseline and post CRT circulating levels and phenotypic and functional activity. METHODS: Forty-one patients with advanced HF scheduled for CRT were included in this study. The quantification and phenotypic determination of classical (cMo), intermediate (iMo) and non-classical monocytes (ncMo), as well as of myeloid (mDC) and plasmacytoid DC (pDC) were performed by flow cytometry in a FACSCanto™II (BD) flow cytometer. The functional characterization of total monocytes and mDC was performed by flow cytometry in a FACSCalibur flow cytometer, after in vitro stimulation with lipopolysaccharide from Escherichia coli plus interferon (IFN)-γ, in the presence of Brefeldina A. Comparisons between the control and the patient group, and between responders and non-responders to CRT were performed. RESULTS: Compared to the control group, HF population presented a significantly lower frequency of pDC at baseline and a higher proportion of monocytes and mDC producing IL-6 and IL-1ß, both before and 6-months after CRT (T6). There was a remarkable decrease of cMo and an increase of iMo after CRT, only in responders. The responder group also presented higher ncMo values at T6 compared to the non-responder group. Both responders and non-responders presented a decrease in the expression of CD86 in all monocyte and DC populations after CRT. Moreover, in non-responders, the increased frequency of IL-6-producing DC persisted after CRT. CONCLUSION: Our study provides new knowledge about the possible contribution of pDC and monocytes subsets to cardiac reverse remodelling and response to CRT. Additionally, CRT is associated with a reduction on CD86 expression by monocytes and DC subsets and in their potential to produce pro-inflammatory cytokines, contributing, at least in part, for the well described anti-inflammatory effects of CRT in HF patients.

Phenogrouping and risk stratification of patients undergoing cardiac resynchronization therapy upgrade using topological data analysis.

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 ).