Cardiac Resynchronization Therapy Response Research Articles

Safety and efficacy of orthodromic snare technique in left ventricular lead delivery in cardiac resynchronization implantation.

Cardiac resynchronization therapy (CRT) improves ventricular function, but a positive response to CRT is often limited due to left ventricular (LV) lead placement in a suboptimal position. Complex coronary venous anatomy can hinder the placement of an LV lead in the target vessel, leading to poor CRT response. To report experience with snare-assisted LV lead delivery in CRT and compare outcomes with the conventional LV lead delivery. This is a single-center retrospective case-control study of CRT implants between 2016 and 2021. Snare-assisted lead delivery was performed in cases where conventional lead placement failed or when a preferred target vessel had anatomy amenable to the technique. Safety and outcomes were compared to conventional LV lead placement cases. Among 180 CRT cases, 33 were snare-assisted, and 147 were conventional LV lead placements. Median follow-up was 924 days in the snare and 618.5 days in the control group. The lead placement was successful in 28/33 snare and 138/147 control cases. A mid-vessel segment was attained in 89.3% of snare and 72.5% of control cases(p=.03). The apical position was more frequently observed in the control group (26.8% vs. 7.1%, p=.03). All-cause mortality trended lower in the snare group (6.1%) compared to (17.1%) in the control group (p=.13). Snare-assisted LV lead delivery is a safe and effective technique that can be utilized for overcoming complex venous anatomy.

A Novel Liver Fibrosis Marker FIB-5 Index Predicted Response to Cardiac Resynchronization Therapy and Prognostic Outcomes in Patients With Heart Failure.

The fibrosis-5 (FIB-5) index is a noninvasive marker for assessing the progression of liver fibrosis and predictor in patients with heart failure (HF). This study investigated the association between the FIB-5 index and response to cardiac resynchronization therapy (CRT) and evaluated its predictive value for prognosis. In total, 203 patients who underwent CRT/CRT-defibrillator (CRT-D) implantation were retrospectively included. The FIB-5 index was calculated using blood samples obtained before and after CRT/CRT-D. Response to CRT was defined as a relative reduction in left ventricular end-systolic volume of ≥15% 6 months after CRT/CRT-D. We compared the prognosis after CRT/CRT-D between the groups according to the FIB-5 index. One hundred and twenty-three patients (61%) responded to CRT. The responder group demonstrated a significantly higher FIB-5 index than the nonresponder group (-2.76 ± 3.85 vs. -4.67 ± 3.29, p < 0.001). Receiver-operating characteristic analysis demonstrated that the area under the curve of the FIB-5 index was 0.660 with a cutoff value of -4.00 for responders. In multivariate analysis, FIB-5 index ≥ -4.00 was an independent predictor for CRT response (odds ratio: 3.665, p = 0.003), in addition to QRS duration ≥ 150 ms and echocardiographic dysynchrony. The FIB-5 index increased significantly after 6 months in the responder group but not in the nonresponder group. The FIB-5 index ≥ -4.00 group showed a significantly better prognosis for cardiac death, HF hospitalization, and composite endpoint than the FIB-5 index < -4.00 group. The FIB-5 index in addition to classical predictors may be a useful marker for predicting response to CRT.

A nomogram for predicting CRT response based on multi-parameter features

ObjectiveTo construct a nomogram for predicting the responsiveness of cardiac resynchronization therapy (CRT) in patients with chronic heart failure and verify its predictive efficacy.MethodA retrospective study was conducted including 109 patients with chronic heart failure who successfully received CRT from January 2018 to December 2022. According to patients after six months of the CRT preoperative improving acuity in the left ventricular ejection fraction is 5% or at least improve grade 1 NYHA heart function classification, divided into responsive group and non-responsive group. Clinical data of patients were collected, and LASSO regression analysis and multivariate logistic regression analysis were used to explore relative factors. A nomogram was constructed, and the predictive performance of the nomogram was evaluated using the calibration curve and decision curve analysis (DCA).ResultsAmong the 109 patients, 61 were assigned to the CRT-responsive group, while 48 were assigned to the non-responsive group. LASSO regression analysis showed that left ventricular end-systolic volume, diffuse fibrosis, and left bundle branch block (LBBB) were independent factors for CRT responsiveness in patients with heart failure (P < 0.05). Based on the above three predictive factors, a nomogram was constructed. The ROC curve analysis showed that the area under the curve (AUC) was 0.865 (95% CI 0.794–0.935). The calibration curve analysis showed that the predicted probability of the nomogram is consistent with the actual occurrence rate. DCA showed that the line graph model has an excellent clinical net benefit rate.ConclusionThe nomogram constructed based on clinical features, laboratory, and imaging examinations in this study has high discrimination and calibration in predicting CRT responsiveness in patients with chronic heart failure.

Role of Strauss ECG criteria as predictor of response in patients undergoing cardiac resynchronization therapy

Abstract Background Cardiac resynchronization therapy( CRT) is a standard treatment in patients with heart failure, however, approximately 20–40% of recipients of (CRT) do not respond to it based on the current patients’ election criteria. The purpose of this study was to identify the baseline parameters that predict the CRT response and how the ECG morphology can affect the outcome. Objective To evaluate the Strauss ECG criteria as predictor of response in patients undergoing Cardiac resynchronization therapy. Material and Methods From March 2020 to March 2022, 70 patients underwent CRT or CRT-D insertion with LBBB morphology in Ain Shams university hospitals, Cardiology department were enrolled in the study. All patients subjected to history, clinical examination, Electrocardiogram and echocardiography before CRT insertion and after 6 months. We analyzed the QRS morphology of the patients with LBBB-like pattern as we classified patients in two groups, Strauss LBBB criteria (SLBBB) which was (a QRS duration of &amp;lt; 140 ms for men and &amp;lt;130 ms for women, along with mid-QRS notching or slurring in at least 2 of the leads V1, V2, V5, V6, I, or aVL and also rS or QS morphology in lead V1 patients) and the other group that was not meeting the previous criteria as non-strauss LBBB (non-SLBBB), also all patients subjected to echocardiography ( conventional 2D and speckle tracking “global longitudinal strain and global circumferential strain), Ejection fraction was assessed together with LV volumes and speckle tracking to assess response to CRT. Results Out of 70 patients, 3 patients missed the 6 months follow up after CRT implantation, so the study enrolled 67 patients that have been classified according to ECG morphology of LBBB to 37 patients with non-Strauss ECG criteria- one of whom died after 4 months- and 30 patients with Strauss ECG criteria. The number of responders in the study was 50 patients with percentage 75.8%, 52% of CRT responder (26 patients) had non Strauss ECG criteria while 48% of CRT responders (24 patients) had Strauss ECG criteria with P value=0.463. While there was no statistical significance of overall CRT response nor 6 months hospitalization and mortality between patients of Strauss and non-Strauss ECG criteria, there was a significant improvement in NYHA class, EF assessed by biplane Simpson’s, End- systolic volume, Global longitudinal strain and Global circumferential strain by speckle tracking echocardiography in patients with Strauss ECG criteria of LBBB. Conclusion There is no statistical significance in overall CRT response nor the 6 months hospitalization and mortality after 6 months of follow up between patients with Strauss and non-Strauss ECG criteria of LBBB, however, patients with Strauss ECG criteria have better improvement in NYHA class, echocardiographic parameters such as EF and ESV and speckle tracking parameters (GLS and GCS).

Unexpected Genetic Twists in Patients with Cardiac Devices.

Objective: To assess the frequency and types of genetic mutations in patients with arrhythmias who underwent cardiac device implantation. Methods: Retrospective observational study, including 38 patients with different arrhythmias and cardiac arrest as a first cardiac event. Treatment modalities encompass pacemakers, transvenous defibrillators, loop recorders, subcutaneous defibrillators, and cardiac resynchronization therapy. All patients underwent genetic testing, using commercially available panels (106-174 genes). Outcome measures include mortality, arrhythmia recurrence, and device-related complications. Results: Clinical parameters revealed a family history of sudden cardiac death in 19 patients (50%), who were predominantly male (58%) and had a mean age of 44.5 years and a mean left ventricle ejection fraction of 40.3%. Genetic testing identified mutations in various genes, predominantly TMEM43 (11%). In two patients (3%) with arrhythmogenic cardiomyopathy, complete subcutaneous defibrillator extraction with de novo transvenous implantable cardioverter-defibrillator implantation was needed. The absence of multiple associations among severe gene mutations was crucial for cardiac resynchronization therapy response. Mortality in this group was around 3% in titin dilated cardiomyopathy patients. Conclusions: Integration of genetic testing into the decision-making process for patients with electronic devices represents a paradigm shift in personalized medicine. By identifying genetic markers associated with arrhythmia susceptibility, heart failure etiology, and cardiac resynchronization therapy response, clinicians can tailor device choices to optimize patient outcomes.

Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial.

Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. This is a post hoc analysis of the MORE-CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing)trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle-branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end-diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%, P<0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle-branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (P<0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708, P<0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value (P=0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms. In the nonischemic cardiomyopathy left bundle-branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex-specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

Tighter is better: Can a simple and cost-free parameter predict response to cardiac synchronization therapy?

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 nonresponders. Our study aimed to determine the correlation between the relative change in QRS index (QI) compared to clinical outcome and prognosis in patients who underwent CRT implantation. A three-centers study involving 398 patients with a CRT device was conducted. Clinical, echocardiographic and pharmacological variables, QRSd before and after CRT implantation and QI were measured. In a 6-month follow-up, a significant improvement in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and systolic volumes (LVEDV and LVESV) were observed. QI was related to reverse remodeling (multiple r-squared: 0.48, adjusted r-squared: 0.43, p=.001), and the cut-off value that best predicted LV reverse remodeling after 6 months of CRT was 12.25% (AUC 0.7, p=.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=.04). The mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes (p=.0179). A correlation between pre-CRT QRSd/LVEDV and QI was observed (r=+ 0.20; p=.0003). A higher QRSd/LVEDV ratio was associated with an improved LVEF, LVEDV, and LVESV (p<.0001) at follow-up. QI narrowing after CRT was related to greater echocardiographic reverse remodeling and a lower rate of adverse events (death or cardiovascular hospitalizations). The QI can improve the prediction of adverse events in a population with CRT regardless of comorbidities according to the Charlson Comorbidity Index. QI could be used to predict 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&amp;lt;0.01), with the group of NICM exhibiting the greatest benefit (p&amp;lt;0.01). St-LBBB CRT responders displayed significantly lower rates of HF hospitalization (p&amp;lt;0.0001) compared to non-St-LBBB group. This was mostly evident in patients with NICM (p&amp;lt;0.0001) according to Kaplan-Meier time curves. CRT responders displayed significantly fewer VA events (p&amp;lt;0.001) and lower mortality rates (p&amp;lt;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&amp;lt;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.

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 &amp;lt; 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

CRT with triple fusion: results of the multicentric, randomized, doble-blinded CRUSTY trial

Abstract Background The possible benefit in terms of cardiac resynchronization therapy (CRT) response using a dynamic automatic algorithm designed to provide triple fusion as compared to conventional optimized biventricular pacing (CBP) is not known. Methods In this randomized, doble blinded, multicentric (13 centers) clinical trial we assigned patients with heart failure, reduced left ventricular ejection fraction and left bundle branch block, who underwent CRT implantation to be optimized using the SyncAV dynamic algorithm or through a conventional method. The primary endpoint was the rate of echocardiographic CRT responders at 6-month follow-up defined as a reduction of the left ventricular end diastolic volume (LVEDV) &amp;gt;15%. Results The study had to be stopped for slow recruitment in the context of the COVID-19 pandemic after enrolling 56 patients; 54 patients were finally analyzed. Patients’ basal characteristics are shown in TABLE. Patients assigned to the SyncAV group presented a narrowest paced QRS (128±16 ms vs. 145±19 ms; p &amp;lt;0.01) and a greater reduction in QRS duration (FIGURE A). Furthermore, more patients in the SyncAV group achieved a paced QRSd &amp;lt;120 mseg (7% vs 35%, p = 0.02). 21 (81%) patients in the SyncAV group and 19 (68%) in the CBP group were classified as CRT responders (OR = 1.99; 95% CI 0.57–7). While patients in the SyncAV group demonstrated a trend towards superior reverse remodeling across all secondary endpoints, statistical significance was not reached (FIGURE B). In the SyncAV group, 2 (8%) patients were categorized as negative responders, and 4 (16%) in the CBP group. A total of 43% of patients improved by at least one category in the NYHA functional classification, while 2 patients experienced worsening, both in the CBP group (clinical negative responders) (FIGURE C). No adverse events directly associated with device programming or the activation of the SyncAV algorithm were reported. Conclusions In this multicenter randomized controlled trial comparing CRT with triple fusion pacing using the SyncAV algorithm to conventional optimized biventricular pacing, there was not reached adequate statistical power to draw a conclusion regarding a potential increase in the CRT response rate. Nevertheless, the use of the SyncAV algorithm resulted in a high proportion of CRT responders. A significant greater reduction of the QRS duration was observed when employing the SyncAV algorithm, leading to a high percentage of cases achieving QRS width normalization. Nonetheless, further investigations are warranted to thoroughly assess the possible clinical benefits associated with triple fusion of LV pacing, RV pacing and intrinsic conduction in HF patients with LBBB.FIGURE

Cardiac resynchronization therapy guided by interventricular delay: how to choose between biventricular pacing or conduction system pacing

Abstract Background Biventricular pacing (BIV) is gold standard for cardiac resynchronization therapy (CRT). Thirty % of patients result non responder to CRT. Conduction system pacing (CSP) represents a feasible alternative. Interventricular conduction delay (IVCD), as electrical desynchrony marker, is a CRT response predictor. The aim of the study was to assess CRT responder’s incidence when it has been achieved choosing best approach between BIV and CSP according to intraoperative IVCD measurement in patients with HFrEF and LBBB. Methods Ninety-eight patients have been 1:1 randomized in a standard BIV group (control group, CG) and a group in which CRT approach has been chosen based on IVCD evaluation (study group, SG), as reported in Figure 1. If the right ventricular sensed electrogram (RVs)-left ventricular sensed electrogram (LVs) interval was ≥100 ms, the left ventricular lead was left in its original position; otherwise, the lead was removed and CSP was performed instead, as reported in Figure 2. Clinical, EKG and echocardiographic features have been assessed pre- and 6 months post-implant. Echocardiographic and clinical response have been evaluated. Results Twenty-four % of patients in the SG underwent CSP, according to the operative algorithm adopted. CRT responders’ incidence was significantly higher in the SG (echocardiographic criterion: SG 93,9% vs CG 69,8%; clinical criterion SG 87,9% vs CG 62,8%). Patients in SG presented a significant improvement in EF between pre- and post-implant and a significantly reduced End Diastolic Volumes and End Systolic Volumes vs CG. Univariate and multivariate regression analysis showed that enrolment in SG was the only factor consistently associated to CRT response. Conclusion Intraoperative evaluation of IVCD may guide the choice of the best resynchronization approach between BIV and CSP, allowing to achieve a significant improvement of CRT responders’ rate.Figure 1Figure 2

Impact of left bundle branch block morphology in predicting response to left bundle branch area pacing for cardiac resynchronization therapy

Abstract Background Left bundle branch area pacing (LBBAP) is a novel pacing technique with an emerging role in resynchronization therapy [1-4]. QRS morphology has shown to significantly influence cardiac resynchronization therapy (CRT) response [5-6]. Purpose The aim of this study was to assess whether different left bundle branch block (LBBB) definitions are associated with response to LBBAP resynchronization therapy. Methods 40 consecutive CRT candidates with previously unsuccessful biventricular (BiV) pacing or in which effective CRT could not be achieved with BiV pacing based on anatomical or functional criteria were selected for this study. Both ischemic and non-ischemic heart failure (HF) patients were included. Patients were divided into two groups according to LBBB morphology. Group 1 included 20 patients (45% ischemic HF) with strict LBBB definition according to Strauss criteria [7], while 20 patients in Group 2 (55% ischemic HF) had conventional LBBB morphology. Response to CRT was defined for (1) reduction in QRS duration; (2) increase in left ventricular ejection fraction (LVEF) ≥ 5% and (3) decrease in left ventricular end systolic volume (LVESV) ≥ 15%. Results LBBAP was successfully achieved in all patients (mean age: 72.0 years; male: 29). The mean baseline QRS duration before implantation was 178.6±13.8 in the Group 1 and 170.8±29.4 in the Group 2, without a statistically significant difference. Over a mean follow-up of 5.6 months, LBBAP resulted in QRS narrowing in both groups, with a greater reduction in Group 1 (-40.6 ms) compared to Group 2 (-15.1 ms), (p 0.002). Pre-implantation ventricular systolic function did not show significant differences between the two groups, with a mean of 30.1±3.5% in the Strauss LBBB group and 31.0±6.0% in the conventional LBBB group. After implantation LVEF was 42.1±8.5 % in the true LBBB patients and 33.2±7.5 in the conventional LBBB group. Echocardiographic response was observed in 65% of patients with a statistically significant difference between Group 1 (90% of responders) and Group 2 (40% of responders), (p 0,001). HF etiology did not impact the response to LBBAP CRT. Conclusions Strict LBBB definition is associated to a greater electrocardiographic and echocardiographic response in patients receiving LBBAP CRT compared to conventional LBBB criteria.\

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 &amp;lt;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&amp;lt;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&amp;lt;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&amp;lt;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

A time-dependent analysis of sacubitril/valsartan and gliflozins benefits in patients receiving cardiac resynchronization therapy

Abstract Background While sacubitril/valsartan (ARNi), gliflozins (or SGLT2i) and cardiac resynchronization therapy (CRT) are firmly recognized as cornerstones of therapy for heart failure with reduced ejection fraction (HFrEF), robust evidence validating the long-term efficacy of their combination remains elusive. The few data suggesting a synergistic advantage of these drugs alongside CRT have not rigorously considered their time-varying administration, leading to potential selection bias, since only patients with longer initial survival could commence these treatments. As a result, the literature to date lacks a comprehensive and persuasive demonstration of the additional survival benefits conferred by ARNi and gliflozins over CRT alone in HFrEF. Purpose To evaluate the impact of ARNi and gliflozins on reducing cardiovascular and overall mortality among HFrEF patients undergoing CRT. Methods Patients with heart failure and an ejection fraction ≤ 35%, who were referred for CRT-D implantation from 2015 to 2023, were retrospectively recruited for the study. These patients were grouped into two cohorts: those not receiving drugs (no drugs group) and those treated with ARNi and/or SGLT2i (ARNi/SGLT2i group). Importantly, ARNi and SGLT2i treatments were considered as time-dependent covariates in order to account for patients who initiated or discontinued therapy during follow-up. Results The cohort included 183 ischemic and non-ischemic HFrEF patients (148 male [80.9 %], 113 ischemic [61.7 %], median [IQR] age 73 [65-80] years). 117 (74 %) patients started ARNi (61, 52.1 %), gliflozins (7, 6 %) or both drugs (49, 41.9 %) and were assigned to ARNi/SGLT2i group. During a median follow-up of 5.67 (CI 95 %, 5 – 6.5) years, 63 (34.4 %) patients died, of whom 47 (74.6 %) died of cardiovascular HF-related death. Specifically, 44 (of whom 35 (79 %) due to HF-related death) died in the no drugs group vs 19 (12 (63 %) due to HF-related death) in ARNi/SGLT2i patients. At univariable analysis (Panel A in the Figure), ARNi and/or SGLT2i treatments reduced all-cause (HR 0.59 [0.34-1.02], p = 0.056) and cardiovascular (HR 0.47 [0.24-0.92], p = 0.029) mortality. However, after multivariable adjustment for key covariates (1-year CRT response, age, atrial fibrillation, baseline LVEF, chronic obstructive pulmonary disease, glomerular filtration rate), the survival benefits of ARNi and SGLT2i use diminished, and the only factor strongly associated with reduced mortality risk remained 1-year positive response to CRT (Panel B). Conclusions Despite their recognized therapeutic benefits, ARNi and SGLT2i have not demonstrated additional survival benefit compared to CRT alone in patients with HFrEF. A 1-year positive response to CRT remains the most significant prognostic factor. Further studies with larger sample sizes and extended follow-up periods are needed to confirm this hypothesis, also evaluating whether the timing of introduction of these medications may impact survival.

Clinical performance and safety of a two-lead cardiac resynchronization therapy system with a floating atrial sensing dipole

Abstract Background The incidence of complications after implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy (CRT-D) implantations is dependent on the number of implanted leads. The majority of CRT-D patients have unimpaired sinus node function and do not require atrial pacing. A two-lead CRT-D system with a floating atrial sensing dipole mounted on the right ventricular lead ((CRT-DX) allows dual chamber tachyarrhythmia detection, and atrio-ventricular sequential pacing with a reduced amount of implanted material. Purpose This study investigated the clinical efficacy and safety of the CRT-DX system. Methods This multicentre, single-arm study observed patients after de novo implantation of a CRT-DX system for 12 months. Patients were eligible for the study when chronotropic competence was proven by heart rates ≥100 bpm during exercise, premature ventricular contractions rate of &amp;lt; 5%/h and absence of atrioventricular block ≥ II. Intraoperatively measured p-wave amplitude of ≥ 1 mV was recommended. The primary safety endpoint was the additional implantation of a right atrial (RA) lead after the initial implantation. As indicators of efficacy, we report the changes in left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) class over the follow-up period. Results Overall, 110 patients were implanted with the complete CRT-DX system. Mean age of study participants was 62 ± 12 years and 77 (70%) were male. The underlying heart disease was non-ischemic in 66 (60%) patients and 103 (93%) had a left bundle branch block. NYHA class was II in 60 (54.5%) and III in 50 (45.5%) patients. ICD placement was performed in 13 (11.8%) patients for the secondary prevention of sudden cardiac death. A total of 104 patients completed the follow-up, 2 patients died, 1 had the system explanted for infection, 2 withdrew consent and 1 was lost to follow-up. The primary endpoint of RA lead implantation was met in 2 (1.8%) participants (Figure 1). One patient required atrial pacing and one patient, who had shown a p-wave amplitude &amp;lt; 1 mV at implantation, lost atrial sensing. The mean RA sensing amplitude remained stable during follow-up (4.6 ± 1.8 mV, 4.9 ± 1.8 mV and 4.6 ± 1.8 mV at 1, 6 and 12 months, respectively; Figure 2). The LVEF improved by 14.7% ± 11.0%, from 26.3% ± 6.9% to 40.8% ± 10.7% (p &amp;lt; 0.00001). Changes in NYHA class were available in 87 patients with 35 (40.2%) improved by one class and 13 (14.9 %) by two classes. Thirty-four (39.1%) had no change and 5 (5.7%) worsened by one class (global p &amp;lt; 0.00001). Conclusion The two-lead CRT-DX system showed a low requirement of subsequent RA lead implantations (1.8%) and stable RA sensing amplitudes. Our results suggest a CRT response similar to that of conventional three-lead CRT-D systems. CRT-DX systems appear to be a feasible alternative for patients with chronotropic competence.Kaplan-Meier curve for primary endpointDaily mean RA sensing amplitude

Machine learning of ECG waveforms and cardiac magnetic resonance for response and survival after cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) can lead to marked symptom reduction and improved survival in selected patients with heart failure with reduced ejection fraction (HFrEF); however, many candidates for CRT based on clinical guidelines do not have a favorable response. A better way to identify patients expected to benefit from CRT that applies machine learning to accessible and cost-effective diagnostic tools such as the 12-lead electrocardiogram (ECG) could have a major impact on clinical care in HFrEF by helping providers personalize treatment strategies and avoid delays in initiation of other potentially beneficial treatments. This study addresses this need by demonstrating that a novel approach to ECG waveform analysis using functional principal component decomposition (FPCD) performs better than measures that require manual ECG analysis with the human eye and also at least as well as a previously validated but more expensive approach based on cardiac magnetic resonance (CMR). Analyses are based on five-fold cross validation of areas under the curve (AUCs) for CRT response and survival time after the CRT implant using Cox proportional hazards regression with stratification of groups using a Gaussian mixture model approach. Furthermore, FPCD and CMR predictors are shown to be independent, which demonstrates that the FPCD electrical findings and the CMR mechanical findings together provide a synergistic model for response and survival after CRT. In summary, this study provides a highly effective approach to prognostication after CRT in HFrEF using an accessible and inexpensive diagnostic test with a major expected impact on personalization of therapies.

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 &amp;lt; 12.25% and those with a QI &amp;gt; 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 &amp;lt;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.

Atrioventricular optimization improves cardiac resynchronization response in patients with long interventricular electrical delays: A pooled analysis of the SMART-AV and SMART-CRT trials

BackgroundThe utility of atrioventricular (AV) optimization (AVO) algorithms remains in question. A substudy of the SMART-AV trial found that patients with prolonged interventricular delays ≥70 ms were more likely to benefit from cardiac resynchronization therapy (CRT) with AVO. The SMART-CRT trial evaluated AVO on the basis of these results, but the study was underpowered. ObjectiveTo increase statistical power, data from SMART-AV patients meeting the inclusion criterion of interventricular delay ≥70 ms were pooled with data from SMART-CRT to reassess AVO. MethodsSMART-CRT and SMART-AV were prospective, randomized, multicenter clinical trials. Patients in both studies were randomized to be programmed with an AVO algorithm (SmartDelay) or fixed AV delay (120 ms). Paired echocardiograms obtained at baseline and 6 months were compared, with CRT response defined as ≥15% reduction in left ventricular end-systolic volume. ResultsA total of 451 complete patient data sets were pooled and analyzed. The baseline demographics between studies did not differ statistically in terms of age, sex, left ventricular ejection fraction, or left ventricular end-systolic volume. The AVO group had a greater proportion of CRT responders (SmartDelay, 73.9%; fixed, 63.1%; P = .014) and greater changes in measures of reverse remodeling. SmartDelay patients with a recommended sensed AV delay outside the nominal range (100–120 ms) had 2.3 greater odds of CRT response than fixed AV delay patients. ConclusionGreater CRT response and measures of reverse remodeling were observed in patients with SmartDelay enabled vs a fixed AV delay. This study supports the use of SmartDelay in patients with a CRT indication and interventricular delay ≥70 ms. ClinicalTrials.gov registrationNCT00677014 and NCT03089281

Evaluation of synchronized left ventricular pacing rate over biventricular pacing in cardiac resynchronization therapy

BackgroundThe adaptive cardiac resynchronization therapy (aCRT) algorithm enables synchronized left ventricular pacing (sLVP) to achieve fusion with intrinsic right ventricular activation. Although sLVP presents benefits over biventricular pacing, the adequate sLVP rate for better clinical outcomes remains unclear. We aimed to assess the association between sLVP rates and clinical outcomes. MethodsOur study cohort included 271 consecutive patients, who underwent CRT implantation between April 2016 and August 2021. ResultsWe evaluated 63 patients on whom we applied the aCRT algorithm [48 men, mean age: 64 ± 14 years; median follow-up period: 316 days (interquartile range: 212–809 days)]. At the 6-month follow-up after CRT implantation, the frequency of CRT responders was 71 % (n = 45). The sLVP rate was significantly higher in responders than in non-responders (75 ± 30 % vs. 47 ± 40 %, p = 0.003). Receiver operating characteristics curve analysis revealed that the optimal cut-off value during the sLVP rate was 59.4 % for the prediction of CRT responders (area under the curve, 0.70; sensitivity, 80 %; specificity, 61 %; positive predictive value, 84 %; and negative predictive value, 55 %). Kaplan–Meier analysis demonstrated that the higher-sLVP group (sLVP ≧59.4 %, n = 43) had a better prognosis (cardiac death and heart failure hospitalization) than the lower-sLVP group (sLVP <59.4 %, n = 20) (log-rank p < 0.001). Multivariate Cox hazard analysis revealed that a higher sLVP rate was associated with a good prognosis (p < 0.001). ConclusionssLVP was associated with CRT response, and a higher sLVP rate (≧59.4 %) was important for good prognosis in patients with aCRT.

A novel method combining gated SPECT and vectorcardiography to guide left ventricular lead placement to improve response to cardiac resynchronization therapy: A proof of concept study

BackgroundThe segment of the latest mechanical contraction (LMC) does not always overlap with the site of the latest electrical activation (LEA). By integrating both mechanical and electrical dyssynchrony, this proof-of-concept study aimed to propose a new method for recommending left ventricular (LV) lead placements, with the goal of enhancing response to cardiac resynchronization therapy (CRT). MethodsThe LMC segment was determined by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) phase analysis. The LEA site was detected by vectorcardiogram. The recommended segments for LV lead placement were as follows: (1) the LMC viable segments that overlapped with the LEA site; (2) the LMC viable segments adjacent to the LEA site; (3) If no segment met either of the above, the LV lateral wall was recommended. The response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) 6-months after CRT. Patients with LV lead located in the recommended site were assigned to the recommended group, and those located in the non-recommended site were assigned to the non-recommended group. ResultsThe cohort comprised of 76 patients, including 54 (71.1%) in the recommended group and 22 (28.9%) in the non-recommended group. Among the recommended group, 74.1% of the patients responded to CRT, while 36.4% in the non-recommended group were responders (P = .002). Compared to pacing at the non-recommended segments, pacing at the recommended segments showed an independent association with an increased response by univariate and multivariable analysis (odds ratio 5.00, 95% confidence interval 1.73-14.44, P = .003; odds ratio 7.33, 95% confidence interval 1.53-35.14, P = .013). Kaplan–Meier curves showed that pacing at the recommended LV lead position demonstrated a better long-term prognosis. ConclusionOur findings indicate that pacing at the recommended segments, by integrating of mechanical and electrical dyssynchrony, is significantly associated with an improved CRT response and better long-term prognosis.