Predict Cardiac Resynchronization Therapy Response Research Articles

Utilizing unsupervised machine learning to uncover novel phenogroups within the broad QRS complex

Abstract Background Conduction disease can manifest as a broad QRS complex on the ECG. Broad QRS is conventionally categorised as left bundle branch block (LBBB) and right bundle branch block (RBBB) or non-specific intraventricular conduction delay (IVCD), based on QRS morphology. These subgroups were coined over a century ago and have been relevant for heart failure with reduced ejection fraction and cardiac resynchronization therapy (CRT). However, there may be more precise phenogroups underlying broad QRS complexes. Purpose Using unsupervised machine learning to define novel broad QRS phenogroups and characterise them using clinical variables and disease outcomes. Methods We extracted 51 relevant features using a Variational Autoencoder from 47,456 median-beat ECGs with broad QRS intervals (QRS ≥ 130ms) from a secondary care cohort. These were input into Discriminative Dimensionality Reduction via Learning a Tree (DDRTree), a clustering method that models the continuum of heterogeneity by projecting the underlying distribution as a tree structure in a low-dimensional space, while assigning distinct branch/cluster labels. Results Six distinct phenogroups were identified within broad QRS morphologies (Figure-1). Two branches were RBBB dominant (Branch 1: more males, high-comorbidity; Branch 6: low-comorbidity/healthy-RBBB). Two branches were LBBB dominant (Branch 4: mixed IVCD with CHB burden; Branch 5: more females, CRT responders). Two branches were IVCD/mixed-phenotype (Branch 2: IVCD-dominant, high risk of future cardiovascular events; Branch 3: average/core branch). Within LBBB, Branch 4 and 5 showed similar trends with improving echocardiography profiles and CRT response when adjusted for covariates, each compared against the core branch. Branch 5 was distinct due its high risk of future HF (HR 1.19 [1.07-1.33] p < 0.01), cardiovascular death (HR 1.35 [1.20-1.50] p < 0.0001), all-cause mortality (HR 1.08 [1.01-1.16] p < 0.05) and CHB (HR 1.35 [1.16-1.56] p < 0.0001) (Figure-2). Conversely within RBBB, Branch 1 and 6 showed stark differences across various traits. Branch 1 captured a high-risk profile associated to higher risk of cardiovascular death (HR 1.37 [1.24-1.52] p < 0.0001), all-cause mortality (HR 1.20 [1.12-1.29] p < 0.0001) and CHB (HR 1.15 [1.01-1.32] p < 0.05) (Figure-2), while Branch 6 retained a low-risk phenotype. The tree dimensions also revealed relevant trends in cardiac anatomy and valvular dysfunction; the top-left region in Figure-1 associated with higher left ventricular ejection fraction and lower left ventricular end-diastolic dimension, lower left ventricular end-systolic dimension and a greater CRT response. Conclusion Through unsupervised methods we have identified conduction disease phenogroups with additive value for disease prognosis and CRT response prediction beyond traditional LBBB and RBBB labels. These novel phenogroups may help guide precision care for patients with a broad QRS complex.Figure-1Figure-2

Prediction of CRT response using a novel CRT responder score in an Asian patient population

Abstract Introduction Cardiac Resynchronization Therapy (CRT) guidelines, derived from trials among U.S. and European patients, assign weaker recommendations to those with midrange QRS duration (<150ms). Patient height and body size may modulate CRT efficacy. Moreover, these factors may affect CRT utilization and efficacy in Asia. Aim The purpose of this analysis was to determine the prediction scoring system model for CRT responders in a Japanese patient population. Methods We analyzed the database of the Multicenter Prospective Pilot Study to Test LV Intracardiac Conduction Time as a Predictor of CRT Response (BIO|SELECT) which was a single-arm study conducted at 28 hospitals in Japan. This study enrolled patients eligible for a de-novo CRT-defibrillator (CRT-D) based on current guideline indications, who had no recent or planned cardiac surgery and were planned to receive a Sentus ProMRI OTW quadripolar LV lead and a BIOTRONIK CRT-D with multipole pacing feature. Patients were followed for 7 months after implantation. Four accepted parameters to define CRT response [LVESV (cut-off -15%), LVEF (+5%), BNP (-25%), and NYHA class (one class improvement)] were combined into a composite benefit index (CBI) by forming the normalized sum, with CBI = 4.0 meaning response. The CBI was found to be more robust than the individual 4 parameters due to the reduced influence of noise and measurement errors in single parameters. Several factors were studied to create the scoring tool. The CRT responder score was the sum of these individual scores (range 0-100). To construct a predictive scoring system, logistic regression analysis was performed with a backward selection procedure. In addition, the Akaike information criterion (AIC) was applied to determine the best model among those tested. The score was then assigned employing the β coefficient of each variable divided by the reference value. The model's calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Results A total of 196 patients were enrolled in this study (mean age 69 years, mean LVEF 30%, left bundle-branch block [LBBB] 58%). The Ooccurrence of CRT response during the 7-month follow-up was 54%. Future CRT responders were significantly predicted by low age (< 70 years)(18 points), female (19 points), prior heart failure hospitalization (16 points), body mass index (<20) (17 points), QRS/height (<0.858)(30 points). This score predicted CRT response well (area under curve 0.72; 95% CI 0.643-0.798). When the cut-off of 63 points or more was applied the sensitivity was 0.56, the specificity was 0.72, and the negative predictive value was 0.58. Conclusions The CRT responder score is a novel approach for the prediction of CRT response, but should be validated and further improved to increase its predictive value. This approach highlights the role of preventing the development of severe heart failure and could help to identify individuals who might benefit from 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.

Vitamin D as a predictor of clinical response among patients with cardiac resynchronization therapy (CRT).

Cardiovascular and noncardiovascular comorbidities have been recognized as predictors of clinical response in patients receiving cardiac resynchronization therapy (CRT). However, data on vitamin D as a predictor of CRT response are conflicting. We identified studies from MEDLINE and Embase databases, searching from inception to May 2024, to investigate the association between 25-OH vitamin D levels before CRT implantation and outcomes. Studies had to report 25-OH vitamin D levels or the proportion of patients with vitamin D insufficiency and categorize outcomes as CRT responders or nonresponders. We extracted mean 25-OH vitamin D and standard deviations for both groups from each study and calculated the pooled mean difference (MD). We also retrieved risk ratios, and 95% confidence intervals (CIs) for the association between vitamin D insufficiency and lack of CRT response, combining them using the generic inverse variance method. Our meta-analysis included four studies. CRT responders had higher levels of 25-OH vitamin D than nonresponders, with a pooled MD of 8.04 ng/mL (95% CI: 3.16-12.93; I 2 = 48%, p < .001). Patients with vitamin D insufficiency before implantation had higher odds of lacking response to CRT, with a pooled RR of 3.28 (95% CI: 1.43-7.50; I 2 = 0%, p = .005) compared to those with normal vitamin D. CRT responders had higher 25-OH vitamin D levels compared to nonresponders. Vitamin D insufficiency was associated with a higher risk of nonresponse to CRT. These findings highlight the importance of monitoring and managing vitamin D levels in these patients.

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.

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.

Cardiac Magnetic Resonance Identifies Responders to Cardiac Resynchronization Therapy with an Assessment of Septal Scar and Left Ventricular Dyssynchrony.

Background: The response to cardiac resynchronization therapy (CRT) depends on septal viability and correction of abnormal septal motion. This study investigates if cardiac magnetic resonance (CMR) as a single modality can identify CRT responders with combined imaging of pathological septal motion (septal flash) and septal scar. Methods: In a prospective, multicenter, observational study of 136 CRT recipients, septal scar was assessed using late gadolinium enhancement (LGE) (n = 127) and septal flash visually from cine CMR sequences. The primary endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume with echocardiography after 6 months. The secondary endpoint was heart transplantation or death of any cause assessed after 39 ± 13 months. Results: Septal scar and septal flash were independent predictors of CRT response in multivariable analysis (both p < 0.001), while QRS duration and morphology were not. The combined approach of septal scar and septal flash predicted CRT response with an area under the curve of 0.86 (95% confidence interval (CI): 0.78-0.94) and was a strong predictor of long-term survival without heart transplantation (hazard ratio 0.27, 95% CI: 0.10-0.79). The accuracy of the approach was similar in the subgroup with intermediate (130-150 ms) QRS duration. The combined approach was superior to septal scar and septal flash alone (p < 0.01). Conclusions: The combined assessment of septal scar and septal flash using CMR as a single-image modality identifies CRT responders with high accuracy and predicts long-term survival.

Abstract 18159: Cardiac Resynchronization Therapy Response Predicted by Tissue Characterization Using Cardiac Magnetic Resonance Imaging in Non-Ischemic Dilated Cardiomyopathy

Introduction: Tissue characterization using cardiac magnetic resonance (CMR) is helpful for risk stratification in non-ischemic dilated cardiomyopathy (NIDCM). Hypothesis: This study aimed to investigate the predictive role of tissue characterization identified by CMR on cardiac resynchronization therapy (CRT) response. Methods: We retrospectively reviewed the patients who underwent CMR within 1 year before CRT implantation in NIDCM patients at a single tertiary center from January 2018 to September 2022. Late gadolinium enhancement (LGE), native T1, T2 and extracellular volume (ECV) were analyzed. CRT response was defined as a decrease in left ventricular end-systolic volume (LVESV) &gt; 15% or an increase in left ventricular ejection fraction &gt; 5% on TTE after at least 3 months after CRT implantation. Results: Among a total of 101 patients (mean age 66 years, 52.5% of male), 76 (75.2%) patients were defined as CRT responders. CRT responders had more LBBB (96.1% vs. 60.0%, p&lt;0.001) and longer QRS duration (156.0±178.5 vs. 167.0±176.5ms, p=0.005) compared with CRT non-responders. However, LGE burden (34.3 vs. 13.3%, p&lt;0.001), native T1 (1371.6 vs. 1336.8ms, p=0.033), T2 (45.9 vs. 42.1ms, p&lt;0.001), and extracellular volume (ECV, 36.8 vs. 31.0%, p&lt;0.001) were significantly higher in CRT non-responders. The area under the curve (AUC) to predict CRT response is the highest in LGE burden (0.817, 95% confidence interval [CI]: 0.710-0.925), followed by ECV (0.808, 95% CI: 0.711-0.905), T2 (0.779, 95% CI: 0.663-0.895), and native T1 (0.643, 95% CI: 0.520-0.766). After adjustment, LGE burden&gt;20% (odds ratio [OR]: 0.15, 95% CI: 0.02-0.71, p=0.024) and ECV &gt; 34% (OR: 0.13, 95% CI: 0.01-0.78, p=0.037) were independently poor CRT response predictors. Conclusions: The tissue characterization by using CMR is helpful to predict CRT response and clinical outcomes in patients with NIDCM, independently of conventional CRT response predictors.

Relationship between left ventricular mechanical dyssynchrony with cardiac resynchronization therapy response in chronic heart failure patients with left bundle branch block

Aim. To investigate the relationship between left ventricular (LV) mechanical dyssynchrony with cardiac resynchronization therapy (CRT) response in chronic heart failure (CHF) pts with left bundle branch block.Methods. Forty-nine pts (male - 34 [69.4%], average age 58.3±11.4 years) with sinus rhythm, permanent left bundle branch block with QRS duration ≥150 ms and New York Heart Association (NYHA) II-III functional class of CHF were included in the study. In addition to full examination, myocardial perfusion scintigraphy (MPS) and gated blood pool single-photon emission computed tomography (gBPS) were performed before and 6 months after CRT devices with cardioverter-defibrillator function implantation. Pts were considered as responders to CRT if they fulfilled after 6-month follow-up the following combined criteria: NYHA FC improvement ≥1 class + LV end systolic volume decrease &gt;15% or NYHA FC improvement ≥1 class + LV ejection fraction improvement &gt;5%.Results. The 1st and 2nd groups included 35 (71.4%) and 14 (28.6%) pts with and without response to CRT respectively. Groups were comparable in terms of pre-CRT implantation clinical and instrumental parameters, except for MPS and gBPS parameters. The multivariate logistic regression had shown that only ∆interventricular dyssynchrony (adjusted odds ratio [OR] 1,0349; 95% confidence interval [CI] 1.0075-1,0631; р=0.01) and phase standard deviation of the anterior LV wall (OR 1.0669; 95% CI 1.0118-1.1251; p=0.01) were independently related with CRT response. An increase in the prognostic coefficient, calculated using the ∆interventricular dyssynchrony and phase standard deviation of the anterior LV wall, more than 0.67 was a predictor of CRT response (area under the curve 0.918; sensitivity 85.71; specificity 85.71; p &lt;0.001).Conclusion. The mechanical dyssynchrony assessed by MPS and gBPS is associated with CRT response. According to our predictive model, an increase in prognostic coefficient more than 0.67 is a predictor of CRT response.

Significance of effective cardiac resynchronization therapy pacing for clinical responses: An analysis based on the effective cardiac resynchronization therapy algorithm

High percent ventricular pacing maximizes cardiac resynchronization therapy (CRT) response. An effective CRT algorithm classifies each left ventricular (LV) pace as effective or ineffective on the basis of the detection of QS or QS-r morphology on the electrogram; however, the relationship between percent effective CRT pacing (%e-CRT) and responses is unclear. We aimed to clarify the association between %e-CRT and clinical outcomes. Of the 136 consecutive CRT patients, 49 using the adaptive and effective CRT algorithm with percent ventricular pacing > 90% were evaluated. The primary and secondary outcomes were heart failure (HF) hospitalization and prevalence of CRT responders, defined as patients with an improvement in LV ejection fraction of ≥10% or a reduction in LV end-systolic volume of ≥15% after CRT device implantation, respectively. We divided the patients into the effective group (n = 25) and the less effective group (n = 24) by the median value of %e-CRT (97.4%). During the median follow-up period of 507 days (interquartile range 335-730 days), the effective group had a significantly lower risk of HF hospitalization than did the less effective group as revealed by Kaplan-Meier analysis (log-rank, P = .016). Univariate analysis revealed %e-CRT ≥ 97.4% (hazard ratio 0.12; 95% confidence interval 0.01-0.95; P = .045) as a predictor of HF hospitalization. The effective group had a higher prevalence of CRT responders than did the less effective group (23 [92%] vs 9 [38%]; P < .001). Univariate analysis revealed that %e-CRT ≥ 97.4% (odds ratio 19.20; 95% confidence interval 3.63-101.00; P < .001) was a predictor of CRT response. High %e-CRT is associated with high CRT responder prevalence and low HF hospitalization risk.

P247 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 predictor of response to cardiac resynchronization therapy (CRT) in order to reduce non–responders. However, their results have been conflicting. In our study we analyzed retrospectively a cohort of patients from three centers to better correlate the association between the relative change in QRS narrowing index (QI) and clinical outcome and prognosis in patients who underwent CRT implantation. Methods We included 398 patients in whom a CRT device was implanted in accordance with current guidelines in our three centres. Baseline clinical variables, echocardiographic parameters and pharmacological therapies were included. QRS duration before and after CRT implantation and QI [(pre implant QRS duration – QRS duration during CRT)/pre implant QRS duration × 100] were measured. Results Respect to echocardiographic follow up at 6 months, a significant improvement in all parameters (EF, LVEDV, LVESV) was observed. In 68% of patients, LVESV decreased by 10% or more. QI was significantly related to reverse remodelling (r = + 0.22; 95% CI: 0.11 to 0.32, p = 0.001). The cut–off value of QI that predicted best LV reverse remodelling after 6 months of CRT was 12.25% (sensitivity 65,49%, specificity 75%, area under the curve 0.7, p = 0.001). Regarding clinical outcomes at 12 mounths, a statistically significant difference was found between patients with a QI &amp;lt; 12.25%, and those with a QI &amp;gt; 12.25%, in terms of NYHA class worsening (p 0,04). Another statistically significant difference was found analyzing the relation between QI and the causes of deaths, the mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes. (p 0,0179). Conclusions Therefore decrease in QRSd after CRT initiation was related to greater echocardiographic reverse remodelling and better outcome from death or cardiovascular hospitalization. Even if larger studies are needed, QI seems to be an easy–to– measure variable that could be used or evaluated to predict CRT response.

PO-02-021 DIRECTION OF REPOLARIZATION IN BASELINE ECG IS PREDICTIVE OF RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY

Cardiac resynchronization therapy (CRT) is a cornerstone of treatment for advanced heart failure, but not all patients derive equal benefit from this intervention. Current approaches of using electrocardiographic and echocardiographic parameters to identify likely CRT responders demonstrate poor predictive ability. We seek to identify electrocardiographic parameters that can improve prediction of benefit with CRT This was a retrospective analysis of patients who underwent CRT-D placement at University of Pittsburgh Medical Center from 2014-2020. Patients were excluded if pre-implantation EKG or pre- and post-implantation echocardiograms were not available. Each patient’s immediate pre-implantation ECG was processed using the CineECG software (EKG Excellence) to obtain the mean temporospatial isochrone of ventricular activation. 192 features quantifying the activation and recovery pathways were computed for each patient. Response to CRT was defined as an improvement in ejection fraction (EF) of 5% on follow-up transthoracic echocardiogram 3-12 months after CRT implantation. Forward sequential feature selection was used to identify the features of highest importance based on negative logistic loss. 276 patients were included in this analysis (36% female, mean age 69 years, mean pre-procedural EF 27%). The 10 most important CineECG features were identified. When these features were used in a multivariate logistic regression, three features were independently predictive of CRT response: left bundle branch block (LBBB); leftward direction of late repolarization potentials (i.e., Tpeak - Tend rotated toward LV in the horizontal plane); and location of center-of-mass of terminal cardiac activation. Compared to CRT responders (n=169, 62%), non-responders were more likely to have abnormal direction of late repolarization potentials in both LBBB group (-0.34±0.30 vs. -0.45±0.30 vs, p=0.027) and RBBB group (0.25±0.51 vs. 0.61±0.27, p=0.031). In the latter group, direction of later repolarization potentials correlated with magnitude of change in post-procedural EF (r=0.23, p=0.016). Our findings confirm that the presence of LBBB is predictive of response to CRT. In addition, our data suggests that in patients with RBBB, a more leftward direction of late repolarization potentials is independently predictive of CRT response. Further studies into repolarization dynamics as a predictor of CRT response in RBBB are warranted.

Prognostic value of non-alcoholic fatty liver disease fibrosis score in patients undergoing cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an effective option in the treatment of patients with heart failure and wide QRS. Non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been shown to predict cardiac events in several patient populations. However, the relationship between NFS and response to CRT has not been investigated. The aim of the study was to investigate the predictive role of NFS in the assessment of response after CRT. Three hundred thirty-six patients with heart failure undergoing CRT were prospectively studied. Liver fibrosis were assessed according to the non-alcoholic fatty liver disease fibrosis score (NFS), which includes age, body mass index, impaired fasting glycemia or diabetes mellitus, aspartate aminotransferase /alanine aminotransferase ratio, platelets, and albumin. Echocardiographic response to CRT was defined by a ≥15% reduction in left ventricular end-systolic volume at six months at follow-up. Two hundred thirty-eight patients (71%) had CRT response after 6 months of follow-up. Receiver-operator characteristic curve analysis showed NFS cutoff value of<-1.12 for predicting CRT response with a sensitivity of 70.4% and a specificity of 52.9%. The patients were also divided into four groups according to the quartiles of NFS. The proportion of response to CRT was increased with lower level of NFS value. Multivariate logistic regression analysis demonstrated the NFS score<-1.12 and LVIDs were independent predictors of the CRT response. In the second model of analysis which included NFS, quartiles demonstrated that fourth NFS quartile and LVIDs were independent predictors of CRT response. Liver fibrosis assessed by NFS can provide valuable information to predict reverse remodeling in patients undergoing CRT. The present study supports monitoring of NFS to improve preoperative risk stratification of these patients.

A possible easy way to predict response to cardiac resynchronization therapy: The role of QRS Index

Background: Some studies have evaluated the role of QRS duration (QRSd) as predictor of response to Cardiac Resynchronization Therapy (CRT). However, their results are still not entirely clear. The goal 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: We collected clinical and echocardiographic data of 115 patients in whome a CRT device was implanted in accordance with current guidelines. QRS duration before and after CRT implantation and QI were measured. Results: After 6 months, a significant improvement in all echocardiographic parameters was detected. QI was correlated to reverse remodelling (r = +0.19; 95% CI: 0.006 to 0.35, p = 0,049). The value of QI that predicted best LV reverse remodelling after 6 months of CRT was 12.25% (sensitivity = 65,5%, specificity = 75%, area under the curve = 0.737, p = 0,001). Independent predictors of QI are sex, serum creatinine and eGFR measured at baseline and LVEF pre-CRT performed by echocardiography. We observed an betterment in their HF clinical composite score and NYHA class at 12 months. We have also investigated the clinical outcomes and the possible sex differences related to QI. Conclusions: Patients with a larger QI after CRT initiation showed greater echocardiographic reverse remodelling and better outcome from death or cardiovascular hospitalization. QI seems to be an easy-to- measure variable that could be used or evaluated to predict CRT response but further studies are needed.

640 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 predictor of response to cardiac resynchronization therapy (CRT) in order to reduce non-responders. However, their results have been conflicting. In our study we analyzed retrospectively a cohort of patients from three centers to better correlate the association between the relative change in QRS narrowing index (QI) and clinical outcome and prognosis in patients who underwent CRT implantation. Methods We included 398 patients in whom a CRT device was implanted in accordance with current guidelines in our three centres. Baseline clinical variables, echocardiographic parameters and pharmacological therapies were included. QRS duration before and after CRT implantation and QI [(pre implant QRS duration - QRS duration during CRT)/pre implant QRS duration × 100] were measured. Results Respect to echocardiographic follow up at 6 months, a significant improvement in all parameters (EF, LVEDV, LVESV) was observed. In 68% of patients, LVESV decreased by 10% or more. QI was significantly related to reverse remodelling (r = + 0.22; 95% CI: 0.11 to 0.32, p = 0.001). The cut-off value of QI that predicted best LV reverse remodelling after 6 months of CRT was 12.25% (sensitivity 65,49%, specificity 75%, area under the curve 0.7, p = 0.001). Regarding clinical outcomes at 12 mounths, a statistically significant difference was found between patients with a QI ≤ 12.25%, and those with a QI &amp;gt; 12.25%, in terms of NYHA class worsening (p 0,04). Another statistically significant difference was found analyzing the relation between QI and the causes of deaths, the mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes. (p 0,0179). Conclusions Therefore decrease in QRSd after CRT initiation was related to greater echocardiographic reverse remodelling and better outcome from death or cardiovascular hospitalization. Even if larger studies are needed, QI seems to be an easy-to- measure variable that could be used or evaluated to predict CRT response.

Electrocardiographic predictors of echocardiographic response in cardiac resynchronization therapy: Update of an old story

BackgroundA better selection of patients with left bundle branch block (LBBB) might increase the response to cardiac resynchronization therapy (CRT). The aim of the study was to investigate the association between the Strauss criteria, absence of S wave in V5-V6, the Selvester score and response to CRT. Methods and resultsThe retrospective analysis included all consecutive patients having undergone implantation of biventricular defibrillators in primary prevention between 2018 and 2020.The final analysis included 236 patients (mean age 69.7 ± 9.9; 77.5% of males). The Strauss criteria were significantly associated with CRT response (p < 0.01) with a sensitivity of 71.3% and specificity of 64.1%. The Strauss criteria along with the absence of S wave in V5 and V6 showed a sensitivity of 56.7%, a specificity of 82.6% and a positive predictive value of 90.5%. The Selvester score was significantly and inversely associated with CRT response (OR 0.818, 95% CI 0.75–0.89; p < 0.001). The multivariable model showed that left ventricular ejection fraction (LVEF) and QRS duration (≥140 ms in males and ≥ 130 ms in females) were independently associated with CRT response (respectively OR 0.92, CI 95% 0.86–0.98, p = 0.01 and OR 3.70, CI 95% 1.12–12.21, p = 0.03). ConclusionsStrauss criteria, especially in association with absence of S wave in V5 and V6, were able to increase specificity and positive predictive value for predicting CRT response. The Selvester score was inversely associated with CRT response. Finally, LVEF and QRS duration were independently associated with echocardiographic response to CRT.

Prediction of response to cardiac resynchronization therapy using cardiac magnetic resonance imaging in non-ischemic dilated cardiomyopathy

Abstract Background Cardiac resynchronization therapy (CRT) is a well-established therapy for symptomatic heart failure with reduced ejection fraction, but the response is different for individuals. Although many modalities have been conducted to predict CRT response, cardiac magnetic resonance (CMR) to predict CRT response has still insufficient usefulness. Purpose We determine whether the parameters including late gadolinium enhancement (LGE) identified in CMR could act as predictors of CRT response. Methods We retrospectively investigated 124 patients with non-ischemic dilated cardiomyopathy who underwent CMR before CRT implantation between Jan 2010 and July 2021 in a single center. CRT response was defined as a decrease in left ventricular end-systolic volume (LVESV) &amp;gt;15% on echocardiography after at least 3 months after CRT implantation. Results Among the study population (mean age 65.7±11.2 years, mean EF 25±6.5%, 50% of female), 85 (69%) patients were defined as CRT responder. The CRT responders had more left bundle branch block (LBBB) compared with non-responders [79 (92.9%) vs. 23 (59.0%), p&amp;lt;0.001], but there was a no difference of QRS duration (158.7 vs 165.0ms, p=0.054) between two groups. CMR analysis showed that there were no significant differences in the left ventricular (LV) chamber volume and LV ejection fraction between CRT-responder and non-responder. However, the right ventricular (RV) chamber volume was smaller (RV end-diastolic volume index, 86.3 vs 103.5 ml/m2, p=0.039; RV end-systolic volume index, 49.3 vs 68.5 ml/m2, p=0.013) and the RV ejection fraction (RVEF) was higher (46.9 vs 37.6%, p=0.002) in CRT-responders compared with non-responders. The LGE on CMR was more shown in non-responders than in CRT-responders [33 (84.6%) vs 45 (52.9%), p&amp;lt;0.001]. In CMR parameters, RV dysfunction (RVEF &amp;lt;45%) [Odds ratio (OR), 0.21 (0.05–0.93), p=0.045] and LGE [OR, 0.21 (0.05–0.58), p=0.01] were significantly associated with poor CRT response. Conclusions The presence of LGE and RV dysfunction on CMR were associated with poor CRT response in patients with non-ischemic dilated cardiomyopathy. Further investigation with CMR for pre-CRT patients is needed to support these results. Funding Acknowledgement Type of funding sources: None.

The role of cardiac magnetic resonance in identifying appropriate candidates for cardiac resynchronization therapy - a systematic review of the literature.

Despite the strict indications for cardiac resynchronization therapy (CRT) implantation, a significant proportion of patients will fail to adequately respond to the treatment. This systematic review aims to present the existing evidence about the role of cardiac magnetic resonance (CMR) in identifying patients who are likely to respond better to the CRT. A systematic search in the MedLine database and Cochrane Library from their inception to August 2021 was performed, without any limitations, by two independent investigators. We considered eligible observational studies or randomized clinical trials (RCTs) that enrolled patients &gt; 18years old with heart failure (HF) of ischaemic or non-ischaemic aetiology and provided data about the association of baseline CMR variables with clinical or echocardiographic response to CRT for at least 3months. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA Statement). Following our search strategy, 47 studies were finally included in our review. CMR appears to have an additive role in identifying the subgroup of patients who will respond better to CRT. Specifically, the presence and the extent of myocardial scar were associated with increased non-response rates, while those with no scar respond better. Furthermore, existing data show that scar location can be associated with CRT response rates. CMR-derived markers of mechanical desynchrony can also be used as predictors of CRT response. CMR data can be used to optimize the position of the left ventricular lead during the CRT implantation procedure. Specifically, positioning the left ventricular lead in a branch of the coronary sinus that feeds an area with transmural scar was associated with poorer response to CRT. CMR can be used as a non-invasive optimization tool to identify patients who are more likely to achieve better clinical and echocardiographic response following CRT implantation.

A method using deep learning to discover new predictors from left-ventricular mechanical dyssynchrony for CRT response

BackgroundStudies have shown that the conventional parameters characterizing left ventricular mechanical dyssynchrony (LVMD) measured on gated SPECT myocardial perfusion imaging (MPI) have their own statistical limitations in predicting cardiac resynchronization therapy (CRT) response. The purpose of this study is to discover new predictors from the polarmaps of LVMD by deep learning to help select heart failure patients with a high likelihood of response to CRT. MethodsOne hundred and fifty-seven patients who underwent rest gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at 6 ± 1 month follow up. The autoencoder (AE) technique, an unsupervised deep learning method, was applied to the polarmaps of LVMD to extract new predictors characterizing LVMD. Pearson correlation analysis was used to explain the relationships between new predictors and existing clinical parameters. Patients from the IAEA VISION-CRT trial were used for an external validation. Heatmaps were used to interpret the AE-extracted feature. ResultsComplete data were obtained in 130 patients, and 68.5% of them were classified as CRT responders. After variable selection by feature importance ranking and correlation analysis, one AE-extracted LVMD predictor was included in the statistical analysis. This new AE-extracted LVMD predictor showed statistical significance in the univariate (OR 2.00, P = .026) and multivariate (OR 1.11, P = .021) analyses, respectively. Moreover, the new AE-extracted LVMD predictor not only had incremental value over PBW and significant clinical variables, including QRS duration and left ventricular end-systolic volume (AUC 0.74 vs 0.72, LH 7.33, P = .007), but also showed encouraging predictive value in the 165 patients from the IAEA VISION-CRT trial (P < .1). The heatmaps for calculation of the AE-extracted predictor showed higher weights on the anterior, lateral, and inferior myocardial walls, which are recommended as LV pacing sites in clinical practice. ConclusionsAE techniques have significant value in the discovery of new clinical predictors. The new AE-extracted LVMD predictor extracted from the baseline gated SPECT MPI has the potential to improve the prediction of CRT response.

Predictive Value of Left Atrial Remodeling for Response to Cardiac Resynchronization Therapy.

Response to cardiac resynchronization therapy varies significantly among patients, with one third of them failing to demonstrate left ventricular reverse remodeling after cardiac resynchronization therapy. Left atrial size and function is increasingly recognized as a marker of disease severity in the heart failure population. The aim of this study was to evaluate whether echocardiographic left atrial indices predict left ventricular reverse remodeling after cardiac resynchronization therapy. Ninety-nine cardiac resynchronization therapy candidates were prospectively included in the study and underwent echocardiography before and 3-months after cardiac resynchronization therapy implantation. Cardiac resynchronization therapy response was defined as a 15% relative reduction in left ventricular end-systolic volume. Indexed left atrial volume, left atrial reservoir strain, left ventricular end-diastolic volume, and left ventricular ejection fraction along with other known predictors of cardiac resynchronization therapy response (gender, etiology of heart failure, presence of typical left bundle branch block pattern, QRS duration >150 ms) were included in a multivariate logistic regression model to identify predictors for cardiac resynchronization therapy response. Cardiac resynchronization therapy response occurred in n = 63 (64%) patients. The presence of a typical left bundle branch block (OR 4.2, 95 CI: 1.4-12.1, p = 0.009), QRS duration >150 ms (OR 4.2, 95 CI: 1.4-11.0, p = 0.029), and left atrial volume index (OR: 0.6, 95 CI: 0.4-0.9, p = 0.012) remained the only significant predictors for cardiac resynchronization therapy response after three months. None of the baseline left ventricular parameters showed an independent predictive value. Left atrial size at baseline is an independent predictor and is inversely proportional to left ventricular volumetric reverse remodeling in cardiac resynchronization therapy candidates.