A multimodal deep learning model for cardiac resynchronisation therapy response prediction.

PurposeTo investigate the relationship between vectorcardiography (VCG) and myocardial scar on cardiac magnetic resonance (CMR) imaging, and whether combining these metrics may improve cardiac resynchronization therapy (CRT) response prediction. MethodsThirty-three CRT patients were included. QRSarea, Tarea and QRSTarea were derived from the ECG-synthesized VCG. CMR parameters reflecting focal scar core (Scar2SD, Gray2SD) and diffuse fibrosis (pre-T1, extracellular volume [ECV]) were assessed. CRT response was defined as ≥15% reduction in left ventricular end-systolic volume after six months' follow-up. ResultsVCG QRSarea, Tarea and QRSTarea inversely correlated with focal scar (R = −0.44–−0.58 for Scar2SD, p ≤ 0.010), but not with diffuse fibrosis. Scar2SD, Gray2SD and QRSarea predicted CRT response with AUCs of 0.692 (p = 0.063), 0.759 (p = 0.012) and 0.737 (p = 0.022) respectively. A combined ROC-derived threshold for Scar2SD and QRSarea resulted in 92% CRT response rate for patients with large QRSarea and small Scar2SD or Gray2SD. ConclusionQRSarea is inversely associated with focal scar on CMR. Incremental predictive value for CRT response is achieved by a combined CMR-QRSarea analysis.

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) > 15% or an increase in left ventricular ejection fraction > 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<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<0.001), native T1 (1371.6 vs. 1336.8ms, p=0.033), T2 (45.9 vs. 42.1ms, p<0.001), and extracellular volume (ECV, 36.8 vs. 31.0%, p<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>20% (odds ratio [OR]: 0.15, 95% CI: 0.02-0.71, p=0.024) and ECV > 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.

Impact of Mechanical Activation, Scar, and Electrical Timing on Cardiac Resynchronization Therapy Response and Clinical Outcomes

The absence of clinical response in 30% to 40% of patients receiving cardiac resynchronization therapy (CRT) poses a great challenge to heart failure clinicians and device implanters.It is well documented that positioning of the left ventricular (LV) lead in areas of myocardial scar in patients with ischemic cardiomyopathy is associated with a diminished response to CRT.Regions of slow conduction exist in both nonischemic and ischemic cardiomyopathy that can be delineated using noncontact mapping, whereby the electrophysiological properties of a chamber can be characterized using a multielectrode array.Using this technique, the authors evaluated the effect of pacing inside and outside regions of slow conduction on acute hemodynamic response to CRT.Procedures were performed in a combined x-ray and MRI environment so that tissue characterization by delayed-enhancement cardiac MRI could be correlated with electrophysiological assessment.Both endocardial and transvenous epicardial LV pacing were performed with the hypothesis that endocardial pacing may be more effective as a result of reproducing the physiological pattern of activation of the LV myocardium as well as a lack of constraint by the coronary venous anatomy.The authors found that zones of slow conduction could be identified using delayed-enhancement cardiovascular magnetic resonance in patients with an ischemic heart failure etiology but not in patients with nonischemic cardiomyopathy.The short-term effect of CRT was superior in response to endocardial compared with epicardial pacing.Stimulation within zones of slow conduction was associated with a diminished response to CRT.This is a potential explanation for lack of response to CRT and reinforces the need for positioning the LV lead on an individual basis. Conclusions:Endocardial LV pacing appears superior to conventional CRT, although the optimal site varies among patients and is influenced by pacing within areas of slow conduction.Delayedenhancement cardiovascular magnetic resonance was a poor predictor of zones of slow conduction in patients without ischemia. 1 Relative Merits of Left Ventricular Dyssynchrony, Left Ventricular Lead Position, and Myocardial Scar to Predict Long-Term Survival of Ischemic Heart Failure Patients Undergoing Cardiac Resynchronization TherapySummary: The beneficial effects of cardiac resynchronization therapy on long-term survival are influenced by several pathophysiolog-ical factors.The present study demonstrated the relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome of patients with ischemic heart failure treated with cardiac resynchronization therapy.With speckletracking radial strain analysis, the extent of LV dyssynchrony, site of latest mechanical activation, and presence of myocardial scar at the LV segment where the LV pacing lead is placed were evaluated.In addition, the LV lead position was derived from chest radiograph and was defined as concordant when the LV pacing lead coincided with the site of latest mechanical activation.Mean baseline LV radial dyssynchrony was 133Ϯ98 ms.A concordant LV lead position was reported in 271 (68%) patients, and the mean value of peak radial strain at the targeted segment was 18.9Ϯ12.6%.During a median follow-up of 21 months, 88 (22%) patients died.Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995 per 1-ms increment; Pϭ0.001), whereas a discordant LV lead position (hazard ratio, 2.086; Pϭ0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913; PϽ0.001) were independent predictors of worse outcome.Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters.These data underscore the need for integrated evaluation that includes assessment of these 3 parameters to further improve patient selection and survival after cardiac resynchronization therapy.Conclusions: Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in patients with ischemic heart failure treated with cardiac resynchronization therapy.Larger baseline LV dyssynchrony predicted superior longterm survival, whereas discordant LV lead position and myocardial scar predicted worse outcome. 2 Prediction of Cardiac Resynchronization Therapy Response: Value of Calibrated Integrated Backscatter ImagingSummary: According to current guidelines, candidates for cardiac resynchronization therapy (CRT) are patients in New York Heart Association functional class III to IV heart failure with left ventricular (LV) ejection fraction Յ35% and QRS duration Ն120 ms.However, by applying these selection criteria, more than one third of the patients do not show clinical response or LV reverse remodeling.Among several factors that determine a favorable response to CRT, the amount of LV fibrosis as assessed, for example, with cardiovascular magnetic resonance has been shown to be an important issue.This study demonstrated that myocardial ultrasound reflectivity is an important determinant of CRT response in the overall heart failure

Introduction: Late gadolinium enhancement on cardiac magnetic resonance imaging (LGE-CMR) has been shown to predict adverse cardiovascular outcomes, especially ventricular arrhythmic events. Hypothesis: A few studies, limited by small sample size, have examined the relationship between myocardial scar and cardiac resynchronization therapy (CRT) response. We performed a meta-analysis to determine whether scar identified on LGE predicts response to CRT in cardiomyopathy. Methods: We searched PubMed and Embase for clinical trials reporting CRT response based on scar determined by LGE -CMR. Primary outcome was defined as improvement in NYHA class or echocardiographic parameters (not limited to but including dP/dT, radial strain and reduction of LV end systolic volume). Random effects model was used to pool the data across the studies. Results: After screening 1876 articles, we identified 14 clinical trials that met inclusion criteria. A total of 984 patients were included in the analysis. There was no significant heterogeneity across the studies (I 2 =30%, p= 0.13). Presence of scar on LGE-CMR decreased CRT response by 39% (RR: 0.61 (95% CI 0.53 - 0.71; p<0.001). Exclusion sensitivity analysis did not change the effect size. Pooled analysis of studies reporting only ischemic cardiomyopathy revealed that any myocardial scar reduced CRT response by 38% (RR: 0.62 (0.44 - 0.86; p=0.004). Conclusions: The presence of any myocardial scar detected by LGE predicts sub-optimal response to CRT in cardiomyopathy. This shows that identification of scar using LGE- CMR can be used as an important risk stratification tool for CRT response.

Background Myocardial scar presence and extent, has a considerable influence on response to cardiac resynchronization therapy (CRT). Apical rocking (ApRock) and septal flash (SF) are associated with favourable outcome after CRT. Little is known however to which extent visual assessment of mechanical dyssynchrony by ApRock, SF and scar predicts CRT response. We therefore investigated, if additional scar assessment by cardiac magnetic resonance imaging (MRI) adds to the predictive value of the visual evaluation of echocardiographic images in CRT candidates. Methods A total of 201 unselected patients referred for CRT, who fulfil the contemporary guidelines for CRT implantation, were enrolled in this prospective multicentre study. Two experienced observers visually assessed echocardiographic images before CRT implantation, focussing on the presence of ApRock, SF and location and extent of scar segments of the left ventricle (LV), resulting in a CRT response prediction (i.e. Integrative Prediction). A third observer provided a consensus reading in case of disagreement. All observers were blinded to all patient information other than the ischaemic aetiology of heart failure. Independent from that, segmental myocardial scar burden was objectified by late gadolinium enhancement (LGE) cardiac MRI (LGE > 50%). CRT response was defined as ≥15% reduction in LV end-systolic volume on echocardiography, one year after device implantation. Results Overall, 69 (34%) patients had an ischaemic aetiology of heart failure. Before CRT, ApRock and SF were present in 129 (64%) and 136 (68%) patients, respectively. ApRock and SF alone predicted CRT response with an area under the curve (AUC) of 0.85 (95% CI: 0.79-0.91) and 0.84 (95% CI: 0.77-0.91) (Figure A), while the echocardiographic Integrative Prediction had an AUC of 0.90 (95% CI: 0.84-0.95), with a sensitivity of 93% and a specificity of 87% for the prediction of CRT response (Figure B) (p < 0.05 vs. ApRock and SF alone). When combining information on ApRock, SF and the number of scarred segments on MRI in a statistical model, the AUC was comparable to the echocardiographic Integrative Prediction [0.90 (95% CI: 0.84-0.96)] as was sensitivity and specificity (91% and 83%, respectively, p = N.S. vs. Integrative Prediction) (Figure C). Conclusions An integrative visual assessment of LV function has an excellent predictive value for CRT response. Our data show, that the echocardiographic estimation of scar burden is sufficiently accurate and cannot be further improved by an additional MRI scar assessment. Abstract 160 Figure.

QRS duration (QRSd) is known to be affected by body weight and length. We tested the hypothesis that adjusting the QRSd by body mass index (BMI) may provide individualization for patient selection and improve prediction of cardiac resynchronization therapy (CRT) response. A total of 125 CRT recipients was analyzed to assess functional (≥1 grade reduction in NYHA class) and echocardiographic (≥15% reduction in LVESV) response to CRT at 6 months of implantation. Baseline QRSd was adjusted by BMI to create a QRS index (QRSd/BMI) and tested for prediction of CRT response in comparison to QRSd. Overall, 81 patients (65%) responded to CRT volumetrically. The mean QRS index was higher in CRT responders compared to nonresponders (6.2 ± 1.1 vs 5.2 ± 0.8 ms.m(2) /kg, P < 0.001). There was a positive linear correlation between the QRS index and the change in LVESV (r = 0.487, P < 0.001). Patients with a high QRS index (≥5.5 ms.m(2) /kg, derived from the ROC analysis, AUC = 0.787) compared to those with a prolonged QRSd (≥150 ms, AUC = 0.729) had a greater functional (72% vs 28%, P < 0.001) and echocardiographic (80% vs 44%, P < 0.001) improvement at 6 months. QRS index predicted CRT response at regression analysis. Indexing the QRSd by BMI improves patient selection for CRT by eliminating the influence of body weight and length on QRSd. QRS index is a novel indicator that provides promising results for prediction of CRT response.

0324: Prognostic value of epicardial-endocardial gradient measured by echocardiography to predict Cardiac Resynchronization Therapy (CRT) response

Funding AcknowledgementsType of funding sources: None.Background/introductionOptimisation of cardiac resynchronisation therapy (CRT) response still represents a significant challenge to cardiac electrophysiology. In this regard, perhaps the area of greatest uncertainty revolves around optimal left ventricular lead (LVL) position and in particular whether this should be directed at areas of latest electrical or mechanical activation given the equivocal evidence on their precise relationship in heart failure (HF) patients. Furthermore, while echocardiography has demonstrated that LVL aimed at regions of greatest mechanical delay maximises CRT response, cardiac magnetic resonance (CMR) with its greater spatial resolution and tissue definition is yet to demonstrate a role in doing so.PurposeTo retrospectively evaluate concordance between latest electrical and CMR-determined mechanical activation in a CRT population and its relationship with reverse remodeling.MethodsThis is a retrospective single center analysis of 104 CRT patients. All patients had CMR and echocardiography performed before implantation. During implantation, coronary sinus angiogram was performed and electrical delay (QLV time with RV-LV time greater than 80 ms) was mapped on all veins suitable for lead implantation and LVL was positioned in the region of latest electrical activation programming LVL cathode accordingly. LVL cathode position was thus assumed to represent the region of latest electrical delay. A post-hoc analysis was then conducted by means of CART-Tech® software providing radial strain and scar maps on a 36-segment anatomical model. Patients were then stratified based on concordance between LVL cathode position (using 3D heart models superimposed on 2D angiography images) and most mechanically delayed segments (either the three most delayed segments or adjacent ones) or non concordance (one or more segments between LVL cathode and three most mechanically delayed segments). Data from patient follow-up was collected with echocardiography at least 3 months after implant date. CRT response was expressed as reduction in end-systolic volume (ESV) greater than 15%.ResultsA preliminary analysis of the first 30 patients of our cohort was conducted. Electromechanical concordance and non-concordance were present in 24 and 6 patients, respectively. Baseline patient characteristics including demographics, comorbidities, HF aetiology, ECG and echocardiography features were comparable between groups except for scar burden, which was higher in the non-concordance group. Response to CRT was 80% in the concordant vs. 20% in the non-concordant group.ConclusionsWhile a confounding effect of scar burden cannot be excluded, these preliminary data suggest that electromechanical concordance in LVL cathode placement may represent a predictor of optimal CRT response. The full scope of this study will be fully appreciated in the coming month on completion of analysis of the entire patient cohort.Figure 1Figure 2, Table 1

Background: Despite contemporary restrictive clinical and electrocardiographic selection criteria, up to one-third of chronic heart failure patients with implanted cardiac resynchronization therapy (CRT) are non-responders. Previous studies reported that some electrocardiographic patterns, such as the longer the intrinsicoid deflection (ID) in lead I, the higher the R wave amplitude in V₆, and other patterns may be helpful for CRT response prediction. Objective: To establish a simplified model using electrocardiographic parameters as predictors of CRT response among chronic heart failure patients. Materials and Methods: Eighty chronic heart failure patients meeting the current guideline recommendation for CRT implantation were enrolled in the present retrospective cohort study. The patients’ clinical and electrocardiographic parameters at the time of CRT implantation and during follow-up were analyzed. The response to CRT was evaluated after six months of implantation, defined as a decrease in the left ventricular end systolic volume (LVESV) of 15% or more or an increase in the left ventricular ejection fraction (LVEF) of 10% or more. Results: During a median follow-up period of 34 months, there were 45 (56.3%) responders. In multivariate analysis, the independent predictors for CRT response were the greater the reduction of the QRS complex duration after implantation (QRS post – QRS pre), the higher the time to ID in the lead I/QRS ratio (ID I/QRS), and the higher the difference in the amplitude of the R and S waves in lead V₁ and V₆ [(S1+R6) – (S6+R1)] (QRS post – QRS pre: adjusted odds ratio [OR] 0.97, 95% CI 0.94 to 0.99, p=0.004; ID I/QRS: OR 18.65, 95% CI 1.02 to 342.64, p=0.049; (S1+R6) – (S6+R1): OR 1.1, 95% CI 1.04 to 1.17, p=0.002). The new equation for calculating the predictive CRT response model, generated from multiple logistic regression analysis, was –3.414 – 0.035(QRS post – QRS pre) + 2.926(ID I/QRS) + 0.097[(S1+R6) – (S6+R1)]. The area under the receiver operating characteristic (ROC) curve for the new model for predicting CRT response was 0.853 (95% CI 0.767 to 0.939). A model score of more than 0.3 showed a sensitivity of 85.7% and specificity of 80% for the prediction of CRT response. Conclusion: The new electrocardiographic model achieved a high sensitivity and specificity for the prediction of CRT response among chronic heart failure patients, who met the current guideline recommendation for CRT implantation. Keywords: Cardiac resynchronization therapy, Electrocardiography, Heart failure, Responders, Model

Left ventricular systolic and diastolic dyssynchrony to improve cardiac resynchronization therapy response in heart failure patients with dilated cardiomyopathy

Objective:The aim of the study was to compare, Modified Frailty Index (mFI), EAARN (LVEF <22%, Atrial Fibrillation, Age ≥70 years, Renal function (eGFR <60 mL/min/1.73m2), NYHA class IV), and ScREEN (female Sex, Renal function (eGFR ≥60 mL/min/1.73m2), LVEF ≥25%, ECG (QRS duration ≥150 ms) and NYHA class ≤III) score for predicting cardiac resynchronization therapy (CRT) response and all-cause mortality.Methods:In this prospective, non-randomized, single-center, observational study we enrolled 93 patients receiving CRT from August 2016 to August 2019. Pre-implant scores were calculated, and patients were followed for six months. Performance of each score for prediction of CRT response (defined as ≥15% reduction in left ventricular end-systolic volume [LVESV]) and all-cause mortality was compared.Results:Optimal CRT response was seen in seventy patients with nine deaths. All the three scores exhibited modest performance for prediction of CRT response and all-cause mortality with AUC ranging from 0.608 to 0.701. mFI has an additional benefit for prediction of prolonged post-procedure stay and 30-day rehospitalization events.Conclusion:mFI, ScREEN and EAARN score can be used reliably for predicting all-cause mortality and response to CRT.

Comparison of measures of ventricular delay on cardiac resynchronization therapy response

BackgroundStudies 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.Methods and ResultsThis 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.ConclusionsIn 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.

Effect of Diabetes Mellitus on Cardiac Resynchronization Therapy and to Prognosis in Heart Failure (from the Prospective Evaluation of Asian With Cardiac Resynchronization Therapy for Heart Failure Study)