Efficacy Of CRT Research Articles

QRS length/left ventricular mass index: a novel predictive factor of response to cardiac resynchronization therapy

Abstract Introduction The length of QRS interval is an extensively studied predictor of response to CRT. There is little evidence of the probability of response in patients with QRS between 130 and 150 ms and its relationship with LV mass. (1,2) Objective Evaluation of the QRS length/LV mass index (QRS/LVMi) as a "relative dyssynchrony" marker and its correlation to response after CRT implantation. Methods Retrospective study that included patients over 18 years of age with HFrEF (LVEF ≤ 35%) and CRT implantation between years 2018 – 2022 (n = 92). QRS length (ms) was measured with CardioLab 3.0 Software and divided by LV mass (g), according to Deveraux equation using echocardiography measurements. Primary outcome was response to CRT defined by: Improvement of at least 1-point in NYHA functional class + (i) increase of at least 5% in LVEF or (ii) decrease of at least 15% in LVESD. Results QRS/LVMi value ≥ 0.6 was associated with a higher frequency of response to CRT than values < 0.6 (83% responders vs 17% non responders; OR 5.1; CI 2.7–12.1, p < 0.05). There was no difference in response to CRT between QRS > 150 ms and 130 – 150 ms in patients with QRS/LVMi ≥ 0.6 (80% vs 82% of responders, p = 0.8). A multivariate analysis showed a significantly higher probability of response to CRT in patients with QRS/LVMi ≥ 0.6 compared to other known predictive factors (OR 4.1; CI 1.2–12, p < 0.05). Conclusions The use of QRS/LVMi was associated with a better prediction of response to CRT than other traditional factors. There was no difference in response between QRS > 150 ms and 130 - 150 ms in patients with QRS/LVMi ≥ 0.6, suggesting the efficacy of CRT in patients with shorter QRS interval length and less LV mass, highlighting the importance of the concept of relative dyssynchrony.Total Response according QRS/LMViMultivariate analysis

Clinical utility of QRS duration normalized to left ventricular volume for predicting cardiac resynchronization therapy efficacy in patients with “mid-range” QRS duration

BackgroundCardiac resynchronization therapy (CRT) is effective for patients with heart failure with QRS duration (QRSd) ≥150 ms. However, its beneficial effect seems to be limited for those with “mid-range” QRSd (120–149 ms). Recent studies have demonstrated that modifying QRSd to left ventricular end-diastolic volume (LVEDV)—modified QRSd—improves the prediction of clinical outcomes of CRT. ObjectiveThe purpose of this study was to investigate the clinical impact of the modified QRSd on the efficacy of CRT in patients with “mid-range” QRSd. MethodsWe conducted a retrospective, multicenter, observational study, with heart failure hospitalization (HFH) after CRT as the primary endpoint. Modified QRSd is defined as QRSd divided by LVEDV, determined through the Teichholtz method of echocardiography. ResultsAmong the 506 consecutive patients considered, 119 (mean age 61 ± 15 years; 80% male, QRSd 135 ± 9 ms) with a “mid-range” QRSd who underwent de novo CRT device implantation were included for analysis. During median follow-up of 878 days [interquartile range 381–1663 days], HFH occurred in 45 patients (37%). Fine-Gray analysis revealed modified QRSd was an independent predictor of HFH (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.96–0.99; P <.01). Receiver operating characteristic curve analysis revealed a cutoff value of 0.65 ms/mL for the modified QRSd in predicting HFH. Patients above the threshold exhibited a significantly lower incidence of HFH than patients below the threshold (HR 0.46; 95% CI 0.25–0.86; P = .01). ConclusionModified QRSd can effectively predict the efficacy of CRT in patients with a “mid-range” QRSd.

Clinical characteristics and outcome of cardiac resynchronization therapy for heart failure in National Hospital of Sri Lanka from year 2005 to 2020 – a retrospective observational study

BackgroundCardiac resynchronization therapy (CRT) has been a well-established treatment modality for moderate to severe left ventricular systolic dysfunction with left ventricular desynchrony. This is the pioneering study that analyses the cohort who underwent CRT implantation at the National Hospital of Sri Lanka (NHSL) in Colombo from 2005 to 2020.ObjectivesThis study was carried out to describe socio-demographic factors, improvements in clinical outcome (symptoms, electrocardiographic, and echocardiographic features), and post-CRT complications in the study population, as well as to determine the efficacy of CRT in heart failure.MethodA retrospective observational study was conducted on all the living patients who had undergone CRT implantation from 2005 to 2020. The data was gathered from all the consented patients who visited the device programming clinic using a physician-administered questionnaire and clinical records. Data was analyzed using SPSS 25, and significant statistics were assessed with the McNemer test, the Student T test, and the Chi-Squared test.ResultsThe study included 50 patients with a mean age of 52.82+/− 11.66 years and female predominance (56%, n = 28). Idiopathic dilated cardiomyopathy (50%, n = 25) was the leading etiological factor, followed by ischemic cardiomyopathy (28%, n = 14). Clinical symptoms have improved significantly with CRT implantation (p < 0.001). A significant improvement was found in NYHA functional class (p < 0.001, 95% CI = 0.072 to 0.284), QRS width (p < 0.001, 95% CI = 0.229 to 0.534), ejection fraction (p < 0.001, 95% CI = − 16.437 to − 8.504), and LV EDD (p < 0.001, 95% CI = 2.89 to 9.24). Post-CRT complications included lead malfunction (6%, n = 3) and chronic (14%, n = 7), bleeding or hematoma (2%, n = 1), pocket erosion or infection (6%, n = 3), and infective endocarditis (2%, n = 1).ConclusionAccording to the study, CRT significantly improves both clinical and functional outcomes in patients with moderate to severe heart failure.

Abstract PR013: Association of a polymorphic variant in JMJD1C with response to chemoradiotherapy in rectal cancer and head and neck cancer: Implications for a diverse population

Abstract Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer (LARC). Although nCRT has improved outcomes for many patients, ~70-80% of patients show poor or no response, and CRT is toxic. No biomarker exists that can predict which patients may benefit from nCRT. CRT efficacy arises from unrepaired double-strand breaks (DSBs). Recent work has suggested that dynamic changes in lysine modification of chromatin regulate DSB repair. This study investigated the association of germline single nucleotide polymorphisms (SNPs) in lysine-modifying genes with DSB repair and CRT outcomes in LARC. The LARC patients (n=84) were segregated into poor (PoR) and complete (CR) responders using the Neoadjuvant Rectal score. Blood DNA was sequenced to identified SNPs, matched LARC patient-derived cells were tested for sensitivity to DNA damage, and results correlated. Significant SNP-response correlations were confirmed in an independent cohort of CRT-treated head and neck squamous cell carcinoma (HNSCC) patients who had received chemoradiation (n=90). The HNSCC patients were segregated into 3 groups based on response: disease-free (n=30), recurrent disease (n=28), and never-disease free (n=32). Isogenic HNSCC lines with either the wildtype (WT) or SNP were generated using CRISPR/Cas9 technology, and bulk RNA sequencing and immunofluorescence-based studies were performed to assess pathways affected. LARC CRs were significantly enriched versus PoRs for a germline SNP in the lysine H3K9 demethylase, JMJD1C, resulting in a missense variant (discovery (n=30, p&amp;lt;0.00001), validation (n=54, p=0.001); Fisher’s Exact). In the HNSCC cohort, the JMJD1C SNP was significantly associated with no recurrence (p=0.0003, Fisher’s Exact). LARC patient-derived cell lines carrying the SNP were significantly more sensitive to DSB damage versus those carrying the WT (n=12, p&amp;lt;0.001, Mann-Whitney). Cells bearing the SNP were significantly enriched for altered mRNA levels of genes associated with DNA repair compared with WT cells (q-value&amp;lt;0.05). On irradiation, the SNP cells showed robust activation of DSB repair (γH2AX, BRCA1 foci, JMJD1C nuclear localization) versus the WT cells. Finally, analysis of the JMJD1C SNP frequency in large population datasets found that while it was abundant in European Americans (EAs), it is relatively rare in African Americans (AAs) (EA= 0.3139 vs. AA=0.072; gnomAD population). This study provides novel insight into a SNP in a lysine-modifying gene affecting DSB repair that may serve as a predictive biomarker for CRT response in 2 different cancer types. Our data suggest that host genetics impact DSB repair and warrant further investigation to better understand disparities in response to CRT. Future research will further explore the racial/ethnic disparities in tumor recurrence and confirm results in in vitro and in vivo models of cancer, and in large patient datasets. Citation Format: Adria Hasan, Elena Demidova, Philip Czyzewicz, Shreya Shah, Karthik Devarajan, Thomas J. Galloway, Margret B. Einarson, Barbara Burtness, Erica A. Golemis, Joshua E. Meyer, Sanjeevani Arora. Association of a polymorphic variant in JMJD1C with response to chemoradiotherapy in rectal cancer and head and neck cancer: Implications for a diverse population [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr PR013.

Managing ventricular arrhythmias and implantable cardiac defibrillator shocks after left ventricular assist device implantation.

Continuous flow left ventricular assist devices (CF-LVADs) have been shown to reduce mortality and morbidity in patients with advanced heart failure with reduced ejection fraction. However, ventricular arrhythmias (VA) are common, are mostly secondary to underlying myocardial scar, and have a higher incidence in patients with pre-LVAD VA. Sustained VA is well tolerated in the LVAD patient but can result in implantable defibrillator (ICD) shocks, right ventricular failure, hospitalizations, and reduced quality of life. There is limited data regarding best practices for the medical management of VA as well as the role for procedural interventions in patients with uncontrolled VA and/or ICD shocks. Vast majority of CF-LVAD patients have a preexisting cardiovascular implantable electronic device (CIED) and ICD and/or cardiac resynchronization therapies are continued in many. Several questions, however, remain regarding the efficacy of ICD and CRT following CF-LVAD. Moreover, optimal CIED programming after CF-LVAD implantation. Therefore, the primary objective of this review article is to provide the most up-to-date evidence and to provide guidance on the clinical significance, pathogenesis, predictors, and management strategies for VA and ICD therapies in the CF-LVAD population. We also discuss knowledge gaps as well as areas for future research.

Electrical Resynchronization and Clinical Outcomes During Long-Term Follow-Up in Intraventricular Conduction Delay Patients Applied Left Bundle Branch Pacing-Optimized Cardiac Resynchronization Therapy.

Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) has shown encouraging results for QRS duration reduction and heart function improvement. However, the feasibility and efficacy of LOT-CRT have not been well established in intraventricular conduction delay patients. This study aims to assess and compare the efficacy and clinical outcome of CRT based on left bundle branch pacing, combined with coronary sinus left ventricular pacing (LOT-CRT) with CRT via biventricular pacing (BiV-CRT) in intraventricular conduction delay patients indicated for CRT. Consecutive patients with intraventricular conduction delay and CRT indications were assigned nonrandomized to LOT-CRT (n=30) or BiV-CRT (n=55). Addition of the left bundle branch pacing (or coronary venous) lead was at the discretion of the implanting physician guided by suboptimal paced QRS complex and on clinical grounds. Echocardiographic parameters and clinical characteristics were accessed at baseline and during 2-years' follow-up. Success rate for LOT-CRT and BiV-CRT was 96.8% and 96.4%. LOT-CRT had greater reduction of QRS duration compared with BiV-CRT (42.7±17.4 ms versus 21.9±21.5 ms; P<0.001). Higher left ventricular ejection fraction was also achieved in LOT-CRT than BiV-CRT at 6-month (36.7±9.8% versus 30.5±6.4%; P<0.05), 12-month (34.8±7.6% versus 30.3±6.2%; P<0.05), 18-month (36.3±7.9% versus 28.1±6.6%; P<0.005), and 24-month follow-up (37±9.5% versus 30.5±7%; P<0.05). Adverse clinical outcomes including heart failure rehospitalization and mortality were lower in LOT-CRT group for 24 months follow-up (hazard ratio, 0.33; P=0.035). LOT-CRT improves ventricular electrical synchrony and may provide greater clinical outcomes as compared with BiV-CRT in intraventricular conduction delay patients. These findings need further evaluation in future randomized controlled trials.

Concurrent Chemoradiotherapy Followed by Surgery for Borderline Resectable Esophageal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> This study aimed to clarify the efficacy and safety of induction CRT followed by esophagectomy for borderline resectable esophageal squamous cell carcinoma (BR-ESCC) in which tumors grow very close to the adjacent vital organs. <h3>Materials/Methods</h3> The cohort of this retrospective single-center study included 31 patients who received CRT (41.4 Gy/23 fractions) and radical minimally invasive esophagectomy for T4 BR-ESCC between June 2017 and November 2020. The overall survival (OS), disease-free survival (DFS) and the patterns of recurrence were analyzed. <h3>Results</h3> A total of 14 (45.16%) patients had T4a and 17 (54.84%) had T4b. The median age was 58 (53-65). The clinically involved site were as follows: pleura invasion (15/31), thoracic aorta (14/31), pericardium (13/31), tracheobronchial tree (4/31). The median number of dissected lymph nodes was 28 (16-35). Eight Patients (25.81%) were identified as having a pathologic complete response(pCR). The most surgical complication was anastomotic leakage (16.13%, 5/31) classified as Clavien-Dindo grade II. Respiratory failure was observed in one patient during the early postoperative phase. At a median follow-up interval of 38 months, neither median OS nor DFS was reached. The 3-OS and 3-DFS rates were 62.75% and 61.53%, respectively. Specifically, Patients with pCR showed significantly longer DFS than those who did not (stratified log-rank test: p=0.0301). The OS tended to be better in patients with pCR than in those without pCR (stratified log-rank test: p=0.5635), but not statistically significant. Ten patients (32.3%%) experienced progression during the follow-up period. The recurrence rate of lymph node and distant metastasis were 16.13% (5/31) and 25.81% (8/31). The most frequent metastatic organ was the lung (16.13%) . <h3>Conclusion</h3> The tolerability and efficacy for patients who obtained R0 resection after induction CRT for borderline resectable ESCC was encouraging. The long-term results are worthy of further exploration.

SY17-3 Current status and perspective of the combination of immunotherapy and chemoradiotherapy for locally advanced head and neck cancer

The standard treatment for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is surgery ± postoperative (chemo)radiation therapy [(C)RT] or definitive CRT. The standard concurrent chemotherapy regimen is tri-weekly cisplatin. In the postoperative setting, weekly cisplatin is an alternative option. For laryngeal preservation, induction docetaxel, cisplatin, and 5-FU followed by (C)RT is the treatment option. Recently, the efficacy of combined immunotherapy and CRT for curative intent has been reported.

Baseline PD-L1 expression and tumour-infiltrated lymphocyte status predict the efficacy of durvalumab consolidation therapy after chemoradiotherapy in unresectable locally advanced patients with non-small-cell lung cancer

BackgroundChemoradiotherapy (CRT) followed by durvalumab treatment improved prognosis in unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study aimed to evaluate whether the status of the immune-related tumour microenvironment (TME) at baseline associates with the efficacy. MethodsThis retrospective study evaluated immune-related TME factors, including programmed cell death ligand 1 (PD-L1) (clone: 22C3) expression on tumour cells and the density of CD8-positive tumour-infiltrating lymphocytes (TILs) at pre-CRT in patients with unresectable LA-NSCLC treated with CRT only (CRT alone group) and those treated with CRT followed by durvalumab (Durva group). ResultsA total of 551 patients were included (N = 113 in the Durva group). Progression-free survival (PFS) in the Durva group was significantly greater than that in the CRT alone group (not reached [NR] vs 12.9 months; p = 0.002). In the CRT alone group, neither PD-L1 expression nor TIL status affected PFS; in contrast, in the Durva group, high density of CD8-positive TILs (TILHigh ≥100/mm2) and PD-L1-positive expression (tumour proportion score ≥1%; PD-L1+) was significantly associated with longer PFS (TIL: NR vs 9.5 months; p = 0.002; and PD-L1: NR vs 7.7 months; p = 0.003). On the other hand, in patients with epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, there was no significant difference in PFS between the groups (Durva vs CRT alone: 9.9 months vs 14.0 months; p = 0.77). ConclusionsPD-L1+ and TILHigh at baseline could be predictive markers of the efficacy of CRT followed by durvalumab.

QRS narrowing predicts left ventricular reverse remodelling after resynchronization therapy in patients with end-stage heart failure

Abstract Introduction Cardiac resynchronization therapy (CRT) is an established treatment for heart failure (HF) patients, however one-third of the patients fail to benefit from CRT. The relationship between the QRS duration, severity of mechanical dyssynchrony and efficacy of CRT is not completely understood. We determined if QRS duration shortening after CRT implantation was predictive of left ventricular reverse remodelling. Methods We retrospectively enrolled 227 patients undergoing CRT implantation between 2013 and 2020 according to the guidelines. 88 patients were included in our analysis, from whom all data were available, and these represent our sample. Clinical, electrocardiographic and echocardiographic parameters were evaluated at baseline and after 6 months of CRT implantation. Response to CRT was defined as a reduction in left ventricular end-diastolic volume (LVEDV) &amp;gt;15%. Linear regression models were used. Results 88 patients were included (mean age 69±10 years, 62.5% males, 36.4% ischemic etiology). Baseline left ventricular ejection fraction (LVEF) was 27,5±5,8% and LVEDV was 181±69 ml. After 6 months of CRT, 52 patients (59.1%) were considered responders. Baseline LVEDV was superior in responders when compared with non responders (199±85 ml vs 168±53 ml, p=0.038). No significant differences were noted in male gender (p=0.823), ischemic cardiomyopathy (p=0.065), LVEF (p=0.853), atrial fibrillation (p=0.390), left bundle branch block (p=0.950) or biventricular pacing (p=0.154) between them. QRS duration at baseline was similar between responders and non-responders (165±17 ms vs 163±17 ms, p=0.620). After 6 months of CRT, the reduction of QRS duration in responders was significantly higher than non-responders (p&amp;lt;0.001). QRS duration was reduced from 165±17 ms to 136±15 ms in responders vs 163±17 ms to 160±17 ms in non-responders, (p&amp;lt;0.001). The change in QRS duration positively correlated with the change in LVEDV (0. 654; p&amp;lt;0.001). Multi-linear regression analysis suggested that QRS duration shortening had a significant effect on LVEDV (y = 14,375 + 1.354 X, R2 0.337, p&amp;lt;0.001) Conclusion QRS duration shortening after CRT implantation was predictive of LV reverse remodelling in end-stage heart failure patients. Further prospective studies should be conducted to assess the prognostic value of QRS narrowing in response to CRT. Funding Acknowledgement Type of funding sources: None.

B-PO01-103 IMMEDIATE CHANGE IN SYSTOLIC STRETCH FRACTION PREDICTS RESPONSIVENESS TO CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH CONGENITAL HEART DISEASE

Anatomic heterogeneity and a lack of standardized functional assessment limit current predictive modeling for CRT responsiveness and efficacy. Echocardiographic electromechanical-discoordination indices provide a novel assessment platform for myocardial deformation with defined advantages over traditional measures of mechanical dyssynchrony. The purpose of this study was to evaluate electromechanical-discoordination indices (systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF)) before and after CRT in patients with CHD-related heart failure. Functional echocardiography was analyzed pre- and post-CRT (n=12) for defined markers of mechanical dyssynchrony: time-to-peak (TTP) deviation, global circumferential strain (GCS), SSF and DRF. SSF and DRF were derived from the relative proportion of myocardial contraction to relaxation in systole and diastole, respectively, using a myocardial-specific strain rate curve. Five patients were classified as CRT responders and seven as non-responders. While there were no differences in immediate pre- vs post- echocardiographic markers for the entire cohort (Fig A), patients classified as responders had a significant immediate reduction in SSF (P=0.025) (Fig B). Change in echocardiographic markers when comparing responder status revealed no change in TTP (P=0.268), GCS (P=0.267), and DRF (P=0.531). Patients who respond to CRT therapy show immediate improvement in SSF. Analyzing the proportion of myocardial contraction to relaxation during systole might serve as a potential marker of peri-operative optimization and CRT responsiveness.

Should different ECG QRS duration criteria be used for men and women with heart failure for cardiac resynchronization therapy

In the present paper we review data of the efficacy of CRT based on baseline QRS duration and morphology in patients with heart failure due to left ventricle systolic dysfunction. We specifically review data that analyzed men and women separately. The main findings suggest benefit of CRT in patients with baseline LBBB, but not in patients without LBBB. Benefit is directly related to QRS duration at baseline with increasing rates and magnitude of echocardiographic response ( in terms of improvement in ejection fraction and decrease un LV size) and clinical response with increasing baseline QRS. The effect was most pronounced when QRSd was above 150 ms. Among women treated with CRT, similar to men, the benefit is also confined mainly to patients with baseline LBBB. In contrast to men benefit is evident starting with QRSd >130 ms. These findings may suggest that different QRS duration criteria should be used for men and women considered for CRT.

Translational research of VOLTAGE-A: Efficacy predictors of preoperative chemoradiotherapy and consolidation nivolumab in patients with both microsatellite stable and microsatellite instability-high locally advanced rectal cancer.

100 Background: In VOLTAGE-A, chemoradiotherapy (CRT; 50.4Gy with capecitabine, 1,650mg/m2) followed by five cycles of consolidation nivolumab (nivo) (240mg q2 weeks) showed 30% pathological complete response [pCR; AJCC tumor regression grade (TRG) 0] and 38% major pathological responses (AJCC TRG 0-1) in patients with microsatellite stable (MSS) locally advanced primary rectal cancer (LARC). In addition, 60% pCR was observed in patients with microsatellite instability-high (MSI-H) LARC. In this study, we aimed to determine the predictive biomarkers for efficacy of sequential preoperative CRT and consolidation nivo. Methods: Serial tumor biopsies were performed at four time points:pre-CRT; post-CRT; post-3 cycles of nivo; and pre-surgery. We analyzed the immune status of the patients by flow cytometry using the collected tumor-infiltrating lymphocytes (TILs) dissociated from tumor samples. Whole exome and RNA sequencing analyses were conducted using the extracted DNA and RNA from tumor, respectively. The PD-L1 status of tumor samples was also evaluated by in vitro diagnostic immunohistochemistry staining. Results: Of the 38 MSS patients whose PD-L1 tumor proportion score (TPS) was analyzable in pre-CRT samples, the pCR rates were 67% (6/9) and 17% (5/29) in positive (≥1%) and negative PD-L1 status (p = 0.009), respectively. Among the 24 MSS patients whose samples were serially collected, the pCR rates according to CD8+ T cells/effector regulatory T cells (CD8/eTreg) ratio in TILs of pre-CRT samples ≥2.5 and &lt; 2.5 were 78% (7/9) and 13% (2/15), respectively (p = 0.003). The CD8/eTreg ratio in TILs was consistently high in patients with pCR during the study treatments. Ki-67 and PD-1 expression by CD8+ T cells in TILs was significantly high in pre-CRT samples from patients TRG 0-1. Conversely, in patients with TRG 2-3, CTLA-4 expression by both CD4+ T cells and CD8+ T cells in TILs was significantly high after five cycles of nivo, suggesting the potential resistance mechanisms of nivo monotherapy. Of the 21 MSS patients whose consensus molecular subtype (CMS) was analyzable, those with CMS1 and CMS3 tumors achieved 100% (2/2) and 60% (4/6) TRG 0-1, respectively. In contrast, patients with CMS2 and CMS4 tumors achieved 43% (3/7) and 29% (2/7) TRG 0-1, respectively. The tumor mutational burden (TMB) of pre-CRT samples in five MSI-H patients was higher than that in the 24 MSS patients (median: 13.2 vs. 0.99 mutation/Mbp, p &lt; 0.0001). Among MSS patients, TMB was higher in patients with TRG 0-1 than in patients with TRG 2-3 (median: 1.45 vs. 0.84 mutation/Mbp, p = 0.016). Conclusions: Positive PD-L1 TPS; high CD8/eTreg ratio; Ki-67, PD-1, and CTLA-4 expression by CD8+ T cells in TILs; CMS 1 or 3; and high TMB can be good predictors of efficacy of preoperative CRT followed by nivo. Clinical trial information: NCT02948348.

Predictors of 5-year mortality in patients with congestive heart failure and implanted devices for cardiac resynchronization therapy

Abstract Cardiac resynchronization therapy (CRT) has a wide range of therapeutic benefits including reduction in hospitalizations and death in appropriately selected patients, while the appropriate selection remains the cornerstone of CRT. Apart from the current selection criteria, many additional factors may play an incremental role affecting cardiac prognosis and CRT efficacy. Aim To examine the ability of a multiparametric score to predict 5-year mortality in patients with congestive heart failure (HF) treated with CRT. Methods The study enrolled 218 HF patients (83% men, 17% women; mean age of 58.7±10.7 years) with left ventricular ejection fraction (LVEF) ≤35%, NYHA class II-IV. 130 patients (59.6%) had ischemic etiology of HF (84 with prior myocardial infarction), 88 patients (31.4%) – non-ischemic cardiomyopathy. 57.3% of patients had left bundle branch block (LBBB), mean QRS width was 150.5±38.4 ms. Results The mean follow-up period was 38.8±20.9 months. The 5-year survival was 69.3%. Points were calculated from 11 parameters identified as factors associated with all-cause mortality in multivariate analysis: gender (female – 0, male – 1); etiology of HF (non-ischemic – 0, ischemic – 1); history of myocardial infarction (no – 0, yes – 1); NYHA (II or III – 0, IV – 1); QRS (≥150 ms or ≤120 ms + 3 parameters of mechanical dyssynchrony – 0, 120–149 ms – 1); rhythm (sinus or radiofrequency ablation of atrial fibrillation (AF) – 0, AF – 1); LBBB (LBBB – 0, non-LBBB – 1); LVEF (&amp;gt;30% – 0, ≤30% – 1); frailty (not frail – 0, frail – 1); PR interval (&amp;lt;200 ms – 0; ≥200 ms – 1); NT-proBNP (median value) (&amp;lt;1788 pg/ml – 0, ≥1788 pg/ml – 1). To calculate the score, the sum of points was divided by the number of parameters. If less than 3 items were missing the denominator adjusted accordingly. The 5-year survival rate for patients with highest tertile score (&amp;gt;0.44; n=43) was 43.1%, for middle tertile (0.44≤ score ≥0.22; n=124) – 73.4% and 88.4% for lowest tertile (&amp;lt;0.22; n=51) (Log rank p&amp;lt;0.001). Conclusions Multiparametric score can be used to predict 5-year mortality in patients with CRT. Survival curves in groups by tertiles Funding Acknowledgement Type of funding source: None

Should different ECG QRS duration criteria be used for men and women with heart failure for cardiac resynchronization therapy?

In the present paper we review data of the efficacy of CRT based on baseline QRS duration and morphology in patients with heart failure due to left ventricle systolic dysfunction. We specifically review data that analyzed men and women separately. The main findings suggest benefit of CRT in patients with baseline LBBB, but not in patients without LBBB. Benefit is directly related to QRS duration at baseline with increasing rates and magnitude of echocardiographic response (in terms of improvement in ejection fraction and decrease in LV size) and clinical response with increasing baseline QRS. The effect was most pronounced when QRSd was above 150 ms. Among women treated with CRT, similar to men, the benefit is also confined mainly to patients with baseline LBBB. In contrast to men benefit is evident starting with QRSd >130 ms. These findings may suggest that different QRS duration criteria should be used for men and women considered for CRT.

P541Cardiac resynchronization therapy: left or non-left bundle branch block? That is the question

Abstract Introduction Cardiac resynchronization therapy (CRT) is associated with reduced mortality and improved quality of life in patients (pts) with low ejection fraction (EF) and conduction delays. Patients with left bundle branch block (LBBB) seem to be the ones who benefit the most from CRT and there is controversy about its efficacy in patients with non-LBBB. Purpose To compare the prognostic impact and the response rate to CRT in patients with LBBB and non-LBBB. Methods Prospective single-center study of patients who implanted CRT between 2015 and 2019. Clinical, electrocardiographic and echocardiographic evaluations were made before CRT implant and between 6-12 months post-implant. Patients with EF elevation ≥ 10% or left ventricle end-systolic volume (ESV) reduction ≥ 15% were classified as responders. Patients with EF elevation ≥ 20% or LV ESV reduction ≥ 30% were classified as super-responders. All the parameters were compared between patients with or without LBBB. Prognostic impact of resynchronization therapy was evaluated by comparing total mortality using the Cox regression and Kaplan-Meier methods. Results From 2015-2019, 566 CRTs were implanted (26.1% female, 72 ± 10.2 years old, follow-up duration 18.9 ± 15.8 months). From these patients, 59% had LBBB (69% males, mean age 71.6 ± 10.8 years, 34.5% ischemic, EF &amp;lt; 30% in 65.5%). The cardiovascular risk factors and comorbidities were similar in both populations (with and without LBBB), except for diabetes which was more frequent in non-LBBB patients (33% vs 50.6%, p = 0.007). Mean duration of QRS was similar between LBBB vs non-LBBB patients (163 ± 19ms vs 160 ± 22ms, p = NS) and baseline ejection fraction was also equivalent (29.8 ± 13.6% vs 27.9 ± 8.9%). The prevalence of complications and surgical revisions were similar in both groups. The response rate according to left ventricle remodelling criteria was higher in LBBB pts (65.9% vs 49.1%, p &amp;lt; 0.05), but the super-responders were similar in both groups (32.5% vs 26.4% p = NS). The 4-year survival rate of patients with LBBB and non-LBBB was similar (86.5% vs 85.3%). Conclusion In our population the response rate to CRT was higher in LBBB pts. However, and despite the actual controversy about the efficacy of CRT in non-LBBB, the long-term mortality was similar in patients with or without LBBB. Abstract Figure. lon-term survival

P1162Atrial fibrillation and Cardiac resynchronization therapy - is this combination truly bad?

Abstract Introduction Cardiac resynchronization therapy (CRT) significantly reduces mortality and hospitalizations in patients with heart failure and reduced ejection fraction (EF). Atrial fibrillation (AF) is a very common comorbidity in these patients, however, CRT benefit in AF patients has been controversial. Purpose To compare the prognostic impact of CRT in patients (pts) with and without AF. Methods Prospective, single-center study that included pts undergoing CRT implantsince 2015. Clinical and echocardiographicevaluation were made before CRT implant and between 6-12 months post-implant. Pts with EF elevation ≥10% or LV end-systolic volume (ESV) reduction ≥15% were classified as responders. Patients with EF elevation ≥ 20% or ESV reduction ≥30% were classified as super-responders. All the parameters were compared between patients with and without AF.Prognostic impact of CRT was evaluated by comparing total mortality using the Cox regression and Kaplan-Meier methods. Results From 2015-2019, 566 CRTs were implanted (26.1% female, 72 ± 10.2 years old, follow-up duration 18.9 ± 15.8 months). From these patients, 166 patients (31%) had AF (73.5% males, mean age 72.2 ± 10.2 years, 37.3% ischemic, LVEF &amp;lt; 30% in 65.5%). The cardiovascular risk factors and comorbidities were similar in both populations (with and without AF), except for chronic kidney disease which was more frequent in AF pts(28% vs 17%, p = 0.012). The prevalence of complications and surgical revision were similar in both groups. The CRT response rate was similar in both groups (50% in AF group vs 59.6%, p = NS) as was the super-response rate (22.4% in FA pts vs 31.5%, p = NS). The 4-year survival rate of patients with AF was similar to non-AF (83.7% vs 84.3%). Conclusion Despite the controversy about the efficacy of CRT in AF pts, in our population the long-term survival and CRT response rates were comparable between patients with and without AF. Abstract Figure.

2401Cardiac resinchronization therapy for the systemic right ventricle: a single center experience

Abstract Introduction Cardiac resynchronization therapy (CRT) has become a treatment of choice in patients with chronic heart failure (HF). About 25% of patients with systemic right ventricle (SRV) progress to symptomatic HF, which may be refractory to drug therapy and is commonly associated with significant morbidity and mortality. For these reasons, CRT has been emerging as an effective treatment strategy for patients with SRV failure and electrocardiographic signs of ventricular dyssynchrony. Few studies have reported the acute and long - term effects of CRT in SRV subjects, with different findings. Our study aimed to describe the experience with CRT in SRV patients in a single tertiary centre. Purpose Assess the long term efficacy of CRT in patient with SRV Materials and methods All consecutive SRV patients who underwent CRT implantation and/or upgrading between 1994 and 2018 at our tertiary centre were included. Clinical and echocardiographic parameters before and after CRT implantation were collected and analyzed. Results A total of 21 patients (mean age 47.8±14.8 years, 13 M) were implanted with CRT-P (12, 57%) or CRT-D (9,43%) during the study period. 90% of patients showed an anatomy of congenitally corrected transposition of the great arteries (CCTGA), whereas 9.5% underwent Mustard procedure for transposition of the great arteries (TGA). Among CCTGAs, 11 (52.5%) subjects underwent previous surgical procedures, including implant of a conduit between the left ventricle (LV) and the pulmonary artery (PA) in 8 (38%) patients, tricuspid valve repair in 2 (9.5%) and surgical closure of atrial septal defect in 1 (5%). Before CRT implant/upgrading, 10 (48%) patients had a moderate to severe reduction in the SRV ejection fraction (EF) and 7 (33%) had a moderate to severe tricuspid regurgitation (TR). Overall, 15 (71%) patients referred a NYHA II or III. After a median follow up of 57 months (IQR 35–83), 43% of patients showed an improvement in their functional status, which was associated with an improvement of SRV EF and TR only in 22% and 33% of these patients. On the contrary, no patient reported a worsening in NYHA class, while SRV EF decreased in 28.5% and the grade of TR worsen in 23.8% of patients. Conclusions CRT is emerging as an effective treatment for SRV dysfunction. However, criteria for implantation are not well defined and the deterioration of SRV function related to subpulmonary univentricular pacing should be considered. Moreover, TR did not improve in this study, suggesting that concurrent tricuspid valve interventions may be necessary in patients with severe TR and may facilitate the improvement in RV function achieved with CRT. Proper planning, tertiary expertise and international collaborations are all paramount in this field.

P4354Regional Strain Pattern Index - A novel technique to predict CRT response

Abstract Background Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in heart failure individuals. Despite many efforts 30–40% patients with CRT still do not respond to therapy. Purpose The purpose was to propose and evaluate a novel dyssynchrony scoring system – Regional Strain Pattern Index (RSPI) in prediction of response to CRT. Methods Forty-nine HF patients (age: 66.5±10 years, LV ejection fraction: 24.9±6.4%, QRS: 173.1±19.1 ms, NYHA class II/III: 34.7%/63.3%, ischemic aetiology: 57.1%) underwent CRT implantation. Transthoracic echocardiography was performed before and 15±7 months after CRT implantation. Baseline dyssynchrony was studied by standard indices, strain pattern analysis and novel, author's index- RSPI. RSPI constitutes a method of quantification of LBBB-related strain curve pattern analysis. RSPI was calculated using longitudinal strain by 2D speckle tracking as the sum of dyssynchronous components across 12 segments from all three apical views. In one view, four components were assessed: 1) the contraction of the early-activated wall, 2) the prestretching of the late activated wall, 3) the contraction of the early-activated wall in the first 70% of the systolic ejection phase and 4) the peak contraction of the late-activated wall after aortic valve closure. One point was attributed to each component, thus the maximum was 12 points. RSPI was prospectively evaluated in predicting response to CRT. The response to CRT was defined as ≥15% reduction in the left ventricular end-systolic volume after 15 month follow-up. Results Thirty-six (73.5%) patients were responders. There were no significant differences in the baseline demographics, clinical, echocardiographic parameters between responders and non-responders. The mean RSPI in the overall population was 5.39±2.9 and higher RSPI values were observed in responders (5.86±2.9) than in non-responders (4.08±2.4, p=0.044). The ROC curve indicated that RSPI significantly predicted CRT response (area under curve, AUC=0.691, p=0.014) with the cut-off value at 7 points. Therefore, study population was divided into two groups according to RSPI score: ≥7 points (19 patients, 38.8% of population) and &lt;7 points (30 patients, 61.2%). In univariate logistic regression analysis, among all of the dyssynchrony indices only RSPI≥7 points predicted the positive response to CRT (OR: 12; 95% CI=1.33–108.17; p=0.0036) with specificity of 92.3%, sensitivity of 50%, positive of 64.7% and negative of 40% predictive value for CRT response. ROC curve for RSPI Conclusion RSPI constitutes a novel, valuable predictor for CRT response. Acknowledgement/Funding Grant for scientific research in the field of CRT efficacy funded by Medical University of Silesia.

AB022. S4-2. Role of radiotherapy in cholangiocarcinoma

Cholangiocarcinoma represents a heterogeneous cohort of biliary tract cancers in intrahepatic, perihilar, or distal location. Although surgical resection is recognized to offer the chance for cure, the patients with intrahepatic (IHCC) or perihilar cholangiocarcinoma (PCC) present mostly advanced disease, which results in not only limiting curative resection but also high recurrence even after resection. This notion urges active consideration of multimodal therapeutic strategies; neoadjuvant treatment converting from unresectable to resectable one and postop adjuvant treatment to reduce recurrence. With regard to neoadjuvant aim, radiotherapy in combination with chemotherapy (CRT) is gaining attention in many cancers for increasing resectability. My group investigated the efficacy of CRT as a neoadjuvant role. We identified 120 IHCC patients (pts) who were treated either with surgery (56 pts) for resectable disease or with CRT (64 pts) for locally advanced unresectable one. In CRT cohort, we achieved 25% partial response as well as 35% biologic response (>70% decrease of CA19-9), which subsequently allowed curative resection in 8 patients (12.5%). We also identified some factors associated with conversion to curative resection after CRT. Benefit of postop adjuvant treatment hasn’t been well established in cholangiocarcinoma due to limited evidence particularly in PCC. My group investigated a role of postop adjuvant treatment in 189 PCC patients involving no adjuvant (89 pts), adjuvant chemotherapy (62 pts), adjuvant radiotherapy (16 pts), and adjuvant CRT (22 pts). Adjuvant CRT produced the highest 5-year survival rate (50%) followed by adjuvant chemotherapy (26.8%) in R1 resection and stage III–IVA, which was far superior to 5-year survival 0% in no adjuvant group. Our data suggest that adjuvant CRT should be considered in high-risk resected PC patients. Taken together, radiotherapy in a form of chemoradiotherapy seems to improve oncologic outcome in cholangiocarcinoma either in neoadjuvant or in postop adjuvant setting.