Predict Cardiac Resynchronization Therapy Response Research Articles

The use of mechanical dyssynchrony for predicting response to cardiac resynchronization therapy in patients with non-ischemic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Aim/Introduction: Assessment of mechanical dyssynchrony by myocardial perfusion gated-SPECT in patients with non-ischemic cardiomyopathy for predict response to cardiac resynchronization therapy (CRT). Materials and Methods We examined 32 patients with non-ischemic cardiomyopathy before and six months after CRT. Left ventricular mechanical dyssynchrony and contractility were assessed for all patients by myocardial perfusion gated-SPECT. The phase standard deviation (PSD), histogram bandwidth (HBW), phase histogram skewness (S) and phase histogram kurtosis (K) were used as an indicator of mechanical dyssynchrony for the both ventricles. Results Mechanical dyssynchrony of both ventricles before CRT was increased in all patients. Median value PSD 53°(41-61°), HBW 176°(136-202°), S 1,62(1,21-1,89), K 2,81(1,21-3,49). Six months after CRT 22(68%) respondents were identified. We divided the patients into two groups (responders and non-responders) and compared phase parameters. It was found that the PSD (44°(35-54°)) and HBW (158°(118-179°) in the responders were significantly lower than in the non-responders (PSD (68°(58-72°); HBW (205°(199-249°)). The value of phase histogram skewness and kurtosis in responders were significantly higher (Responders: S 1,77(1,62-2,02); K 3,03(2,60-3,58). Non-responders: S 1,21(0,93-1,31); K 1,21(0,19-1,46)). We found that all four indicators of mechanical dyssynchrony can predict CRT response according to the results of univariate logistic regression analysis. Moreover, It was found that only phase histogram kurtosis (OR = 1.196, 95% CI 1.04-1.37) is an independent predictor of CRT response according to multivariate logistic regression. Conclusion Radionuclide assessment of mechanical dyssynchrony may be the optimal diagnostic method for selecting patients with non-ischemic cardiomyopathy on CRT.

The prognostic significance of cardiac sympathetic activity and dyssynchrony in cardiac resynchronization therapy in ischemic and non-ischemic heart failure patients

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Russian Foundation for Basic Research Introduction Impaired cardiac sympathetic activity and contractility are associated with poor prognosis in patients with heart failure after cardiac resynchronization therapy (CRT). There are few prognostic data of the cardiac sympathetic activity and dyssynchrony in patients with chronic heart failure of various etiologies. Purpose To examine the prognostic significance of scintigraphic cardiac sympathetic activity and contractility in predicting the response to CRT and to assess the differences between patients with ischemic (IHF) and non-ischemic (NIHF) heart failure. Methods This study included 38 heart failure patients (24 male; mean age of 56 ± 11 years; 16 patients with ischemic etiology), who were submitted to CRT. Before CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging for cardiac sympathetic activity evaluating: early and delay heart to mediastinum ratio (eH/M and dH/M), summed MIBG Score (eSMS and dSMS). Moreover all patients underwent gated SPECT with the assessments of left ventricle dyssynchrony indexes: standard deviation (SD) and histogram bandwidth (HBW). In addition, all patients underwent gated blood-pool SPECT (GBPS) to assessed ejection fraction (EF) and stroke volume (SV) of both ventricles. Results One year after CRT response defined as LV ESV decreased by≥15% and/or LV EF increase by≥5%. Baseline cardiac sympathetic activity parameters showed significant differences between responders and non-responders only in NIHF patients: eH/M: 2.27 (2.02–2.41) vs. 1.64 (1.32–2.16); dH/M: 2.18 (2.11–2.19) vs. 1.45 (1.23 – 1.61); eSMS: 7 (5-7) vs. 15.5 (10–28.5); dSMS: 10 (10–13) vs. 16.5 (15.5–29). Significant differences in baseline LV dyssynchrony indexes between responders and non-responders were in patients of both group: in NIHF patients - SD: 54.3 (43–58) degree vs. 65 (62–66) degree; HBW: 179.5 (140–198) degree vs. 211 (208-213) degree, p < 0.054 in IHF patients - HBW: 162 (115.2–180) degree vs. 115.2 (79.2–136.8) degree. Contractility of RV was significantly differed between responders and non-responders in IHF patients: RV EF: 54.5 (41-56) % vs. 44.5 (37–49.5) %; RV SV: 80 (69-101) ml vs. 55.5 (50–72.5) ml. According to univariate logistic regression analyses in IHF patients LV dyssynchrony indexes – SD (OR = 1.55; 95% CI 1.09-2.2; p < 0.5) and HBW (OR = 1.13; 95% CI 1.02-1.24; p < 0.5), as well as RV indexes – RV EF (OR = 1.11; 95% CI 1.001-1.23; p < 0.5), RV SV (OR = 1.07; 95% CI 1.003-1.138; p < 0.5) were predictors of CRT response. In the group of NIHF patients, dH/M (OR = 1.47; 95% CI 1.08-2; p < 0.5), SD (OR = 0.83; 95% CI 0.73-0.95; p < 0.5), HBW (OR = 0.96; 95% CI 0.93-0.99; p < 0.5) showed the predictive value in terms of CRT response. Conclusion Scintigraphic methods can be used to select patients for CRT. Cardiac 123I-MIBG scintigraphy and gated SPECT may be used for predicting CRT response in NIHF patients. Whereas in IHF patients ECG-gated SPECT and GBPS may be valuable for predicting the response to CRT.

Importance of systematic right ventricular assessment in cardiac resynchronization therapy candidates: a machine-learning approach

Abstract Funding Acknowledgements Type of funding sources: None. Background Despite having all a systolic heart failure and broad QRS, patients proposed for cardiac resynchronization therapy (CRT) are highly heterogeneous and it remains extremely complicated to predict the impact of the device on left ventricular (LV) function and outcomes. Objectives We sought to evaluate the relative impact of clinical, electrocardiographic, and echocardiographic data on the left ventricular (LV) remodeling and prognosis of CRT-candidates by the application of machine learning (ML) approaches. Methods 193 patients with systolic heart failure undergoing CRT according to current recommendations were prospectively included in this multicentre study. We used a combination of the Boruta algorithm and random forest methods to identify features predicting both CRT volumetric response and prognosis (Figure 1). The model performance was tested by the area under the receiver operating curve (AUC). We also applied the K-medoid method to identify clusters of phenotypically-similar patients. Results From 28 clinical, electrocardiographic, and echocardiographic-derived variables, 16 features were predictive of CRT-response; 11 features were predictive of prognosis. Among the predictors of CRT-response, 7 variables (44%) pertained to right ventricular (RV) size or function. Tricuspid annular plane systolic excursion was the main feature associated with prognosis. The selected features were associated with a very good prediction of both CRT response (AUC 0.81, 95% CI: 0.74-0.87) and outcomes (AUC 0.84, 95% CI: 0.75-0.93) (Figure 1, Supervised Machine Learning Panel). An unsupervised ML approach allowed the identifications of two phenogroups of patients who differed significantly in clinical and parameters, biventricular size and RV function. The two phenogroups had significant different prognosis (HR 4.70, 95% CI: 2.1-10.0, p < 0.0001; log –rank p < 0.0001; Figure 1, Unsupervised Machine Learning Panel). Conclusions Machine learning can reliably identify clinical and echocardiographic features associated with CRT-response and prognosis. The evaluation of both RV-size and function parameters has pivotal importance for the risk stratification of CRT-candidates and should be systematically assessed in patients undergoing CRT. Abstract Figure 1

Regional Strain Pattern Index-A Novel Technique to Predict CRT Response.

Background: Cardiac resynchronization therapy (CRT) improves outcome in patients with heart failure (HF) however approximately 30% of patients still remain non-responsive. We propose a novel index—Regional Strain Pattern Index (RSPI)—to prospectively evaluate response to CRT. Methods: Echocardiography was performed in 49 patients with HF (66.5 ± 10 years, LVEF 24.9 ± 6.4%, QRS width 173.1 ± 19.1 ms) two times: before CRT implantation and 15 ± 7 months after. At baseline, dyssynchrony was assessed including RSPI and strain pattern. RSPI was calculated from all three apical views across 12 segments as the sum of dyssynchronous components. From every apical view, presence of four components were assessed: (1) contraction of the early-activated wall; (2) prestretching of the late activated wall; (3) contraction of the early-activated wall in the first 70% of the systolic ejection phase; (4) peak contraction of the late-activated wall after aortic valve closure. Each component scored 1 point, thus the maximum was 12 points. Results: Responders reached higher mean RSPI values than non-responders (5.86 ± 2.9 vs. 4.08 ± 2.4; p = 0.044). In logistic regression analysis value of RSPI ≥ 7 points was a predictor of favorable CRT effect (OR: 12; 95% CI = 1.33–108.17; p = 0.004). Conclusions: RSPI could be a valuable predictor of positive outcome in HF patients treated with CRT.

Left ventricular regional glucose metabolism in combination with septal scar extent identifies CRT responders.

Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain. We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT. Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and 18F-fluorodeoxyglucose (FDG) PET within 1week before CRT implantation. Echocardiography was additionally performed 12months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent. We evaluated 88 patients (67 ± 10 years, 72% males). 18F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively. FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

Importance of Systematic Right Ventricular Assessment in Cardiac Resynchronization Therapy Candidates: A Machine Learning Approach

Despite all having systolic heart failure and broad QRS intervals, patients screened for cardiac resynchronization therapy (CRT) are highly heterogeneous, and it remains extremely challenging to predict the impact of CRT devices on left ventricular function and outcomes. The aim of this study was to evaluate the relative impact of clinical, electrocardiographic, and echocardiographic data on the left ventricular remodeling and prognosis of CRT candidates by the application of machine learning approaches. One hundred ninety-three patients with systolic heart failure receiving CRT according to current recommendations were prospectively included in this multicenter study. A combination of the Boruta algorithm and random forest methods was used to identify features predicting both CRT volumetric response and prognosis. Model performance was tested using the area under the receiver operating characteristic curve. The k-medoid method was also applied to identify clusters of phenotypically similar patients. From 28 clinical, electrocardiographic, and echocardiographic variables, 16 features were predictive of CRT response, and 11 features were predictive of prognosis. Among the predictors of CRT response, eight variables (50%) pertained to right ventricular size or function. Tricuspid annular plane systolic excursion was the main feature associated with prognosis. The selected features were associated with particularly good prediction of both CRT response (area under the curve, 0.81; 95% CI, 0.74-0.87) and outcomes (area under the curve, 0.84; 95% CI, 0.75-0.93). An unsupervised machine learning approach allowed the identification of two phenogroups of patients who differed significantly in clinical variables and parameters of biventricular size and right ventricular function. The two phenogroups had significantly different prognosis (hazard ratio, 4.70; 95% CI, 2.1-10.0; P<.0001; log-rank P<.0001). Machine learning can reliably identify clinical and echocardiographic features associated with CRT response and prognosis. The evaluation of both right ventricular size and functional parameters has pivotal importance for the risk stratification of CRT candidates and should be systematically performed in patients undergoing CRT.

Importance of systematic right ventricular assessment in patients undergoing cardiac resynchronisation therapy: A machine-learning approach

Patients undergoing cardiac resynchronisation therapy are heterogeneous. Therefore, the prediction of CRT-response and outcome is challenging. The aim of this study was to evaluate the relative impact of clinical, electrocardiographic, and echocardiographic variables on the left ventricular (LV) remodelling and prognosis of CRT-candidates by the application of machine-learning (ML) approaches. In total, 193 patients undergoing CRT (mean age 67 ± 11 years, QRS width: 167 ± 21 msec) were prospectively included in this multicentre study. We used a combination of the Boruta algorithm and random forest methods (RF) to identify features predicting both CRT-volumetric response and prognosis. The model performance was tested by the area under the receiver-operating curve (AUC). We also applied the K-medoid method to identify clusters of phenotipically-similar patients. From 28 clinical, electrocardiographic, and echocardiographic-derived variables, 16 features were predictive of CRT-response, and 11 features were predictive of prognosis. Among the predictors of CRT-response, 6 variables (38%) pertained to right ventricular (RV) size or function. The tricuspid annular plane systolic excursion was the main feature associated with prognosis. The selected features were associated with a very good prediction of both CRT-response (AUC: 0.81, 95% CI: 0.74–0.87) and outcome (AUC 0.84, 95% CI: 0.75–0.93) (Fig. 1A–B). An unsupervised ML approach allowed the identifications of two phenogroups of patients who differed significantly in clinical parameters, biventricular size and RV function and had significantly different prognosis (log-rank P < 0.0001; HR: 4.7, 95% CI: 2.1–10.0, P < 0.001) (Table 1). ML can reliably identify clinical and echocardiographic features associated with CRT-response and prognosis. Our results underscore the value of the assessment of RV-size and function parameters for the risk stratification of CRT-candidates.

СЕРДЕЧНАЯ РЕСИНХРОНИЗИРУЮЩАЯ ТЕРАПИЯ ПРИ ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ С ФИБРИЛЛЯЦИЕЙ ПРЕДСЕРДИЙ: АНАЛИЗ И ПРОГНОЗИРОВАНИЕ РЕЗУЛЬТАТОВ

Aim. To develop a multifactor response prediction model to CRT in patients with CHF complicated by AF taking into consideration myocardium dyssinchrony parameters, clinical, functional, and laboratory predictors of a positive response to interventional treatment. Methods. The article is devoted to the evaluation of cardiac resynchroniza- tion therapy (CRT) clinical results in patients with chronic heart failure (CHF) and persistent atrial fibrillation (AF) within 12 months after interventional treatment. The paper presents multifactor CRT response prediction models taking into consideration electrical and mechanical myocardium dyssinchrony parameters, as well as clinical, functional, and laboratory positive response predictors. Results. CRT results in patients with CHF complicated by AF showed variable patterns dependent on time and persistence of the treatment outcome: long-term outcome retention in a three-month period (39%); “escape” from CRT early outcome (9%); delayed echocardiographic response to CRT (in 12 months); no response to CRT (21%). Early response to CRT predictor complex (during the first 3 months) in patients with CHF and AF mainly includes myocardial dyssinchrony parameters (QR complex width, presystolic aortic valve delay, pulmonary artery valve delay, interventricular delay, dyssinchrony index), as well as CHF severity criteria (CHF FC, NT-proBNP concentration) and myocardial deformity in the apical projection. The most significant contribution to the prediction of the long-term effectiveness of CRT in patients with CHF and AF is made by parameters reflecting the severity of interventricular and intraventricular cardiac dyssinchrony: presystolic delay on the aortic valve and dispersion of intraventricular contraction. Additional prognostic criteria for the CRT response are lower values of myocardial deformity in the apical projection and GFR. Conclusion. The linear model developed to assess the dynamics of LV ESV allows individualizing the patient selection for interventional treatment in case of predicting an unstable early response to CRT.

Comprehensive plasma metabolites profiling reveals phosphatidylcholine species as potential predictors for cardiac resynchronization therapy response.

AimsThis study aimed to identify the plasma metabolite fingerprint in patients with heart failure and to develop a prediction tool based on differential metabolites for predicting the response to cardiac resynchronization therapy (CRT).Methods and resultsWe prospectively recruited 32 healthy individuals and 42 consecutive patients with HF who underwent CRT between January 2018 and January 2019. Peripheral venous blood samples, clinical data, and echocardiographic signatures were collected before CRT implantation. Liquid chromatography‐mass spectrometry was used to perform untargeted metabolites profiling for peripheral plasma under ESI+ and ESI− modes. After 6 month follow‐up, patients were categorized as CRT responders or non‐responders based on the alterations of echocardiographic characteristics. Compared with healthy individuals, patients with HF had distinct metabolomic profiles under both ESI+ and ESI− modes, featuring increased free fatty acids, carnitine, β‐hydroxybutyrate, and dysregulated lipids with heterogeneous alterations such as phosphatidylcholines (PCs) and sphingomyelins. Disparities of baseline metabolomics profile were observed between CRT responders and non‐responders under ESI+ mode but not under ESI− mode. Further metabolites analysis revealed that a group of 20 PCs metabolites under ESI+ mode were major contributors to the distinct profiles between the two groups. We utilized LASSO regression model and identified a panel of four PCs metabolites [including PC (20:0/18:4), PC (20:4/20:0), PC 40:4, and PC (20:4/18:0)] as major predictors for CRT response prediction. Among our whole population (n = 42), receive operating characteristics analysis revealed that the four PCs‐based model could nicely discriminate the CRT responders from non‐responders (area under the curve = 0.906) with a sensitivity of 83.3% and a specificity of 90.0%. Cross‐validation analysis also showed a satisfactory and robust performance of the model with the area under the curve of 0.910 in the training dataset and 0.880 in the testing dataset.ConclusionsPatients with HF held significantly altered plasma metabolomics profile compared with the healthy individuals. Within the HF group, the non‐responders had a distinct plasma metabolomics profile in contrast to the responders to CRT, which was characterized by increased PCs species. A novel predictive model incorporating four PCs metabolites performed well in identifying CRT non‐responders. These four PCs might severe as potential biomarkers for predicting CRT response. Further validations are needed in multi‐centre studies with larger external cohorts.

Abstract 15815: Left Atrial Strain Characterizes the Atrio-ventricular Substrate Responsive to Cardiac Resynchronization Therapy in Patients With Intermediate Electrocardiographic Criteria

Introduction: Guidelines favor patient selection by left bundle branch block (LBBB) with QRS width ≥150 ms for cardiac resynchronization therapy (CRT). Predicting CRT response in patients with QRS width 120 to 149 ms or non-LBBB remains difficult. Left ventricular (LV) global longitudinal strain (GLS) and systolic stretch index (SSI) have shown to characterize the ventricular substrate responsive to CRT. However, the potential application of longitudinal left atrial (LA) strain remains unclear. Hypothesis: Baseline LA strain has prognostic value in CRT patients with intermediate ECG criteria. Methods: We studied 195 patients who underwent CRT based on routine indications: ejection fraction ≤35% and QRS width ≥120 ms. GLS was assessed using the 3 standard apical views. Radial SSI was derived from the mid LV short axis view. Peak longitudinal LA strain was derived from the 2 and 4-chamber apical view. The predefined combined clinical endpoint was death, heart transplant or left ventricular assist device over 4 years after CRT. Results: LA strain was feasible in 162 (83%) of the CRT candidates: QRS duration 156 ± 26 ms, 39.5% had LBBB with QRS ≥ 150ms, 60.5% had intermediate ECG criteria. High peak longitudinal strain (&gt;median, 10.1%) was associated with favorable event-free survival (p&lt;0.001). Patients with intermediate ECG criteria for CRT and both high peak longitudinal LA strain and high GLS (&gt;median, 8.4%) had similar outcome to those with Class I indications for CRT. Multivariable analysis revealed that LA strain had independent prognostic value (hazard ratio 0.9 per LA strain %, p &lt; 0.001) even after adjusted for other clinical, electrophysiological and echocardiographic covariates including QRS morphology and duration, GLS and SSI. Conclusions: Peak LA strain had important prognostic value in candidates for CRT. Prognostic value of LA strain was additive to LV strain characteristics and most significant in CRT patients with intermediate ECG criteria for CRT.

Abstract 217: Glycation of Ryanodine Receptors in Peripheral Lymphocytes Predicts the Response to Cardiac Resynchronization Therapy

Introduction: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with advanced heart failure (HF). The management of these patients depends on biomarkers for monitoring disease progression and therapeutic response. HF patients exhibit a pathologic remodeling of Ryanodine Receptors (RyRs) in heart, muscle, as well as circulating lymphocytes, leading to intracellular calcium leak, which has been shown to correlate with the clinical outcome. Hypotheses: 1) post-translational modifications of RyR in circulating lymphocytes in HF patients can predict CRT response; 2) CRT can improve the remodeling of RyRs and intracellular calcium leak. Methods: To test this hypothesis, we enrolled 34 patients who underwent CRT and examined RyR remodeling in peripheral lymphocytes before and 1 year after CRT using established biochemical and flow-cytometry assays. Non-responders to CRT were defined after 1 year of follow-up as patients with at least one of the following characteristics: deteriorating function (HF-related death, need for heart transplantation), increase in LVEF ≤ 4%, worsening in peak O 2 consumption, in Quality-of-Life score, or in the distance walked in 6 min. Results: We found that post-translational remodeling of RyR ( i.e. oxidation, phosphorylation, glycation) was significantly ( P&lt;0.01 ) reduced in circulating lymphocytes isolated from CRT responders compared to pre-CRT levels and to non-responders. Similarly, the binding to RyR of its stabilizing subunit (calstabin) was markedly increased by CRT, whereas intracellular Ca 2+ leak was attenuated ( P&lt;0.01 ). Importantly, these phenomena were not observed in CRT non-responders. Moreover, in a multivariate regression analysis, we observed that RyR glycation in peripheral lymphocytes at baseline was independently associated with CRT response at 1-year follow-up ( P&lt;0.05 ). Conclusions: This is the first study showing that CRT response can be predicted by the level of RyR glycation in peripheral blood lymphocytes. Moreover, we demonstrate that CRT responders exhibit a significantly reduced intracellular Ca 2+ leak through RyR in lymphocytes, mirrored by diminished post-translational modifications compared to baseline and to CRT non-responders.

Evaluation of Pattern Recognition Techniques in Response to Cardiac Resynchronization Therapy (CRT)

Cardiac resynchronization therapy (CRT) improves cardiac function in patients with heart failure (HF), and the result of this treatment is decrease in death rate and improving quality of life for patients. This research is aimed at predicting CRT response for the prognosis of patients with heart failure under CRT. According to international instructions, in the case of approval of QRS prolongation and decrease in ejection fraction (EF), the patient is recognized as a candidate of implanting recognition device. However, regarding many intervening and effective factors, decision making can be done based on more variables. Computer-based decision-making systems especially machine learning (ML) are considered as a promising method regarding their significant background in medical prediction. Collective intelligence approaches such as particles swarm optimization (PSO) algorithm are used for determining the priorities of medical decision-making variables. This investigation was done on 209 patients and the data was collected over 12 months. In HESHMAT CRT center, 17.7% of patients did not respond to treatment. Recognizing the dominant parameters through combining machine recognition and physician’s viewpoint, and introducing back-propagation of error neural network algorithm in order to decrease classification error are the most important achievements of this research. In this research, an analytical set of individual, clinical, and laboratory variables, echocardiography, and electrocardiography (ECG) are proposed with patients’ response to CRT. Prediction of the response after CRT becomes possible by the support of a set of tools, algorithms, and variables.

A Novel and Simple Exercise Test Parameter to Assess Responsiveness to Cardiac Resynchronization Therapy.

This study assessed the value of heart rate recovery index (HRRI), a new parameter of an exercise test, as the predictor of response to cardiac resynchronization therapy (CRT). Methods: Consecutive patients receiving a CRT device were followed up after implantation and every 6 months. An effort test (ET) was quantified by minimum heart rate/maximum heart rate, as well as acceleration and deceleration times. HRRI was calculated as the ratio between acceleration and deceleration time (AT/DT) and compared to outcome. We used logistic regression to assess the predictive value of HRRI for responders and non-responders to CRT. The area under the curve (AUC) was computed to distinguish between positive and negative outcomes. Results: A total of 109 patients (74 men, mean age 63.3 ± 9.8 years) were analyzed; permanent long-term fusion CRT pacing was possible in 65 patients. Patients were assigned to two groups: responders and non-responders (98/11 patients). During a mean follow-up of 36 months, 545 ETs were performed. HRRI was significantly higher in responders versus non-responders (3.16 ± 2 vs. 1.4 ± 0.5, p < 0.001). The optimal cutoff value for HRRI as a predictor of CRT response was 1.51 (area under the receiver operating characteristic (ROC) curve = 0.844). Responders had significant left-ventricular (LV) reverse remodeling (LV end-diastolic volume = 240 ± 90 mL vs. 217 ± 89 mL, p < 0.001) and higher LV ejection fraction (26 ± 5.8% vs. 35 ± 8.7%, p < 0.001). Conclusions: HRRI computation during routine ET is useful for the evaluation of responsiveness to CRT.

Non-invasive myocardial workiIndices derived from left ventricular pressure-strain loops in predicting the response to cardiac resynchronization therapy

Abstract Background Non-invasive left ventricular (LV) pressure-strain loops (PSLs) which generated by combining LV longitudinal strain with brachial artery blood pressure, provide a novel method of quantifying global and segmental myocardial work (MW) indices with potential advantages over conventional echocardiographic strain which is load-dependent. The method has been introduced in echocardiographic software recently, making MW calculations more effectively and rapidly. The aim was to evaluate the role of non-invasive MW indices derived from LV PSLs in the prediction of cardiac resynchronization therapy (CRT) response. Methods 106 heart failure (HF) patients scheduled for CRT were included for MW analysis. Global and segmental (septal and lateral at the mid-ventricular level) MW indices were accessed before CRT. Response to CRT was defined as ≥15% reduction in LV end-systolic volume at 6-month follow-up in comparison with baseline value. Results CRT response was observed in 78 (74%) patients. At baseline, global work index (GWI) and global constructive work (GCW) were significant higher in CRT responders than in non-responders (both P&amp;lt;0.05). Besides, responders exhibited a significantly higher Mid Lateral MW and Mid Lateral constructive work (CW) (both P&amp;lt;0.001) but a significantly lower Mid Septal MW and Mid Septal myocardial work efficiency (MWE), as well as a significantly higher Mid Septal wasted work (WW) than non-responders (all P&amp;lt;0.01). Baseline Mid Septal MWE (OR 0.975, 95% CI 0.959–0.990, P=0.002) and Mid Lateral MW (OR 1.003, 95% CI 1.002–1.004, P&amp;lt;0.001) were identified as independent predictors of CRT response in multivariate regression analysis. Mid Septal MWE ≤42% combined with Mid Lateral MW ≥740 mm Hg% predicted CRT response with the optimal sensitivity of 79% and specificity of 82% (AUC = 0.830, P&amp;lt;0.001). Conclusion Mid Septal MWE and Mid Lateral MW can successfully predict response to CRT, and their combination can further improve the prediction accuracy. Assessment of MW indices before CRT could identify the marked misbalance in LV myocardial work distribution and has the potential to be widely used as a reliable complementary tool for guiding patient selection in clinical practice. Funding Acknowledgement Type of funding source: None

Echocardiographic assessment of CRT candidates. Does it work equally well in intermediate QRS duration?

Abstract Background The presence of mechanical dyssynchrony – such as apical rocking (ApRock) and septal flash (SF) – on echocardiography is associated with favourable outcome after cardiac resynchronization therapy (CRT). Myocardial scar on the other hand, has a considerable negative impact on CRT response. There is growing evidence that a visual echocardiographic assessment of mechanical dyssynchrony by ApRock, SF and scar predicts CRT response. Little is known however if this works equally well in patients with intermediate QRS duration (120–150ms), where guideline recommendation for CRT is weaker. Methods A total of 400 unselected patients referred for CRT, who fulfil the contemporary guidelines, were enrolled in this multicentre study. Echocardiographic images were visually assessed before CRT implantation, focussing on the presence of ApRock, SF and location and extent of scar segments in the left ventricle (LV), resulting in a CRT response prediction (i.e. Reader Interpretation). Readers were blinded to all patient information other than ischaemic aetiology of heart failure. CRT response was defined as ≥15% reduction in LV end-systolic volume on echocardiography, on average 15 months after device implantation. Results Overall, 321 (80%) patients had a left bundle branch block (LBBB), with an average QRS duration of 166±25ms. Ischemic aetiology of heart failure was found in 131 (33%) patients. Before CRT, ApRock and SF were present in 254 (64%) and 244 (61%) patients, respectively. ApRock and SF alone predicted CRT response with an area under the curve (AUC) of 0.79 (95% CI: 0.74–0.84) and 0.78 (95% CI: 0.73–0.83) (Figure A), while the echocardiographic Reader Interpretation had an AUC of 0.85 (95% CI: 0.81–0.89), with a sensitivity of 89% and a specificity of 82% for the prediction of CRT response (Figure B) (p&amp;lt;0.0001 vs. ApRock and SF alone). A total of 92 patients had a QRS duration of 120–150ms, and 48 of them responded to CRT. In these patients, the AUC of Reader Interpretation was comparable to that of the entire study cohort [0.83 (95% CI: 0.75–0.92)], as was sensitivity and specificity (90% and 79%, respectively, p=0.717 vs. the AUC of the entire cohort) (Figure C). Conclusions A visual assessment of LV function, by means of mechanical dyssynchrony and scar, has an excellent predictive value for CRT response, and requires only apical echocardiographic images. Responders were identified equally well in the challenging subgroup of patients with a QRS duration of 120–150 ms. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): KU Leuven

Prognostic significance of cardiac sympathetic innervation and contractility in heart failure patients submitted to cardiac resynchronization therapy

Abstract Introduction In chronic heart failure patients, cardiac resynchronization therapy (CRT) does not lead to the expected result in 30% of cases. There is a lack of prognostic data related to the cardiac sympathetic activity and contractility assessment in ischemic (IHF) and non-ischemic (CHF) heart failure patients. Purpose To assess the prognostic value of radionuclide cardiac sympathetic innervation and contractility assessment in IHF and NIHF patients submitted to CRT. Methods This study included 38 HF patients (24 male; mean age of 56±11 years), who were submitted to CRT: NYHA class II/III (n=10/28), mean QRS=159.3±17.9ms. The etiology of HF was ischemic in 16 patients and non-ischemic in 22 of them. Before CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging for cardiac sympathetic activity evaluating. The following indexes were estimated: early and delayed heart to mediastinum ratio (eH/M and dH/M), summed MIBG Score (eSMS and dSMS). Moreover all patients underwent gated myocardial perfusion scintigraphy with the assessments of LV dyssynchrony indexes: standard deviation (SD) and histogram bandwidth (HBW). In addition, all patients underwent gated blood-pool SPECT with both ventricles ejection fraction (EF) and stroke volume (SV) assessment. Results One year after CRT all patients were divided into two groups: responders (IHF group n=11; NIHF group n=15) and non-responders (IHF group n=5; NIHF group n=7). Among baseline scintigraphic parameters the following ones showed significant differences between responders vs. non-responders. In IHF patients - HBW: 162 (115.2–180) degree vs. 115.2 (79.2–136.8) degree, p&amp;lt;0.05; RV_EF: 54.5 (41–56)% vs. 44.5 (37–49.5)%, p&amp;lt;0.05; RV_SV: 80 (69–101)ml vs. 55.5 (50–72.5)ml, p&amp;lt;0.05. In group of NIHF patients responders and non-responders were significantly differed in the following preoperative parameters: eH/M: 2.27 (2.02–2.41) vs. 1.64 (1.32–2.16), p&amp;lt;0.05; dH/M: 2.18 (2.11–2.19) vs. 1.45 (1.23–1.61), p&amp;lt;0.05; eSMS: 7 (5–7) vs. 15.5 (10–28.5), p&amp;lt;0.05; dSMS: 10 (10–13) vs. 16.5 (15.5–29), p&amp;lt;0.05, SD: 54.3 (43–58) degree vs. 65 (62–66) degree, p&amp;lt;0.05; HBW: 179.5 (140–198) degree vs. 211 (208–213) degree, p&amp;lt;0.05. Univariate logistic regression in IHF patients showed that LV dyssynchrony indexes – SD (OR=1.55; 95% CI 1.09–2.2; p&amp;lt;0.5) and HBW (OR=1.13; 95% CI 1.02–1.24; p&amp;lt;0.5), as well as RV indexes – RV_EF (OR=1.11; 95% CI 1.001–1.23; p&amp;lt;0.5), RV_SV (OR=1.07; 95% CI 1.003–1.138; p&amp;lt;0.5) were predictors of CRT response. In the group of NIHF patients, dH/M (OR=1.47; 95% CI 1.08–2; p&amp;lt;0.5), SD (OR=0.83; 95% CI 0.73–0.95; p&amp;lt;0.5), HBW (OR=0.96; 95% CI 0.93–0.99; p&amp;lt;0.5) showed the predictive value in terms of CRT response. Conclusion(s) The positive response to CRT in IHF patients showed a link with LV dyssynchrony and preserved RV contractility. Whereas in NIHF patients the functional state of cardiac sympathetic activity, as well as LV dyssynchrony, were associated with CRT response. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Russian Foundation for Basic Research

Electrocardiographic Model to Predict Cardiac Resynchronization Therapy Response among Chronic Heart Failure Patients

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

Imaging predictors of response to cardiac resynchronization therapy: left ventricular work asymmetry by echocardiography and septal viability by cardiac magnetic resonance.

Aims Left ventricular (LV) failure in left bundle branch block is caused by loss of septal function and compensatory hyperfunction of the LV lateral wall (LW) which stimulates adverse remodelling. This study investigates if septal and LW function measured as myocardial work, alone and combined with assessment of septal viability, identifies responders to cardiac resynchronization therapy (CRT).Methods and results In a prospective multicentre study of 200 CRT recipients, myocardial work was measured by pressure-strain analysis and viability by cardiac magnetic resonance (CMR) imaging (n = 125). CRT response was defined as ≥15% reduction in LV end-systolic volume after 6 months. Before CRT, septal work was markedly lower than LW work (P < 0.0001), and the difference was largest in CRT responders (P < 0.001). Work difference between septum and LW predicted CRT response with area under the curve (AUC) 0.77 (95% CI: 0.70–0.84) and was feasible in 98% of patients. In patients undergoing CMR, combining work difference and septal viability significantly increased AUC to 0.88 (95% CI: 0.81–0.95). This was superior to the predictive power of QRS morphology, QRS duration and the echocardiographic parameters septal flash, apical rocking, and systolic stretch index. Accuracy was similar for the subgroup of patients with QRS 120–150 ms as for the entire study group. Both work difference alone and work difference combined with septal viability predicted long-term survival without heart transplantation with hazard ratio 0.36 (95% CI: 0.18–0.74) and 0.21 (95% CI: 0.072–0.61), respectively.ConclusionAssessment of myocardial work and septal viability identified CRT responders with high accuracy.

Evaluation of Pattern Recognition Techniques in Response to Cardiac Resynchronization Therapy (CRT)

Cardiac resynchronization therapy (CRT) improves cardiac function in patients with heart failure (HF), and the result of this treatment is decrease in death rate and improving quality of life for patients. This research is aimed at predicting CRT response for the prognosis of patients with heart failure under CRT. According to international instructions, in the case of approval of QRS prolongation and decrease in ejection fraction (EF), the patient is recognized as a candidate of implanting recognition device. However, regarding many intervening and effective factors, decision making can be done based on more variables. Computer-based decision-making systems especially machine learning (ML) are considered as a promising method regarding their significant background in medical prediction. Collective intelligence approaches such as particles swarm optimization (PSO) algorithm are used for determining the priorities of medical decision-making variables. This investigation was done on 209 patients and the data was collected over 12 months. In HESHMAT CRT center, 17.7% of patients did not respond to treatment. Recognizing the dominant parameters through combining machine recognition and physician’s viewpoint, and introducing back-propagation of error neural network algorithm in order to decrease classification error are the most important achievements of this research. In this research, an analytical set of individual, clinical, and laboratory variables, echocardiography, and electrocardiography (ECG) are proposed with patients’ response to CRT. Prediction of the response after CRT becomes possible by the support of a set of tools, algorithms, and variables.

Acute correction of electromechanical dyssynchrony and response to cardiac resynchronization therapy.

AimsEchocardiographic measures of dyssynchrony at baseline have not demonstrated a good ability to predict response to cardiac resynchronization therapy (CRT). The purpose of this study was to determine if the acute correction of electromechanical dyssynchrony, assessed by the change in simple pulsed‐Doppler measures, was related to CRT response at 6 months.Methods and resultsEchocardiography was performed at baseline and at pre‐discharge after CRT implantation. Intraventricular, interventricular, and atrioventricular dyssynchrony were evaluated by the left pre‐ejection interval (LPEI), the interventricular mechanical delay, and the ratio of left ventricular filling time to RR interval, respectivelxy. A patient was considered responder if he/she was alive without hospitalization for heart failure and had an absolute increase of left ventricular ejection fraction (LVEF) >5 points. Forty‐eight patients (mean age 67 ± 11 years, 73% male, mean LVEF 30 ± 5%) were included. CRT led to an acute correction of intraventricular and interventricular dyssynchrony but not to an acute correction of atrioventricular dyssynchrony. There were 31 (65%) responders at 6 months. Two factors were independently associated with CRT response in multivariate analysis: ischemic cardiomyopathy (odds ratio 0.19, 95% confidence interval 0.04–0.87; P= 0.032) and delta LPEI (odds ratio 1.03 per 1 ms decrease, 95% confidence interval 1.01–1.05; P = 0.007). By receiver operating characteristic analysis, the optimal cut‐off value of delta LPEI was −16 ms. The proportion of responders in patients without ischemic cardiomyopathy and with a delta LPEI greater than −16 ms was 85%.ConclusionsAcute correction of intraventricular electromechanical dyssynchrony evaluated by the LPEI predicted CRT response at 6 months.