Septal scar predicts non-response to cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority Norwegian Health Association Background Scar in the left ventricular (LV) posterolateral wall is associated with poor response to cardiac resynchronization therapy (CRT). The impact of septal scar, however, has been less thoroughly investigated. As recovery of septal function seems to be an important effect of CRT, we hypothesized that CRT response depends on septal viability. Aim The aim of the present study was to investigate the association between septal scar and volumetric response to CRT, and to compare the impact of scar located in septum to scar located in the posterolateral wall. Methods 128 patients with symptomatic heart failure undergoing CRT implantation based on current guidelines (ejection fraction 30 ± 8%, QRS-width 164 ± 17 ms) were included in the study. Volumes and ejection fraction were measured by echocardiography using the biplane Simpson’s method at baseline and six months follow up. Non-response was defined as less than 15% reduction in end-systolic volume. Scar was assessed by late gadolinium enhancement cardiac magnetic resonance, and reported as percentage scar per regional myocardial volume. Numbers are given in [median ;10-90% percentile]. Results Scar was present in 62 patients (48%). Scar burden was equal in septum [0% ;0-34%] and the posterolateral wall [0% ;0-36%], p = 0.10. 31 patients (24%) did not respond to CRT. The non-responders had higher scar burden than the responders in both septum [16% ;0-57% vs 0% ;0-23%, p < 0.001] and the posterolateral wall [6% ;0-74% vs 0% ;0-22%, p < 0.001]. In univariate regression analysis both septal and posterolateral scars correlated with non-response to CRT (r = 0.51 and r = 0.33, respectively). However, combined in a multivariate model only septal scar remained a significant marker of non-response (p < 0.001), while posterolateral scar did not (p = 0.23). Septal scar ≥ 7.1% predicted non-response with a specificity of 81% and a sensitivity of 70% by receiver operating characteristic curve analyses. The area under the curve was 0.79 (95% confidence interval 0.70 – 0.89) (Figure). Conclusions Septal scar is more closely associated with volumetric non-response to CRT than posterolateral scar. Future studies should explore the correlation between regional scar burden and different functional parameters, and how they relate to CRT response. Abstract Figure. Septal scar predicts non-response to CRT

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

European Heart Journal ◽

10.1093/ehjci/ehaa946.0100 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M.R Zhu ◽

X Shu ◽

H.Y Chen ◽

Y.N Wang ◽

Y.F Cheng ◽

...

Keyword(s):

Cardiac Resynchronization Therapy ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Resynchronization Therapy ◽

Systolic Volume ◽

Non Invasive ◽

Work Distribution ◽

Constructive Work ◽

Crt Response

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<0.05). Besides, responders exhibited a significantly higher Mid Lateral MW and Mid Lateral constructive work (CW) (both P<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<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<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<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

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Abstract 12722: Cardiac Resynchronization Therapy in Pacing Induced Cardiomyopathy: A Higher Right Ventricle Pacing Percentage Predicts Greater Improvement in Left Ventricle Ejection Fraction

Circulation ◽

10.1161/circ.142.suppl_3.12722 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Sean Lacy ◽

Jonathan Chandler ◽

NACHIKET MADHAV APTE ◽

Seth Sheldon ◽

Madhu Reddy ◽

...

Keyword(s):

Left Ventricle ◽

Ejection Fraction ◽

Cardiac Resynchronization Therapy ◽

Left Ventricular ◽

Left Ventricle Ejection Fraction ◽

Cardiac Resynchronization ◽

Resynchronization Therapy ◽

Qrs Duration ◽

Rv Pacing ◽

The Impact

Introduction: Cardiac resynchronization therapy (CRT) upgrade is indicated for improvement of cardiac function in patients with chronic right ventricular (RV) pacing burden >40% and heart failure with reduced ejection fraction. It is uncertain whether the CRT response is different among patients with high (≥90%) versus intermediate (<90%) burden of baseline RV pacing. Hypothesis: To assess the impact of baseline RV pacing percent on ECG and echocardiographic response after CRT upgrade for pacing induced cardiomyopathy. Methods: We conducted a retrospective study of all CRT upgrades for pacing induced cardiomyopathy at our hospital from January 2017 to December 2018. Cohorts were grouped by RV pacing burden ≥90% or <90%. QRS duration, left ventricle ejection fraction (LVEF), and left ventricular internal dimension systolic (LVIDs) were assessed at baseline and 3-12 months post CRT upgrade. Results: We included 82 patients (age 74 ± 12 yr., 71% male) who underwent CRT upgrade for pacing induced cardiomyopathy. The RV pacing burden was ≥90% [median 99% (IQR 98-99%)] in 61 patients, and <90% [median 79% (IQR 69-88%)] in 21 patients. There was a trend towards greater reduction in QRS duration in the ≥90% RV pacing group (28 ± 29 ms vs. 22 ± 38 ms, p=0.5). Improvement in LVEF was greater in ≥90% vs. <90% RV pacing group (14.3 ± 10.1% vs. 6.3 ± 10.1%, p=0.003). The association persisted on multivariable adjustment for age, sex and baseline LVEF (p=0.004). There was a trend towards greater % reduction in LVIDs in the ≥90% vs. <90% RV pacing group (6.4 ± 15.5 % vs. 3.9 ± 14.3 %, p=0.5) [Figure]. Conclusions: A higher baseline RV pacing burden predicts a greater improvement in LVEF after CRT upgrade for pacing induced cardiomyopathy.

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

European Heart Journal ◽

10.1093/eurheartj/ehaa603 ◽

2020 ◽

Vol 41 (39) ◽

pp. 3813-3823 ◽

Cited By ~ 7

Author(s):

John M Aalen ◽

Erwan Donal ◽

Camilla K Larsen ◽

Jürgen Duchenne ◽

Mathieu Lederlin ◽

...

Keyword(s):

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Cardiac Resynchronization Therapy ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Resynchronization Therapy ◽

Term Survival ◽

Entire Study ◽

Systolic Volume ◽

Crt Response

Abstract 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. Conclusion Assessment of myocardial work and septal viability identified CRT responders with high accuracy.

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Cardiac resynchronization therapy non-responder to responder conversion rate in the more response to cardiac resynchronization therapy with MultiPoint Pacing (MORE-CRT MPP) study: results from Phase I

European Heart Journal ◽

10.1093/eurheartj/ehz109 ◽

2019 ◽

Vol 40 (35) ◽

pp. 2979-2987 ◽

Cited By ~ 25

Author(s):

Christophe Leclercq ◽

Haran Burri ◽

Antonio Curnis ◽

Peter Paul Delnoy ◽

Christopher A Rinaldi ◽

...

Keyword(s):

Cardiac Resynchronization Therapy ◽

Conversion Rate ◽

Biventricular Pacing ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Resynchronization Therapy ◽

Systolic Volume ◽

Study Results ◽

End Systolic Volume ◽

The Impact

Abstract Aims To assess the impact of MultiPoint™ Pacing (MPP)—programmed according to the physician’s discretion—in non-responders to standard biventricular pacing after 6 months. Methods and results The study enrolled 1921 patients receiving a quadripolar cardiac resynchronization therapy (CRT) system capable of MPP™ therapy. A core laboratory assessed echocardiography at baseline and 6 months and defined volumetric non-response to biventricular pacing as <15% reduction in left ventricular end-systolic volume (LVESV). Clinical sites randomized patients classified as non-responders in a 1:1 ratio to receive MPP (236 patients) or continued biventricular pacing (231 patients) for an additional 6 months and evaluated rate of conversion to echocardiographic response. Baseline characteristics of both groups were comparable. No difference was observed in non-responder to responder conversion rate between MPP and biventricular pacing (31.8% and 33.8%, P = 0.72). In the MPP arm, 68 (29%) patients received MPP programmed with a wide LV electrode anatomical separation (≥30 mm) and shortest LV1–LV2 and LV2–RV timing delays (MPP-AS); 168 (71%) patients received MPP programmed with other settings (MPP-Other). MPP-AS elicited a significantly higher non-responder conversion rate compared to MPP-Other (45.6% vs. 26.2%, P = 0.006) and a trend in a higher conversion rate compared to biventricular pacing (45.6% vs. 33.8%, P = 0.10). Conclusions After 6 months, investigator-discretionary MPP programming did not significantly increase echocardiographic response compared to biventricular pacing in CRT non-responders.

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Using Machine-Learning for Prediction of the Response to Cardiac Resynchronization Therapy: the SMART-AV Study

10.22541/au.160680804.42971359/v1 ◽

2020 ◽

Author(s):

Stacey Howell ◽

Tim Stivland ◽

Kenneth Stein ◽

Kenneth Ellenbogen ◽

Larisa Tereshchenko

Keyword(s):

Machine Learning ◽

Cardiac Resynchronization Therapy ◽

Left Ventricular ◽

Adaptive Lasso ◽

Volume Index ◽

Cardiac Resynchronization ◽

Resynchronization Therapy ◽

Systolic Volume ◽

End Systolic Volume ◽

Crt Response

Introduction—We aimed to apply machine learning (ML) to develop a prediction model for cardiac resynchronization therapy (CRT) response. Methods and Results—Participants from the SmartDelay Determined AV Optimization (SMART-AV) trial (n=741; age, 66 ±11 yrs; 33% female; 100% NYHA III-IV; 100% EF≤35%) were randomly split into training & testing (80%; n=593), and validation (20%; n=148) samples. Baseline clinical, ECG, echocardiographic and biomarker characteristics, and left ventricular (LV) lead position (43 variables) were included in 6 ML models (random forests, convolutional neural network, lasso, adaptive lasso, plugin lasso, elastic net, ridge, and logistic regression). A composite of freedom from death and heart failure hospitalization and a >15% reduction in LV end-systolic volume index at 6-months post-CRT was the endpoint. The primary endpoint was met by 337 patients (45.5%). The adaptive lasso model was more accurate than class I ACC/AHA guidelines criteria (AUC 0.759; 95%CI 0.678-0.840 versus 0.639; 95%CI 0.554-0.722; P<0.0001), well-calibrated, and parsimonious (19 predictors; nearly half are potentially modifiable). The model predicted CRT response with 70% accuracy, 70% sensitivity, and 70% specificity, and should be further validated in prospective studies. Conclusions—ML predicts short-term CRT response and thus may help with CRT procedure planning.

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Improvement of LV Reverse Remodeling Using Dynamic Programming of Fusion-Optimized Atrioventricular Intervals in Cardiac Resynchronization Therapy

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.700424 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhongkai Wang ◽

Pan Li ◽

Bili Zhang ◽

Jingjuan Huang ◽

Shaoping Chen ◽

...

Keyword(s):

Cardiac Resynchronization Therapy ◽

Nyha Class ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Reverse Remodeling ◽

Resynchronization Therapy ◽

Systolic Volume ◽

End Systolic Volume ◽

The Impact

Background: The patient-tailored SyncAV algorithm shortens the QRS duration (QRSd) beyond what conventional biventricular (BiV) pacing can. However, evidence of the ability of SyncAV to improve the cardiac resynchronization therapy (CRT) response is lacking. The aim of this study was to evaluate the impact of CRT enhanced by SyncAV on echocardiographic and clinical responses.Methods and Results: Consecutive heart failure (HF) patients from three centers treated with a quadripolar CRT system (Abbott) were enrolled. The total of 122 patients were divided into BiV+SyncAV (n = 68) and BiV groups (n = 54) according to whether they underwent CRT with or without SyncAV. Electrocardiographic, echocardiographic, and clinical data were assessed at baseline and during follow-up. Echocardiographic response to CRT was defined as a ≥15% decrease in left ventricular end-systolic volume (LVESV), and clinical response was defined as a NYHA class reduction of ≥1. At the 6-month follow-up, the baseline QRSd and LVESV decreased more significantly in the BiV+SyncAV than in the BiV group (QRSd −36.25 ± 16.33 vs. −22.72 ± 18.75 ms, P < 0.001; LVESV −54.19 ± 38.87 vs. −25.37 ± 36.48 ml, P < 0.001). Compared to the BiV group, more patients in the BiV+SyncAV group were classified as echocardiographic (82.35 vs. 64.81%; P = 0.036) and clinical responders (83.82 vs. 66.67%; P = 0.033). During follow-up, no deaths due to HF deterioration or severe procedure related complications occurred.Conclusion: Compared to BiV pacing, BiV combined with SyncAV leads to a more significant reduction in QRSd and improves LV remodeling and long-term outcomes in HF patients treated with CRT.

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A Simple Predictive Marker in Cardiac Resynchronization Therapy Recipients: Prominent S-Wave in Right Precordial Leads

Medicina ◽

10.3390/medicina57080815 ◽

2021 ◽

Vol 57 (8) ◽

pp. 815

Author(s):

Naoya Kataoka ◽

Teruhiko Imamura ◽

Takahisa Koi ◽

Keisuke Uchida ◽

Koichiro Kinugawa

Keyword(s):

Cardiac Resynchronization Therapy ◽

Wave Amplitude ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Reverse Remodeling ◽

Resynchronization Therapy ◽

S Wave ◽

Systolic Volume ◽

The Impact ◽

R Wave Amplitude

Background and objectives: Current guidelines criteria do not satisfactorily discriminate responders to cardiac resynchronization therapy (CRT). QRS amplitude is an established index to recognize the severity of myocardial disturbance and might be a key to optimal patient selection for CRT. Materials and Methods: (1) Initial R-wave amplitude, (2) S-wave amplitude, and (3) a summation of maximal R- or R′-wave amplitude and S-wave amplitude were measured at baseline. These parameters were averaged according to right (V1 to V3) or left (V4 to V6) precordial leads. The impact of these parameters on response to CRT, which was defined as a decrease in left ventricular end-systolic volume ≥15% at six-month follow-up, was investigated. Results: Among 47 patients (71 years old, 28 men) who received guideline-indicated CRT implantation, 25 (53%) achieved the definition of CRT responder. Among baseline electrocardiogram parameters, only the higher S-wave amplitude in right precordial leads was an independent predictor of CRT responders (odds ratio: 2.181, 95% confidence interval: 1.078–4.414, p = 0.030) at a cutoff of 1.44 mV. The cutoff was independently associated with cumulative incidence of heart failure readmission and appropriate electrical defibrillation following CRT implantation (p < 0.05, respectively). Conclusions: Prominent S-wave in right precordial leads might be a promising index to predict left ventricular reverse remodeling and greater clinical outcomes following CRT implantation.

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Using Machine-Learning for Prediction of the Response to Cardiac Resynchronization Therapy: the SMART-AV Study

10.1101/2020.07.16.20155424 ◽

2020 ◽

Author(s):

Stacey Howell ◽

Tim Stivland ◽

Kenneth Stein ◽

Kenneth Ellenbogen ◽

Larisa G Tereshchenko

Keyword(s):

Machine Learning ◽

Cardiac Resynchronization Therapy ◽

Left Ventricular ◽

Adaptive Lasso ◽

Volume Index ◽

Cardiac Resynchronization ◽

Resynchronization Therapy ◽

Systolic Volume ◽

End Systolic Volume ◽

Crt Response

Background: There is a controversy whether the response of both sexes to cardiac resynchronization therapy (CRT) is similar. Optimal CRT delivery requires procedure planning. Objective: To apply machine learning (ML) to develop a prediction model for CRT response. Methods: Participants from the SmartDelay Determined AV Optimization (SMART-AV) trial (n=741; age, 66 ± 11 yrs; 33% female; 100% NYHA III-IV; 100% EF≤35%) were randomly split into training & testing (80%; n=593), and validation (20%; n=148) samples. The entropy balancing procedure was used to match for the means of 30 covariates in male and female groups. Baseline clinical, ECG, echocardiographic and biomarker characteristics, and left ventricular (LV) lead position (43 variables) were included in 6 ML models (random forests, convolutional neural network, lasso, adaptive lasso, plugin lasso, elastic net, ridge, and logistic regression). A composite of freedom from death and heart failure hospitalization and a >15% reduction in LV end-systolic volume index at 6-months post-CRT was the endpoint. Results: The primary endpoint was met by 337 patients (45.5%). Weighting resulted in a perfect balance of means of covariates in men and women. After reweighting, CRT response for women versus men was similar (OR 1.53; 95%CI 0.88-2.65; P=0.131). The adaptive lasso model was more accurate than class I ACC/AHA guidelines criteria (AUC 0.759; 95%CI 0.678-0.840 versus 0.639; 95%CI 0.554-0.722; P<0.0001), well-calibrated, and parsimonious (19 predictors; nearly half are potentially modifiable). Conclusions: After balancing for covariates, both sexes similarly benefit from CRT. ML predicts short-term CRT response and thus may help with CRT procedure planning.

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561 Targeting septal work and viability identifies responders to cardiac resynchronization therapy

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.291 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

J Aalen ◽

E Donal ◽

C K Larsen ◽

J Duchenne ◽

M Cvijic ◽

...

Keyword(s):

Cardiac Resynchronization Therapy ◽

Myocardial Strain ◽

Lateral Wall ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Lv Function ◽

Resynchronization Therapy ◽

Entire Study ◽

Systolic Volume ◽

Crt Response

Abstract Funding Acknowledgements The study was supported by Center for Cardiological Innovation. Introduction Septal dysfunction is the dominant mechanism of left ventricular (LV) failure in left bundle branch block (LBBB). We hypothesize that, provided septum is viable, septal function can recover and hence LV function improve after cardiac resynchronization therapy (CRT). Purpose To determine if combined assessment of septal function and viability identifies responders to CRT. Methods In a prospective multicenter study of 200 unselected patients referred for CRT, we measured myocardial strain by speckle-tracking echocardiography and regional work by pressure-strain analysis before and 7 ± 1 months after CRT. Viability was assessed by late gadolinium enhancement cardiac magnetic resonance imaging (n = 123). CRT response was defined as ≥15% reduction in LV end-systolic volume. Results Before CRT, septal work was 258 ± 463 and LV lateral wall work 1469 ± 674 mmHg·% (p < 0.0001). In CRT responders, septal work was restored to 1243 ± 495 mmHg·%, whereas non-responders showed less marked improvement (p < 0.0001). The figure illustrates a typical CRT responder with negative septal work and a large difference between work in the LV lateral wall and septum (panel A). There was no septal scar (panel B) and, after 6 months with CRT, septal work was recovered (panel C). Pressure-strain loops illustrate that CRT converted inefficient septal contractions with substantial negative (wasted) work to positive work throughout systole. For the entire study population, the difference between work in the LV lateral wall and septum predicted CRT response with area under the curve (AUC) 0.75 (95% CI: 0.68-0.83) and was feasible in 98% of patients. Furthermore, septal scar predicted non-response to CRT with AUC 0.76 (95% CI: 0.65-0.86). Combining work difference and septal viability improved AUC for CRT response to 0.85 (95% CI: 0.76-0.94) (figure panel D). The AUC was similar for QRS 120-150 and >150 ms. Conclusions The proposed combined approach with assessment of septal work and viability identified CRT responders with high precision. Abstract 561 Figure.

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