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Cardiac resynchronization therapy (CRT) can lead to marked symptom reduction and improved survival in selected patients with heart failure with reduced ejection fraction (HFrEF); however, many candidates for CRT based on clinical guidelines do not have a favorable response. A better way to identify patients expected to benefit from CRT that applies machine learning to accessible and cost-effective diagnostic tools such as the 12-lead electrocardiogram (ECG) could have a major impact on clinical care in HFrEF by helping providers personalize treatment strategies and avoid delays in initiation of other potentially beneficial treatments. This study addresses this need by demonstrating that a novel approach to ECG waveform analysis using functional principal component decomposition (FPCD) performs better than measures that require manual ECG analysis with the human eye and also at least as well as a previously validated but more expensive approach based on cardiac magnetic resonance (CMR). Analyses are based on five-fold cross validation of areas under the curve (AUCs) for CRT response and survival time after the CRT implant using Cox proportional hazards regression with stratification of groups using a Gaussian mixture model approach. Furthermore, FPCD and CMR predictors are shown to be independent, which demonstrates that the FPCD electrical findings and the CMR mechanical findings together provide a synergistic model for response and survival after CRT. In summary, this study provides a highly effective approach to prognostication after CRT in HFrEF using an accessible and inexpensive diagnostic test with a major expected impact on personalization of therapies., Competing Interests: Declaration of competing interest Dr. Bilchick has research grant support from Medtronic and Siemens Healthineers. Dr. Mangrum has research grant support from Boston Scientific, CardioFocus, and St. Jude Medical. Dr. Epstein has research grant support from Siemens Healthineers. Dr. Patel has a research grant from GE Healthcare and research support from Circle CVI and Neosoft., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The aim was to test the hypothesis that left ventricular (LV) and right ventricular (RV) activation from body surface electrical mapping (CardioInsight 252-electrode vest, Medtronic) identifies optimal cardiac resynchronization therapy (CRT) pacing strategies and outcomes in 30 patients. The LV80, RV80, and BIV80 were defined as the times to 80% LV, RV, or biventricular electrical activation. Smaller differences in the LV80 and RV80 (|LV80-RV80|) with synchronized LV pacing predicted better LV function post-CRT (p = 0.0004) than the LV-paced QRS duration (p = 0.32). Likewise, a lower RV80 was associated with a better pre-CRT RV ejection fraction by CMR (r =  - 0.40, p = 0.04) and predicted post-CRT improvements in myocardial oxygen uptake (p = 0.01) better than the biventricular-paced QRS (p = 0.38), while a lower LV80 with BIV pacing predicted lower post-CRT B-type natriuretic peptide (BNP) (p = 0.02). RV pacing improved LV function with smaller |LV80-RV80| (p = 0.009). In conclusion, 3-D electrical mapping predicted favorable post-CRT outcomes and informed effective pacing strategies., (© 2023. The Author(s).)

Background Black and Hispanic patients are less likely to receive cardiac resynchronization therapy (CRT) than White patients. Medicaid expansion has been associated with increased access to cardiovascular care among racial and ethnic groups with higher prevalence of underinsurance. It is unknown whether the Medicaid expansion was associated with increased receipt of CRT by race and ethnicity. Methods and Results Using Healthcare Cost and Utilization Project Data State Inpatient Databases from 19 states and Washington, DC, we analyzed 1061 patients from early-adopter states (Medicaid expansion by January 2014) and 745 patients from nonadopter states (no implementation 2013-2014). Estimates of change in census-adjusted rates of CRT with or without defibrillator by race and ethnicity and Medicaid adopter status 1 year before and after January 2014 were conducted using a quasi-Poisson regression model. Following the Medicaid expansion, the rate of CRT did not significantly change among Black individuals from early-adopter states (1.07 [95% CI, 0.78-1.48]) or nonadopter states (0.79 [95% CI, 0.57-1.09]). There were no significant changes in rates of CRT among Hispanic individuals from early-adopter states (0.99 [95% CI, 0.70-1.38]) or nonadopter states (1.01 [95% CI, 0.65-1.57]). There was a 34% increase in CRT rates among White individuals from early-adopter states (1.34 [95% CI, 1.05-1.70]), and no significant change among White individuals from nonadopter states (0.77 [95% CI, 0.59-1.02]). The change in CRT rates among White individuals was associated with the timing of the Medicaid implementation ( P =0.003). Conclusions Among states participating in Healthcare Cost and Utilization Project Data State Inpatient Databases, implementation of Medicaid expansion was associated with increase in CRT rates among White individuals residing in states that adopted the Medicaid expansion policy. Further work is needed to address disparities in CRT among Black and Hispanic patients.

Objectives: The objective was to determine the feasibility and effectiveness of cardiac magnetic resonance (CMR) cine and strain imaging before and after cardiac resynchronization therapy (CRT) for assessment of response and the optimal resynchronization pacing strategy., Background: CMR with cardiac implantable electronic devices can safely provide high-quality right ventricular/left ventricular (LV) ejection fraction (RVEF/LVEF) assessments and strain., Methods: CMR with cine imaging, displacement encoding with stimulated echoes for the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) dyssynchrony parameter, and scar assessment was performed before and after CRT. Whereas the pre-CRT scan constituted a single "imaging set" with complete volumetric, strain, and scar imaging, multiple imaging sets with complete strain and volumetric data were obtained during the post-CRT scan for biventricular pacing (BIVP), LV pacing (LVP), and asynchronous atrial pacing modes by reprogramming the device outside the scanner between imaging sets., Results: 100 CMRs with a total of 162 imaging sets were performed in 50 patients (median age 70 years [IQR: 50-86 years]; 48% female). Reduction in LV end-diastolic volumes (P = 0.002) independent of CRT pacing were more prominent than corresponding reductions in right ventricular end-diastolic volumes (P = 0.16). A clear dependence of the optimal CRT pacing mode (BIVP vs LVP) on the PR interval (P = 0.0006) was demonstrated. The LVEF and RVEF improved more with BIVP than LVP with PR intervals ≥240 milliseconds (P = 0.025 and P = 0.002, respectively); the optimal mode (BIVP vs LVP) was variable with PR intervals <240 milliseconds. A lower pre-CRT displacement encoding with stimulated echoes (DENSE) CURE-SVD was associated with greater improvements in the post-CRT CURE-SVD (r = -0.69; P < 0.001), LV end-systolic volume (r = -0.58; P < 0.001), and LVEF (r = -0.52; P < 0.001)., Conclusions: CMR evaluation with assessment of multiple pacing modes during a single scan after CRT is feasible and provides useful information for patient care with respect to response and the optimal pacing strategy., Competing Interests: Funding Support and Author Disclosures The work on this project performed by Drs Hanson, Robinson, and Schumann was supported by National Institutes of Health (NIH) training grant T32 EB00384. Dr Epstein’s effort was supported by National Institutes of Health (NIH) grant R01 HL147104. Dr Bilchick’s work on this project was funded by NIH grants R56 HL135556 and R03 HL135463, and American Heart Association grant 17GRNT33671086. Dr Malhotra has research grant support from Biosense Webster. Dr Darby has grant support from Medtronic and Biosense Webster. Dr Mangrum has research grant support from Boston Scientific, CardioFocus, and St. Jude Medical. Drs Kramer and Epstein have received grant support from Siemens Healthineers. Dr Bilchick has research grant support from Medtronic and Siemens Healthineers. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This review highlights variability in prescribing of nonpharmacologic heart failure with reduced ejection fraction (HFrEF) therapies by race, ethnicity, and gender. The review also explores the evidence underlying these inequalities as well as potential mitigation strategies., Recent Findings: There have been major advances in HF therapies that have led to improved overall survival of HF patients. However, racial and ethnic groups of color and women have not received equitable access to these therapies. Patients of color and women are less likely to receive nonpharmacologic therapies for HFrEF than White patients and men. Therapies including exercise rehabilitation, percutaneous transcatheter mitral valve repair, cardiac resynchronization therapy, heart transplant, and ventricular assist devices all have proven efficacy in patients of color and women but remain underprescribed. Outcomes with most nonpharmacologic therapy are similar or better among patients of color and women than White patients and men. System-level changes are urgently needed to achieve equity in access to nonpharmacologic HFrEF therapies by race, ethnicity, and gender.

Objectives: This study sought to determine if combining the Seattle Heart Failure Model (SHFM-D) and cardiac magnetic resonance (CMR) provides complementary prognostic data for patients with cardiac resynchronization therapy (CRT) defibrillators., Background: The SHFM-D is among the most widely used risk stratification models for overall survival in patients with heart failure and implantable cardioverter-defibrillators (ICDs), and CMR provides highly detailed information regarding cardiac structure and function., Methods: CMR Displacement Encoding with Stimulated Echoes (DENSE) strain imaging was used to generate the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) circumferential strain dyssynchrony parameter, and the SHFM-D was determined from clinical parameters. Multivariable Cox proportional hazards regression was used to determine adjusted hazard ratios and time-dependent areas under the curve for the primary endpoint of death, heart transplantation, left ventricular assist device, or appropriate ICD therapies., Results: The cohort consisted of 100 patients (65.5 [interquartile range 57.7 to 72.7] years; 29% female), of whom 47% had the primary clinical endpoint and 18% had appropriate ICD therapies during a median follow-up of 5.3 years. CURE-SVD and the SHFM-D were independently associated with the primary endpoint (SHFM-D: hazard ratio: 1.47/SD; 95% confidence interval: 1.06 to 2.03; p = 0.02) (CURE-SVD: hazard ratio: 1.54/SD; 95% confidence interval: 1.12 to 2.11; p = 0.009). Furthermore, a favorable prognostic group (Group A, with CURE-SVD <0.60 and SHFM-D <0.70) comprising approximately one-third of the patients had a very low rate of appropriate ICD therapies (1.5% per year) and a greater (90%) 4-year survival compared with Group B (CURE-SVD ≥0.60 or SHFM-D ≥0.70) patients (p = 0.02). CURE-SVD with DENSE had a stronger correlation with CRT response (r = -0.57; p < 0.0001) than CURE-SVD with feature tracking (r = -0.28; p = 0.004)., Conclusions: A combined approach to risk stratification using CMR DENSE strain imaging and a widely used clinical risk model, the SHFM-D, proved to be effective in this cohort of patients referred for CRT defibrillators. The combined use of CMR and clinical risk models represents a promising and novel paradigm to inform prognosis and device selection in the future., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

As the mechanism for worse prognosis after cardiac resynchronization therapy (CRT) upgrades in heart failure patients with RVP dependence (RVP-HF) has clinical implications for patient selection and CRT implementation approaches, this study's objective was to evaluate prognostic implications of cardiac magnetic resonance (CMR) findings and clinical factors in 102 HF patients (23.5% female, median age 66.5 years old, median follow-up 4.8 years) with and without RVP dependence undergoing upgrade and de novo CRT implants. Compared with other CRT groups, RVP-HF patients had decreased survival (p = 0.02), more anterior late-activated LV pacing sites (p = 0.002) by CMR, more atrial fibrillation (p = 0.0006), and higher creatinine (0.002). CMR activation timing at the LV pacing site predicted post-CRT LV functional improvement (p < 0.05), and mechanical activation onset < 34 ms by CMR at the LVP site was associated with decreased post-CRT survival in a model with higher pre-CRT creatinine and B-type natriuretic peptide (AUC 0.89; p < 0.0001); however, only the higher pre-CRT creatinine partially mediated (37%) the decreased survival in RVP-HF patients. In conclusion, RVP-HF had a distinct CMR phenotype, which has important implications for the selection of LV pacing sites in CRT upgrades, and only chronic kidney disease mediated the decreased survival after CRT in RVP-HF.

BACKGROUND: Cardiac resynchronization therapy (CRT) response is complex, and better approaches are required to predict survival and need for advanced therapies. OBJECTIVE: The objective was to use machine learning to characterize multidimensional CRT response and its relationship with long-term survival. METHODS: Associations of 39 baseline features (including cardiac magnetic resonance [CMR] findings and clinical parameters such as glomerular filtration rate [GFR]) with a multidimensional CRT response vector (consisting of post-CRT left ventricular end-systolic volume index [LVESVI] fractional change, post-CRT B-type natriuretic peptide, and change in peak VO2) were evaluated. Machine learning generated response clusters, and cross-validation assessed associations of clusters with 4-year survival. RESULTS: Among 200 patients (median age 67.4 years, 27.0% women) with CRT and CMR, associations with more than 1 response parameter were noted for the CMR CURE-SVD dyssynchrony parameter (associated with post-CRT brain natriuretic peptide [BNP] and LVESVI fractional change) and GFR (associated with peak VO2 and post-CRT BNP). Machine learning defined 3 response clusters: cluster 1 (n = 123, 90.2% survival [best]), cluster 2 (n = 45, 60.0% survival [intermediate]), and cluster 3 (n = 32, 34.4% survival [worst]). Adding the 6-month response cluster to baseline features improved the area under the receiver operating characteristic curve for 4-year survival from 0.78 to 0.86 (P = .02). A web-based application was developed for cluster determination in future patients. CONCLUSION: Machine learning characterizes distinct CRT response clusters influenced by CMR features, kidney function, and other factors. These clusters have a strong and additive influence on long-term survival relative to baseline features.

BACKGROUND: Mechanisms of sex-based differences in outcomes following cardiac resynchronization therapy (CRT) are poorly understood. OBJECTIVE: To use cardiac magnetic resonance (CMR) to define mechanisms of sex-based differences in outcomes after CRT and describe distinct CMR-based phenotypes of CRT candidates based on sex and non-ischemic/ischemic cardiomyopathy type. MATERIALS AND METHODS: In a prospective study, sex-based differences in three short-term CRT response measures [fractional change in left ventricular end-systolic volume index 6 months after CRT (LVESVI-FC), B-type natriuretic peptide (BNP) 6 months after CRT, change in peak VO2 6 months after CRT], and long-term survival were evaluated with respect to 39 baseline parameters from CMR, exercise testing, laboratory testing, electrocardiograms, comorbid conditions, and other sources. CMR was also used to quantify the degree of left-ventricular mechanical dyssynchrony by deriving the circumferential uniformity ratio estimate (CURE-SVD) parameter from displacement encoding with stimulated echoes (DENSE) strain imaging. Statistical methods included multivariable linear regression with evaluation of interaction effects associated with sex and cardiomyopathy type (ischemic and non-ischemic cardiomyopathy) and survival analysis. RESULTS: Among 200 patients, the 54 female patients (27%) pre-CRT had a smaller CMR-based LVEDVI (p = 0.04), more mechanical dyssynchrony based on the validated CMR CURE-SVD parameter (p = 0.04), a lower frequency of both late gadolinium enhancement (LGE) and ischemic cardiomyopathy (p < 0.0001), a greater RVEF (p = 0.02), and a greater frequency of LBBB (p = 0.01). After categorization of patients into four groups based on cardiomyopathy type (ischemic/non-ischemic cardiomyopathy) and sex, female patients with non-ischemic cardiomyopathy had the lowest CURE-SVD (p = 0.003), the lowest pre-CRT BNP levels (p = 0.01), the lowest post-CRT BNP levels (p = 0.05), and the most favorable LVESVI-FC (p = 0.001). Overall, female patients had better 3-year survival before adjustment for cardiomyopathy type (p = 0.007, HR = 0.45) and after adjustment for cardiomyopathy type (p = 0.009, HR = 0.67). CONCLUSION: CMR identifies distinct phenotypes of female CRT patients with non-ischemic and ischemic cardiomyopathy relative to male patients stratified by cardiomyopathy type. The more favorable short-term response and long-term survival outcomes in female heart failure patients with CRT were associated with lower indexed CMR-based LV volumes, decreased presence of scar associated with prior myocardial infarction and ICM, and greater CMR-based dyssynchrony with the CURE-SVD.

Aims: This study aimed to improve in‐person clinical evaluation on the day of heart failure (HF) hospitalization discharge by adding device‐measured parameters to predict 30 day HF rehospitalization risk in cardiac resynchronization therapy‐defibrillator (CRT‐D) patients. Methods and results: In a cohort of Medicare patients with CRT‐Ds, the independent prognostic value of four device‐measured parameters was assessed relative to typical clinical parameters associated with rehospitalization risk. Medicare registry, claims, and Medtronic CareLink® Network data for these patients were analysed using logistic regression modelling and net reclassification methods. Among 1563 CRT‐D patients, 411 patients had 607 HF hospitalization events during a median 6.3 years of follow‐up. Compared with clinical variables alone, impedance measurements resulted in a 28% improvement between the predicted probabilities of having vs. not having a 30 day HF rehospitalization (relative integrated discrimination improvement = 0.28) and a net 42% improvement in the classification of 30 day HF rehospitalization events and non‐events after an index HF hospitalization (net reclassification index = 0.42; 95% CI: 0.10, 0.74). Conclusions: In CRT patients, intrathoracic impedance measurements improve prediction of 30 day HF rehospitalization over clinical characteristics alone. The present study provides supportive data for the routine evaluation of intrathoracic impedance prior to discharge in patient with CRT devices. Furthermore, the models developed in this study could be used to design interventions to improve compliance with Medicare reimbursement guidelines regarding 30 day HF rehospitalization. [ABSTRACT FROM AUTHOR]