Machine learning of ECG waveforms and cardiac magnetic resonance for response and survival after cardiac resynchronization therapy.

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.

Severe Tricuspid Regurgitation in a Patient with a Transvenous Dual-chamber Pacemaker: Considerations for Diagnosis and Management.

Cardiac implantable electronic device leads can contribute to tricuspid regurgitation and also complicate surgical and transcatheter interventions to manage tricuspid regurgitation. Here we present a case of a patient with sinus node dysfunction and complete heart block who underwent extraction of a right ventricular pacing lead before tricuspid valve surgery. We review the data regarding the contribution of leads to tricuspid regurgitation and the benefits of lead extraction, risks of jailing leads during tricuspid interventions, and pacing considerations around tricuspid valve procedures.

Global LEADR pivotal trial results.

BACKGROUND: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure™ defibrillation lead is a novel small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. OBJECTIVE: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead. METHODS: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. RESULTS: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). CONCLUSION: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and Radiolabeled Leukocyte SPECT/CT Imaging for the Evaluation of Cardiovascular Infection in the Multimodality Context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations From ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multisocietal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multifocal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

Cardiac Magnetic Resonance, Electromechanical Activation, Kidney Function, and Natriuretic Peptides in Cardiac Resynchronization Therapy Upgrades.

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.

Noninvasive Electrical Mapping Compared with the Paced QRS Complex for Optimizing CRT Programmed Settings and Predicting Multidimensional Response.

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.

The importance of eggs in an environmentally sustainable diet.

Food and diet globally have a significant environmental impact. Whilst there is broad agreement on the principles underpinning a healthy, sustainable diet, the interpretation of what it might mean in practice is widely debated. Misconceptions are common, including around the environmental impact of eggs and their place in a healthy, sustainable diet. Eggs are often categorised with other animal proteins such as beef, lamb, poultry, meat and dairy when reporting on the potential environmental impact of food and diets. However, the shift towards more planet-friendly diets demands a clear understanding of the evidence base on which such a diet should be based. This review evaluates scientific reports and peer-reviewed articles that have evaluated the environmental impact of hens' eggs in terms of greenhouse gas emissions (GHGEs), and land and water use and compared the impacts of eggs with those of other animal and plant proteins. This overview shows that eggs are responsible for less carbon, land and water use than other animal proteins, particularly beef and only slightly more than most plant proteins. Eggs are a nutritious, convenient and relatively inexpensive food, which traditionally has had an important place in the diet both in the United Kingdom and globally. It is therefore important to understand where they fit in terms of environmental impact and into advice on healthier, more sustainable dietary patterns.

First-in-human noninvasive left ventricular ultrasound pacing: A potential screening tool for cardiac resynchronization therapy.

Background: A screening tool to predict response to cardiac resynchronization therapy (CRT) could improve patient selection and outcomes. Objective: The purpose of this study was to investigate the feasibility and safety of noninvasive CRT via transcutaneous ultrasonic left ventricular (LV) pacing applied as a screening test before CRT implants. Methods: P-wave-triggered ultrasound stimuli were delivered during bolus dosing of an echocardiographic contrast agent to simulate CRT noninvasively. Ultrasound pacing was delivered at a variety of LV locations with a range of atrioventricular delays to achieve fusion with intrinsic ventricular activation. Three-dimensional cardiac activation maps were acquired via the Medtronic CardioInsight 252-electrode mapping vest during baseline, ultrasound pacing, and after CRT implantation. A separate control group received only the CRT implants. Results: Ultrasound pacing was achieved in 10 patients with a mean of 81.2 ± 50.8 ultrasound paced beats per patient and up to 20 consecutive beats of ultrasound pacing. QRS width at baseline (168.2 ± 17.8 ms) decreased significantly to 117.3 ± 21.5 ms (P <.001) in the best ultrasound paced beat and to 125.8 ± 13.3 ms (P <.001) in the best CRT beat. Electrical activation patterns were similar between CRT pacing and ultrasound pacing with stimulation from the same area of the LV. Troponin results were similar between the ultrasound pacing and the control groups (P = .96), confirming safety. Conclusion: Noninvasive ultrasound pacing before CRT is safe and feasible, and it estimates the degree of electrical resynchronization achievable with CRT. Further study of this promising technique to guide CRT patient selection is warranted.

Rationale and design of the Lead Evaluation for Defibrillation and Reliability study: Safety and efficacy of a novel ICD lead design.

BACKGROUND: Implantable cardioverter defibrillators (ICD) are indicated for primary and secondary prevention of sudden cardiac arrest. Despite enhancements in design and technologies, the ICD lead is the most vulnerable component of the ICD system and failure of ICD leads remains a significant clinical problem. A novel, small-diameter, lumenless, catheter-delivered, defibrillator lead was developed with the aim to improve long-term reliability. METHODS AND RESULTS: The Lead Evaluation for Defibrillation and Reliability (LEADR) study is a multi-center, single-arm, Bayesian, adaptive design, pre-market interventional pivotal clinical study. Up to 60 study sites from around the world will participate in the study. Patients indicated for a de novo ICD will undergo defibrillation testing at implantation and clinical assessments at baseline, implant, pre-hospital discharge, 3 months, 6 months, and every 6 months thereafter until official study closure. Patients may be participating for a minimum of 18 months to approximately 3 years. Fracture-free survival will be evaluated using a Bayesian statistical method that incorporates both virtual patient data (combination of bench testing to failure with in-vivo use condition data) with clinical patients. The clinical subject sample size will be determined using decision rules for number of subject enrollments and follow-up time based upon the observed number of fractures at certain time points in the study. The adaptive study design will therefore result in a minimum of 500 and a maximum of 900 patients enrolled. CONCLUSION: The LEADR Clinical Study was designed to efficiently provide evidence for short- and long-term safety and efficacy of a novel lead design using Bayesian methods including a novel virtual patient approach.

Machine learning for multidimensional response and survival after cardiac resynchronization therapy using features from cardiac magnetic resonance.

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.

Cardiac magnetic resonance defines mechanisms of sex-based differences in outcomes following cardiac resynchronization therapy.

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.

Utility of Ischemia Testing Prior to Ablation for Sustained Monomorphic Ventricular Tachycardia.

The aim of this study was to determine the relationship between ischemia testing prior to ablation for sustained monomorphic ventricular tachycardia (VT) (SMVT) and post-ablation mortality and VT recurrence. As SMVT is generally caused by myocardial scar and not active ischemia, the utility of ischemia testing prior to SMVT ablation is unclear. Patients who underwent ablation for SMVT at 2 tertiary care centers between January 2016 and July 2018 were included in a retrospective study. A Kaplan-Meier survival analysis was performed, stratifying patients by pre-ablation ischemia testing for the endpoints of mortality and VT recurrence. A Cox multivariable regression analysis was performed to identify predictors of post-ablation VT recurrence. A total of 163 patients were included, with 46 (28%) patients undergoing ischemia testing prior to ablation. Only 5 of the 46 patients (11%) received revascularization pre-ablation. After a median follow-up period of 625 days (interquartile range, 292-982 days) following ablation, 97 of 163 patients (60%) had VT recurrence, and 32 patients (20%) had died. There was no difference in mortality or VT recurrence between patients who did or did not experience ischemia testing or revascularization. In the multivariable regression analysis, predictors of VT recurrence were the number of anti-arrhythmics failed, non-ischemic cardiomyopathy, sex, and cardiac magnetic resonance imaging pre-ablation. Neither ischemia testing nor revascularization was a significant predictor of VT recurrence in univariable or multivariable regression analysis. In conclusion, ischemia testing is frequently ordered prior to SMVT ablation but infrequently leads to revascularization and is not associated with post-ablation outcomes. The findings support adopting an individualized approach rather than performing routine ischemia testing.