Al‐Khatib, Sana M.

AbstractCardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Atrial fibrillation (AF) is one of the strongest risk factors for ischemic stroke, which is a leading cause of disability and death. Given the aging population, increasing prevalence of AF risk factors, and improved survival in those with cardiovascular disease, the number of individuals affected by AF will continue increasing over time. While multiple proven stroke prevention therapies exist, important questions remain about the optimal approach to stroke prevention at the population and individual patient levels. Our report summarizes the National Heart, Lung, and Blood Institute virtual workshop focused on identifying key research opportunities related to stroke prevention in AF. The workshop reviewed major knowledge gaps and identified targeted research opportunities to advance stroke prevention in AF in the following areas: (1) improving risk stratification tools for stroke and intracranial hemorrhage; (2) addressing challenges with oral anticoagulants; and (3) delineating the optimal roles of percutaneous left atrial appendage occlusion and surgical left atrial appendage closure/excision. This report aims to promote innovative, impactful research that will lead to more personalized, effective use of stroke prevention strategies in people with AF.

Importance Only modest attention has been paid to the contributions of social determinants of health to atrial fibrillation (AF) risk factors, diagnosis, symptoms, management, and outcomes. The diagnosis of AF provides unique challenges exacerbated by the arrhythmia’s often paroxysmal nature and individuals’ disparate access to health care and technologies that facilitate detection. Social determinants of health affect access to care and management decisions for AF, increasing the likelihood of adverse outcomes among individuals who experience systemic disadvantages. Developing effective approaches to address modifiable social determinants of health requires research to eliminate the substantive inequities in health care delivery and outcomes in AF. Observations The National Heart, Lung, and Blood Institute convened an expert panel to identify major knowledge gaps and research opportunities in the field of social determinants of AF. The workshop addressed the following social determinants: (1) socioeconomic status and access to care; (2) health literacy; (3) race, ethnicity, and racism; (4) sex and gender; (5) shared decision-making in systemically disadvantaged populations; and (6) place, including rurality, neighborhood, and community. Many individuals with AF have multiple adverse social determinants, which may cluster in the individual and in systemically disadvantaged places (eg, rural locations, urban neighborhoods). Cumulative disadvantages may accumulate over the life course and contribute to inequities in the diagnosis, management, and outcomes in AF. Conclusions and Relevance Workshop participants identified multiple critical research questions and approaches to catalyze social determinants of health research that address the distinctive aspects of AF. The long-term aspiration of this work is to eradicate the substantive inequities in AF diagnosis, management, and outcomes across populations.

AbstractBackgroundFor cardiac resynchronization therapy (CRT), image‐guided approaches targeting left ventricular (LV) lead placement at the site of latest mechanical activation had inconsistent outcomes. We examined evidence for improved CRT outcomes when LV lead placement concordant with latest mechanical activation occurred.MethodsA review of EMBASE and PubMed was performed for randomized controlled trials or prospective observational studies from October 2008 through October 2020 comparing outcomes with concordant versus discordant LV lead placement. Meta‐analyses were performed to assess the association between concordance and death, death or heart failure (HF) hospitalization, ≥ 15% reduction in LV end systolic volume (LVESV), and changes in LVESV or ejection fraction (LVEF).ResultsFrom 5897 citations, nine publications (eight studies) with 1355 patients were selected; 975 with a concordant LV lead and 380 with a discordant lead. Mean age was 66–68 years, 82% were male, and 64% had ischemic cardiomyopathy. Meta‐analyses demonstrated a statistically significant reduction in death/HF hospitalization at 2 years (OR 0.38; 95% CI 0.16, 0.92) and LVESV at 6 months (mean difference [MD] ‐13.4%; 95% CI ‐6.7%, ‐20.0%), and an increase in LVEF (MD 4.03; 95% CI 0.77, 7.30) with the concordant LV lead. There were trends toward decreased death at 2 years (OR 0.49; 95% CI 0.19, 1.23) and ≥ 15% reduction in LVESV at 6 months (OR 3.81; 95% CI 0.24, 61.24) with concordant LV lead placement.ConclusionA concordant LV lead was associated with better CRT outcomes. Further study of feasible methods to achieve LV lead concordance is needed.

Aim. To assess evidence for an image-guided approach for cardiac resynchronization therapy (CRT) that targets left ventricular (LV) lead placement at the segment of latest mechanical activation. Methods. A systematic review of EMBASE and PubMed was performed for randomized controlled trials (RCTs) and prospective observational studies from October 2008 through October 2020 that compared an image-guided CRT approach with a non-image-guided approach for LV lead placement. Meta-analyses were performed to assess the association between the image-guided approach and NYHA class improvement or changes in end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF). Results. From 5897 citations, 5 RCTs including 818 patients (426 image-guided and 392 non-image-guided) were identified. The mean age ranged from 66 to 71 years, 76% were male, and 53% had ischemic cardiomyopathy. Speckle tracking echocardiography was the primary image-guided method in all studies. LV lead placement within the segment of the latest mechanical activation (concordant) was achieved in the image-guided arm in 45% of the evaluable patients. There was a statistically significant improvement in the NYHA class at 6 months (odds ratio 1.66; 95% confidence interval (CI) [1.02, 2.69]) with the image-guided approach, but no statistically significant change in LVESV (MD −7.1%; 95% CI [−16.0, 1.8]), LVEDV (MD −5.2%; 95% CI [−15.8, 5.4]), or LVEF (MD 0.68; 95% CI [−4.36, 5.73]) versus the non-image-guided approach. Conclusion. The image-guided CRT approach was associated with improvement in the NYHA class but not echocardiographic measures, possibly due to the small sample size and a low rate of concordant LV lead placement despite using the image-guided approach. Therefore, our meta-analysis was not able to identify consistent improvement in CRT outcomes with an image-guided approach.

Introduction: To improve CRT outcomes, image-guided approaches targeting left ventricular (LV) lead placement at the segment of latest mechanical activation have been compared to non-image-guided approaches with mixed results. A meta-analysis was conducted to assess the association between an image-guided approach and CRT outcomes. Methods: A systematic literature review was performed to identify RCTs and prospective observational studies of CRT from October 2008 through October 2020 that compared any image-guided versus any non-image-guided approach for LV lead placement. Two independent reviewers screened titles and abstracts then reviewed full text of identified studies. One reviewer abstracted data and a second over-read for accuracy. Meta-analyses were performed for NYHA class improvement and changes in LV end systolic volume, LV end diastolic volume, and LVEF using random effects models. Results: Of 5715 citations screened, 5 RCTs with a total of 818 patients met the inclusion criteria. Speckle tracking echocardiography (STE) was the primary imaging method in all studies, but 3 studies included CT, CMR, SPECT, and/or PET in addition to STE. The comparator arms were standard of care in 4 studies and an electrically guided approach in one. Mean age ranged from 66 to 72 years, 76% were male, and 53% had ischemic cardiomyopathy. Among 747 evaluable patients, concordant or adjacent LV lead was achieved in 348 of 386 (90%) in the image-guided arm and 291 of 361 (81%) in the control arm. At 6 months, the image-guided approach was statistically significantly associated with a NYHA class improvement, but no other statistically significant differences were found (Figure). Conclusion: An image-guided CRT approach was associated with significant Improvement in NYHA class but not in echocardiographic measures, possibly due to small sample size and high LV concordance with area of latest activation in both study arms - the latter of which merits further investigation.

Introduction: CRT outcomes with image-guided left ventricular (LV) lead placement within the LV segment of latest mechanical activation have been assessed in several randomized controlled trials (RCTs) with equivocal results, possibly due to variable achievement of concordant LV lead placement in the image-guided and comparator arms. We conducted meta-analyses to assess CRT outcomes associated with concordant LV lead placement. Methods: A systematic literature review was performed to identify RCTs and prospective observational studies of CRT from October 2008 through October 2020 that reported outcomes in those with LV lead placement at or adjacent to the site of latest mechanical activation (concordant) versus those with LV lead placement distant to the site of latest mechanical activation (discordant) as determined by any imaging method. Two independent reviewers screened titles and abstracts then reviewed full text for inclusion/exclusion. One reviewer abstracted data and a second over-read for accuracy. Meta-analyses for death, death or HF hospitalization, and changes in LVESV and LVEF were performed using random effects models. Results: Among 5715 citations identified, 9 papers from 8 studies (including 4 RCTs) were selected that included 1004 patients with concordant LV lead placement and 380 with discordant LV lead placement. Mean patient age ranged from 66 to 68 years, 82% were male, and 64% had ischemic cardiomyopathy. Segment of latest activation was determined by speckle tracking echocardiography (STE) in 7 (88%) studies. Meta-analyses demonstrated statistically significant lower all-cause mortality or HF hospitalization and reduction in LVESV with a concordant LV lead (Figure). There were trends toward lower all-cause mortality and increased LVEF. Conclusion: A concordant LV lead, as determined primarily by STE, was associated with better CRT outcomes. Further study of feasible methods to achieve concordance in clinical practice is needed.

Introduction: CRT optimizations has the potential to improve the 30% non-response rate. Randomized trials (RCTs) comparing device and echo-guided CRT optimization have been overall small and results have been conflicting. Methods: We searched the EMBASE and MEDLINE databases from January 2008 through September 2020 for RCTs and prospective observational studies that randomized patients to either echo-guided or device-based CRT optimization. Included studies had to report on at least one of the following outcomes of interest: all-cause mortality, heart failure hospitalization (HFH), NYHA class improvement, mean EF at follow up, LVEDD, 6MWD, and QoL. A meta-analyses on the outcomes of interest was performed using random effects models. Results: We included seven RCTs representing a total of 2,730 patients. Of those, 1,113 patients were randomized to echo-guided optimization, and 1,617 were randomized to device-based optimization. The mean age of patients was 64.5 years, and they were predominantly men (60%). In the device-based optimization group, there was 93 deaths (5.7%) and 142 HFH (5.1%). In the echo-guided optimization group, there was 57 deaths (10.2%) and 112 HFH (12.4%). On random effects meta-analysis, the device-based optimization group had a lower rate of HFH compared with the echo-guided optimization group (OR 0.81, 95% CL 0.70-0.95, Figure). However, differences in the following outcomes between the two groups were not statistically significant: all-cause mortality, mean follow up EF, LVEDD, NYHA class improvement, 6MWD improvement range or QoL. Conclusions: This meta-analysis suggests that echo-guided optimization of CRT is equivalent to device-based optimization in relation to the clinical outcomes of death, EF, LVEDD, NYHA and 6MWD but suggests that device-related optimization could reduce HFH. The latter merits further investigation in relation to different device-base optimization algorithms.

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.

There has been sustained focus on the secondary prevention of coronary heart disease and heart failure; yet, apart from stroke prevention, the evidence base for the secondary prevention of atrial fibrillation (AF) recurrence, AF progression, and AF‐related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced‐based secondary prevention strategies. We report on a National Heart, Lung, and Blood Institute virtual workshop directed at identifying knowledge gaps and research opportunities in the secondary prevention of AF. Once AF has been detected, lifestyle changes and novel models of care delivery may contribute to the prevention of AF recurrence, AF progression, and AF‐related complications. Although benefits seen in small subgroups, cohort studies, and selected randomized trials are impressive, the widespread effectiveness of AF secondary prevention strategies remains unknown, calling for development of scalable interventions suitable for diverse populations and for identification of subpopulations who may particularly benefit from intensive management. We identified critical research questions for 6 topics relevant to the secondary prevention of AF: (1) weight loss; (2) alcohol intake, smoking cessation, and diet; (3) cardiac rehabilitation; (4) approaches to sleep disorders; (5) integrated, team‐based care; and (6) nonanticoagulant pharmacotherapy. Our goal is to stimulate innovative research that will accelerate the generation of the evidence to effectively pursue the secondary prevention of AF.