Cardiac implantable electronic device-induced tricuspid regurgitation: Implications and management.

Tricuspid regurgitation (TR) secondary to cardiac implantable electronic devices (CIEDs) has been well documented and is associated with worse cardiovascular outcomes. A variety of mechanisms have been proposed including lead-induced mechanical disruption of the tricuspid valvular or subvalvular apparatus and pacing-induced electrical dyssynchrony. Patient characteristics such as age, sex, baseline atrial fibrillation, and pre-existing TR have not been consistent predictors of CIED-induced TR. While two-dimensional echocardiography is helpful in assessing the severity of TR, three-dimensional echocardiography has significantly improved accuracy in identifying the etiology of TR and whether lead position contributes to TR. Three-dimensional echocardiography may therefore play a future role in optimizing lead positioning during implant to reduce the risk of CIED-induced TR. Optimal lead management strategies in addition to percutaneous interventions and surgery in alleviating TR are very important.

Atrial fibrillation and risk of adverse outcomes in heart failure with reduced, mildly reduced, and preserved ejection fraction: A systematic review and meta-analysis.

INTRODUCTION: Heart failure (HF) and atrial fibrillation (AF) frequently co-exist. Contemporary classification of HF categorizes it into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). Aggregate data comparing the risk profile of AF between these three HF categories are lacking. METHODS: We conducted a systematic review and meta-analysis aimed at determining any significant differences in AF-associated all-cause mortality, HF hospitalizations, cardiovascular mortality (CV), and stroke between HFrEF, HFmrEF, and HFpEF. A systematic search of PubMed, EMBASE, and Cochrane Library databases until February 28, 2023. Data were combined using DerSimonian-Laird random effects model. RESULTS: A total of 22 studies comprising 248 323 patients were retained: HFrEF 123 331 (49.7%), HFmrEF 40 995 (16.5%), and HFpEF 83 997 (33.8%). Pooled baseline AF prevalence was 36% total population, 30% HFrEF, 36% HFmrEF, and 42% HFpEF. AF was associated with a higher risk of all-cause mortality in the total population with pooled hazard ratio (HR) = 1.13 (95% confidence interval [CI] = 1.07-1.21), HFmrEF (HR = 1.25, 95% CI = 1.05-1.50) and HFpEF (HR = 1.16, 95% CI = 1.09-1.24), but not HFrEF (HR = 1.03, 95% CI = 0.93-1.14). AF was associated with a higher risk of HF hospitalizations in the total population (HR = 1.29, 95% CI = 1.14-1.46), HFmrEF (HR = 1.64, 95% CI = 1.20-2.24), and HFpEF (HR = 1.46, 95% CI = 1.17-1.83), but not HFrEF (HR = 1.01, 95% CI = 0.87-1.18). AF was only associated with CV in the HFpEF subcategory but was associated with stroke in all three HF subtypes. CONCLUSIONS: AF appears to be associated with a higher risk of all-cause mortality and HF hospitalization in HFmrEF and HFpEF. With these findings, the paucity of data and treatment guidelines on AF in the HFmrEF subgroup becomes even more significant and warrant further investigations.

A divergent one-pot thiol-Michael strategy to create ß-thiophene-fused porphyrins.

A divergent one-pot domino strategy for the synthesis of nickel(II) and copper(II) ß-thiophene-fused 5,10,15,20-tetraarylporphyrins was developed through a thiol-Michael addition of thioglycolic/thiolactic acid to the corresponding 2-iminoporphyrins, formed in situ after the reaction of nickel(II) and copper(II) 2-formyl-5,10,15,20-tetraarylporphyrins with sterically hindered tert-butylamine in 1,2-dichloroethane at 80 °C. Interestingly, the reaction of 2-formylporphyrins with comparatively less sterically hindered primary amines and thioglycolic acid afforded a mixture of ß-substituted porphyrinic thiazolidinones and ß-thiophene-fused porphyrins. A similar one-pot thiol-Michael protocol was applied to construct a novel free-base thieno[2,3-b]-meso-tetrakis(4-methoxyphenyl)porphyrin, which underwent zinc insertion by using zinc acetate in a CHCl3-MeOH mixture and afforded zinc(II) ß-thiophene-fused meso-tetrakis(4-methoxyphenyl)porphyrin in an appreciable isolated yield. On photophysical evaluation, these new porphyrins displayed a modest bathochromically shifted electronic absorption in contrast to meso-tetraarylporphyrin building blocks.

Evolution and prognosis of tricuspid and mitral regurgitation following cardiac implantable electronic devices: a systematic review and meta-analysis.

AIMS: Significant changes in tricuspid regurgitation (TR) and mitral regurgitation (MR) post-cardiac implantable electronic devices (CIEDs) are increasingly recognized. However, uncertainty remains as to whether the risk of CIED-associated TR and MR differs with right ventricular pacing (RVP) via CIED with trans-tricuspid RV leads, compared with cardiac resynchronization therapy (CRT), conduction system pacing (CSP), and leadless pacing (LP). The study aims to synthesize extant data on risk and prognosis of significant post-CIED TR and MR across pacing strategies. METHODS AND RESULTS: We searched PubMed, EMBASE, and Cochrane Library databases published until 31 October 2023. Significant post-CIED TR and MR were defined as ≥ moderate. Fifty-seven TR studies (n = 13 723 patients) and 90 MR studies (n = 14 387 patients) were included. For all CIED, the risk of post-CIED TR increased [pooled odds ratio (OR) = 2.46 and 95% CI = 1.88-3.22], while the risk of post-CIED MR reduced (OR = 0.74, 95% CI = 0.58-0.94) after 12 and 6 months of median follow-up, respectively. Right ventricular pacing via CIED with trans-tricuspid RV leads was associated with increased risk of post-CIED TR (OR = 4.54, 95% CI = 3.14-6.57) and post-CIED MR (OR = 2.24, 95% CI = 1.18-4.26). Binarily, CSP did not alter TR risk (OR = 0.37, 95% CI = 0.13-1.02), but significantly reduced MR (OR = 0.15, 95% CI = 0.03-0.62). Cardiac resynchronization therapy did not significantly change TR risk (OR = 1.09, 95% CI = 0.55-2.17), but significantly reduced MR with prevalence pre-CRT of 43%, decreasing post-CRT to 22% (OR = 0.49, 95% CI = 0.40-0.61). There was no significant association of LP with post-CIED TR (OR = 1.15, 95% CI = 0.83-1.59) or MR (OR = 1.31, 95% CI = 0.72-2.39). Cardiac implantable electronic device-associated TR was independently predictive of all-cause mortality [pooled hazard ratio (HR) = 1.64, 95% CI = 1.40-1.90] after median of 53 months. Mitral regurgitation persisting post-CRT independently predicted all-cause mortality (HR = 2.00, 95% CI = 1.57-2.55) after 38 months. CONCLUSION: Our findings suggest that, when possible, adoption of pacing strategies that avoid isolated trans-tricuspid RV leads may be beneficial in preventing incident or deteriorating atrioventricular valvular regurgitation and might reduce mortality.

Admissions for posttransplant lymphoproliferative disorder: a 9-year longitudinal analysis of the National (Nationwide) Inpatient Sample.

Background: Posttransplant lymphoproliferative disorder (PTLD), a term that encompasses a wide array of malignancies that occur after transplant, can be one of the most devastating transplant complications. While there have been major advancements in care, especially after the landmark PTLD-1 trial in 2012, there is a paucity of information on hospitalizations for PTLD and the changes in hospitalizations over time. Methods: This retrospective cohort study used the National Inpatient Sample to identify hospitalizations for PTLD that occurred between 2009 and 2018. We extracted data for hospitalizations with a primary or secondary diagnosis of PTLD and examined a range of variables, including age, gender, race, hospital type, hospital location, and disposition status. We also collected data on hospital region, median household income, insurance status, and bed size. Results: There was a statistically significant increase in the number of hospitalizations from 2009 to 2019 and an increasing rate of hospitalizations over the study period. Hypertension, electrolyte imbalances, renal failure, and anemia were among the most common comorbidities. We found an increased mortality rate, but this was not statistically significant. Conclusion: Our study provides insight into the changes in hospitalizations for PTLD over nearly a decade, showing an increase in hospitalizations and reports of comorbidities.

The potential of artificial intelligence to revolutionize health care delivery, research, and education in cardiac electrophysiology.

The field of electrophysiology (EP) has benefited from numerous seminal innovations and discoveries that have enabled clinicians to deliver therapies and interventions that save lives and promote quality of life. The rapid pace of innovation in EP may be hindered by several challenges including the aging population with increasing morbidity, the availability of multiple costly therapies that, in many instances, confer minor incremental benefit, the limitations of healthcare reimbursement, the lack of response to therapies by some patients, and the complications of the invasive procedures performed. To overcome these challenges and continue on a steadfast path of transformative innovation, the EP community must comprehensively explore how artificial intelligence (AI) can be applied to healthcare delivery, research, and education and consider all opportunities in which AI can catalyze innovation; create workflow, research, and education efficiencies; and improve patient outcomes at a lower cost. In this white paper, we define AI and discuss the potential of AI to revolutionize the EP field. We also address the requirements for implementing, maintaining, and enhancing quality when using AI and consider ethical, operational, and regulatory aspects of AI implementation. This manuscript will be followed by several perspective papers that will expand on some of these topics.

Leadless Ultrasound-Based Cardiac Resynchronization System in Heart Failure.

Importance: Approximately 40% of patients with heart failure (HF) who are eligible for cardiac resynchronization therapy (CRT) either fail to respond or are untreatable due to anatomical constraints. Objective: To assess the safety and efficacy of a novel, leadless, left ventricular (LV) endocardial pacing system for patients at high risk for a CRT upgrade or whose coronary sinus (CS) lead placement/pacing with a conventional CRT system failed. Design, Setting, and Participants: The SOLVE-CRT study was a prospective multicenter trial, enrolling January 2018 through September 2022, with follow-up in March 2023. Data were analyzed from DATE MONTH, YEAR, through DATE MONTH, YEAR. The trial combined data from an initial randomized, double-blind study (n = 108) and a subsequent single-arm part (n = 75). It took place at 36 centers across Australia, Europe, and the US. Participants were nonresponders, previously untreatable (PU), or high-risk upgrades (HRU). All participants contributed to the safety analysis. The primary efficacy analysis (n = 100) included 75 PU-HRU patients from the single-arm part and 25 PU-HRU patients from the randomized treatment arm. Interventions: Patients were implanted with the WiSE CRT System (EBR Systems) consisting of a leadless LV endocardial pacing electrode stimulated with ultrasound energy delivered by a subcutaneously implanted transmitter and battery. Main Outcomes and Measures: The primary safety end point was freedom from type I complications. The primary efficacy end point was a reduction in mean LV end systolic volume (LVESV). Results: The study included 183 participants; mean age was 68.1 (SD, 10.3) years and 141 were male (77%). The trial was terminated at an interim analysis for meeting prespecified stopping criteria. In the safety population, patients were either New York Heart Association Class II (34.6%) or III (65.4%). The primary efficacy end point was met with a 16.4% (95% CI, -21.0% to -11.7%) reduction in mean LVESV (P = .003). The primary safety end point was met with an 80.9% rate of freedom from type I complications (P < .001), which included 12 study device system events (6.6%), 5 vascular events (2.7%), 3 strokes (1.6%), and 7 cardiac perforations which mostly occurred early in the study (3.8%). Conclusions and Relevance: The SOLVE-CRT study has demonstrated that leadless LV endocardial pacing with the WiSE CRT system is associated with a reduction in LVESV in patients with HF. This novel system may represent an alternative to conventional CRT implants in some HF patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT0292203.

Cardiac Contractility Modulation for Heart Failure: Current and Future Directions.

Cardiac contractility modulation (CCM) is a Food and Drug Administration-approved device-based therapy for patients with heart failure. The system delivers biphasic electric stimulation to the ventricular myocardium during the absolute refractory period to augment left ventricular contraction. CCM therapy promotes acute and chronic changes at the cellular level, leading to favorable remodeling throughout the myocardium. CCM improves quality of life, New York Heart Association class, left ventricular ejection fraction, peak oxygen uptake, and the composite end point of cardiovascular death and heart failure hospitalizations. This review will focus on the biological basis, indications, and evidence for CCM, as well as the future applications of this technology.