Nishaki Kiran Mehta

Background: Vascular aging contributes to dementia risk, yet clinically interpretable markers for risk stratification remain limited. Estimated pulse wave velocity (ePWV), derived from age and mean arterial pressure, provides an accessible surrogate of arterial stiffness. We evaluated whether baseline ePWV identifies an interpretable threshold for probable dementia and distinct vascular aging phenotypes.Methods: We conducted a post-hoc analysis of SPRINT-MIND including 8,536 participants free of dementia at baseline. Baseline ePWV was calculated using age and mean arterial pressure. The primary outcome was incident probable dementia adjudicated during follow-up. Associations between ePWV and dementia risk were assessed using spline-based and quartile-based Cox proportional hazards models. Model discrimination was evaluated using Harrell’s C-index.Results: During follow-up, 323 participants developed probable dementia. Dementia risk was lowest at lower ePWV values and increased beyond approximately 10.7 m/s, identifying an interpretable risk threshold. Risk was concentrated in the highest ePWV quartile, consistent with a threshold-like pattern rather than a uniform linear gradient. In exploratory analyses, longitudinal clustering identified distinct ePWV trajectory phenotypes over 24 months.Conclusions: Baseline ePWV identified an interpretable dementia risk threshold and distinct vascular aging phenotypes in SPRINT-MIND. These findings support ePWV as a clinically interpretable marker of vascular aging that may aid dementia risk stratification.

Atrial fibrillation (AF) is the most common tachyarrhythmia worldwide. Accompanying the increasing age of the general population, as well as an increase in underlying cardiovascular disease in the United States, is an explosive rise in the incidence and prevalence of this condition. We reviewed observational cohort studies, systematic reviews, meta-analyses, and randomized controlled trials (RCTs) to determine both underlying risk factors and treatment of AF, with particular focus on comorbid conditions influencing treatment success. Numerous studies have demonstrated a reciprocal relationship between maladaptive cardiac remodeling and AF, with the suggestion that aggressive management of both AF itself and resultant cardiovascular disease can lead to reversal of both conditions. Ultimately, many modifiable risk factors for AF exist, with treatment delays associated with a shift towards these conditions becoming unmodifiable. While a large area of focus for AF research has been on determining the optimal pharmacological strategy (i.e., rate versus rhythm control), results have been mixed, with emerging guidelines now pointing towards a flexible treatment strategy that allows for consideration of patient comorbid conditions, medication ease and affordability, and patient preference. Treatment of AF also includes prevention of thromboembolic events. In recent years, novel strategies for surgical or physical occlusion of the left atrial appendage (LAA) with devices such as the Watchman have arisen. Multiple large RCTs have demonstrated the safety and efficacy of these devices, but consideration must be given towards the patient’s bleeding risk, as short-term courses of blood thinners are still considered the standard of care. Finally, emerging therapies for AF include novel drug combinations, neuromodulation devices, and potentially glucagon-like peptide receptor-1 (GLP-1) agonist medications for reduction in overall metabolic disease.

Atrial fibrillation (AF) is the most common tachyarrhythmia worldwide. Accompanying the increasing age of the general population, as well as an increase in underlying cardiovascular disease in the United States, is an explosive rise in the incidence and prevalence of this condition. We reviewed observational cohort studies, systematic reviews, meta-analyses, and randomized controlled trials (RCTs) to determine both underlying risk factors and treatment of AF, with particular focus on comorbid conditions influencing treatment success. Numerous studies have demonstrated a reciprocal relationship between maladaptive cardiac remodeling and AF, with the suggestion that aggressive management of both AF itself and resultant cardiovascular disease can lead to reversal of both conditions. Ultimately, many modifiable risk factors for AF exist, with treatment delays associated with a shift towards these conditions becoming unmodifiable. While a large area of focus for AF research has been on determining the optimal pharmacological strategy (i.e., rate versus rhythm control), results have been mixed, with emerging guidelines now pointing towards a flexible treatment strategy that allows for consideration of patient comorbid conditions, medication ease and affordability, and patient preference. Treatment of AF also includes prevention of thromboembolic events. In recent years, novel strategies for surgical or physical occlusion of the left atrial appendage (LAA) with devices such as the Watchman have arisen. Multiple large RCTs have demonstrated the safety and efficacy of these devices, but consideration must be given towards the patient’s bleeding risk, as short-term courses of blood thinners are still considered standard of care. Finally, emerging therapies for atrial fibrillation include novel drug combinations, neuromodulation devices, cryo-balloon ablation, and potentially glucagon-like peptide receptor-1 (GLP-1) agonist medications for reduction in overall metabolic disease.

Background Hiatal hernia (HH) is associated with up to a 19-fold increased risk of atrial fibrillation (AF). However, its impact on clinical outcomes in AF patients receiving rhythm control therapy remains unclear. Methods Using the TriNetX research network, we identified adult patients with AF who underwent rhythm control therapy, including antiarrhythmic drugs, cardioversion, or catheter ablation. Patients were categorized into two cohorts based on the presence or absence of HH. Clinical outcomes, including ischemic stroke, major bleeding, all-cause readmission, and heart failure (HF) exacerbation, were assessed at both 1-year and 5-year follow-up. Further subanalyses were performed to compare patients with HH who underwent surgical repair with those who did not, as well as patients with HH who underwent repair with those without HH. Propensity score matching (PSM) was applied separately to each cohort to adjust for differences in age, sex, comorbidities, and medication use, ensuring balanced baseline characteristics. Results We identified 2,348,576 patients with AF who underwent rhythm control strategies. Among them, 246,010 (10.5%; mean age 74.2 ± 11.0 years; 51.2% female) had HH, while 2,102,566 (89.5%; mean age 70.8 ± 12.7 years; 40.0% female) did not. After PSM, 243,376 patients were included in each cohort. The presence of HH was associated with significantly higher odds of ischemic stroke (OR 1.11, 95% CI: 1.09–1.13 at 1 year; OR 1.14, 95% CI: 1.13–1.16 at 5 years), major bleeding (OR 1.90, 95% CI: 1.86–1.93 at 1 year; OR 1.78, 95% CI: 1.75–1.80 at 5 years), and all-cause readmission (OR 1.11, 95% CI: 1.10–1.12 at 1 year; OR 1.16, 95% CI: 1.15–1.18 at 5 years) compared to patients without HH (all p < 0.01). HH was not associated with HF exacerbation at 1 year (OR 1.00, 95% CI: 0.99–1.01, p = 0.68), but a modest increase was observed at 5 years (OR 1.03, 95% CI: 1.02–1.04, p < 0.01). Among patients with symptomatic HH, surgical repair was associated with improved outcomes at 5-year follow-up compared to no repair. An additional subanalysis showed that patients with HH who underwent surgical repair had similar outcomes to those without HH. Conclusion In patients with AF undergoing rhythm control, the presence of HH is associated with poorer clinical outcomes. Among patients with AF and HH, surgical repair is associated with improved outcomes compared to no repair. Furthermore, HH repair is associated with outcomes similar to those observed in patients without HH, suggesting a potential benefit of surgical intervention in this population. Graphical Abstract

Background Electrographic flow (EGF) mapping allows for the near real-time visualization of atrial wavefront propagation. Two factors have been found to be associated with higher rates of atrial fibrillation (AF) recurrence: presence of active extra-pulmonary vein (PV) sources and low electrographic flow consistency (EGFC) representing chaotic flow and abnormal atrial substrate. Based on these characteristics, EGF phenotypes have been identified: Type I patients have no sources + high EGFC, Type II have sources + high EGFC, Type III have sources + low EGFC, and Type IV have no sources + low EGFC. Objective Determine the sex differences in EGF phenotypes and post-ablation outcomes. Methods Patients were pooled from three prospective clinical trials: FLOW-AF, EVAL-AF, and the AF-FLOW Global Registry. From these trials, 104 persistent AF (PeAF) or long-standing PeAF patients underwent EGF mapping in 5 standardized, biatrial basket positions. Phenotyping into one of the 4 types was performed from post-PVI maps, and patients were followed for up to 12 months post-procedure, which included PVI-only and PVI + EGF-guided source ablation procedures. Outcomes were compared by chi-square tests, z-tests of proportions, logistic regression, and cox proportional models. Results There were 30 (29%) female patients with mean age 70 ± 8 years and 74 (71%) males with mean age 64 ± 10 years. There was no significant difference in left atrial dimension, left ventricular ejection fraction, or number of prior ablations between men and women. Men and women had distinct phenotype distributions (p = 0.007). Women had more sources and higher EGFC so were more likely than men to present as Type II (43% vs. 20%, p = 0.016), including when controlling for confounders (aOR 3.17, p = 0.024). Outcomes of these Type II patients were most improved by PVI + EGF-guided ablation when compared to PVI-only (91% vs. 50%, p = 0.038) without differences in intra-phenotype responsiveness to treatment by sex or intragroup hazard ratios by sex. Trends in phenotype differences of women vs. men were also present among those with other factors that increased CHA₂DS₂-VASc scores generally. Conclusions Female patients with PeAF are more likely to have extra-PV sources but healthy underlying substrate (Type II), which responds favorably to PVI + targeted source ablation. Ablation strategies should consequently target an individual’s mechanism of disease. Trial registration numbers FLOW-AF: NCT04473963, FLOW EVAL-AF: NCT06260670, AF-FLOW Global Registry: NCT05481359. Graphical abstract

Background: Obesity is an important risk factor associated with atrial fibrillation (AF). The impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on recurrent AF among patients undergoing catheter ablation is not well described. Objective: This study aimed to evaluate the effect of GLP‐1 RA on the recurrence of AF among obese patients after catheter ablation. Methods: Utilizing the TriNetX research network, we identified patients aged over 18 with obesity (BMI ≥ 30) who underwent AF ablation from January 1, 2015, to December 1, 2022, using Current Procedural Terminology codes. Patients were categorized based on their baseline GLP‐1 RA use. Through propensity‐score matching, each cohort comprised 1558 patients. The primary outcome encompassed a composite of cardioversion, initiation of new antiarrhythmic drug (AAD) therapy, or redo AF ablation. Additional outcomes during the 12‐month follow‐up included AF readmission, heart failure readmissions, readmissions due to ischemic stroke, and mortality, with a separate analysis done for patients with BMI > 40. Results: GLP‐1 RA use in patients with obesity undergoing AF ablation was linked to a significantly reduced risk of cardioversion, new AAD therapy, and the need for redo AF ablation (hazard ratio [HR] 0.72 [0.65–0.80]; p < 0.001). At 12 months, individuals on GLP‐1 agonists exhibited a lower likelihood of mortality (HR 0.61 [0.40–0.93]; p < 0.001). Although all other secondary outcomes were lower in the GLP‐1 RA group, there was no significant difference in ischemic stroke between the groups. These results were consistent among patients with BMI > 40, although apart from ischemic stroke, there was no difference in mortality between the two groups. Conclusion: The utilization of GLP‐1 RA in individuals with obesity is linked to a decreased likelihood of arrhythmia recurrence following AF ablation, leading to a reduced requirement for cardioversion, AAD therapy, or redo AF ablation.