Mortality, Hospitalization, and Cardiac Interventions in Patients With Atrial Fibrillation Aged <65 Years.

BACKGROUND: The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear. METHODS: Adult (n=67 221; mean age, 72.4±12.3 years; and 45% female) patients with AF evaluated at the University of Pittsburgh Medical Center between January 2010 and December 2019 were studied. Hospital system-wide electronic health records and administrative data were utilized to ascertain RFs, comorbidities, and subsequent hospitalization and cardiac interventions. The association of AF with all-cause mortality among those aged <65 years was analyzed using an internal contemporary cohort of patients without AF (n=918 073). RESULTS: Nearly one-quarter (n=17 335) of the cohort was aged <65 years (32% female) with considerable cardiovascular RFs (current smoker, 16%; mean body mass index, 33.0±8.3; hypertension, 55%; diabetes, 21%; heart failure, 20%; coronary artery disease, 19%; and prior ischemic stroke, 6%) and comorbidity burden (chronic obstructive pulmonary disease, 11%; obstructive sleep apnea, 18%; and chronic kidney disease, 1.3%). Over mean follow-up of >5 years, 2084 (6.7%, <50 years; 13%, 50-65 years) patients died. The proportion of patients with >1 hospitalization for myocardial infarction, heart failure, and stroke was 1.3%, 4.8%, and 1.1% for those aged <50 years and 2.2%, 7.4%, and 1.1% for the 50- to 65-year subgroup, respectively. Multiple cardiac and noncardiac RFs were associated with increased mortality in younger patients with AF with heart failure and hypertension demonstrating significant age-related interaction (P=0.007 and P=0.013, respectively). Patients with AF aged <65 years experienced significantly worse survival compared with comorbidity-adjusted patients without AF (males aged <50 years and hazard ratio, 1.5 [95% CI, 1.24-1.79]; 50-65 years and hazard ratio, 1.3 [95% CI, 1.26-1.43]; females aged <50 years and hazard ratio, 2.4 [95% CI, 1.82-3.16]; 50-65 years and hazard ratio, 1.7 [95% CI, 1.6-1.92]). CONCLUSIONS: Patients with AF aged <65 years have significant comorbidity burden and considerable long-term mortality. They are also at a significantly increased risk of hospitalization for heart failure, stroke, and myocardial infarction. These patients warrant an aggressive focus on RF and comorbidity evaluation and management.

"Window of Opportunity" in Ocular Graft-Versus-Host Disease Treatment: Results of a Longitudinal Study and Case Reports.

OBJECTIVE: To perform a longitudinal study for determining the development of ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) and report cases that illustrate the "window of opportunity" concept in oGVHD treatment. METHODS: Patients (n=61) were examined at prescheduled clinic visits before HSCT and three-month intervals after HSCT for 2 years. The presence or absence of oGVHD was determined using the international chronic oGVHD consensus group diagnostic criteria. Ocular surface washings (OSW) were obtained at each visit and analyzed for cytokine levels. RESULTS: In the longitudinal study, 26.2% (n=16; progressed group) developed either probable (11.5%, n=7) or definite oGVHD (14.8%, n=9). In the progressed group, clinically significant changes in signs (corneal staining and Schirmer I test) and symptoms at the post-HSCT visit as compared with the pre-HSCT visit occurred at 9 months. Significant differences in clinical signs and symptoms (whether average post-HSCT values or changes in values over pre-HSCT levels) between the progressed and nonprogressed groups occurred at a 9-month visit or later. In the progressed group, 55.6% of eyes that had negative matrix metalloproteinase 9 (MMP-9) test at pre-HSCT turned MMP-9 positive at 3 to 6 months post-HSCT. In the progressed group, interleukin 8 levels in OSW were significantly increased at 6 months post-HSCT. In the case reports, the "window of opportunity" was detected by MMP-9 turning positive, early corneal staining, interleukin 8 increase in OSW, and peripheral corneal epithelial thinning, which resolved with treatment initiation. CONCLUSIONS: A "window of opportunity" exists before patients developing symptomatic tear-deficient dry eye after HSCT for initiating treatment that may preempt oGVHD development; however, larger-scale longitudinal studies are needed for definitive recommendations.

Heart Rate at Rest and Incident Atrial Fibrillation in Patients With Diastolic Dysfunction.

Diastolic dysfunction (DD) is associated with incident atrial fibrillation (AF). The influence of heart rate at rest (RHR) on incident AF in patients with DD has not been investigated. The goal of this study is to assess the influence of RHR on incident AF in patients with DD. Patients from a large health system with no previous history of AF, a left ventricular ejection fraction ≥50%, and documented DD on echocardiography were divided into quartiles (<66, 66 to 76, 77 to 91, >91 beats per minute) based on RHR. Incident AF was estimated using AF hospitalization during follow-up. Hazard ratios (HR) for AF hospitalization and all-cause death were calculated with a Cox proportional hazards model. A total of 19,046 patients were analyzed. Over a median follow-up of 42.2 months, 742 (3.9%) patients were hospitalized for AF. Both slower and faster RHR were associated with increased risk of AF hospitalization (HR 1.40, confidence interval [CI] 1.14 to 1.71, p = 0.001, HR 1.23, CI 0.99 to 1.53, p = 0.06 and HR 1.72, CI 1.38 to 2.14, p <0.001, for quartiles 1, 2, and 4, respectively), suggesting a J-shaped relation. Progressive increase in all-cause death was noted with faster RHR (HR1.19 per quartile increase, CI 1.16 to 1.22, p <0.001). These results persisted after adjustment for age, cardiovascular co-morbidities, grade of DD, and ß-blocker use. In conclusion, this large, real-world analysis indicates increased risk of incident AF with slower and faster RHR in patients with DD. Randomized trials are needed to evaluate the potential of RHR modification to mitigate the risk of incident AF.

Age and Aspirin Dosing in Secondary Prevention of Atherosclerotic Cardiovascular Disease.

BACKGROUND: In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease. METHODS AND RESULTS: In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow-up: 26.2 months; interquartile range: 19.0-34.9 months). Median age was 67.6 years (interquartile range: 60.7-73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01-1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82-1.10]). The age-dose interaction was not significant (P=0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points (P>0.05 for all). CONCLUSIONS: Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.

Patient Outcomes by Ventricular Systolic and Diastolic Function.

BACKGROUND: Left ventricular dysfunction is characterized by systolic and diastolic parameters, leading to heart failure (HF) with reduced or preserved ejection fraction (EF), respectively. The goal of this study is to examine the impact of left ventricular systolic and diastolic dysfunction (DD) on patient outcomes. METHODS AND RESULTS: Two cohorts were used in this analysis: Cohort A included 136 455 patients with EF ≥50%, stratified by the presence and grade of DD. Cohort B included 16 850 patients with EF <50%, stratified by EF quartiles. Patients were followed to the end points of all-cause death and cardiovascular, HF, or cardiac arrest hospitalizations. Over a median follow-up of 3.42 years, 23 946 (16%) patients died and 31 113 (20%), 13 305 (9%), and 1269 (1%) were hospitalized for cardiovascular, HF, or cardiac arrest causes, respectively. With adjustment for comorbidities, the risk of all-cause mortality and of cardiovascular and HF hospitalizations increased steadily with increasing grade of DD in patients with normal EF, and even more so in patients with worsening EF. The risk of hospitalization for cardiac arrest in patients with grade III DD, however, was comparable to that of patients with EF <25% (hazard ratio, 1.00 [95% CI, 0.98-1.01]) and worse than that of patients in better EF quartiles. CONCLUSIONS: Although systolic dysfunction is associated with a greater risk of overall death and HF hospitalizations than DD, the risk of cardiac arrest in patients with grade II and III DD is comparable to that of patients with moderate and severe systolic dysfunction, respectively. Future studies are needed to examine treatment strategies than can improve these outcomes.

Recombinant Deoxyribonuclease I Eye Drops for Ocular Graft Versus Host Disease: Results of a Randomized Clinical Trial.

OBJECTIVE: We have previously shown that neutrophil extracellular traps (NETs) are present on the ocular surface of patients with ocular graft versus host disease (oGVHD), contributing to inflammation and surface disease. Therefore, we performed a clinical trial using deoxyribonuclease I (DNAase) eye drops to test the hypothesis that reducing the abundance of NETs from the ocular surface will reduce signs and symptoms of oGVHD. METHODS: A prospective, phase I or II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNAase (0.1%) eye drops four times daily for 8 weeks in patients with oGVHD (n=58). Intent-to-treat analysis was performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (ocular surface disease index [OSDI] score and corneal staining) between baseline and week 8. RESULTS: Tolerability and adverse events were similar in the vehicle and DNAase groups. Within the DNAase group (but not the vehicle group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 (3.50 [2.75; 5.00]) compared with baseline (5.00 [3.00; 7.00]). The OSDI score also showed a statistically significant clinically meaningful reduction of 18.4 (9.16; 33.1) ( P <0.001) at week 8 compared with baseline (45.5 [31.8; 50.0]) within the DNAase group. The proportion of eyes that had improvement in subjective global assessment (SGA) and mucous discharge was significantly greater in the DNAase group (55.6% and 57.7% at weeks 4 and 8, respectively; P <0.0001 at both time points) as compared with the vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively). CONCLUSIONS: Treatment of patients with oGVHD using DNAase eye drops is safe and demonstrates preliminary efficacy. Deoxyribonuclease I eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in patients with oGVHD.

Novel Management of Ocular Surface Inflammation in Patients With Ocular Graft-Versus-Host Disease in the Setting of Cataract Surgery.

PURPOSE: To report the outcomes of cataract surgery in patients with ocular graft-versus-host disease (oGVHD) using a novel preoperative immunomodulatory regimen in a collaborative subspecialty care setting. METHODS: Retrospective case series of patients with oGVHD who underwent cataract surgery using a novel preoperative immunomodulatory regimen in a collaborative care setting. A preoperative regimen consisting of pooled human immune globulin 1%, autologous serum 50%, and methylprednisolone 1% eye drops was prescribed. Outcome measures included visual acuity (VA), ocular surface disease index (OSDI) score, lissamine green staining, and complications with a minimum of 2 years of follow-up. RESULTS: Thirty-five eyes from 20 patients with oGVHD were studied. The mean age was 59 years (range 30-70 years). A healthy comparison group included 35 eyes from 24 patients with a mean age of 63 years (range 44-74 years). At the 2-year follow-up, the mean corneal staining score was 2.3/15, the mean OSDI score was 37.5, and the mean VA was 20/30 (logarithm of the minimal angle of resolution 0.17). The global complication rate was 2.8% at the last follow-up with no difference versus a healthy comparison group. CONCLUSIONS: A collaborative care model improving ocular surface health before cataract surgery with dry eye and cataract subspecialists can optimize outcomes in patients with oGVHD.

Graphical Presentations in Systemic Anticancer Treatment Network Meta-Analyses: A Systematic Review.

Network meta-analysis (NMA) draws conclusions about indirect comparisons of randomized clinical trials and is considered high-level evidence. Most NMA publications make use of network plots to portray results. Network plots are complex graphics that can have many visual attributes to portray useful information, such as node size, color, and graph layout. We analyzed the network plots from 162 NMAs of systemic anticancer therapy efficacy using a set of 16 attributes. Our review showed that the current state of network plot data visualizations within the NMA space lacks diversity and does not make use of many of the visual attributes available to convey information. More thoughtful design choices should be placed behind these important visualizations, which can carry clinical significance and help derive treatment plans for patients.

Optimizing nutrients from fly ash-amended soil through microbial-assisted phytoremediation using response surface methodology.

Nutrients are vital ingredients to boost plant health. The availability of nutrients is limited in fly ash (FA) waste to properly implement phytoremediation. The research explored the integration of microbes and treated wastewater irrigation in phytoremediation to provide the necessary nutrients for plant growth in fly ash-amended soils. The Box-Behnken method was used to design the experimental layout for the pot study. Response surface methodology (RSM) was applied as the optimization approach to model predictions for nutrient accumulation. The implemented pot study attained the highest morphological indicators with a plastochron index of 33.40, an absolute growth rate of 2.63 cm/day, and a leaf area of 2681.68 cm2 and attained maximum biomass of 24.91 g for the treatments that included a mid-range of the variables. The combination of FA 14.98%, microbial dose 4.07 mL, and treated wastewater as the irrigation source was found to be the optimized combination for nitrogen and phosphorus accumulation of 212.4 and 8.867 mg/L.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial.

OBJECTIVE: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. RESULTS: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). CONCLUSIONS: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.

Association of pre-left ventricular assist device defibrillator shocks for ventricular arrhythmia with clinical outcomes after left ventricular assist device implantation.

Background: Implantable cardioverter-defibrillation (ICD) shocks after left ventricular assist device therapy (LVAD) are associated with adverse clinical outcomes. Little is known about the association of pre-LVAD ICD shocks on post-LVAD clinical outcomes and whether LVAD therapy affects the prevalence of ICD shocks. Objectives: The purpose of this study was to determine whether pre-LVAD ICD shocks are associated with adverse clinical outcomes post-LVAD and to compare the prevalence of ICD shocks before and after LVAD therapy. Methods: Patients 18 years or older with continuous-flow LVADs and ICDs were retrospectively identified within the University of Pittsburgh Medical Center system from 2006-2020. We analyzed the association between appropriate ICD shocks within 1 year pre-LVAD with a primary composite outcome of death, stroke, and pump thrombosis and secondary outcomes of post-LVAD ICD shocks and ICD shock hospitalizations. Results: Among 309 individuals, average age was 57 ± 12 years, 87% were male, 80% had ischemic cardiomyopathy, and 42% were bridge to transplantation. Seventy-one patients (23%) experienced pre-LVAD shocks, and 69 (22%) experienced post-LVAD shocks. The overall prevalence of shocks pre-LVAD and post-LVAD were not different. Pre-LVAD ICD shocks were not associated with the composite outcome. Pre-LVAD ICD shocks were found to predict post-LVAD shocks (hazard ratio [HR] 5.7; 95% confidence interval [CI] 3.42-9.48; P <.0001) and hospitalizations related to ICD shocks from ventricular arrhythmia (HR 10.34; 95% CI 4.1-25.7; P <.0001). Conclusion: Pre-LVAD ICD shocks predicted post-LVAD ICD shocks and hospitalizations but were not associated with the composite outcome of death, pump thrombosis, or stroke at 1 year. The prevalence of appropriate ICD shocks was similar before and after LVAD implantation in the entire cohort.

Omics and Extreme Phenotyping Reveal Longitudinal Association Between Left Atrial Size and Pulmonary Vascular Resistance in Group 2 Pulmonary Hypertension.

BACKGROUND: Left heart disease is the most common cause of pulmonary hypertension (PH) and is frequently accompanied by increases in pulmonary vascular resistance. However, the distinction between phenotypes of PH due to left heart disease with a normal or elevated pulmonary vascular resistance-isolated postcapillary PH (IpcPH) and combined pre- and postcapillary PH (CpcPH), respectively-has been incompletely defined using unbiased methods. METHODS AND RESULTS: Patients with extremes of IpcPH versus CpcPH were identified from a single-center record of those who underwent right heart catheterization. Individuals with left ventricular ejection fraction <40% or with potential causes of PH beyond left heart disease were excluded. Medication usage in IpcPH and CpcPH was compared across Anatomical Therapeutic Chemical classes and identified vitamin K antagonists as the only medication with pharmacome-wide significance, being more commonly used in CpcPH and for an indication of atrial fibrillation in ≈90% of instances. Accordingly, atrial fibrillation prevalence was significantly higher in CpcPH in a phenome-wide analysis. Review of echocardiographic data most proximal to right heart catheterization revealed that left atrial diameter indexed to body surface area-known to be associated with atrial fibrillation-was increased in CpcPH regardless of the presence of atrial fibrillation. An independent cohort with serial right heart catheterizations and PH-left heart disease showed a significant positive correlation between change in left atrial diameter indexed to body surface area and change in pulmonary vascular resistance. CONCLUSIONS: Guided by pharmacomic and phenomic screens in a rigorously phenotyped cohort, we identify a longitudinal association between left atrial diameter indexed to body surface area and pulmonary vascular resistance with implications for the future development of diagnostic, prognostic, and therapeutic tools.

Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial.

Importance: Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations. Objective: To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes. Design, Setting, and Participants: This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15 076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023. Intervention: ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months. Main Outcomes and Measures: The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population. Results: Baseline aspirin formulation used in ADAPTABLE was self-reported for 10 678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07). Conclusions and Relevance: In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors.

Background The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high- versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22-1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91-2.22]). We found no interaction in the relative effectiveness and safety of high- versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high- versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.

Cardiovascular Hospitalizations and Resource Use Following Atrial Fibrillation Ablation.

Background Over the next few years, atrial fibrillation (AF)-related morbidity and costs will increase significantly. Thus, it is prudent to examine the impact of AF treatment on health care resource use. This study examined the impact of AF ablation on hospitalization, length of stay, and resource use for patients undergoing AF ablation in a multihospital system. Methods and Results In an observational analysis, outcomes of total, cardiovascular, and AF hospitalizations, emergency department visits, and length of stay were compared for 3417 patients between 12 months before and 24 months following AF ablation. Use of electrical cardioversions and antiarrhythmic use were also compared 1 year before to 2 years after AF ablation. There were fewer total (0.7±1.3 versus 0.3±0.7; P<0.001), cardiovascular (0.7±1.2 versus 0.2±0.6; P<0.001), and AF (0.6±1.1 versus 0.1±0.3; P<0.001) hospitalizations and emergency department visits (0.8±2.1 versus 0.4±0.9; P<0.001) per patient-year for the 2 years following AF ablation compared with 1 year before. Average length of stay per patient-year (1.4±7.9 versus 3.6±5.3 days; P<0.0001), the percentage of patients on antiarrhythmic therapy (21.2% versus 58.5%; P<0.0001), and those undergoing electrical cardioversions (16.1% versus 28.1%; P<0.0001) were lower 2 years following AF ablation versus 1 year before. Conclusions We noted a decrease in total, cardiovascular, and AF hospitalizations and health care resource use during the 2-year period after index AF ablation, compared with the 1 year before. AF ablation may portend a decline in patient morbidity and health care costs.

Targeted left ventricular lead positioning to the site of latest activation in cardiac resynchronization therapy: a systematic review and meta-analysis.

AIMS: Several studies have evaluated the use of electrically- or imaging-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT) recipients. We aimed to assess evidence for a guided strategy that targets LV lead position to the site of latest LV activation. METHODS AND RESULTS: A systematic review and meta-analysis was performed for randomized controlled trials (RCTs) until March 2023 that evaluated electrically- or imaging-guided LV lead positioning on clinical and echocardiographic outcomes. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization, and secondary endpoints were quality of life, 6-min walk test (6MWT), QRS duration, LV end-systolic volume, and LV ejection fraction. We included eight RCTs that comprised 1323 patients. Six RCTs compared guided strategy (n = 638) to routine (n = 468), and two RCTs compared different guiding strategies head-to-head: electrically- (n = 111) vs. imaging-guided (n = 106). Compared to routine, a guided strategy did not significantly reduce the risk of the primary endpoint after 12-24 (RR 0.83, 95% CI 0.52-1.33) months. A guided strategy was associated with slight improvement in 6MWT distance after 6 months of follow-up of absolute 18 (95% CI 6-30) m between groups, but not in remaining secondary endpoints. None of the secondary endpoints differed between the guided strategies. CONCLUSION: In this study, a CRT implantation strategy that targets the latest LV activation did not improve survival or reduce heart failure hospitalizations.

Primary orbital yolk sac tumor in an infant: A rare entity.

We report a case of pure orbital yolk sac tumor (YST) in an 11-month-old infant, which is a rare entity. The child presented with progressive painless swelling of the right eye and on examination had proptosis, chemosis, and lid edema. Systemic examination was within normal limits. Magnetic resonance imaging (MRI) orbit revealed a lobulated heterogeneously enhancing right retroocular mass extending up to the orbital apex, displacing the optic nerve and eroding the medial orbital wall. Biopsy of the lesion revealed pure YST histology. Serum alpha-fetoprotein (AFP) was markedly raised at 76900 ng/mL. She was started on infant bleomycin etoposide cisplatin (BEP) chemotherapy protocol. There was a good clinical and radiological response. A high index of malignancy is required in young children presenting with orbital proptosis. A multidisciplinary approach and early intervention are essential to save both vision and life.