Gerberi, Dana

Background The natural history of asymptomatic moderate or severe aortic regurgitation (AR) remains uncertain, with conflicting reports about its progression and surgical timing. We aimed to quantify adverse outcomes under conservative management and evaluate the association of aortic valve replacement/repair (AVR) with mortality. Methods Systematic searches (inception–July 2025) identified cohort studies of asymptomatic moderate/severe AR. Random-effects models estimated pooled incidence rates of adverse events; fixed-effects models were used for hazard ratios (HRs) of AVR vs conservative management. Results Twenty-seven studies (4720 patients; mean age 49 years; mean follow-up 3.9 years) were included. Pooled incidence rates per 100 person-years were 1.75 (95% CI 1.27 to 2.41) for all-cause mortality, 1.29 for cardiac death, 0.29 for sudden death, 4.30 for new symptoms and 7.01 for AVR. Asymptomatic low left ventricular ejection fraction occurred in only 0.9 per 100 person-years. Mortality rates were more than double those of the general population across age groups—2.45 (1.90 to 3.18) per 100 person-years for cohorts with mean age ≥50 years versus 0.59 (0.29 to 1.21) for younger cohorts. Early AVR was associated with lower mortality (pooled HR 0.33; 95% CI 0.30 to 0.37). Conclusion Asymptomatic moderate/severe AR carries significant excess mortality irrespective of age, contradicting its historically benign reputation. Given the rarity of asymptomatic LV dysfunction, earlier intervention guided by more sensitive markers of LV damage may improve outcomes, although heterogeneity and study quality warrant cautious interpretation. PROSPERO registration number CRD42024522683.

ABSTRACTBackgroundEsophageal‐pericardial fistula (EPF) is rare with an incidence of 0.016%–0.04%. With novel procedures involving intracardiac or esophageal instrumentation in the last few decades, including atrial fibrillation (AF) ablation, further understanding of this unique entity is warranted. In this systematic review, we summarize the etiology, diagnostic features, management, and outcomes of EPF.MethodsA librarian conducted a systematic literature review of case reports/series describing adults diagnosed with EPF through 7 major databases/registries from inception to 7/30/2024.ResultsOne hundred twenty patients from 115 papers met the inclusion criteria. Median age(IQR) was 57(44–67) years, with a male predominance (73.7%). The primary etiology of EPF shifted from benign esophageal diseases before 2000 to AF ablation on/after 2000. Median time(IQR) from AF ablation to EPF presentation/diagnosis was 17(13–23) days. Chest pain (70.8%) and pneumopericardium (90.0%) were, respectively, the most common presenting symptom and pericardial finding. Water‐soluble contrast esophagram (WSCE) had the highest diagnostic sensitivity (82.8%). Management included surgery (47.5%), stent placement (22.5%), combined surgery/stenting (19.2%), and conservative (10.8%). Overall mortality was 37.5%; median(IQR) time to death was 20(9–41) days. EPF from malignancy had poorer survival than those from benign esophageal causes (HR 2.65 [1.36–5.17]; p = 0.004) and cardiac ablation (HR 5.74 [2.41–13.65]; p < 0.0001). Patients who received any intervention (HR 0.28 [0.13‐0.57]; p = 0.0005) or had confirmed EPF resolution (HR 0.27 [0.12–0.59]; p = 0.0009) demonstrated better survival. There was no difference in survival between surgery and stenting alone (p = 0.91).ConclusionsAF ablation is now the leading etiology of EPF. Given its high mortality, a high degree of clinical suspicion is essential in those presenting with key signs/symptoms following AF ablation to enable urgent diagnosis and multi‐disciplinary management. WSCE may be the diagnostic modality to perform, given its high sensitivity. Future studies are warranted to investigate whether stenting should be the primary management given possible non‐inferiority to surgery.

Empirical evidence suggests direct thrombin inhibitors (DTIs) produce more favorable hemostatic outcomes than heparin in patients supported by extracorporeal membrane oxygenation (ECMO), yet the exact mechanisms responsible are unknown. We systematically searched databases and registers for studies comparing DTIs to heparin in humans receiving ECMO. A total of 28 studies were identified, most of which (n = 25) used bivalirudin, while the rest (n = 3) used argatroban. In random-effects meta-analysis, DTIs achieved the therapeutic anticoagulation range faster (mean difference = −6.96 hours, 95% confidence interval [CI] = −11.98 to −1.95, p = 0.006) and maintained the therapeutic range for a greater proportion of time (mean difference = 18.6%, 95% CI = 8.78–28.42, p < 0.001) than heparin. Subgroup analysis revealed these effects were similarly significant in adult patients and when bivalirudin was the DTI; however, they were not significant in pediatric patients or when argatroban was the DTI. Sensitivity analysis confirmed robustness of the primary findings in only low-risk of bias studies and in only studies published as full papers. In summary, DTIs—specifically bivalirudin—were associated with faster time to therapeutic anticoagulation and maintained the goal range for a greater percentage of time than heparin during ECMO support.

Background and importance Rapid sequence intubation in emergency settings may involve opioid pretreatment to blunt hemodynamic responses during laryngoscopy and intubation; however, opioids may lead to postintubation hypotension, increasing morbidity and mortality. Global clinical practice varies significantly, reflecting uncertainty about opioids’ benefits and risks. Objective Our goal was to evaluate the association between opioid pretreatment and hemodynamic instability, focusing on postintubation hypotension in adult patients undergoing emergency intubation. Design, settings, and participants We performed a systematic review of randomized controlled trials and observational studies comparing opioid administration vs. no opioids before adult emergency intubations. Searches included Cochrane, Embase, Medline, Scopus, and Web of Science databases until November 2024. Elective intubations were excluded. Eight (6708 patients) studies met criteria. Outcomes measure and analysis The primary outcome was postintubation hypotension, variably defined across studies. Secondary outcomes included hypoxemia, first-attempt success, cardiac arrest, and vasopressor use. Independent reviewers conducted data extraction, risk-of-bias assessments, and certainty evaluation. Results were qualitatively synthesized. Main results Among 6708 (2757 opioids and 3951 controls) patients, postintubation hypotension incidence varied widely (risk differences: −12.5% favoring opioids to +13.2% favoring controls). The single low-risk randomized study reported opioids increased hypotension (risk difference: 13%, odds ratio: 2.15, 95% confidence interval: 1.22–3.78). Observational studies yielded inconsistent results. Secondary outcomes showed no consistent differences. Evidence certainty was very low because of risk of bias, inconsistency, and imprecision. Conclusions Current evidence regarding opioid pretreatment effect on postintubation hypotension risk during emergency intubation is limited and conflicting.

INTRODUCTION: Current guidelines recommend endoscopic surveillance of Barrett's esophagus (BE) but do not account for competing mortality unrelated to esophageal cancer (EC). We conducted a systematic review and meta-analysis to estimate EC and non-EC mortality risk in BE patients. METHODS: We searched multiple databases for studies reporting mortality in BE. We included population-based studies providing standardized mortality ratio (SMR). The primary outcome was SMR from all causes and EC and non-EC etiologies. SMR was calculated by dividing the observed mortality over the expected mortality. Logarithmic form of SMRs was pooled using random-effects model. RESULTS: Our search yielded 2,826 articles, of which 7 studies (n = 34,454) were included. All-cause mortality was elevated in BE patients compared with population controls (pooled SMR 1.24, 95% confident interval [CI] 1.01–1.53) driven in part by increased EC mortality risk (SMR 8.98, 95 CI 5.12–15.77). The mortality risk was still increased but attenuated after excluding EC mortality (SMR 1.21, 95% CI 1–1.46). There was no increased mortality risk of non-EC malignancies (SMR 1.22, 95% CI 0.82–1.82) or mortality due to noncancer etiologies (SMR 1.13, 95% CI 0.90–1.43). Death due to cardiovascular diseases was higher in BE (SMR 1.16, 95% CI 1.02–1.33). BE patients were 10 times more likely to die from noncancer etiologies than EC (risk ratio 10.71, 95% CI 5.98–19.16). Subgroup analysis of studies that excluded prevalent EC at baseline (3 studies) also showed increased all-cause (SMR 1.12, 95% CI 1.07–1.18) and EC mortality (SMR 4.7, 95% CI 3.58–6.17) among BE patients. DISCUSSION: BE patients exhibit a higher all-cause mortality, driven in part by risk of EC mortality. A personalized approach to surveillance, mitigating risk of EC while recognizing the broader mortality risks, is warranted.

ABSTRACTBackgroundMitral transcatheter edge‐to‐edge repair (TEER) is a minimally invasive therapy for severe mitral regurgitation (MR) in patients with high surgical risk. TEER results in a tissue bridge that decreases mitral valve area, potentially leading to elevated mean gradient. The clinical impact of elevated gradient on outcomes is unclear.MethodsThis systematic review and meta‐analysis was based on a comprehensive search of five databases. We included studies that evaluated post mitral TEER gradient on one of the following outcomes: all‐cause mortality, combined endpoints, symptoms, hospitalizations, and mitral valve re‐intervention. Meta‐analysis was conducted using the random‐effects model.ResultsOut of 6458 citations, 17 studies were included (2017−2024) reporting on 7748 patients. There was significant heterogeneity between studies related to the cutoff used to define elevated gradient, etiology of MR, and outcomes. Elevated mitral gradient post TEER (4, 4.5, 5 mmHg) was associated with worse combined endpoint (HR = 1.35, 95% CI 1.07−1.71; I2 64%), but not all‐cause mortality (HR = 1.25, 95% CI 0.97−1.59; I2 45%) or risk of hospitalization. For the combined endpoint, this association was mainly significant in patients who had mitral gradient assessed using discharge echocardiogram (HR = 1.39, 95% CI 1.07−1.81; I2 62%) for all patients and for those with degenerative MR.ConclusionDespite the heterogeneity between studies, the current analysis suggests that patients with elevated mitral gradient post TEER are at risk of worse clinical outcomes, particularly in patients who had mitral gradient assessed using discharge transthoracic echocardiogram.

Objective Extracorporeal cardiopulmonary resuscitation (ECPR) utilizes veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in cardiac arrest patients to reduce the risk of mortality and multiorgan dysfunction from systemic hypoperfusion. We aimed to compare clinical outcomes of patients receiving ECPR versus conventional cardiopulmonary resuscitation (CCPR) for refractory cardiac arrest. Data Sources This was a systematic review and meta-analysis. A librarian searched the main databases, Ovid MEDLINE (including epub ahead of print, in-process & other non-indexed citations), Ovid EMBASE and Ovid Cochrane Central Register of Controlled Trials from inception through July 2024. Study Selection We included randomized controlled trials and observational studies that compared the outcomes of ECPR to CCPR in cardiac arrest patients. Primary outcomes were neurological sequelae and survival. Data Extraction We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened articles, extracted data on selected articles and performed risk of bias assessments using ROBINS-I for non-randomized controlled trials and the revised Cochrane risk of bias tool for randomized controlled trials with disagreements settled by a third independent reviewer. Data Synthesis Out of 3458 studies identified and screened, 28 studies including 304,360 cardiac arrest patients met eligibility criteria and were included. Survival at hospital discharge was 20% for ECPR versus 3.3% for CCPR (OR 0.48 [CI 0.27, 0.84]). Favorable neurological outcome at hospital discharge was 11.8% for ECPR versus 1.9% for CCPR (OR 0.41 [CI 0.17, 1.01]). Complications from bleeding were ten times higher in the ECPR group (35.3% vs 3.7%; OR 0.08 [0.03, 0.24]). Conclusions ECPR appeared to be superior to CCPR for improved neurological outcome and survival in cardiac arrest patients, although bleeding was increased. There was large heterogeneity in the included studies and outcomes reported. Future prospective studies may improve the identification of subgroups of patients that will benefit most from ECPR. Systematic review and meta-analysis registration: PROSPERO - CRD42023394128.