Verghese, Dhiran

Introduction: Endothelin receptor antagonists (ERAs) are the mainstay therapy for pulmonary arterial hypertension (PAH). However, there is limited data on cardiac adverse drug events (ADEs) associated with ERA medications. We performed a pharmacovigilance study comparing bosentan and ambrisentan using the FDA Adverse Event Reporting System (FAERS) data. Methods: Cardiac ADE data for bosentan and ambrisentan from January 1, 2004, to December 31, 2023, in the FAERS database were retrieved. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) aligned with p-values. The following cardiac ADEs were included: atrial fibrillation (AF), right ventricular failure (RVF), and cardiac arrest (CA). Results: For adults ≥ 18 years, a total of 12,058 cardiac ADEs were reported for both bosentan (38%) and ambrisentan (62%). Among the selected cardiac ADEs, AF was more frequently reported with bosentan (ROR 3.99, 95% CI: 3.62-4.40) than ambrisentan (ROR 1.91, 95% CI: 1.77-2.07). RVF showed a significantly higher ROR for bosentan (73.60, 95% CI: 66.68-81.25) than ambrisentan (23.11, 95% CI: 20.99-25.46). CA was also more commonly associated with bosentan (ROR 2.25, 95% CI: 1.98-2.55) than with ambrisentan (ROR 0.69, 95% CI: 0.61-0.78), with all comparisons showing p-values < 0.001. Conclusion: Our study identifies a significantly higher frequency of cardiac ADEs, particularly AF, RVF, and CA, in patients treated with bosentan compared to ambrisentan. This finding corroborates previous literature that has suggested differential safety profiles among ERAs, emphasizing the need for vigilant cardiac monitoring. Clinicians should integrate these insights into their practice, potentially favoring ambrisentan in patients with elevated cardiac risk, thus optimizing the management of PAH and improving patient outcomes.

Background: Sex disparities exist in acute cardiovascular care. Despite sex-specific cardiac arrest (CA) research being identified as a priority by professional societies, there are limited studies on this topic. Objectives: To assess sex disparities in management and outcomes of CA complicating acute myocardial infarction (AMI) in a contemporary United States population. Methods: Adult admissions with a primary diagnosis of AMI and concomitant diagnosis of CA were identified using the National Inpatient Sample. Outcomes of interest included sex disparities in in-hospital mortality, coronary angiography (CAG), percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS) use. Results: Between January 1, 2000 and December 31, 2017, 11,622,528 admissions for AMI were identified, of which 584,216 (5.0%) were complicated by CA. Men had higher prevalence of CA compared to women (5.4% vs 4.4%, p< 0.001) in both STEMI and NSTEMI (2017 vs 2000, STEMI-men: 12.3% vs 7.8%, STEMI-women: 10.4% vs 7.5%, NSTEMI-men: 3.1% vs 2.7%, NSTEMI-women: 2.4% vs 2.5%). Women with AMI-CA were on average older (70.4 vs 65.0, p<0.001), of black race (12.6% vs 7.9%, p<0.001) and had higher comorbidity. Women were more likely to present with NSTEMI (36.4% vs 32.3%, p<0.001) and a non-shockable rhythm (47.6% vs 33.3%, p<0.001). Women less frequently received CAG (56.0% vs 66.2 %), early CAG (32.0% vs 40.2%), PCI (40.4% vs 49.7%), MCS (17.6% vs 22.0%), and CABG (all p<0.001). Women had significantly higher unadjusted in-hospital mortality (52.6% vs 40.6%, p < 0.001). In a multivariable logistic regression analysis, female sex was associated with higher in-hospital mortality (OR 1.13 [95% CI 1.11-1.14]; p< 0.001). When stratified by type of rhythm, type of AMI, presence of cardiogenic shock and location of CA, women consistently received less frequent CAG and experienced higher in-hospital mortality. Conclusion: In the largest 18-year study evaluating management and outcomes of CA in AMI, we identified the presence of significant sex disparities. Women with AMI-CA were older, with higher rates of non-shockable rhythm, were less likely to undergo therapeutic procedures including CAG, PCI, and MCS. Women had higher unadjusted and adjusted in-hospital mortality.

Abstract Aims There are limited contemporary data on the use of initial fibrinolysis in ST-segment elevation myocardial infarction cardiogenic shock (STEMI-CS). This study sought to compare the outcomes of STEMI-CS receiving initial fibrinolysis vs. primary percutaneous coronary intervention (PPCI). Methods Using the National (Nationwide) Inpatient Sample from 2009 to 2017, a comparative effectiveness study of adult (&gt;18 years) STEMI-CS admissions receiving pre-hospital/in-hospital fibrinolysis were compared with those receiving PPCI. Admissions with alternate indications for fibrinolysis and STEMI-CS managed medically or with surgical revascularization (without fibrinolysis) were excluded. Outcomes of interest included in-hospital mortality, development of non-cardiac organ failure, complications, hospital length of stay, hospitalization costs, use of palliative care, and do-not-resuscitate status. Results During 2009–2017, 5297 and 110 452 admissions received initial fibrinolysis and PPCI, respectively. Compared with those receiving PPCI, the fibrinolysis group was more often non-White, with lower co-morbidity, and admitted on weekends and to small rural hospitals (all P &lt; 0.001). In the fibrinolysis group, 95.3%, 77.4%, and 15.7% received angiography, PCI, and coronary artery bypass grafting, respectively. The fibrinolysis group had higher rates of haemorrhagic complications (13.5% vs. 9.9%; P &lt; 0.001). The fibrinolysis group had comparable all-cause in-hospital mortality [logistic regression analysis: 28.8% vs. 28.5%; propensity-matched analysis: 30.8% vs. 30.3%; adjusted odds ratio 0.97 (95% confidence interval 0.90–1.05); P = 0.50]. The fibrinolysis group had comparable rates of acute organ failure, hospital length of stay, rates of palliative care referrals, do-not-resuscitate status use, and lesser hospitalization costs. Conclusions The use of initial fibrinolysis had comparable in-hospital mortality than those receiving PPCI in STEMI-CS in the contemporary era in this large national observational study.

AbstractDespite significant progress in the care of patients suffering from cardiovascular disease, there remains a persistent sex disparity in the diagnosis, management, and outcomes of these patients. These sex disparities are seen across the spectrum of cardiovascular care, but, are especially pronounced in acute cardiovascular care. The spectrum of acute cardiovascular care encompasses critically ill or tenuous patients with cardiovascular conditions that require urgent or emergent decision-making and interventions. In this narrative review, the disparities in the clinical course, management, and outcomes of six commonly encountered acute cardiovascular conditions, some with a known sex-predilection will be discussed within the basis of underlying sex differences in physiology, anatomy, and pharmacology with the goal of identifying areas where improvement in clinical approaches are needed.

Background: There are limited data on acute myocardial infarction with cardiogenic shock (AMI-CS) stratified by chronic kidney disease (CKD) stages. Objective: To assess clinical outcomes in AMI-CS stratified by CKD stages. Methods: A retrospective cohort of AMI-CS during 2005–2016 from the National Inpatient Sample was categorized as no CKD, CKD stage-III (CKD-III), CKD stage-IV (CKD-IV) and end-stage renal disease (ESRD). CKD-I/II were excluded. Outcomes included in-hospital mortality, use of coronary angiography, percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS). We also evaluated acute kidney injury (AKI) and acute hemodialysis in non-ESRD admissions. Results: Of 372,412 AMI-CS admissions, CKD-III, CKD-IV and ESRD comprised 20,380 (5.5%), 7367 (2.0%) and 18,109 (4.9%), respectively. Admissions with CKD were, on average, older, of the White race, bearing Medicare insurance, of a lower socioeconomic stratum, with higher comorbidities, and higher rates of acute organ failure. Compared to the cohort without CKD, CKD-III, CKD-IV and ESRD had lower use of coronary angiography (72.7%, 67.1%, 56.9%, 61.1%), PCI (53.7%, 43.8%, 38.4%, 37.6%) and MCS (47.9%, 38.3%, 33.3%, 34.2%), respectively (all p < 0.001). AKI and acute hemodialysis use increased with increase in CKD stage (no CKD–38.5%, 2.6%; CKD-III–79.1%, 6.5%; CKD-IV–84.3%, 12.3%; p < 0.001). ESRD (adjusted odds ratio [OR] 1.25 [95% confidence interval {CI} 1.21–1.31]; p < 0.001), but not CKD-III (OR 0.72 [95% CI 0.69–0.75); p < 0.001) or CKD-IV (OR 0.82 [95 CI 0.77–0.87] was predictive of in-hospital mortality. Conclusions: CKD/ESRD is associated with lower use of evidence-based therapies. ESRD was an independent predictor of higher in-hospital mortality in AMI-CS.