Immune Checkpoint Inhibitors and Cardiotoxicity: A Comparative Meta-Analysis of Observational Studies and Randomized Controlled Trials.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have uncommon associations with cardiotoxicity, yet these cardiotoxic effects are associated with high mortality. An accurate assessment of risk for cardiotoxicity is essential for clinical decision-making, but data from randomized controlled trials often differ from real-world observational studies. METHODS AND RESULTS: A systematic search of PubMed, Embase, Cochrane Library, and Scopus was performed, including phase II and III randomized controlled trials (RCTs) and observational studies (OSs) reporting myocarditis or pericardial disease, myocardial infarction, or stroke with an immunotherapy. Odds ratios (ORs) were used to pool results between ICIs and other cancer therapy in RCTs and OSs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed. In total, 54 RCTs (N=38 264) and 24 OSs (N=12 561 455) were included. In RCTs, ICI use resulted in higher risk of myocarditis (OR, 3.55 [95% CI, 2.10-5.98]), pericardial disease (OR, 2.73 [95% CI, 1.57-4.77]), and myocardial infarction (OR, 1.83 [95% CI, 1.03-3.25]), compared with non-ICI (placebo or chemotherapy). In OSs, ICI use was not associated with myocarditis, pericardial disease, or myocardial infarction compared with controls; however, combination ICIs demonstrated higher risk of myocarditis compared with single ICI use (OR, 3.07 [95% CI, 1.28-7.39]). Stroke risk was not increased with use of ICIs in RCTs. CONCLUSIONS: We demonstrated increased risk of ICI myocarditis, pericardial disease, and myocardial infarction in RCTs but not OSs. Results of this study suggest there are differences between ICI cardiotoxicity risk, possibly suggesting differences in diagnoses and management, in clinical trials versus the OSs.

Risk factors for hemolysis with centrifugal pumps in pediatric extracorporeal membrane oxygenation: Is pump replacement an answer?

INTRODUCTION: Hemolysis during pediatric extracorporeal membrane oxygenation (ECMO) is associated with increased risk for renal failure and mortality. OBJECTIVES: We aim to describe risk factors for hemolysis in pediatric ECMO supported by centrifugal pumps. METHODS: We conducted an analysis of retrospective data collected at an academic children's hospital from January 2017 to December 2019. MEASUREMENTS AND RESULTS: Plasma-free hemoglobin (PFH) levels were measured daily, and hemolysis was defined as PFH>50 mg/dL. Of 46 ECMO runs over 528 ECMO days, hemolysis occurred in 23 (58%) patients over a total of 40 (8%) ECMO days. In multivariable logistic regression models, VA-ECMO (aOR=4.69, 95% CI: 1.01-21.83) and higher hemoglobin (aOR = 1.38, 95% CI: 1.06-1.81) were independently associated with hemolysis. There were also non-significant trends toward increased risk for hemolysis with higher rotational pump speed (aOR=2.39, 95% CI: 0.75-7.65), higher packed red blood cell transfusions (aOR=1.15, 95% CI: 0.99-1.34), and higher cryoprecipitate transfusions (aOR=2.01, 95% CI: 0.83-4.86). Isolated pump exchanges that were performed in 12 patients with hemolysis led to significant decreases in PFH levels within 24 h (89 vs 11 mg/dL, p<0.01). CONCLUSIONS: Hemolysis is common in pediatric ECMO using centrifugal pumps. Avoidance of high pump speeds and conservative administration of blood products may help to mitigate the risk for hemolysis. Furthermore, pump exchange may be an effective first-line treatment for hemolysis.

Coronary artery calcium and atherosclerotic cardiovascular disease risk in women with early menopause: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background and Aims: We aimed to determine the utility of coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk stratification in women with and without early menopause (EM). Methods: To examine the association between CAC and incident ASCVD, we performed Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling using data from 2,456 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA) with or without EM, defined as occurring at <45 years of age. Results: The cohort was 64.1 ± 9.1 years old and 28.0% experienced EM. There were 291 ASCVD events over 12.5 ± 3.6 year follow-up with a higher event rate among those with EM compared to those without EM of 13.6 vs. 9.0 per 1,000 year follow-up (p < 0.01). Women with EM had a slightly lower prevalence of CAC = 0 (55.1%) than women without EM (59.7%) (p = 0.04) despite no difference in mean age. Among women with CAC = 0, the cumulative incidence of ASCVD at 10 years was low-to-borderline for women with (5.4%) and without EM (3.2%) (p = 0.06). However, women with EM had a significantly higher 15-year risk with an adjusted HR of 1.96 (95% CI: 1.26-3.04). In multivariable Cox models, women with CAC ≥ 1 had progressively increased ASCVD risk that did not significantly differ by EM status. Conclusion: In MESA, >50% of middle-aged postmenopausal women with EM had CAC = 0, similar to those without EM. Among women with CAC = 0, those with EM had a low to borderline 10-year risk of ASCVD, but the 15-year risk was significantly higher for women with EM versus those without EM. When CAC ≥ 1, the incidence of ASCVD was similar for women with and without EM. These findings support the use of CAC to help improve ASCVD risk stratification in women with EM. Condensed abstract: This study investigated the association between coronary artery calcium (CAC) and incident atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women with and without early menopause (EM). We found that >50% of women had CAC = 0 and an associated low-to-borderline 10-year cumulative incidence of ASCVD. However, the risk for ASCVD was significantly higher for women with EM after 15-years follow-up. Additional research is needed to better understand the differences in long-term ASCVD risk between women with and without EM who have CAC = 0.