Electrocardiographic features of immune checkpoint inhibitor associated myocarditis.

BACKGROUND: Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis. METHODS: From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested. RESULTS: Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p CONCLUSIONS: The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification

Outcomes Of Pacemaker Implantation In The Elderly

Data are scarce on outcomes of pacemaker (PM) implantation in the very elderly, limiting the ability to make informed decisions. We used national data to assess the hypothesis that increasing age is associated with significantly worse procedural outcomes (in-hospital mortality and complications). Patients ≥ 70 years with a new PM implant were identified in the 2004-2008 HCUP-Nationwide Inpatient Sample. Patient demographic and clinical variables as well as hospital characteristics were analyzed. Clinical outcomes were compared using χ², Mantel-Haenszel tests, and multivariate hierarchical logistic models. We identified 115,683 patients (mean age 81.47 years; SEM 0.02), of which 45,507 (39.3%) were 70-79 years old, 57,259 (49.5%) were 80-89, and 12,917 (11.2%) were ≥ 90. Unadjusted mortality and complication rates respectively were 0.60% and 5.61% in age group 70-79, 0.99% and 6.13% in age 80-89, and 1.87% and 6.31% in age ≥ 90, p\u3c0.001. Multivariable analysis revealed severe comorbidity (OR 5.00; 95% CI 4.05-6.17) and nonelective admission (OR 3.09; CI 2.46-3.88) were greater predictors of mortality than increasing age (OR 2.81; CI 2.35-3.35), all p\u3c0.0001. For complications, severe comorbidity (Charlson score ≥ 5) (OR 1.35; CI 1.20-1.51) and female gender (OR 1.35; CI 1.28-1.42) were larger predictors than increasing age (OR 1.07; CI 1.01-1.13), all p\u3c0.02. Although increasing age is a predictor of worsening outcomes in the elderly, the absolute rates are modest, even in nonagenarians, and other factors are more important predictors than age

Cardio-oncology: the role of big data.

Despite its challenges, a big data approach offers a unique opportunity within the field of cardio-oncology. A pharmacovigilant approach using large data sets can help characterize cardiovascular toxicities of the rapidly expanding armamentarium of targeted therapies. Creating a broad coalition of data sharing can provide insights into the incidence of cardiotoxicity and stimulate research into the underlying mechanisms. Population health necessitates the use of big data and can help inform public health interventions to prevent both cancer and cardiovascular disease. As a relatively new discipline, cardio-oncology is poised to take advantage of big data

Carfilzomib Treatment Causes Molecular and Functional Alterations of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes

Background Anticancer therapies have significantly improved patient outcomes; however, cardiac side effects from cancer therapies remain a significant challenge. Cardiotoxicity following treatment with proteasome inhibitors such as carfilzomib is known in clinical settings, but the underlying mechanisms have not been fully elucidated. Methods and Results Using human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) as a cell model for drug‐induced cytotoxicity in combination with traction force microscopy, functional assessments, high‐throughput imaging, and comprehensive omic analyses, we examined the molecular mechanisms involved in structural and functional alterations induced by carfilzomib in hiPSC‐CMs. Following the treatment of hiPSC‐CMs with carfilzomib at 0.01 to 10 µmol/L, we observed a concentration‐dependent increase in carfilzomib‐induced toxicity and corresponding morphological, structural, and functional changes. Carfilzomib treatment reduced mitochondrial membrane potential, ATP production, and mitochondrial oxidative respiration and increased mitochondrial oxidative stress. In addition, carfilzomib treatment affected contractility of hiPSC‐CMs in 3‐dimensional microtissues. At a single cell level, carfilzomib treatment impaired Ca2+ transients and reduced integrin‐mediated traction forces as detected by piconewton tension sensors. Transcriptomic and proteomic analyses revealed that carfilzomib treatment downregulated the expression of genes involved in extracellular matrices, integrin complex, and cardiac contraction, and upregulated stress responsive proteins including heat shock proteins. Conclusions Carfilzomib treatment causes deleterious changes in cellular and functional characteristics of hiPSC‐CMs. Insights into these changes could be gained from the changes in the expression of genes and proteins identified from our omic analyses