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Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS.This study aimed to detail the role of GCS and GRS in ICI myocarditis.In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death.Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n=42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P< 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P< 0.001). Over a median follow-up of 30days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95%CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95%CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95%CI: 0.70-0.91]) and GRS (AUC: 0.76 [95%CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95%CI: 0.58-0.82]), LVEF (AUC: 0.69 [95%CI: 0.56-0.81]), and age (AUC: 0.54 [95%CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002).GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.

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 Ca 2+ 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.

BACKGROUND: Prostate-specific antigen (PSA) surveillance testing is a cornerstone of prostate cancer survivorship because patients with biochemical recurrence often have no symptoms. However, the investigation of guideline-concordant PSA surveillance across racial groups is limited. We examined racial differences in PSA surveillance testing 5-years post-definitive treatment for localized prostate cancer. METHODS: We created a population-based retrospective cohort from the Surveillance, Epidemiology, and End Results-Medicare linked database for men diagnosed with prostate cancer between the years 2007 to 2011 with Medicare claims through 2016 (N = 21,372). Multivariable log-binomial regression models were used to examine the effect of race on the likelihood of not receiving at least one PSA surveillance test annually 5-years post-definitive treatment. RESULTS: Black men had 90%, 71%, 44%, 34%, and 23% increased risk of not receiving at least one PSA surveillance test annually in the first, second, third, fourth, and fifth years of post-definitive treatment follow-up, respectively. The adjusted relative risk [ARR] for Black men compared to White men were 1.68 (95% Confidence Interval [CI], 1.37–2.07), 1.52 (95% CI, 1.32–1.75), 1.32 (95% CI, 1.17–1.48), and 1.16 (95% CI, 1.05–1.29) in the first, second, third, and fourth year of post-definitive treatment, respectively. CONCLUSION: Black men were more likely not to receive guideline-concordant PSA surveillance testing following definitive treatment for localized prostate cancer during the first 4 years post-treatment. This study suggest room for improvement in defining survivorship care plans for Black men to increase use of PSA surveillance testing.

The purpose of this study was to assess whether the presence and extent of fibrosis changes over time in patients with nonischemic, dilated cardiomyopathy (DCM) receiving optimal medical therapy and the implications of any such changes on left ventricular ejection fraction (LVEF) and clinical outcomes.Myocardial fibrosis on cardiovascular magnetic resonance (CMR) imaging has emerged as important risk marker in patients with DCM.In total, 85 patients (age 56 ± 15 years, 45% women) with DCM underwent serial CMR (median interval 1.5 years) for assessment of LVEF and fibrosis. The primary outcome was all-cause mortality; the secondary outcome was a composite of heart failure hospitalization, aborted sudden cardiac death, left ventricular (LV) assist device implantation, or heart transplant.On CMR-1, fibrosis (median 0.0 [interquartile range: 0% to 2.6%]) of LV mass was noted in 34 (40%) patients. On CMR-2, regression of fibrosis was not seen in any patient. Fibrosis findings were stable in 70 (82%) patients. Fibrosis progression (increase1.8% of LV mass or new fibrosis) was seen in 15 patients (18%); 46% of these patients had no fibrosis on CMR-1. Although fibrosis progression was on aggregate associated with adverse LV remodeling and decreasing LVEF (40 ± 7% to 34 ± 10%; p 0.01), in 60% of these cases the change in LVEF was minimal (5%). Fibrosis progression was associated with increased hazards for all-cause mortality (hazard ratio: 3.4 [95% confidence interval: 1.5 to 7.9]; p 0.01) and heart failure-related complications (hazard ratio: 3.5 [95% confidence interval: 1.5 to 8.1]; p 0.01) after adjustment for clinical covariates including LVEF.Once myocardial replacement fibrosis in DCM is present on CMR, it does not regress in size or resolve over time. Progressive fibrosis is often associated with minimal change in LVEF and identifies a high-risk cohort.

BackgroundMyocarditis 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.MethodsFrom 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.ResultsBoth 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, pConclusionsThe 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.

Background Treatment-induced cardiotoxicity is a leading noncancer-related cause of acute and late onset morbidity and mortality in cancer patients on antineoplastic drugs such as melphalan—increasing clinical case reports have documented that it could induce cardiotoxicity including severe arrhythmias and heart failure. As the mechanism by which melphalan impairs cardiac cells remains poorly understood, here, we aimed to use cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) to investigate the cellular and molecular mechanisms of melphalan-induced cardiotoxicity. Methods hiPSC-CMs were generated and treated with clinically relevant doses of melphalan. To characterize melphalan-induced cardiotoxicity, cell viability and apoptosis were quantified at various treatment durations. Ca2+ transient and contractility analyses were used to examine the alterations of hiPSC-CM function. Proteomic analysis, reactive oxygen species detection, and RNA-Sequencing were conducted to investigate underlying mechanisms. Results Melphalan treatment of hiPSC-CMs induced oxidative stress, caused Ca2+ handling defects and dysfunctional contractility, altered global transcriptomic and proteomic profiles, and resulted in apoptosis and cell death. The antioxidant N-acetyl-l-cysteine attenuated these genomic, cellular, and functional alterations. In addition, several other signaling pathways including the p53 and transforming growth factor-β signaling pathways were also implicated in melphalan-induced cardiotoxicity according to the proteomic and transcriptomic analyses. Conclusions Melphalan induces cardiotoxicity through the oxidative stress pathway. This study provides a unique resource of the global transcriptomic and proteomic datasets for melphalan-induced cardiotoxicity and can potentially open up new clinical mechanism-based targets to prevent and treat melphalan-induced cardiotoxicity.

Introduction: myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). While corticosteroids are the cornerstones of the treatment, there are no data to guide the dose and timing. Methods: from an international registry of patients with ICI myocarditis diagnosed between 2013 and 2019, data on the type, dose (in methylprednisolone equivalent dose) and timing of steroids were extracted. Major cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically-significant complete heart block. Results: in total, 143 ICI myocarditis patients (67±13 years old, 29% women) were included. Among them, 125 received corticosteroids (87%), with the initial agent being either methylprednisolone (95, 76%), prednisone (25, 20%), hydrocortisone (2, 1.6%) or dexamethasone (3, 2.4%). The rates of overall MACE (by admission time tertile 1: 45.8%, tertile 2: 43.8%, tertile 3: 38.3%, P=0.746) and individual elements of MACE were unchanged from 2013 to 2019. The initial corticosteroid dose was categorized as low (500mg). There was an inverse relationship between the occurrence of MACE and initial dose of corticosteroid, where MACE declined with increasing doses (low 61.9%, intermediate 54.6%, high 20.4%, P72 hours (85.7%, P

To describe the role of big data in cardio-oncology. There is a trend towards developing cloud-based, integrated registries to improve data collection, access, and analysis. Using a template from pediatric oncology, a cardio-oncology data commons is a novel opportunity to integrate data elements into a cloud-based platform. A cloud-based registry provides advantages of multi-institutional collaboration, rapid data access, a virtual visualization, and analytic tools to reduce infrastructure redundancy. The data commons would include integrated clinical data, blood samples, and genomic data to streamline discovery and analysis for researchers. A cardio-oncology data commons would be a large step forward in bringing cardio-oncology to the forefront 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.

Background— Data are scarce on outcomes of pacemaker implantation in nonagenarians (age≥90 years). Methods and Results— We identified patients >70 years of age (n=115 683) who underwent initial pacemaker implantation in the 2004 to 2008 Healthcare Cost and Utilization Project–Nationwide Inpatient Sample. Outcomes included in-hospital mortality, complications, length of stay, and charges. Unadjusted outcomes were compared using χ 2 and Mantel-Haenszel tests. Multivariate hierarchical logistic models and stepwise linear regression models adjusted for case-mix variation and clustering. Eleven percent (12 917) were >90 years of age. Relative to patients aged 70 to 79 years, patients >90 years of age were more likely to have moderate/severe comorbidity (Charlson score >1; 43.2% versus 40.1%) and less likely to be admitted electively (17.5% versus 29.9%), all P 90 years were 1.87% (CI, 1.63–2.11%) and 6.31% (CI, 5.89–6.72%). Length of stay and charges in patients aged 70 to 79 years were 3.22 days (CI, 3.20–3.24 days) and $38 871 (CI, $38 700–$39 043), and in patients aged >90 years, 4.27 days (CI, 4.25–4.30 days) and $41 373 (CI, $41 190–$41 556). Multivariable analysis revealed severe comorbidity (odds ratio, 5.00; 95% CI, 4.05–6.17) was a greater predictor of mortality than increasing age (odds ratio, 2.81 per decade; CI, 2.35–3.35), all P 5) was more strongly associated with complications, length of stay, and charges than age. Conclusions— Although increasing age predicts worsening outcomes in the elderly, the absolute rates are modest, even in nonagenarians, and comorbidity is a stronger predictor.

PURPOSE To compare in a population-based analysis the in-hospital mortality and complications following endovascular aneurysm repair (EVAR) vs. open repair in patients transferred for the management of ruptured abdominal aortic aneurysm (RAAA). METHODS Interrogation of the 2003-2007 Nationwide Inpatient Sample database identified 271 patients (205 men; mean age 71.7 years) who were transferred for RAAA treatment. Demographic, patient, and hospital characteristics were analyzed. Hierarchical multivariate logistic regression analyses were employed to identify predictors of in-hospital mortality and complications; results are presented as the odds ratio (OR) and 95% confidence interval (CI). RESULTS In comparison to open repair (n=207), endovascular repair (n=64) was associated with lower in-hospital mortality (36% vs.

To evaluate the effect of physician volume and specialty and hospital volume on population-level outcomes after endovascular repair of aortoiliac occlusive disease (AIOD).A retrospective cross-sectional analysis of all inpatients undergoing endovascular repair of AIOD. Physician volume was classified as low (17 procedures per year [50th percentile]) or high (≥17 procedures per year). Physicians were defined as surgeons if they performed at least 1 carotid, aortic, or iliac endarterectomy; open aortic repair; above- or below-knee amputation; or aortoiliac-femoral bypass. Hospital volume was low (116 procedures per year [50th percentile]) or high (≥116 procedures per year).Eight hundred eighteen inpatients who underwent endovascular repair of AIOD in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from January 2003 through December 2007.National hospital database.In-hospital complications and mortality, length of stay, and cost.Of the 818 procedures, 59.0% of high-volume physicians were surgeons and 65.0% practiced at high-volume hospitals. Unadjusted complication rates were significantly higher for low-volume compared with high-volume physicians (18.7% vs 12.6%; P = .02); rates were not significantly different by physician specialty (P = .88) or hospital volume (P = .16). Shorter length of stay was associated with high-volume physicians (P = .001), high-volume hospitals (P = .001), and surgeon providers (P = .03), whereas decreased cost was associated with physician specialty (P = .004). On multivariate analysis, high physician volume was associated with significantly lower complications (P = .04); high hospital volume, with shorter length of stay (P = .002); and nonsurgeons, with higher costs (P = .05).Overall, volume at the physician and hospital levels appears to be a robust predictor of patient outcomes after endovascular interventions for AIOD. Surgeons performing endovascular procedures for AIOD have a decreased associated hospital cost compared with nonsurgeons.

The purpose of this study was to compare the in-hospital mortality and complication rates after early and delayed initiation of plasma exchange (PLEX) in patients with myasthenia gravis (MG).Our cohort was identified from the Nationwide Inpatient Sample database for the years 2000 through 2005. Early treatment was defined as therapy with PLEX administered within the first 2 days from hospital admission. Univariate and multivariate analyses were employed.One thousand fifty-three patients were treated and included in the analysis. A delay in receiving PLEX was associated with higher mortality (6.56% vs. 1.15%, P0.001) and increased complications (29.51% vs. 15.29%, P0.001). Adjusted analysis showed increased mortality [odds ratio (OR) 2.812; 95% confidence interval (CI) 1.119-7.069] and complications (OR 1.672; 95% CI 1.118-2.501) with delayed PLEX therapy.Delaying PLEX therapy for MG by more than 2 days after admission may lead to higher mortality and complication rates, and thus prompt therapy is warranted.

ObjectivesThere has been a rapid increase in the number of endovascular procedures performed for peripheral artery disease, and especially aorto-iliac occlusive disease (AIOD). Results from single-center reports suggest a benefit for endovascular procedures; however, these benefits may not reflect general practice. We used a population-based analysis to determine predictors of clinical and economic outcomes following open and endovascular procedures for inpatients with AIOD.MethodsAll patients with AIOD who underwent open and endovascular procedures in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample, 2004 to 2007, were identified. Independent patient- and provider-related characteristics were analyzed. Clinical outcomes included complications and mortality; economic outcomes included length of stay (LOS) and cost (2007 dollars). Outcomes were compared using χ2, ANOVA, and multivariate regression analysis.ResultsFour thousand, one hundred nineteen patients with AIOD were identified. Endovascular procedures increased by 18%. Patients who underwent endovascular procedures were more likely to be ≥65 years of age (46% vs 37%), female (54% vs 49%), and in the highest quartile of household income (20% vs 16%), all P < .05. Endovascular patients were more likely to be non-elective (41% vs 20%), in the highest comorbidity index group (8% vs 5%), and with iliac artery disease (67% vs 33%), all P ≤ .05. In bivariate analysis, endovascular procedures were associated with lower complication rates (16% vs 25%), shorter LOS (2.2 vs 5.8 days), and lower hospital costs ($13,661 vs $17,161), all P < .001. In multivariate analysis, endovascular procedures had significantly lower complication rates and cost, and shorter LOS.ConclusionsEndovascular procedures have superior short-term clinical and economic outcomes compared with open procedures for the treatment of AIOD in the inpatient setting. Further studies are needed to examine long-term outcomes and access-related issues.

The elderly comprise a sizeable segment of patients with aortoiliac occlusive disease (AIOD). We analyzed outcomes in elderly patients who underwent open and endovascular procedures for AIOD.Elderly patients with AIOD who underwent open and endovascular procedures in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database from 2004 to 2007 were identified. Patients were stratified into age groups: 65-69 years, 70-79 years, and 80 years or older. The clinical outcomes were complications and mortality; the economic outcomes were duration of stay and hospital cost. Both open and endovascular procedures were compared using chi(2) analysis, analysis of variance (ANOVA), and multivariate linear and logistic regression.Patients aged 80 years or older were more likely be nonelective admissions (43%), have a high Charlson Comorbidity Index (12%), and have iliac artery disease (63%, all P.05). Patients aged 80 years or older who underwent open procedures had higher complication and mortality rates compared with younger patients (both P.05). Endovascular procedures had a lower complication rate, duration of stay, and hospital cost for all age groups (P.05). Mortality was significantly lower for endovascular treatment in patients aged 70 years or older (P.05). A multivariate analysis showed patients aged 70 years or older were at increased risk of complications (P.05).For both procedures, clinical outcomes worsen as patient age increases. In patients aged 70 years or older, endovascular treatment conferred a lower complication rate than open repair.