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Abstract Venetoclax is a promising drug for patients with acute myeloid leukemia (AML) ineligible for anthracycline-based treatments. In rats, venetoclax is reported to cause myocardial injury. Our objectives were to report the frequency of cardiovascular (CV) events in patients treated with venetoclax, and, subsequently, to compare CV outcomes in matched patients treated with venetoclax or anthracyclines. Patients diagnosed with AML and treated with venetoclax or anthracyclines from January 2017 to July 2021 were identified. Major adverse cardiac events (MACE, including new-onset heart failure (HF), acute myocardial infarction, new onset atrial fibrillation (AF)) were recorded. Propensity-score method was then used to compare patients treated with venetoclax or anthracyclines. Patients treated with venetoclax (n=103) were older, with more hyperlipidemia than patients treated with anthracyclines (n=217). However, only 63% of patients treated with venetoclax underwent echocardiographic screening (vs. 93% of patients treated with anthracyclines, P< 0.001). Eighteen patients with venetoclax (17%) and 27 patients with anthracyclines (12%) developed MACE, including 10 % of new HF in each group. The median time to MACE was 8 days (interquartile range 5-98 days). In the matched cohort (n=132 patients), the cumulative incidence of MACE at one year was not different (17.5 % venetoclax, 9.2% anthracyclines, p =0.27). Thus, MACE incidence is similar in matched patients receiving venetoclax or anthracyclines. Close CV monitoring during the early phase of treatment may be helpful in patients treated with venetoclax.

Abstract Background The risk of incident atrial fibrillation (AF) among breast cancer survivors, especially for younger women, and cancer treatment effects on the association remain unclear. This study aimed to investigate the risk of AF among breast cancer survivors and evaluate the association by age group, length of follow-up, and cancer treatment. Methods Using data from the Korean Health Insurance Service database (2010–2017), 113,232 women newly diagnosed with breast cancer (aged ≥ 18 years) without prior AF history who underwent breast cancer surgery were individually matched 1:5 by birth year to a sample female population without cancer (n = 566,160) (mean[SD] follow-up, 5.1[2.1] years). Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) considering death as a competing risk were estimated, adjusting for sociodemographic factors and cardiovascular/non-cardiovascular comorbidities. Results BCS had a slightly increased AF risk compared to their cancer-free counterparts (sHR 1.06; 95% CI 1.00–1.13), but the association disappeared over time. Younger BCS (age 65 years. Use of anthracyclines was associated with increased AF risk among BCS (sHR 1.57; 95% CI 1.28–1.92), which was more robust in younger BCS (sHR 1.94; 95% CI 1.40–2.69 in those aged ≤ 50 years). Conclusions Our findings suggest that younger BCS had an elevated risk of incident AF, regardless of the length of follow-up. Use of anthracyclines may be associated with increased mid-to-long-term AF risk among BCS. Graphical Abstract

Abstract As a treatment for relapsed or refractory multiple myeloma (MM), carfilzomib has been associated with a significant risk of cardiovascular adverse events (CVAE). The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib‐CVAE to inform potential strategies to protect patients from this cardiotoxicity. Global metabolomic profiling was performed on the baseline and post‐baseline plasma samples of 60 MM patients treated with carfilzomib‐based therapy, including 31 who experienced CVAE, in a prospective cohort study. Baseline metabolites and post‐baseline/baseline metabolite ratios that differ between the CVAE and no‐CVAE patients were identified using unadjusted and adjusted methods. A baseline metabolomic risk score was created to stratify patients. We observed a lower abundance of tauroursodeoxycholic acid (T‐UDCA) in CVAE patients at baseline (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.21–0.94, p = 0.044) compared with the no‐CVAE patients. A metabolite risk score was able to stratify patients into three risk groups. The area under the receiver‐operating curve of the model with clinical predictors and metabolite risk score was 0.93. Glycochenodeoxycholic acid (OR = 0.56, 95% CI = 0.31–0.87, p = 0.023) was significantly lower in post‐baseline/baseline ratios of CVAE patients compared with no‐CVAE patients. Following metabolomic analysis, we created a baseline metabolite risk score that can stratify MM patients into different risk groups. The result also provided intriguing clues about the mechanism of carfilzomib‐CVAE and potential cardioprotective strategies.

Abstract Background Chimeric antigen receptor T- Cell (CAR-T) immunotherapy has been a breakthrough treatment for various hematological malignancies. However, cardiotoxicities such as new-onset heart failure, arrhythmia, acute coronary syndrome and cardiovascular death occur in 10–15% of patients treated with CAR-T. This study aims to investigate the changes in cardiac and inflammatory biomarkers in CAR-T therapy to determine the role of pro-inflammatory cytokines. Methods In this observational study, ninety consecutive patients treated with CAR-T underwent baseline cardiac investigation with electrocardiogram (ECG), transthoracic echocardiogram (TTE), troponin-I, and B-type natriuretic peptide (BNP). Follow-up ECG, troponin-I and BNP were obtained five days post- CAR-T. In a subset of patients (N = 53), serum inflammatory cytokines interleukin (IL)-2, IL-6, IL-15, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and angiopoietin 1 & 2 were tested serially, including baseline and daily during hospitalization. Adverse cardiac events were defined as new-onset cardiomyopathy/heart failure, acute coronary syndrome, arrhythmia and cardiovascular death. Results Eleven patients (12%) had adverse cardiac events (one with new-onset cardiomyopathy and ten with new-onset atrial fibrillation). Adverse cardiac events appear to have occurred among patients with advanced age (77 vs. 66 years; p = 0.002), higher baseline creatinine (0.9 vs. 0.7 mg/dL; 0.007) and higher left atrial volume index (23.9 vs. 16.9mL/m2; p = 0.042). Day 5 BNP levels (125 vs. 63pg/mL; p = 0.019), but not troponin-I, were higher in patients with adverse cardiac events, compared to those without. The maximum levels of IL-6 (3855.0 vs. 254.0 pg/mL; p = 0.021), IFN-γ (474.0 vs. 48.8pg/mL; p = 0.006) and IL-15 (70.2 vs. 39.2pg/mL; p = 0.026) were also higher in the adverse cardiac events group. However, cardiac and inflammatory biomarker levels were not associated with cardiac events. Patients who developed cardiac events did not exhibit worse survival compared to patients without cardiac events (Log-rank p = 0.200). Conclusion Adverse cardiac events, predominantly atrial fibrillation, occur commonly after CAR-T (12%). The changes in serial inflammatory cytokine after CAR-T in the setting of adverse cardiac events suggests pro-inflammation as a pathophysiology and require further investigation for their role in adverse cardiac events. Tweet brief handle CAR-T related Cardiotoxicity has elevated cardiac and inflammatory biomarkers. #CARTCell #CardioOnc #CardioImmunology.

BackgroundProteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-coding genes in CFZ-CVAE among MM patients using whole-exome sequencing (WES) analysis.MethodsExome-wide single-variant association analysis, gene-based analysis, and rare variant analyses were performed on 603,920 variants in 247 patients with MM who have been treated with CFZ and enrolled in the Oncology Research Information Exchange Network (ORIEN) at the Moffitt Cancer Center. Separate analyses were performed in European Americans and African Americans followed by a trans-ethnic meta-analysis.ResultsThe most significant variant in the exome-wide single variant analysis was a missense variant rs7148 in the thymosin beta-10/TraB Domain Containing 2A (TMSB10/TRABD2A) locus. The effect allele of rs7148 was associated with a higher risk of CVAE [odds ratio (OR) = 9.3 with a 95% confidence interval of 3.9—22.3, p = 5.42*10−7]. MM patients with rs7148 AG or AA genotype had a higher risk of CVAE (50%) than those with GG genotype (10%). rs7148 is an expression quantitative trait locus (eQTL) for TRABD2A and TMSB10. The gene-based analysis also showed TRABD2A as the most significant gene associated with CFZ-CVAE (p = 1.06*10−6).ConclusionsWe identified a missense SNP rs7148 in the TMSB10/TRABD2A as associated with CFZ-CVAE in MM patients. More investigation is needed to understand the underlying mechanisms of these associations.

Background Cyclin‐dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor–positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies. Methods and Results Using the OneFlorida Data Trust, adult patients without prior cardiovascular disease who received at least 1 CDK4/6 inhibitor were included in the analysis. CVAEs identified from International Classification of Diseases, Ninth and Tenth Revisions (ICD‐9/10) codes included hypertension, atrial fibrillation(AF)/atrial flutter (AFL), heart failure/cardiomyopathy, ischemic heart disease, and pericardial disease. Competing risk analysis (Fine–Gray model) was used to determine the association between CDK4/6 inhibitor therapy and incident CVAEs. The effect of CVAEs on all‐cause death was studied using Cox proportional hazard models. Propensity‐weight analyses were performed to compare these patients to a cohort of patients treated with anthracyclines. A total of 1376 patients treated with CDK4/6 inhibitors were included in the analysis. CVAEs occurred in 24% (35.9 per 100 person‐years). CVAEs were slightly higher in patients who received CKD4/6 inhibitors compared with anthracyclines (P=0.063), with higher death rate associated with the development of AF/AFL or cardiomyopathy/heart failure in the CDK4/6 group. The development of cardiomyopathy/heart failure and AF/AFL was associated with increased all‐cause death (adjusted hazard ratio [HR], 4.89 [95% CI, 2.98–8.05]; and 5.88 [95% CI, 3.56–9.73], respectively). Conclusions CVAEs may be more common with CDK4/6 inhibitors than previously recognized, with increased death rates in these patients who develop AF/AFL or heart failure. Further research is needed to definitively determine cardiovascular risk associated with these novel anticancer treatments.

Background Anthracyclines remain a key treatment for many malignancies but can increase the risk of heart failure or cardiomyopathy. Specific guidelines recommend echocardiography and serum cardiac biomarkers such as BNP (B‐type natriuretic peptide) or NT‐proBNP (N‐terminal proBNP) evaluation before and 6 to 12 months after treatment. Our objective was to evaluate associations between racial and ethnic groups in cardiac surveillance of survivors of cancer after exposure to anthracyclines. Methods and Results Adult patients in the OneFlorida Consortium without prior cardiovascular disease who received at least 2 cycles of anthracyclines were included in the analysis. Multivariable logistic regression was performed to estimate the odds ratios (ORs) and 95% CIs for receiving cardiac surveillance at baseline before anthracycline therapy, 6 months after, and 12 months after anthracycline exposure among different racial and ethnic groups. Among the entire cohort of 5430 patients, 63.4% had a baseline echocardiogram, with 22.3% receiving an echocardiogram at 6 months and 25% at 12 months. Non‐Hispanic Black (NHB) patients had a lower likelihood of receiving a baseline echocardiogram than Non‐Hispanic White (NHW) patients (OR, 0.75 [95% CI, 0.63–0.88]; P=0.0006) or any baseline cardiac surveillance (OR, 0.76 [95% CI, 0.64–0.89]; P=0.001). Compared with NHW patients, Hispanic patients received significantly less cardiac surveillance at the 6‐month (OR, 0.84 [95% CI, 0.72–0.98]; P=0.03) and 12‐month (OR, 0.85 [95% CI, 0.74–0.98]; P=0.03) time points, respectively. Conclusions There were significant racial and ethnic differences in cardiac surveillance among survivors of cancer at baseline and following anthracycline‐based treatment in NHB and Hispanic cohorts. Health care providers need to be cognizant of these social inequities and initiate efforts to ensure recommended cardiac surveillance occurs following anthracyclines.

Abstract Background The aim of this study is to assess the burden of AF-related hospitalizations inclusive of inflation-adjusted cost-of-care and length-of-stay (LOS) among cancer patients and the impact of direct current cardioversion (DCCV) on these outcomes. Methods Using the National Inpatient Sample (NIS), patients hospitalized with either a primary or secondary diagnosis of AF and comorbid cancer were identified and both cost of hospitalization and LOS were evaluated for each group. Subgroup analyses were performed for specific cancer types (breast, lung, colon, prostate and lymphoma), and those receiving DCCV. Results The prevalence of co-morbid AF was 8.2 million (16%) and 35.5 million (10%) among those with vs. those without cancer, respectively (odds ratio = 1.6, 95% confidence interval = 1.5–1.7; P

Abstract Background Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood. Methods This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF/MEK inhibitors (vemurafenib/cobimetinib; dabrafenib/trametinib; encorafenib/binimetinib). We utilized the cross‐sectional FDA’s Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart failure (HF), and venous thromboembolism (VTE), were studied using adjusted regression techniques. Results In FAERS, 7752 AEs were reported (40% BRAF and 60% BRAF/MEK). Median age was 60 (IQR 49–69) years with 45% females and 97% with melanoma. Among these, 567 (7.4%) were cardiovascular adverse events (mortality rate 19%). Compared with monotherapy, combination therapy was associated with increased risk for HF (reporting odds ratio [ROR] = 1.62 (CI = 1.14–2.30); p = 0.007), arterial hypertension (ROR = 1.75 (CI = 1.12–2.89); p = 0.02) and VTE (ROR = 1.80 (CI = 1.12–2.89); p = 0.02). Marketscan had 657 patients with median age of 53 years (IQR 46–60), 39.3% female, and 88.7% with melanoma. There were 26.2% CVAEs (CI: 14.8%–36%) within 6 months of medication start in those receiving combination therapy versus 16.7% CVAEs (CI: 13.1%–20.2%) among those receiving monotherapy. Combination therapy was associated with CVAEs compared to monotherapy (adjusted HR: 1.56 (CI: 1.01–2.42); p = 0.045). Conclusions and Relevance In two independent real‐world cohorts, combination BRAF/MEK inhibitors were associated with increased CVAEs compared to monotherapy, especially HF, and hypertension.

Abstract Objective Women with breast cancer (BCA) and cardiovascular disease (CVD) risk factors are at increased risk of developing cardiovascular complications when exposed to potentially cardiotoxic cancer therapy. The benefit of aggressive CVD risk factor modification to reduce adverse treatment-related psychologic and biologic effects is not well established. Methods Using a single group pre-test, post-test design, 33 women with BCA receiving anthracycline and/or trastuzumab therapy participated in a 6-month comprehensive CVD risk reduction program involving formal cardio-oncology evaluation along with regular motivational counseling for improved nutrition and physical activity. Study parameters were assessed at baseline and 6 months with paired t-tests used to evaluate changes after the intervention. Results The mental component summary score assessed by SF-36V2 improved significantly after program completion (45.0 to 48.8, effect size 0.37, p = 0.017), however the physical component summary score declined (46.2 to 40.9, effect size − 0.53, p = 0.004). Despite this decline in perceived physical health, markers of health-related fitness and nutritional status were maintained or improved. Systolic and diastolic blood pressure also improved after the intervention (136.7 to 124.1 mmHg, p = 0.001 and 84.0 to 78.7 mmHg, p = 0.031, respectively). No significant change in resting heart rate, body mass index, lipids, hemoglobin A1C, or left ventricular ejection fraction was observed. Conclusions Patient-reported mental health improved significantly in women with BCA enrolled in a comprehensive CVD risk reduction program despite exposure to potentially cardiotoxic therapies. This study provides preliminary data for future randomized controlled trials evaluating the effects CVD risk reduction program in high-risk breast cancer cohorts.

Abstract Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center. Methods All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. Results Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55–4.95, p = 0.0006). Conclusions This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.

The development of cardiovascular toxicity attributable to anticancer drugs is a pivotal event that is associated with cardiovascular morbidity as well as with worse cancer‐specific and overall outcomes. Although broad consensus exists regarding the importance of cardiovascular safety assessment in cancer drug development, real‐world data suggest that cardiovascular events are significantly underestimated in oncology trials. This drug safety discrepancy has profound implications on drug development decisions, risk‐benefit evaluation, formulation of surveillance and prevention protocols, and survivorship. In this article, we review the contemporary cardiovascular safety evaluation of new pharmaceuticals in hematology and oncology, spanning from in vitro pharmacodynamic testing to randomized clinical trials. We argue that cardiovascular safety assessment of anticancer drugs should be reformed and propose practical strategies, including development and validation of preclinical assays, expansion of oncology trial eligibility, incorporation of cardiovascular end points in early‐phase studies, and design of longitudinal multi‐institutional cardiotoxicity registries.

The discipline of cardio-oncology has expanded at a remarkable pace. Recent developments and challenges to clinicians who practice cardio-oncology were presented at the Global Cardio-Oncology Summit on October 3 to 4, 2019, in São Paulo, Brazil. Here, we present the top 10 priorities for our field that were discussed at the meeting, and also detail a potential path forward to address these challenges. Defining robust predictors of cardiotoxicity, clarifying the role of cardioprotection, managing and preventing thromboembolism, improving hematopoietic stem cell transplant outcomes, personalizing cardiac interventions, building the cardio-oncology community, detecting and treating cardiovascular events associated with immunotherapy, understanding tyrosine kinase inhibitor cardiotoxicity, and enhancing survivorship care are all priorities for the field. The path forward requires a commitment to research, education, and excellence in clinical care to improve our patients' lives.

Abstract Aims Heart failure (HF) outcomes continue to improve with widespread use of new therapies. Concurrently, cancer survival has dramatically improved. Yet whether cancer patients share similar strategies and outcomes of inpatient HF treatment to those without HF is unknown. We sought to assess the contemporary impacts of cancer on inpatient HF outcomes over time. Methods and results The retrospective National Inpatient Sample (2003–15) and National Readmissions Database (2013–14) registries were queried for adults admitted for HF and stratified for cancer status, excluding cases of metastatic disease. Temporal trends in HF admissions, hospital charge rates, length of hospitalization, HF‐related procedure utilization, in‐hospital mortality, and hospital readmissions were analysed. Over 13 years of follow‐up, there were 12 769 077 HF admissions (mean age 73 years, 50.8% female, 30.8% non‐White), among which 1 413 287 (11%) had a co‐morbid cancer diagnosis. Cancer patients were older, were predominantly male, and tended to be smokers. Over time, HF admission rates among cancer patients increased, despite a concurrent decrease among patients without cancer (P

Multiple myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), an irreversible proteasome inhibitor being used to treat relapsed and refractory MM, has been associated with cardiotoxicity, including heart failure. We hypothesized that a multi-omics approach integrating data from different omics would provide insights into the mechanisms of CFZ-related cardiovascular adverse events (CVAEs). Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with CVAEs and 6 with no CVAEs) at the University of Florida Health Cancer Center. These samples were evaluated in global metabolomic profiling, global proteomic profiling, and microRNA (miRNA) profiling. Integrative pathway analysis was performed to identify genes and pathways differentially expressed between patients with and without CVAEs. The proteomics analysis identified the up-regulation of lactate dehydrogenase B (LDHB) [fold change (FC) = 8.2, p = 0.01] in patients who experienced CVAEs. The metabolomics analysis identified lower plasma abundance of pyruvate (FC = 0.16, p = 0.0004) and higher abundance of lactate (FC = 2.4, p = 0.0001) in patients with CVAEs. Differential expression analysis of miRNAs profiling identified mir-146b to be up-regulatein (FC = 14, p = 0.046) in patients with CVAE. Pathway analysis suggested that the pyruvate fermentation to lactate pathway is associated with CFZ-CVAEs. In this pilot multi-omics integrative analysis, we observed the down-regulation of pyruvate and up-regulation of LDHB among patients who experienced CVAEs, suggesting the importance of the pyruvate oxidation pathway associated with mitochondrial dysfunction. Validation and further investigation in a larger independent cohort are warranted to better understand the mechanisms of CFZ-CVAEs.

Although ibrutinib-associated atrial and ventricular arrhythmias have been well described, there is little information about ibrutinib’s effects on other electrocardiographic parameters, particularly the QT interval. Using our database of 137 patients treated with ibrutinib, we retrospectively identified 21 patients in whom an electrocardiogram (ECG) was obtained both prior to and after ibrutinib exposure. All traditional ECG parameters as well as QT dispersion were manually measured by an electrophysiologist. Compared to baseline ECGs, post ibrutinib ECGs demonstrated QT interval shortening from 386 ms to 356 ms ( P = .007), corrected QT interval shortening using Bazett’s formula from 446 ms to 437 ms ( P = .04), and corrected QT interval shortening using Fridericia’s formula from 425 ms to 407 ms ( P = .003). QT dispersion also increased post ibrutinib exposure compared to baseline (39.8 ms vs 57.3 ms, P = .002). There was no significant change in other ECG parameters. In conclusion, both the absolute and corrected QT intervals significantly shortened after ibrutinib exposure, while there was a significant increase in QT dispersion. These findings may point to a common underlying electrophysiologic mechanism of ibrutinib-associated arrhythmias.

Abstract Carfilzomib, an epoxyketone proteasome inhibitor, has demonstrated improved progression-free survival in patients when used with standard treatment (lenalidomide and dexamethasone) in patients with relapsed multiple myeloma (MM). However, there are reports of adverse cardiac events with carfilzomib manifested by dyspnea and heart failure. A patient is presented who had recurrent, clinically mild cardiotoxicity, as manifested by recurrent heart failure with preserved ejection fraction, with ongoing maintenance carfilzomib in a patient with resistant MM is presented.

Background: Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe.Aims: This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) is designed to evaluate the safety and efficacy of early anticoagulation, based on stroke size, secondary prevention of ischemic stroke, and risks of subsequent hemorrhagic transformation.Methods: Subjects are randomly assigned in a 1:1 ratio to receive early apixaban at day 0–3 for transient ischemic attack (TIA), 3–5 for small-sized AIS (

BackgroundInfluenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs.MethodsPatients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death.ResultsThe FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002).ConclusionThe rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.

Cardio-oncology is a multidisciplinary field focusing on the management and prevention of cardiovascular complications in cancer patients and survivors. While the initial focus of this specialty was on heart failure associated with anthracycline use, novel anticancer agents are increasingly utilized and are associated with many other cardiotoxicities including hypertension, arrhythmias and vascular disease. Since its inception, the field has developed at a rapid pace with the establishment of programs at many major academic institutions and community practices. Given the complexities of this patient population, it is important for providers to possess knowledge of not only cardiovascular disease but also cancer subtypes and their specific therapeutics. Developing a cardio- oncology program at a stand-alone cancer center can present unique opportunities and challenges when compared to those affiliated with other institutions including resource allocation, cardiovascular testing availability and provider education. In this review, we present our experiences establishing the cardio-oncology program at Moffitt Cancer Center and provide guidance to those individuals interested in developing a program at a similar independent cancer institution.

Incorporating sexual orientation, gender identity, and expression (SOGIE) data into cardiovascular research design is necessary to reduce cardiovascular healthcare disparities among sexual and gender minority (SGM) people. To achieve this, researchers should not only understand appropriate terminology, but also implement inclusive survey tools that respect privacy and cultural nuances, as the benefit of obtaining SOGIE information is critical to tailoring cardiovascular interventions and ensuring equitable healthcare outcomes. In order to address potential concerns related to disclosing SOGIE information, we must prioritize sensitivity training for healthcare professionals to foster an inclusive environment for data collection, ethical considerations, and confidentiality safeguards. This review aims to develop and inform critical thinking about sex and gender and to identify strategic mechanisms to include SOGIE data in cardiovascular research, thus improving cardiovascular health outcomes for SGM individuals. By embracing a more comprehensive and inclusive approach to data collection, cardiovascular research can contribute significantly to advancing personalized and inclusive healthcare practices and medical education, and ultimately promote better health outcomes for all SGM individuals.

Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. Traditionally, bortezomib was thought to have little cardiovascular toxicity; however, there is increasing evidence that bortezomib can lead to cardiac complications including left ventricular dysfunction and atrioventricular block. We present the case of a 66-year-old man with multiple myeloma and persistent asymptomatic elevations of cardiac biomarkers who developed complete heart block and evidence of myocardial scar after his eighth cycle of bortezomib, requiring permanent pacemaker placement. In addition to discussing the cardiovascular complications of bortezomib therapy, we propose a potential role for biomarkers in the prediction and monitoring of bortezomib cardiotoxicity.

Although both coronary artery dissection and heparin-induced thrombocytopenia may provoke myocardial infarction, it is extremely rare for both conditions to develop simultaneously in a single patient. We report a case of a 69-year-old woman who sustained a head-on motor vehicle accident with associated chest trauma. During a subsequent hospitalization, she was exposed to subcutaneous heparin and developed significant thrombocytopenia. Shortly thereafter, she re-presented with an acute myocardial infarction. Coronary angiography revealed a spiral dissection with superimposed thrombosis within the right coronary artery, while laboratory testing confirmed the diagnosis of heparin induced thrombocytopenia. She was treated with catheter-based thrombectomy and adjunctive direct thrombin inhibitor therapy, followed by three months of systemic anticoagulation with warfarin. To our knowledge, this represents the first published case of a native vessel myocardial infarction due to the combination of coronary artery dissection and heparin-induced thrombocytopenia.