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Introduction: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. Methods: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7–30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). Results: We evaluated 509 patients; median infarct volume was 1.5 (0.1–7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0–3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30–1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17–1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84–16.24], p Conclusions: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.

Introduction: Combination therapy of Immunomodulatory drugs (iMiDs) (Thalidomide, Lenalidomide, Pomalidomide) and Proteasome Inhibitors (PIs) (Bortezomib, Carfilzomib, Ixazomib) constitutes the backbone of treatment in MM patients. Cardiotoxic side-effect profile of iMiDs is not well-documented. Although Carfilzomib has been associated with cardiotoxicity, whether its adverse effects also mirror the class-specific cardiotoxic profile of PI remain obscure. Proper assessment of cardiotoxicity due to treatment reagents is necessary for optimal patient management. In this pairwise meta-analysis, we explored direct cardiotoxicity with iMiDs and PIs use in patients with multiple myeloma (MM). Hypothesis: Treatment with iMiDs and PIs in MM patients leads to independent cardiotoxicity that is associated with individual class of drugs. Methods: Published randomized control trials (RCTs) were searched up to May 2021 reporting cardiotoxicity (cumulative reported events of ischemia, arrhythmia, failure, stenosis) in MM patients (newly diagnoses and/or relapsed) treated with iMiD and/or PI. Studies, where iMiD or PI were used atop the chemotherapy vs placebo or no additional drugs (control) in the other arm, were included. The primary outcome was presence of cardiotoxicity after follow-up. Meta-analysis was performed using frequentist’s approach to estimate odds ratio (OR). Results: Eighteen RCTs including 8,479 MM patients were included in this analysis. Eleven studies compared iMiDs and seven studies compared PIs with control. CTACE high-grade (≥ grade 3) cardiotoxic events were increased with iMiDs in comparison to their control counterpart (OR 2.05; 95% CI 1.30-3.26). Cardiotoxicity was also noted more frequently with PI use when compared to the control group (OR 1.47; 95% CI 1.19-1.82). Similar difference was observed between high-grade cardiotoxic complication between these groups. There was no evidence of publication bias among studies. Conclusions: Our results showed iMiDs and PIs are independently associated with cardiotoxicity, which may warrant increased awareness among treating physicians and close monitoring of patients. The adverse cardiac event profile with these drugs require further investigation in future studies.

Background Immune checkpoint inhibitor (ICI)-associated myocarditis is associated with a markedly increased risk of morbidity and mortality. The occurrence of ventricular arrhythmias (VA) in patients with ICI-associated myocarditis has not been well characterized. Purpose The aim of this study was to determine the characteristics and risk factors for severe VA in patients with ICI myocarditis. Methods The cohort consisted of 202 patients with ICI myocarditis. Ventricular arrhythmias were defined as a composite of sustained ventricular tachycardia and ventricular fibrillation. We used a multivariable logistic regression model to test the association between clinical variables and the development of VA. Results From a cohort of 202 patients with ICI myocarditis (67±13 years, 35% female, 60% hypertension, 23% diabetes mellitus), 41 (20.3%) developed VA, of which, 33 had VT and 8 had VF. The median time from admission to VF was 144 hours and to VT was 72 hours. A VA occurred in 17.5% of patients with a normal LVEF, and 25% of patients with reduced LVEF. On univariate analysis, a QRS duration >110ms (OR 2.88, 95% CI 1.40 to 6.16, P=0.005) and a QTc duration >470ms were associated with an increased probability of VA (OR 2.58, 95% CI 1.23, 5.41, P=0.012). The association remained significant after adjustment for age and gender. Additionally, a longer time from admission to initiation of corticosteroids was associated with a higher probability of VA (OR 1.06, 95% CI 1.01 to 1.13, P=0.027). The association between the time from admission to administration of corticosteroids and probability of VA remained significant after adjustment for age, gender, and LVEF on admission (OR, 1.06, 95% CI 1.00, 1.13, P=0.037) where each 6-hour delay in the initiation of corticosteroids was associated with a 4% increase in the risk for VA. Conclusions Ventricular arrhythmias are common in the setting of ICI myocarditis and are observed in patients presenting with both a preserved and a reduced LVEF. Wider QRS and longer QT at presentation and longer time from admission to initiation of corticosteroids were associated with an increased risk of VA. Funding Acknowledgement Type of funding sources: None.

Cardiometabolic disease (CMD) is the most common preventable cause of death in the world. A number of components are included in the spectrum of CMD, such as metabolic syndrome/obesity, hyperglycemia/diabetes, dyslipidemia, and hypertension, which are independently associated with cardiovascular disease risk. These conditions often occur together, and patients with cancer frequently undergo treatments that can generate or worsen CMD. This review highlights and presents mechanistic and epidemiological evidence regarding CMD in four categories of anticancer medications, namely, mTOR/PI3K-Akt inhibitors, multi-targeted tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor therapy, and endocrine therapy. Patients taking these medications need careful monitoring during therapy. There is a role for cardio-oncology and onco-primary care specialists in optimally managing patients at risk to mitigate CMD during treatment with these and other investigational anti-cancer medications.

Melanoma is the least common but most dangerous skin cancer, accounting for 75% of all deaths from a primary cutaneous malignancy, with incidence rates rising significantly over the last decade. Traditional treatments for melanoma including interferon and cytotoxic chemotherapy had marginal efficacy. With the advent of targeted and immunotherapies, the prognosis for patients with advanced melanoma has significantly improved including those with metastatic disease to the heart. BRAF and MEK inhibitors as well as immune checkpoint inhibitors have become front line therapy for eligible patients with metastatic melanoma and have led to long-term durable response and in some cases can be curative. Despite these oncologic advances, various treatment-limiting side effects can occur. In particular, cardiovascular toxicities can contribute to overall morbidity and mortality in these patients. Toxicities range from asymptomatic QT prolongation and mild LV dysfunction to fulminant myocarditis and potentially life-threatening arrhythmias. A multidisciplinary approach to the care of these patients which includes cardio-oncology evaluation is necessary to develop both risk mitigation and treatment strategies to ensure patients continue receiving necessary and effective melanoma treatments while minimizing long-term adverse cardiovascular effects.

BackgroundIbrutinib is a tyrosine kinase inhibitor most commonly associated with atrial fibrillation. However, additional cardiotoxicities have been identified, including accelerated hypertension. The incidence and risk factors of new or worsening hypertension following ibrutinib treatment are not as well known.MethodsWe conducted a retrospective study of 144 patients diagnosed with B cell malignancies treated with ibrutinib (n=93) versus conventional chemoimmunotherapy (n=51) and evaluated their effects on blood pressure at 1, 2, 3 and 6 months after treatment initiation. Descriptive statistics were used to compare baseline characteristics for each treatment group. Fisher’s exact test was used to identify covariates significantly associated with the development of hypertension. Repeated measures analyses were conducted to analyse longitudinal blood pressure changes.ResultsBoth treatments had similar prevalence of baseline hypertension at 63.4% and 66.7%, respectively. There were no differences between treatments by age, sex and baseline cardiac comorbidities. Both systolic and diastolic blood pressure significantly increased over time with ibrutinib compared with baseline, whereas conventional chemoimmunotherapy was not associated with significant changes in blood pressure. Baseline hypertensive status did not affect the degree of blood pressure change over time. A significant increase in systolic blood pressure (defined as more than 10 mm Hg) was noted for ibrutinib (36.6%) compared with conventional chemoimmunotherapy (7.9%) at 1 month after treatment initiation. Despite being hypertensive at follow-up, 61.2% of patients who were treated with ibrutinib did not receive adequate blood pressure management (increase or addition of blood pressure medications). Within the ibrutinib group, of patients who developed more than 20 mm Hg increase in systolic blood pressure, only 52.9% had hypertension management changes.ConclusionsIbrutinib is associated with the development of hypertension and worsening of blood pressure. Cardiologists and oncologists must be aware of this cardiotoxicity to allow timely management of blood pressure elevations.

Background Chimeric antigen receptors redirect T cells (CAR-T) to target cancer cells. There are limited data characterizing cardiac toxicity and cardiovascular (CV) events among adults treated with CAR-T. Objectives The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T. Methods The registry included 137 patients who received CAR-T. Covariates included the occurrence and grade of cytokine release syndrome (CRS) and the administration of tocilizumab for CRS. Cardiac toxicity was defined as a decrease in the left ventricular ejection fraction or an increase in serum troponin. Cardiovascular events were a composite of arrhythmias, decompensated heart failure, and CV death. Results The median age was 62 years (interquartile range [IQR]: 54 to 70 years), 67% were male, 88% had lymphoma, and 8% had myeloma. Approximately 50% were treated with commercial CAR-T (Yescarta or Kymriah), and the remainder received noncommercial products. CRS, occurring a median of 5 days (IQR: 2 to 7 days) after CAR-T, occurred in 59%, and 39% were grade ≥2. Tocilizumab was administered to 56 patients (41%) with CRS, at a median of 27 h (IQR: 16 to 48 h) after onset. An elevated troponin occurred in 29 of 53 tested patients (54%), and a decreased left ventricular ejection fraction in 8 of 29 (28%); each occurred only in patients with grade ≥2 CRS. There were 17 CV events (12%, 6 CV deaths, 6 decompensated heart failure, and 5 arrhythmias; median time to event of 21 days), all occurred with grade ≥2 CRS (31% patients with grade ≥2 CRS), and 95% of events occurred after an elevated troponin. The duration between CRS onset and tocilizumab administration was associated with CV events, where the risk increased 1.7-fold with each 12-h delay to tocilizumab. Conclusions Among adults, cardiac injury and CV events are common post–CAR-T. There was a graded relationship among CRS, elevated troponin, and CV events, and a shorter time from CRS onset to tocilizumab was associated with a lower rate of CV events.

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., Central Illustration, Highlights • The discipline of cardio-oncology has enjoyed extensive and complex development at a breathtaking pace. • Extensive ongoing clinical and basic research continue to shape and formulate the practice of cardio-oncology. • The path forward for the field needs to be centered on excellence in clinical care, transformative research, and broad education principles.

Multiple cancer therapies are associated with cardiac arrhythmias through a variety of pathophysiologic mechanisms. Atrial fibrillation and atrial flutter are common during cancer therapy but should rarely limit continued delivery of therapy. Ventricular arrhythmias are not common during cancer therapy and are more often secondary to other cardiac pathologies. QT interval monitoring is recommended for some agents, although it is often not a reliable predictor of ventricular arrhythmias. Bradyarrhythmias are common and rarely require intervention, but special attention must be paid to heart block in checkpoint inhibitor therapy.

The objective of this study was to determine whether survival and post-arrest procedural utilization following in-hospital cardiac arrest (IHCA) differ in patients with and without comorbid cancer.We retrospectively reviewed all adult (age ≥18 years old) hospital admissions complicated by IHCA from 2003 to 2014 using the National Inpatient Sample (NIS) dataset. Utilizing propensity score matching using age, gender, race, insurance, all hospital level variables, HCUP mortality score, diabetes, hypertension and cardiopulmonary resuscitation use, rates of survival to hospital discharge and post-arrest procedural utilization were compared.From 2003 to 2014, there were a total of 1,893,768 hospitalizations complicated by IHCA, of which 112,926 occurred in patients with history of cancer. In a propensity matched cohort from 2012 to 2014, those with cancer were less likely to survive the hospitalization (31% vs. 46%, p 0.0001). Following an IHCA, rates of procedural utilization in patients with cancer were significantly less when compared to those without a concurrent malignancy: coronary angiography (4.0% vs. 13.0%), percutaneous coronary intervention (2.2% and 8.0%), targeted temperature management (0.8% vs. 6.0%); p 0.0001 for all comparisons. This patient population was less likely to have acute coronary syndrome (12.6% vs. 27.0%) or congestive heart failure (24.5% vs. 38.2%); p 0.0001 for both comparisons. Survival improved in both groups over the study period (p 0.0001).Patients with a history of cancer who sustain IHCA are less likely to receive post-arrest procedures and survive to hospital discharge. Given the expected rise in the rates of cancer survivorship, these findings highlight the need for broader application of potentially life-saving interventions to lower risk cancer patients who have sustained a cardiac arrest.

There is increasing evidence that rates of atrial arrhythmias (AA), specifically atrial fibrillation and flutter are elevated in patients treated with the tyrosine kinase inhibitor, ibrutinib; however, the exact risk of ibrutinib-associated AA is not definitively established. We conducted a retrospective study of 137 patients diagnosed with B-cell malignancies treated with ibrutinib compared with 106 patients treated with chemotherapy for the same cancers in order to quantify the rates and risk of AA in a "real-world" sample of cancer patients. Fisher's exact test was used to evaluate for any statistically significant differences between groups. Logistic regression was used to generate odds ratios, adjusting for potential confounders. Incidence of AA was 14% (n = 17) in ibrutinib-treated patients compared with 3% (n = 3) in patients treated with chemotherapy (p = 0.009). Ibrutinib-treated patients were significantly older (mean age 67 vs 63 years, p = 0.003); however, there were no other significant differences in baseline characteristics. Ibrutinib use, age, hypertension, and previous use of ACE inhibitors, angiotensin receptor blocker use, β blocker use, and aspirin use were independently associated with incident arrhythmias. In multivariable analysis, patients treated with ibrutinib were associated with a 5-fold increased risk of developing AA (odds ratio = 5.18, 95% confidence interval 1.42 to 18.89). In conclusion, the rates and risk of AA are higher in patients treated with ibrutinib compared with chemotherapy, and this study provides strong evidence that ibrutinib itself is an independent risk factor for the development of incident AA.

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

With the advent of novel cancer therapeutics and improved screening, more patients are surviving a cancer diagnosis or living longer with advanced disease. Many of these treatments have associated cardiovascular toxicities that can manifest in both an acute and a delayed fashion. Arrhythmias are an increasingly identified complication with unique management challenges in the cancer population. The purpose of this scientific statement is to summarize the current state of knowledge regarding arrhythmia identification and treatment in patients with cancer. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. Despite increased recognition, dedicated prospective studies evaluating true incidence are lacking. Moreover, few studies have addressed appropriate prevention and treatment strategies. As such, this scientific statement serves to mobilize the cardio-oncology, electrophysiology, and oncology communities to develop clinical and scientific collaborations that will improve the care of patients with cancer who have arrhythmias.

Purpose of Review To give an overview of the role of social media (SoMe) in cardio-oncology during the COVID-19 pandemic. Recent Findings SoMe has been critical in fostering education, outreach, awareness, collaboration, dissemination of information, and advocacy in cardio-oncology. This has become increasingly evident during the COVID-19 pandemic, during which SoMe has helped share best practices, community, and research focused on the impact of COVID-19 in cardiology and hematology/oncology, with cardio-oncology at the interface of these two subspecialty fields. Summary A strength of SoMe is the ability to amplify a message in real-time, globally, with minimal investment of resources. This has been particularly beneficial for the emerging field of cardio-hematology/cardio-oncology, a field focused on the interplay of cancer and cardiovascular disease. SoMe field especially during the COVID-19 pandemic. We illustrate how social media has supported innovation (including telemedicine), amplification of healthcare workers’ voice, and illumination of pre-existing and continued health disparities within the field of cardio-oncology during the pandemic.

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.

International audience; BACKGROUND Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.OBJECTIVES This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.METHODS In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.RESULTS Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 +/- 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction

Background Global budget payments (GBP) are considered effective in containing health care expenditures; however, information on their impact on quality of cardiovascular care is limited. We aimed to evaluate the effects of GBP on utilization, outcomes, and costs for 3 major cardiovascular conditions. Methods We analyzed claims data of hospital admissions in Maryland from fiscal year 2013 to 2018. Using segmented regression, we evaluated temporal trends in hospitalizations, length of stay, percutaneous coronary intervention and coronary artery bypass grafting volumes, case mix-adjusted 30-day readmission rates, risk-standardized mortality rates, and hospitalization charges in patients with principal diagnosis of heart failure, acute ischemic stroke, and acute myocardial infarction (AMI) in relation to GBP implementation. Trends in global cardiovascular procedure charges/volumes were also studied. Results Hospitalization rates for congestive heart failure and AMI remained unaffected by GBP, while the gradient of ischemic stroke admissions decreased ( P trend P trend =0.03). Inpatient coronary artery bypass grafting surgeries decreased ( P trend P trend =0.0069). There were no significant changes in mortality for any of the 3 conditions. Hospitalization charges increased for ischemic stroke ( P trend P trend =0.1), and decreased for AMI ( P trend =0.0005). We observed a significant increase in electrocardiography rate charges ( P trend P trend =0.0003). Conclusions Introducing GBP in Maryland had no perceivable adverse effects on inpatient outcomes and quality indicators for 3 major cardiovascular conditions. Savings were observed in the AMI cohort, possibly due to reduced unnecessary readmissions, efficiency improvements, or shifts to outpatient care. Reduced cardiovascular procedure volumes were counterbalanced by a proportional rise in charges. State-level adoption of GBP with pay-for-performance incentives may be effective for cost containment without adversely impacting quality of cardiovascular care.

Background and Purpose: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. Methods: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS ( Results: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P =0.78), death (4.9% versus 8.5%, P =0.68), fatal strokes (2.4% versus 8.5%, P =0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P =0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. Conclusions: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/ ; Unique identifier: NCT02283294.

Precision medicine has ushered in a new era of targeted treatments for numerous malignancies, leading to improvements in overall survival. Unlike traditional chemotherapy, many molecular targeted antineoplastic agents are available in oral formulation, leading to enhanced patient convenience and a perception of reduced risk of adverse effects. Although oral antineoplastic agents are generally well-tolerated, cardiovascular toxicities are being reported with increasing frequency in part due to U.S. Food and Drug Administration and manufacturer recommended cardiac monitoring. Monitoring strategies have focused on left ventricular dysfunction, hypertension, and QT prolongation/arrhythmias. Given the rapid pace of development and availability of new oral antineoplastic agents, the purpose of this review is to provide clinicians with an up-to-date practical approach to monitoring and management of cardiovascular toxicities with the aim of improving overall outcomes for patients with cancer.

The number of patients with cancer-related cardiovascular disorders is increasing. This is attributed to increased survival of cancer patients who live longer (and are thus at risk for age-related cardiovascular disease) and the cardiovascular toxicities of many newer cancer drugs. Anthracyclines have been long associated with the development of dilated cardiomyopathy, especially when used with trastuzumab. Antiangiogenic targeted therapies cause new or worsening of pre-existing hypertension. Immune checkpoint inhibitors (ICIs) are associated with an increased incidence of myocarditis, while radiation therapy is associated with ischemic heart disease, valve dysfunction, conduction abnormalities, pericardial disease, and cardiomyopathy. Additionally, some cytotoxic chemotherapeutics, such as cisplatin, increase the risk of venous thromboembolism, while some antimetabolites such as fluoropyrimidines have long been associated with a broad range of cardiotoxicities. This chapter focuses on the cardiovascular conditions associated with cancer and its management, including cardiomyopathy, myocarditis, arrhythmia, valvular heart disease, and ischemic and non-ischemic vascular disease. As with any pathologic entity, the frontline efforts are geared toward treatment of those with the most emergent or severe manifestations of the disease. Simultaneous efforts are targeted at prevention of the occurrence or progression of disease. Here, we briefly discuss putative underlying mechanisms whereby cancer and its treatments can lead to the development of emergent cardiovascular conditions in oncologic patients and provide guidance for clinicians. Finally, we end the chapter with brief comments on implications for cardio-oncology during the COVID-19 pandemic and beyond.

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.

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.

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.

Our knowledge of associated cardiotoxicities from novel therapeutics in oncology continues to expand. These include arrhythmias from cancer-therapy induced cardiomyopathy resulting from both direct and indirect effects on cardiomyocytes and other mechanisms that can adversely impact cardiovascular outcomes and overall mortality. In this review, we focus on both the arrhythmias of various classes of oncologic agents as well as the use of cardiac implantable electronic devices (cardioverter-defibrillators, permanent pacemakers, and cardiac resynchronization therapy) in cardio-oncology patients.

Introduction: Cyclin Dependent Kinase (CDK) 4/6 inhibitors are a novel class of cancer therapeutics which have significantly improved survival in patients with hormone receptor positive, HER2 negative metastatic breast cancer. There is little data regarding the epidemiology of cardiotoxicity with these therapies. Methods: Using the OneFlorida Data Trust , adult patients without prior cardiovascular disease who received at least one CDK 4/6 inhibitor between January 1, 2012 and December 31, 2018 were included in the analysis. CAEs identified from ICD 9/10 codes include: new hypertension (HTN); arrhythmias (excluding sudden cardiac death); new hypertension (HTN); heart failure/cardiomyopathy; ischemic heart disease, pericardial disease. Log-rank tests were performed to compare time to all-cause mortality in patients with or without CAE. Multivariable cox proportional hazard regressions were performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for mortality adjusting for age, gender, race, obesity, HTN, diabetes (DM) and hyperlipidemia (HLD). Results: A total of 1,035, predominantly female (96%) patients were included in the analysis. The mean age was 61±13 years, and CV risk factors were prevalent at baseline: obesity (17.1%), HTN (22.2%), DM (9.9%), HLD (10.5%). Cardiotoxicity occurred in 174 (16.8%) patients of which 30 (17.2%) died (p Conclusions: Cardiotoxicity is common with CDK 4/6 inhibitors and are associated with overall increased mortality and arrhythmias and HTN accounting for a significant proportion of this finding. Patients taking CDK 4/6 inhibitors should be monitored for CAEs with aggressive risk mitigation strategies to minimize morbidity and mortality.

Introduction: Ibrutinib is a widely used treatment option for patients with chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. There is limited investigation on the relationship between ibrutinib and the development of ventricular arrhythmias. Hypothesis: We hypothesized that the incidence of ventricular arrhythmias in patients taking ibrutinib compared to the patients on other treatment regimens would be higher. Methods: We performed an aggregate data meta-analysis on nine studies to examine the incidence of ventricular arrhythmias. We further assessed a meta-regression analysis to evaluate the effect of duration of therapy on incidence of ventricular arrhythmias. Relative risk (RR) and 95% confidence intervals (CI) were estimated using a random-effects model. Results: Of 3809 patients being treated with ibrutinib, the incidence of ventricular arrhythmias was almost 8-fold higher in patients being treated with ibrutinib compared to other tyrosine kinase inhibitors (TKIs), other chemotherapies, or immunotherapy. (RR 8.13, 95% CI 4.37-15.10, p Conclusions: For patients treated with ibrutinib, there was a markedly higher rate of ventricular arrhythmias and an increased incidence with longer duration of treatment. These data highlight the need for guidelines on surveillance and management for ventricular arrhythmias for patients taking ibrutinib.

Introduction: Anthracyclines remain a key treatment for many malignancies but can increase the risk of heart failure or cardiomyopathy. Different guidelines recommend echocardiography (echo) and BNP or NT-proBNP evaluation before and 6-12 months after treatment. It is unknown however if racial/ethnic disparities exist in the cardiac surveillance of cancer survivors exposed to anthracyclines. Hypothesis: Racial/ethnic disparities are present in the adoption rates of cardiac surveillance guidelines among survivors treated with anthracyclines. Methods: 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 (OR) and 95% confidence intervals (CI) for receiving echo, BNP or NT-proBNP at 6 months prior (baseline), 6 months after (6M), and 12 months after (12M) treatment among different racial/ethnic groups. Results: A total of 2758 patients were identified, with mean age of 54 ± 16 years and 60% were women. Among the entire cohort, 43% had a baseline echo, with 18% receiving an echo at 6M and 21% at 12M. BNP or NT-proBNP were lower: 5.3% at baseline, 6.5% at 6M and 8.7% at 12M. The prevalence of baseline cardiovascular risk factors ranged from 13% for hyperlipidemia and diabetes to 19% for obesity and 29% for hypertension. Compared to Whites, Blacks (OR: 0.56, 95% CI: 0.45-0.70) and Hispanics (0.52, 0.43-0.64) were less likely to receive echo surveillance at baseline. These differences were also observed at 6M and 12M in Hispanics (Figure). Conclusions: Significant racial/ethnic differences in cardiac surveillance among cancer survivors were present before and after anthracycline-based treatment as Hispanics are least likely to receive cardiac surveillance. This points to the need for improved education and outreach to ensure all cancer survivors receive appropriate and equitable care.

Introduction: Hormone therapy has been associated with adverse cardiovascular events including arterial vascular events in men with prostate cancer. It is unclear if the risk of arterial vascular events varies by type of hormone therapy used. Methods: The Food and Drug Administration’s Adverse Event Reporting System (FAERS) was used to compare arterial vascular event reporting in men receiving hormone therapy from 01/01/2000 to 04/30/2020 for prostate cancer. Therapies evaluated were gonadotrophin-releasing hormone (GnRH) agonists (i.e. leuprolide), GnRH antagonists (i.e. degarelix), androgen receptor (AR) antagonists (i.e. bicalutamide) and abiraterone. Arterial vascular events included coronary artery disease, myocardial infarction, ischemic stroke, peripheral vascular disease, and hypertension requiring hospitalization. Polytomous logistic regression (adjusted for age, need for hospitalization, and event reporting source) was performed for non-GnRH agonists as compared to GnRH agonists. Results: Among 34,466 events reported during the study period on single agent therapy, 10.6% were arterial vascular events (5.9% hypertension requiring hospitalization, 2.3% coronary artery disease or myocardial infarction, 2.1% ischemic stroke, and 0.3% peripheral vascular disease). Median age of those with reported arterial vascular events was 76 years (IQR 70 - 82). Arterial vascular events were reported less commonly in men receiving AR antagonists (adjusted reporting odds ratio [ROR] 0.7 [95% CI 0.7-0.8], p Conclusion: Arterial vascular events are reported more commonly in men receiving GnRH agonists for prostate cancer as compared with other types of hormone monotherapy. Use of non-GnRH agonists may reduce the risk of adverse cardiovascular events on hormone therapy in men with prostate cancer.

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 ICI-related cardiotoxicity 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 2011-2017 were included. Cardiotoxicity 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 possible form of cardiotoxicity 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. Cardiotoxicity was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in those who developed ICI-attributable cardiotoxicity was higher compared to those who did not (66.1% vs. 41.4%, odds ratio=2.77, 1.55-4.95, p=0.0006). There was no evidence that use of cardioprotective agents such as beta-blockers or statins was associated with lower rates of cardiotoxicity or mortality.Conclusions: This study suggests that the incidence of ICI-related cardiotoxicity may be higher than previously reported.

Atrial fibrillation (AF) in the setting of malignancy poses a unique challenge given the confluent pathologies and risks of current treatments. Oral anticoagulation is recommended to reduce the risk of systemic thromboembolism in high-risk individuals with AF. The ‘Watchman’ device for left atrial appendage closure has shown comparable efficacy compared with anticoagulation with warfarin; however, patients with cancer were not included in trials testing Watchman safety and efficacy. We present the current treatment approaches for the management of AF in patients with malignancy. We review contemporary guidelines and propose a novel clinical decision tree by which physicians can consider left atrial appendage closure in cancer patients, and at last, suggest future investigation that might further clarify the clinical benefit of this approach.

There has been a significant shift in the management of B cell malignancies over the past decade. Initial strategies involving the use of systemic chemotherapies have been gradually replaced by more targeted therapies to improve survival and overall tolerability. Bruton’s tyrosine kinase inhibitors are breakthrough drugs that have been approved to treat many B cell malignancies. Despite their demonstrated benefits, unintended events still occur including various cardiotoxicities. In this review, we discuss the rationale behind developing these agents, their common cardiovascular toxicities, and associated management challenges.

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

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.

Adoptive cellular therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has emerged as an effective treatment option for unresectable stage III/IV metastatic melanoma. Acute toxicities, particularly cardiovascular (CV), can have a significant effect on the completion of therapy. We abstracted information on 43 patients who received ACT-TIL treatment for melanoma at the Moffitt Cancer Center between 2010 and 2016. The Student t tests and χ2 tests were used to compare patient characteristics by presence versus absence of specific CV complications. In this cohort, 32.6% developed hypotension requiring treatment with intravenous fluids and pressors, 14% atrial fibrillation, and 2.3% troponin elevations suggestive of myocardial damage. No patients developed clinical heart failure, and among the patients that underwent echocardiography, there was no significant difference in mean left ventricular ejection fraction before or after therapy (62.9% vs. 63.5%, respectively, P=0.79). There was also no statistically significant difference in survival between those with and without CV complications (overall survival=61.9%, mean: 26.0 mo and progression-free survival=45.2%, mean: 18.1 mo). CV toxicities are common in ACT-TIL protocols; however, survival does not appear to be significantly affected. Further research is needed to define mechanisms and potential prevention strategies to help clinicians manage these complications and mitigate risk.

Background: Global budgets (GB), an innovative method of hospital payment, have been considered effective in containing expenditures. In January 2014, the state of Maryland introduced Global Budget Revenues (GBR), transitioning from per case to capitated, population-based payments (PBP). Under this model, hospitals are provided yearly funds, thus being financially incentivized to improve efficiency of services. Prices are set by the Health Services Cost Review Commission (HSCRC), which collects data and monitors hospitals’ quality of care. Potential adverse incentives of GB would include underprovision of necessary services or avoiding sicker, high cost patients (cream skimming). This study aimed to evaluate the effects of GBR on the care of hospitalized patients with important CV conditions. Methods: We analyzed HSCRC inpatient claim databases containing anonymized information on statewide hospital admissions between fiscal years 2013 and 2018. Using ICD codes, we identified patients with a principal diagnosis of heart failure (CHF), acute myocardial infarction (AMI), and acute ischemic stroke (AIS) from a pool of 1,959,237 inpatient admissions. Outcome measures were: hospitalizations, length of stay (LOS), inpatient PCI and CABG procedure rates, casemix adjusted 30-day readmission rates (CARR), risk standardized in-hospital mortality, and hospitalization charges. Trends in outcome measures before and after GBR implementation were compared using segmented regression analysis, with p values indicating trend change. Results: With introduction of GBR, CHF and AMI hospitalization trends did not change significantly, whereas AIS admissions stabilized downward (p Conclusions: Adoption of GBR in Maryland had no harmful effects on in-hospital outcomes and quality measures. There was a modest improvement in potentially avoidable hospitalizations and mildly reduced utilization offset by significant rise in charges. Some observations could result from care shifts to the outpatient setting. Quality of CV care was not affected by GBR suggesting that efficiency improvements might have occurred in other areas of the healthcare system. Additionally, combining GB with pay for performance programs and assiduous quality monitoring might have mitigated adverse incentives. As GBR transitions to Maryland Total Cost of Care, long-term effects of PBP on CV outcomes will require further investigation.

Advances in cancer screening and improved treatment approaches have led to an increase in survivorship and, consequently, recognition of an association between cancer treatments and the development of cardiovascular complications. In addition, as the population becomes proportionally older, comorbid cardiovascular risk factors are more prevalent in the population and compound the risk of developing cancer treatment–related cardiovascular toxicity. Cardio-oncology has emerged as a new subspecialty of medicine that provides a multidisciplinary approach, bringing together oncologists, cardiologists, and allied health care providers who are tasked with optimizing the cardiovascular health of patients exposed to potentially cardiotoxic cancer therapy. Using a case-based approach, practical advice on how to identify, monitor, and treat patients with cancer who are at risk for developing cancer treatment–related cardiovascular dysfunction is discussed. Cardiovascular risk factors (e.g., age, hypertension, diabetes) and cancer therapies (chemotherapy, targeted therapy, radiation) associated with cardiovascular toxicity are presented. Current cardiac monitoring strategies such as two- and three-dimensional echocardiography, cardiac MRI, and biomarkers (troponin and brain natriuretic peptide [BNP]) are discussed. Last, the current literature on pharmacologic (e.g., angiotensin-converting enzyme inhibitors, β-blockers, statins) and lifestyle (diet and exercise) strategies to mitigate cardiovascular toxicity during and following completion of cancer therapy are reviewed.

Author(s): Zhang, Lili; Awadalla, Magid; Mahmood, Syed S; Nohria, Anju; Hassan, Malek Z O; Thuny, Franck; Zlotoff, Daniel A; Murphy, Sean P; Stone, James R; Golden, Doll Lauren Alexandra; Alvi, Raza M; Rokicki, Adam; Jones-O'Connor, Maeve; Cohen, Justine V; Heinzerling, Lucie M; Mulligan, Connor; Armanious, Merna; Barac, Ana; Forrestal, Brian J; Sullivan, Ryan J; Kwong, Raymond Y; Yang, Eric H; Damrongwatanasuk, Rongras; Chen, Carol L; Gupta, Dipti; Kirchberger, Michael C; Moslehi, Javid J; Coelho-Filho, Otavio R; Ganatra, Sarju; Rizvi, Muhammad A; Sahni, Gagan; Tocchetti, Carlo G; Mercurio, Valentina; Mahmoudi, Michael; Lawrence, Donald P; Reynolds, Kerry L; Weinsaft, Jonathan W; Baksi, A John; Ederhy, Stephane; Groarke, John D; Lyon, Alexander R; Fradley, Michael G; Thavendiranathan, Paaladinesh; Neilan, Tomas G | Abstract: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented.From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE.These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

Introduction Pembrolizumab is an immune checkpoint inhibitor targeting the programmed death receptor with clinical effect on multiple malignancies including sarcoma. Associated cardio-toxicities include myocarditis, cardiomyopathy, heart failure, and arrhythmias. Although in most cases of immune checkpoint inhibitor cardiotoxicity the offending agent is discontinued, we report a case of successful and safe re-challenge with a checkpoint inhibitor in a patient with mild myocarditis. Case report We describe a 37-year-old female with alveolar soft part sarcoma, metastatic to the lungs on cycle 13 of pembrolizumab who presented with dyspnea, cough, and vague chest discomfort. Telemetry showed bigeminal bradycardia that transitioned to self-terminating torsades de pointes. Cardiac MRI showed subtle patchy T2 signal increase within the left ventricular septum without late gadolinium uptake, suggesting mild focal myocarditis. Management and outcome: The patient was started on a steroid taper without additional arrhythmias. We have re-challenged the patient who safely tolerated re-challenge with pembrolizumab despite an episode of torsades de pointes and documented myocarditis. She continues to receive pembrolizumab at seven months after the initial event without further cardiovascular events. Discussion To the best of our knowledge, this is the first reported case of successful re-challenge of pembrolizumab after an episode of myocarditis. In patients with mild myocarditis and no evidence of left ventricular dysfunction, re-challenge may be a viable option. However, close monitoring for the development of heart failure, cardiomyopathy, or serious arrhythmias is necessary to ensure patient safety.

Ponatinib is associated with cardiovascular adverse events (CAEs), and its frequency in the real world is limited. In this retrospective study, we examined the survival outcomes and associated toxicities in 78 consecutive ponatinib-treated patients with chronic myeloid leukemia (CML) at the Moffitt Cancer Center from January 2011 through December 2017. The most common non-CAE was thrombocytopenia (39.7%), occurring in a dose-dependent fashion. Eighteen patients (23.1%) experienced some form of CAE, with the most common being arrhythmia (9%) and hypertension (7.7%), whereas 3 patients experienced myocardial infarction (3.8%). Before 2014, most patients were started on ponatinib 45 mg daily. There was an inverse correlation between cardio-oncology referral and the number of CAEs (P = .0440); however, a lower ponatinib starting dose, more frequent dose reduction, and increased cardio-oncology referral all were likely to have contributed to the observed decrease in CAEs after 2014. The response rate and 5-year overall survival (OS) were higher than those observed in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial (major molecular response, 58.7% vs 40% and OS, 76% vs 73%; median follow-up of 32.5 months). Ponatinib-treated patients with chronic phase–CML did not show a significant improvement with allogeneic stem cell transplantation, whereas those with accelerated phase/blast phase–CML had a much better outcome (median OS of 32.9 months vs 9.2 months; P = .01). These results demonstrate that ponatinib is highly effective. Dose adjustments and increased awareness of the cardiotoxicities associated with ponatinib may help maximize its benefits.

BACKGROUND Recent heart failure (HF) patient and informal caregiver (eg, dyadic) studies have either examined self-care from a qualitative or quantitative perspective. To date, the 2 types of data have not been integrated. OBJECTIVE The aim of this study was to understand HF self-care within the context of dyadic engagement. METHODS This was a cross-sectional, mixed methods (quantitative/qualitative) study. Heart failure self-care was measured with the Self-care of Heart Failure Index (v.6) dichotomized to adequate (≥70) or inadequate (

Background Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. Objectives The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. Methods After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. Results The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p Conclusions Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.

In cardiovascular (CV) medicine, the use of social media (SoMe) has increased the dissemination of scientific knowledge, including the sharing of scientific journal articles. With the rapid growth of online methods for communicating scientific research, the critical question is whether online attention correlates with citations in academic journal articles. Traditionally, the performance of a scientific journal article has been determined by the number of times it has been cited. The impact factor and the number of citations in peer-reviewed journals are widely accepted measures of scientific impact. Social media platforms such as Twitter ( Twitter.com ) enable the development of novel article- or journal-level metrics for assessing effect and influence. Indeed, “alternative metrics” for journal article impact have been proposed, with the most frequently used being the Altmetric Attention Score (AAS; Altmetric.com ). The relationship between these new metrics and established indicators such as citations has not been thoroughly investigated. We summarize numerous studies investigating associations between social media posts about journal articles and journal article citations. We then describe our own journal's social media strategy in light of these findings.

Patients with multiple myeloma (MM) have improved treatment options, including immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). Despite their efficacy, increased rates of cardiovascular (CV) complications occur in patients exposed to some of these therapies. While previous research has focused on identifying the toxicities inherent to each specific agent, the CV side effects may be potentiated by the combination of PIs and IMiDs plus dexamethasone. We present a patient with MM with recurrent cardiotoxicity only when exposed to combination PI and IMiD-based therapy. We also review the literature in this context, and propose a potential algorithm for cardiotoxicity prevention in this population.