Search

Aims The national incidence, risk factors, and associated mortality of atrial fibrillation (AF) in breast cancer patients are unknown. Methods and results Using the Surveillance, Epidemiology, and End Results-Medicare-linked database, we identified females, ≥66 years old, with a new primary diagnosis of breast cancer from 2007 through 2014. These patients were individually matched 1:1 to Medicare enrolees without cancer, and each pair was followed for 1 year to identify a primary outcome of AF. Cumulative incidence was calculated using competing risk survival statistics. Following this, identifying risk factors of AF among breast cancer patients was conducted using the adjusted Cox proportional hazards model. Finally, Kaplan–Meier methods and adjusted Cox proportional hazards modelling were performed to estimate mortality in breast cancer patients with incident and prevalent AF. This study included 85 423 breast cancer patients. Among these 9425 (11.0%) had AF diagnosis prior to the breast cancer diagnosis. New-onset AF was diagnosed in 2993 (3.9%) patients in a 1-year period after the breast cancer diagnosis [incidence 3.3%, 95% confidence interval (CI) 3.0–3.5%, at 1 year; higher rate in the first 60 days (0.6%/month)]. Comparatively, the incidence of new-onset AF in matched non-cancer controls was 1.8% (95% CI 1.6–2.0%). Apart from traditional demographic and cardiovascular risk factors, breast cancer stage was strongly associated with the development of AF [American Joint Committee on Cancer (AJCC) Stage II/III/IV vs. I: adjusted hazard ratio (aHR) 1.51/2.63/4.21, respectively]. New-onset AF after breast cancer diagnosis (aHR 3.00) is associated with increased 1-year cardiovascular mortality. Conclusion AF incidence is significantly higher in women after a breast cancer diagnosis. Higher breast cancer stages at diagnos are significantly associated with a higher risk of AF. New-onset AF in the new breast cancer diagnosis setting increases 1-year cardiovascular mortality but not breast cancer-related mortality. Key Question What are the incidence, prevalence, risk factors and mortality outcomes of atrial fibrillation (AF) in a multi-ethnic representative United States cohort of breast cancer patients? Key Finding Annual incidence for AF is 3.9% with highest rate in the first 60 days after cancer diagnosis. Cancer stage and grade are the strongest risk factors for AF. New onset AF after breast cancer increases all-cause and cardiovascular mortality. Take Home Message AF incidence is higher in breast cancer patients and is associated with later stage and grade at diagnosis of breast cancer. Involving cardio-oncology in those who develop AF after cancer diagnosis should be encouraged to improve their cardiovascular and overall prognosis.

Purpose:The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known.Materials and Methods:We queried the U.S. Food and Drug Adminis...

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.

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., In two independent real‐world cohorts, combination BRAF/MEK inhibitors were associated with increased cardiovascular adverse events compared to monotherapy, especially HF, and hypertension.

Cancer patients face a higher risk of future myocardial infarction (MI), even after completion of anticancer therapies. MI is a critical source of physical and financial stress in non-cancer patients, but its impacts associated with cancer patients also saddled with the worry (stress) of potential reoccurrence is unknown. Therefore, we aimed to quantify MI’s stress and financial burden after surviving cancer and compare to those never diagnosed with cancer. Utilizing cross-sectional national survey data from 2013–2018 derived from publicly available U.S. datasets, the National Health Interview Survey (NHIS), and economic data from the National Inpatient Sample (NIS), we compared the socio-economic outcomes among those with MI by cancer-status. We adjusted for social, demographic, and clinical factors. Overall, 19,504 (10.2%) of the 189,836 NHIS survey responders reported having cancer for more than 1 year. There was an increased prevalence of MI among cancer survivors compared to non-cancer patients (8.8% vs. 3.2%, P0.05). There was no difference in annual residual family income by cancer status; however, 3 lowest deciles of residual income representing 21.1% cancer-survivor with MI had a residual income of

Background Atrial fibrillation (AF) is a common cardiovascular complication affecting patients with cancer, but management strategies are not well established. Objectives The purpose of this retrospective cohort study was to evaluate cross-sectional patterns of anticoagulation (AC) use in patients with cancer with AF or atrial flutter (AFL) on the basis of their risk for stroke and bleeding. Methods Patients with cancer and electrocardiograms showing AF or AFL performed at Moffitt Cancer Center in either the inpatient or outpatient setting were included in this retrospective analysis. We described percentages of AC prescription by stroke and bleeding risk, as determined by individual CHA2DS2-VASc and HAS-BLED scores, respectively. Multivariable logistic regression evaluated clinical variables independently associated with anticoagulant prescription. Results The prevalence of electrocardiography-documented AF or AFL was 4.8% (n = 472). The mean CHA2DS2-VASc score was 2.8 ± 1.4. Among patients with CHA2DS2-VASc scores ≥2 and HAS-BLED scores, Central Illustration

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.

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.

Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.

Background Radiation-induced coronary artery disease (R-CAD) has become an increasingly recognized phenomenon. Although the clinical relationship between radiation therapy and CAD risk is well known, there is minimal investigation of the gender relationship to radiation-induced CAD events and the resulting cardiovascular (CV) events/mortality. We study the gender variation in the incidence of CV events/mortality related to R-CAD in Hodgkin’s Lymphoma (HL) patients. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this systematic review and network meta-analysis. OVID, Cochrane Central Register of Controlled Trials via the Wiley Interface, Web of Science Core Collection, MEDLINE, EMBASE, and Google Scholar were investigated to identify prospective and retrospective observational studies comparing women and men following radiation treatment for Hodgkin’s lymphoma. Ten studies were included (4 prospective, 6 retrospective). The primary outcome was incidence of cardiovascular events/mortality. The secondary outcome was all-cause mortality. Meta-regression for age was also performed. Results Of 13,975 patients, including 41% females and 59% males, CV events/mortality were noted to be significantly higher in women compared to men (OR 3.74, 95% CI 2.44–5.72, p p p = 0.0374). Conclusions Women have a higher rate of R-CAD related CV events/mortality and all-cause mortality compared to men amongst radiation-treated patients. These data highlight the need for increased surveillance to better monitor for R-CAD in female patients treated with mantle or mediastinal radiation.

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.

Background: The TEEL Study was an open labeled, non-randomized; phase I dose escalation followed by a planned phase Ib dose expansion trial of Tamoxifen (Tam) with Ribociclib (Ribo) in adult patients with advanced ER+ (HER2 negative) breast cancer. Ribo is an inhibitor of cyclin D1/CDK4 and CDK6 and has been successfully combined with Letrozole to improve PFS. This trial was done to examine the safety of the combination of Tam and Ribo in pre- and post-menopausal pts. The goal of the phase 1 expansion was to help confirm safety and develop a daily dosing schedule. Both Tam and Ribo were known to cause QTC prolongation and this was a major safety concern of the study. Method: This was an open labeled, non-randomized, phase I escalation study with a phase Ib dose expansion. The phase I portion of the study was a dose escalation to determine the safety of the combination and to determine the MTD and the RP2D for Ribo with Tam. Breast cancer patients with HR+/HER2- locally advanced or metastatic breast cancer with any prior endocrine therapy and up to two lines of prior cytotoxic chemotherapy regimens administered in the metastatic or locally advanced setting. The planned Phase Ib dose expansion was not done but was planned to better characterize the toxicity profile and assess the anti-tumor activity Ribo + Tam and to further evaluate the safety of the combination. Triplicate EKG were done at baseline, at C1D1, C1D15, C1D22, and then every subsequent cycle at day 1. Results: A total of 12 patients were screened and 7 patients were enrolled (with 5 screen failures). Ribociclib was given at 400 mg po daily for 21 days on and 7 days off. Tamoxifen was given per standard at 20 mg daily. The best response was partial response. Each cycle was 4 weeks and 1 patient remained on this combination for at least 12 cycles with PR, after cycle 3 and SD thereafter. Two patients developed significant QTC prolongation. Pt. # 3 was taken off study for QTC prolongation after cycle 8 with QTC >501. Prior to that, her treatment had been interrupted twice due to QTC prolongation. Her First EKG was manually calculated at: QT 370ms, QTcb 427ms, QTcf 407ms. Her Longest EKG: QT 402ms, QTcb 514ms, QTcf 473ms. Pt #12 was also taken off study during cycle 6 due to QTC>501. Her first EKG: QTc382ms, QTcb 480ms, QTcf 445ms. “Longest ekg” QTc 432ms, QTcb 496ms, QTcf 473ms. Both of these patients had prolonged QTC based on manual EKG. Dose limiting toxicity was noted in patient #10 who was noted to develop progression of disease (new leptomeningeal disease) after cycle 1 and subsequently had a CVA off study, thought to be associated with progressive disease. Table 1 describes highest QTC vs. cycle of therapy and there does not appear to be evidence of worsening prolongation with the number of cycles on study drugs. Other AEs were noted - please see table 2 for AEs. Conclusions: The combination of Tam and Ribo was not considered to be safe and there were two DLTs in the phase 1 part of the study, leading to the early stopping. The phase I expansion was not completed. There were 5 events of prolonged QTC, one event was determined to be a DLT. The other DLT was a CVA described above (associated with CNS disease). Unfortunately, the combination was limited by the synergistic effects of QTC prolongation of both Tam and Ribo. The importance of manually calculating the EKGs and utilizing the Fridericia formula was noted in this study. The Fidercicia is more accurate in oncology patients as it demonstrates less overcorrection than the Bazzett formula at faster heart rates which a were re quite common in cancer patients. Rational limits must be implemented to ensure patient safety without unnecessary withholding of potentially lifesaving cancer therapies. The relative risk of arrhythmia is 1.2 for QT intervals >500ms and is exceedingly low at QT intervals less than 500ms. QTC duirng each cycleCyclesC1C3C5C7C9C10C11C12Pt. 1475475468465477457481477Pt. 2412421412Pt. 3463462494689479Pt. 8450443Pt. 10420Pt. 11431435437Pt. 12480475513525 Citation Format: Roohi Ismail-Khan, Hatem Soliman, Deanna Hogue, Hyo Sook Han, Martine Extermann, Michael Fradley. The cardo-oncology concerns of combining tamoxifen and ribociclib based on the TEEL trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-05.

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

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.

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.

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.

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.

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.

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: 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.

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.

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.

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.

Background Cardiac magnetic resonance imaging (MRI) is emerging as an important diagnostic modality in the management of cardiovascular-related dysfunction in oncological diseases. Advances in imaging techniques have enhanced the detection and evaluation of cardiac masses; meanwhile, innovative applications have created a growing role for cardiac MRI for the management of cardiotoxicity caused by cancer therapies. Methods An overview is provided of the clinical indications and technical considerations of cardiac MRI. Its role in the evaluation of cardiac masses and cardiac function is reviewed, and novel sequences are discussed that are giving rise to future directions in cardio-oncology research. A review of the literature was also performed, focusing on cardiac MRI findings associated with cardiac dysfunction related to cancer treatment. Results Cardiac MRI can be used to differentiate benign and malignant primary cardiac tumors, metastatic disease, and pseudotumors with high spatial and temporal resolution. Cardiac MRI can also be used to detect the early and long-term effects of cardiotoxicity related to cancer therapy. This is accomplished through a multiparametric approach that uses conventional bright blood, dark blood, and postcontrast sequences while also considering the applicability of newer T1 and T2 mapping sequences and other emerging techniques. Conclusions Cardio-oncology programs have an expanding presence in the multidisciplinary approach of cancer care. Consequently, knowledge of cardiac MRI and its potential applications is critical to the success of contemporary cancer diagnostics and cancer management.

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.

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: 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 (

With improved screening and the advent of many novel therapeutics, patients with cancer are living longer and often surviving their disease. Cardiovascular complications have significant impact on both short- and long-term morbidity and mortality in these patients. While a great deal of attention has been paid to cardiomyopathy and heart failure, many other cardiotoxicities can occur, often at higher rates. Arrhythmias are a particularly common cardiovascular complication of cancer therapeutics and can range from benign to life threatening. Moreover, management of these rhythm disturbances can be challenging in cancer patients for various reasons including drug interactions, as well as underlying hematologic and metabolic disturbances. In this review, we describe the most common therapeutics associated with arrhythmias in cancer patients and provide a discussion about the potential basic and translational mechanisms leading to the development of the various rhythm disturbances which may help to guide prevention and treatment decisions. Clinicaltrials.gov Identifier: NCT02928497

BACKGROUND Most symptom management takes place in the community, conducted by patient and/or informal carer dyads with guidance from clinicians. Given the prevalence of cancer, there is a critical need for examination of the impact of managing multiple symptoms, particularly those that cluster with fatigue, on informal carers. OBJECTIVES To (1) examine clustering of patient fatigue-related symptom severity and distress in individuals with cancer and (2) test the hypothesis that patient fatigue-related symptom clusters (severity, distress) will be positively associated with carer depressive symptoms. METHODS Secondary analysis of 689 hospice patient/informal carer dyads using exploratory factor analysis and structural equation modeling. Patient symptoms were measured by the Memorial Symptom Assessment Scale, and carer depressive symptoms were measured by the Center for Epidemiological Study-Depression Scale. RESULTS Patients were 73 (SD, 12) years old, and 43% were female. Carers were 65 years (SD, 14) years old, and 74% were female. For symptom severity, dyspnea, dry mouth, lack of appetite, drowsiness, cough, dizziness, and difficulty swallowing clustered with fatigue. For symptom distress, dyspnea, cough, and dry mouth clustered with fatigue. Structural equation modeling results indicated that the patient fatigue severity cluster was positively related to carer depressive symptoms (b = 0.12, P < .05), but distress was not. CONCLUSION Managing multiple symptoms that cluster with fatigue negatively impacts informal carers. IMPLICATIONS FOR PRACTICE When patients complain of severe fatigue, clinicians need to explore all causes and ask about other symptoms while exploring whether the informal carer is feeling burdened or depressed.

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

Cardiovascular toxicities are potentially serious treatment limiting complications of many different cancer therapeutics including traditional cytotoxic chemotherapies as well as targeted- and immunotherapies. As a result, there is increased monitoring for cancer treatment-related cardiotoxicities, ranging from heart failure to arrhythmias. Many anticancer treatments are known to prolong the QT interval through a variety of mechanisms including direct effects on ion channels and indirectly via intracellular signaling pathways. While QT prolongation increases the risk for the potentially life-threatening ventricular arrhythmia torsades de pointes, the incidence of this arrhythmia in the setting of most cancer treatments is quite rare, and the majority of patients can continue safely receiving these medications despite their QT prolonging potential. A multidisciplinary approach to the cardiovascular care of the cancer patient is essential to mitigate risk of cardiotoxicity while minimizing unnecessary treatment disruption of potentially life-saving cancer treatments.

Purpose of Review: The anticoagulation strategies for various cardiac-specific pathologies including atrial fibrillation are changing. Applying these strategies in patients with concomitant active cancer requires additional considerations. Here, we review the most recent changes in the anticoagulation management of common cardiac diseases and their application in cancer patients. Recnt Findings: There are a range of indications for therapeutic anticoagulation in cancer patients including venous thromboembolism (VTE), atrial fibrillation/flutter (AF/AFL), prosthetic heart valves, and intracardiac thrombi. Certain cancer therapeutics such as ibrutinib and anthracycline chemotherapy increase the risk of developing AF/AFL and pose unique challenges in anticoagulation management. Anticoagulation decisions for AF/AFL often utilize the CHADS2 or the CHA2DS2-VASc score with annualized stroke risk; however, these risk stratification models may be inadequate in cancer patients. Cancer type, stage, prognosis, and bleeding risk are all relevant when considering whether to initiate therapeutic anticoagulation. Moreover, thrombocytopenia may limit the ability to provide anticoagulation. Subsequent analyses of direct oral anticoagulants (DOACs) show fewer bleeding complications and thromboembolic events compared to warfarin in AF/AFL with apixaban and edoxaban particularly promising in this population for VTE, pulmonary embolism, and AF/AFL. There is a lack of data regarding ablation therapy and left atrial occlusion devices in this population. There is a growing experience of DOACs for intracardiac thrombi. Warfarin is still appropriate for patients with prosthetic heart valves and left ventricular assist devices. Summary: Anticoagulation management in the cancer patient can be challenging. DOACs are often a safe alternative to warfarin in cancer-associated DVT/PE and AF/AFL, and may be preferable in certain circumstances. Other cardiac indications for anticoagulation including the presence of a mechanical heart valve remain unchanged and dependent on warfarin or heparin-based products.