Cardiotoxicity from bruton tyrosine kinase inhibitors (BTKi)-an analysis of an administrative health claims database.

BACKGROUND: First generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.,acalabrutinib and zanabrutinib) have been associated with lower incidence of cardiotoxicity in clinical trials. OBJECTIVE: Given paucity in real-world data on the overall cardiac risk factor profile, especially with the newer BTKi, our study evaluated the incidence of cardiotoxicity with various BTKi among a large, commercially insured population of patients. METHODS: We performed a retrospective cohort analysis of all adults with a diagnosis of B-cell malignancy undergoing treatment with BTKi acalabrutinib and ibrutinib between January 2018 and June 2020 using Optum's de-identified Clinformatics® Data Mart Database. We then identified patients who had pre-existing cardiac disease one year prior to starting BTKi. New incidence of atrial fibrillation/flutter, hypertension, bleeding, ventricular tachycardia/fibrillation and sudden cardiac death from the time of index presciption were compared with standard Chi Square or Student t-test where appropriate. Multivariate logistic regression models were also estimated to evaluate for confounding. RESULTS: A total of 1691 patients were included in the final analysis. 1595 (94%, median age 75 (19-90) years, 61% male gender) patients received ibrutinib, and 96 (6%, median age 73.5 (32-90) years, 62.5% male gender) patients received acalabrutinib. The median duration of drug exposure of ibrutinib was 238 (2-1084) days vs. 150 (30-870) days for acalabrutinib. There was lower new incidence of atrial fibrillation/flutter (4.6%-vs-17%, p = 0.013), hypertension (6.3%-vs-25%, p = NS), sudden cardiac arrest/death (0% vs. 1.5%, p = NS) in the acalabrutinib group compared to ibrutinib, of which only the lower incidence of atrial fibrillation/flutter was statistically significant. This was despite the finding of a higher prevalence of atrial fibrillation/flutter at baseline in patients receiving acalabrutinib. CONCLUSIONS: There was lower incidence of new atrial fibrillation/flutter with acalabrutinib when compared to ibrutinib in a real-world cohort of patients.

Cardiac radiation dose is associated with inferior survival but not cardiac events in patients with locally advanced non-small cell lung cancer in the era of immune checkpoint inhibitor consolidation.

PURPOSE: We assessed the association of cardiac radiation dose with cardiac events and survival post-chemoradiation therapy (CRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) after adoption of modern radiation therapy (RT) techniques, stricter cardiac dose constraints, and immune checkpoint inhibitor (ICI) consolidation. METHODS AND MATERIALS: This single-institution, multi-site retrospective study included 335 patients with LA-NSCLC treated with definitive, concurrent CRT between October 2017 and December 2021. All patients were evaluated for ICI consolidation. Planning dose constraints included heart mean dose < 20 Gy (<10 Gy if feasible) and heart volume receiving ≥ 50 Gy (V50Gy) < 25 %. Twenty-one dosimetric parameters for three different cardiac structures (heart, left anterior descending coronary artery [LAD], and left ventricle) were extracted. Primary endpoint was any major adverse cardiac event (MACE) post-CRT, defined as acute coronary syndrome, heart failure, coronary revascularization, or cardiac-related death. Secondary endpoints were: grade ≥ 3 cardiac events (per CTCAE v5.0), overall survival (OS), lung cancer-specific mortality (LCSM), and other-cause mortality (OCM). RESULTS: Median age was 68 years, 139 (41 %) had baseline coronary heart disease, and 225 (67 %) received ICI consolidation. Proton therapy was used in 117 (35 %) and intensity-modulated RT in 199 (59 %). Median LAD V15Gy was 1.4 % (IQR 0-22) and median heart mean dose was 8.7 Gy (IQR 4.6-14.4). Median follow-up was 3.3 years. Two-year cumulative incidence of MACE was 9.5 % for all patients and 14.3 % for those with baseline coronary heart disease. Two-year cumulative incidence of grade ≥ 3 cardiac events was 20.4 %. No cardiac dosimetric parameter was associated with an increased risk of MACE or grade ≥ 3 cardiac events. On multivariable analysis, cardiac dose (LAD V15Gy and heart mean dose) was associated with worse OS, driven by an association with LCSM but not OCM. CONCLUSIONS: With modern RT techniques, stricter cardiac dose constraints, and ICI consolidation, cardiac dose was associated with LCSM but not OCM or cardiac events in patients with LA-NSCLC.

Feasibility and outcomes from using a commitment device and text message reminders to increase adherence to time-restricted eating: A randomized trial.

BACKGROUND: Obesity is strongly associated with cardiovascular disease, particularly through its effects on blood pressure. Though maintaining a negative caloric balance leads to weight loss, many patients struggle to adhere to low calorie diets over the long term. Time-restricted eating, a subtype of intermittent fasting (IF), may be an easier dietary pattern for patients to initiate and maintain. We tested the feasibility of a bidirectional texting strategy to help patients with obesity and hypertension initiate and maintain time-restricted eating, and whether a commitment device, a pledge to behave in a certain way in the future while making nonadherence costlier, would increase adherence beyond bidirectional texting. METHODS: Patients with obesity and hypertension seen in cardiology clinics were provided education on time-restricted eating and randomized to a commitment device versus attention control. Attention control consisted of daily bidirectional text messages asking whether patients adhered to IF and weekly text messages asking participants to send their weight and blood pressure. The commitment device involved the same text messages as attention control, plus a commitment contract, setting of implementation intentions with respect to details of time-restricted eating, and involvement of a support partner who received weekly updates on the participant's adherence to time-restricted eating. The intervention lasted 12 weeks, followed by a 6-week follow-up period. The primary outcome was days per week adherent to time-restricted eating over the 18-week study period, measured by daily self-report. We also compared change from baseline weight and blood pressure between randomized groups. RESULTS: A total of 37 patients were randomized and started the study-20 to attention control and 17 to the commitment device. Mean age was 60 years old, and mean BMI was 38.4 kg/m2. Over the 18-week study period, the mean ± standard deviation (SD) number of days per week adherent to time-restricted eating was 4.7 ± 1.9 in the control arm and 5.4 ± 1.7 in the intervention arm (P = .23). Mean systolic blood pressure declined from 135 to 128 mm Hg among all participants (P = .006) with no difference between groups in change from baseline blood pressure (P = .74). Weight decreased from 229 to 223 pounds among all participants (P = .25) with no significant difference between groups in change from baseline weight (P = .84). CONCLUSIONS: A bidirectional texting strategy was feasible for helping patients with obesity and hypertension initiate and adhere to time-restricted eating. Adding a commitment device to bidirectional texting did not increase adherence to time-restricted eating compared with attention control, nor were there significant between group changes in blood pressure or weight, but these comparisons were underpowered. A larger randomized trial of the effect of this scalable intervention, compared with usual care, on blood pressure and weight among patients with obesity and hypertension is warranted. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov; unique identifier: NCT04836312.

Death without progression as an endpoint to describe cardiac radiation effects in locally advanced non-small cell lung cancer.

Background and purpose: Prior studies have examined associations of cardiovascular substructure dose with overall survival (OS) or cardiac events after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC). Herein, we investigate an alternative endpoint, death without cancer progression (DWP), which is potentially more specific than OS and more sensitive than cardiac events for understanding CRT toxicity. Materials and methods: We retrospectively reviewed records of 187 patients with locally advanced or oligometastatic NSCLC treated with definitive CRT from 2008 to 2016 at a single institution. Dosimetric parameters to the heart, lung, and ten cardiovascular substructures were extracted. Charlson Comorbidity Index (CCI), excluding NSCLC diagnosis, was used to stratify patients into CCI low (0-2; n = 66), CCI intermediate (3-4; n = 78), and CCI high (≥5; n = 43) groups. Primary endpoint was DWP, modeled with competing risk regression. Secondary endpoints included OS. An external cohort consisted of 140 patients from another institution. Results: Median follow-up was 7.3 years for survivors. Death occurred in 143 patients (76.5 %), including death after progression in 118 (63.1 %) and DWP in 25 (13.4 %). On multivariable analysis, increasing CCI stratum and mean heart dose were associated with DWP. For mean heart dose ≥ 10 Gy vs < 10 Gy, DWP was higher (5-year rate, 16.9 % vs 6.7 %, p = 0.04) and OS worse (median, 22.9 vs 34.1 months, p < 0.001). Ventricle (left, right, and bilateral) and pericardial but not atrial substructure dose were associated with DWP, whereas all three were inversely associated with OS. Cutpoint analysis identified right ventricle mean dose ≥ 5.5 Gy as a predictor of DWP. In the external cohort, we confirmed an association of ventricle, but not atrial, dose with DWP. Conclusion: Cardiovascular substructure dose showed distinct associations with DWP. Future cardiotoxicity studies in NSCLC could consider DWP as an endpoint.

Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement.

The discipline of Cardio-Oncology has seen tremendous growth over the past decade. It is devoted to the cardiovascular (CV) care of the cancer patient, especially to the mitigation and management of CV complications or toxicities of cancer therapies, which can have profound implications on prognosis. To that effect, many studies have assessed CV toxicities in patients undergoing various types of cancer therapies; however, direct comparisons have proven difficult due to lack of uniformity in CV toxicity endpoints. Similarly, in clinical practice, there can be substantial differences in the understanding of what constitutes CV toxicity, which can lead to significant variation in patient management and outcomes. This document addresses these issues and provides consensus definitions for the most commonly reported CV toxicities, including cardiomyopathy/heart failure and myocarditis, vascular toxicity, and hypertension, as well as arrhythmias and QTc prolongation. The current document reflects a harmonizing review of the current landscape in CV toxicities and the definitions used to define these. This consensus effort aims to provide a structure for definitions of CV toxicity in the clinic and for future research. It will be important to link the definitions outlined herein to outcomes in clinical practice and CV endpoints in clinical trials. It should facilitate communication across various disciplines to improve clinical outcomes for cancer patients with CV diseases.

Characterization of Pericarditis following Allogeneic Hematopoietic Cell Transplantation.

Pericarditis is an uncommon cardiac complication following allogeneic hematopoietic cell transplantation (alloHCT), with limited data characterizing its incidence, presentation, and management. The etiology of pericarditis in this setting is poorly understood and may include conditioning-related toxicity, infection, or graft-versus-host disease (GVHD). The objective of the present study was to characterize the clinical presentation, management, and outcomes of post-alloHCT pericarditis observed at a single center. This retrospective case-control study of consecutive adults undergoing alloHCT over 5 years was conducted to identify patients who developed pericarditis. Pericarditis was diagnosed using clinical, electrocardiography, and echocardiography findings. Identified cases were compared with a cohort of patients who underwent alloHCT during the same period but did not develop pericarditis. A total of 620 patients underwent alloHCT over the 5-year period, 20 of whom developed pericarditis (3.2% incidence). One patient had a pre-alloHCT history of pericarditis. All but 3 patients had received anthracycline therapy and 1 patient had received chest irradiation before undergoing alloHCT. Patients with pericarditis were more likely than patients without pericarditis to have received total body irradiation (odds ratio [OR], 4.57; P = .003) or cyclophosphamide (OR, 2.35; P = .07) as conditioning or GVHD prophylaxis. Fourteen patients experienced their initial episode of pericarditis before day +100 post-alloHCT, with a median time to onset at day +7. Six patients had their initial episode on day +100 or later, with a median time to onset at day +268. Only 1 patient had active, previously diagnosed GVHD, and 3 patients were on systemic steroid therapy at the time of pericarditis diagnosis. Pericarditis was treated primarily with colchicine (median duration 91 days). Seven episodes of recurrence occurred in 5 patients. Two patients experienced cardiac tamponade following their initial diagnosis, and 3 developed tamponade at recurrence. Recurrence was more common in patients who received no or <90 days of colchicine compared with those who received ≥90 days (45.5% vs 0%; P = .02). No cardiac-related deaths occurred. Overall survival was 85% at a median follow-up of 30 months post-alloHCT. Pericarditis occurred in 3.2% of patients in this single-center study, with cases observed both before and after day +100 and some cases occurring ≥1 year after alloHCT. Colchicine was an effective intervention, with ≥90 days of treatment associated with reduced recurrence. Pericarditis should be considered in patients presenting with chest pain following alloHCT.

Cardiac Magnetic Resonance in Cardio-Oncology: Advantages, Importance of Expediency, and Considerations to Navigate Pre-Authorization.

Diagnosis of acute and late cardiotoxicity from cancer therapeutics has become increasingly important as the scope of cardio-oncology increases exponentially, both in terms of the number of people affected and the types of therapies it encompasses. Cardiac magnetic resonance (CMR) is a tool that can offer unparalleled diagnostic information compared with other imaging modalities, but its utilization is often delayed, at the expense of patient care, due to the need for insurance pre-authorization. This paper highlights situations in which CMR is preferred as the diagnostic modality and provides examples of diagnoses more likely to be approved by insurance companies. It also provides specific cardio-oncology diagnoses or questions to help the clinical cardio-oncologist navigate the pre-authorization process.

Clinical Approach to Cardiovascular Toxicity of Oral Antineoplastic Agents: JACC State-of-the-Art Review.

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.

Treatment of corticosteroid refractory immune checkpoint inhibitor myocarditis with Infliximab: a case series.

BACKGROUND: Glucocorticoid treatment remains the cornerstone of therapy for immune checkpoint inhibitor (ICI) myocarditis, but data supporting the use of additional immunotherapy for steroid refractory cases remains limited. We investigate the safety and efficacy of infliximab in patients with ICI myocarditis who are refractory to corticosteroids. Additionally, we highlight the importance of a multi-disciplinary approach in the care for these complex patients. METHODS: We retrospectively identified consecutive patients who developed ICI myocarditis at our institution between January 2017 and January 2020. Baseline characteristics, laboratory data and clinical outcomes were compared between patients who received infliximab and those who did not. RESULTS: Of a total of 11 patients who developed ICI myocarditis, 4 were treated with infliximab. Aside from age, there were no significant differences in baseline patient characteristics between the two groups including total number of ICI doses received and duration from initial ICI dose to onset of symptoms. The time to troponin normalization was 58 vs. 151.5 days (p = 0.25). The duration of prednisone taper was longer in the infliximab group (90 vs. 150 days p = 0.32). All patients survived initial hospital admission. Over a median follow-up period of 287 days, two of the 4 patients died from sepsis 2 and 3 months after initial treatment of their myocarditis; one of these patients was on a steroid taper and the other patient had just completed a steroid taper. CONCLUSIONS: Infliximab, despite its black box warning in patients with heart failure, may be a safe and effective treatment for ICI myocarditis.

Perspectives on the COVID-19 pandemic impact on cardio-oncology: results from the COVID-19 International Collaborative Network survey.

BACKGROUND: Re-allocation of resources during the COVID-19 pandemic has resulted in delays in care delivery to patients with cardiovascular disease and cancer. The ability of health care providers to provide optimal care in this setting has not been formally evaluated. OBJECTIVES: To assess the impact of COVID-19 resource re-allocation on scheduling, testing, elective procedures, telemedicine access, use of new COVID-19 therapies, and providers' opinions on healthcare policies among oncology and cardiology practitioners. METHODS: An electronic survey was conducted by a cardio-oncology collaborative network through regional and state chapters of the American College of Cardiology, American Society of Clinical Oncology, and the International Cardio-Oncology Society. Descriptive statistics were reported by frequency and proportion for analyses, and stratified categorically by geographic region and specialty. RESULTS: One thousand four hundred fifteen providers (43 countries) participated: 986 cardiologists, 306 oncologists, and 118 trainees/internal medicine. 63% (195/306) of oncologists vs 92% (896/976) of cardiologists reported cancellations of treatments/elective procedures (p = 0.01). 46% (442/970) of cardiologists and 25% (76/303) of oncologists modified the scope of their practice (p = < 0.001). Academic physicians (74.5%) felt better supplied with personal protective equipment (PPE) vs non-academic (74.5% vs 67.2%; p = 0.018). Telemedicine was less common in Europe 81% (74/91), and Latin America 64% (101/158), than the United States, 88% (950/1097) (p = < 0.001). 95% of all groups supported more active leadership from medical professional societies. CONCLUSIONS: These results support initiatives to promote expanded coverage for telemedicine, increased access to PPE, better testing availability and involvement of medical professional societies to help with preparedness for future health care crisis.

Patient Characteristics Associated With Telemedicine Access for Primary and Specialty Ambulatory Care During the COVID-19 Pandemic.

Importance: The coronavirus disease 2019 (COVID-19) pandemic has required a shift in health care delivery platforms, necessitating a new reliance on telemedicine. Objective: To evaluate whether inequities are present in telemedicine use and video visit use for telemedicine visits during the COVID-19 pandemic. Design, Setting, and Participants: In this cohort study, a retrospective medical record review was conducted from March 16 to May 11, 2020, of all patients scheduled for telemedicine visits in primary care and specialty ambulatory clinics at a large academic health system. Age, race/ethnicity, sex, language, median household income, and insurance type were all identified from the electronic medical record. Main Outcomes and Measures: A successfully completed telemedicine visit and video (vs telephone) visit for a telemedicine encounter. Multivariable models were used to assess the association between sociodemographic factors, including sex, race/ethnicity, socioeconomic status, and language, and the use of telemedicine visits, as well as video use specifically. Results: A total of 148 402 unique patients (86 055 women [58.0%]; mean [SD] age, 56.5 [17.7] years) had scheduled telemedicine visits during the study period; 80 780 patients (54.4%) completed visits. Of 78 539 patients with completed visits in which visit modality was specified, 35 824 (45.6%) were conducted via video, whereas 24 025 (56.9%) had a telephone visit. In multivariable models, older age (adjusted odds ratio [aOR], 0.85 [95% CI, 0.83-0.88] for those aged 55-64 years; aOR, 0.75 [95% CI, 0.72-0.78] for those aged 65-74 years; aOR, 0.67 [95% CI, 0.64-0.70] for those aged ≥75 years), Asian race (aOR, 0.69 [95% CI, 0.66-0.73]), non-English language as the patient's preferred language (aOR, 0.84 [95% CI, 0.78-0.90]), and Medicaid insurance (aOR, 0.93 [95% CI, 0.89-0.97]) were independently associated with fewer completed telemedicine visits. Older age (aOR, 0.79 [95% CI, 0.76-0.82] for those aged 55-64 years; aOR, 0.78 [95% CI, 0.74-0.83] for those aged 65-74 years; aOR, 0.49 [95% CI, 0.46-0.53] for those aged ≥75 years), female sex (aOR, 0.92 [95% CI, 0.90-0.95]), Black race (aOR, 0.65 [95% CI, 0.62-0.68]), Latinx ethnicity (aOR, 0.90 [95% CI, 0.83-0.97]), and lower household income (aOR, 0.57 [95% CI, 0.54-0.60] for income <$50 000; aOR, 0.89 [95% CI, 0.85-0.92], for $50 000-$100 000) were associated with less video use for telemedicine visits. These results were similar across medical specialties. Conclusions and Relevance: In this cohort study of patients scheduled for primary care and medical specialty ambulatory telemedicine visits at a large academic health system during the early phase of the COVID-19 pandemic, older patients, Asian patients, and non-English-speaking patients had lower rates of telemedicine use, while older patients, female patients, Black, Latinx, and poorer patients had less video use. Inequities in accessing telemedicine care are present, which warrant further attention.

Cardio-oncology care in the era of the coronavirus disease 2019 (COVID-19) pandemic: An International Cardio-Oncology Society (ICOS) statement.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a pandemic of unprecedented proportions in the modern era because of its highly contagious nature and impact on human health and society: coronavirus disease 2019 (COVID-19). Patients with cardiovascular (CV) risk factors and established CV disease (CVD) are among those initially identified at the highest risk for serious complications, including death. Subsequent studies have pointed out that patients with cancer are also at high risk for a critical disease course. Therefore, the most vulnerable patients are seemingly those with both cancer and CVD, and a careful, unified approach in the evaluation and management of this patient population is especially needed in times of the COVID-19 pandemic. This review provides an overview of the unique implications of the viral outbreak for the field of cardio-oncology and outlines key modifications in the approach to this ever-increasing patient population. These modifications include a shift toward greater utilization of cardiac biomarkers and a more focused CV imaging approach in the broader context of modifications to typical practice pathways. The goal of this strategic adjustment is to minimize the risk of SARS-CoV-2 infection (or other future viral outbreaks) while not becoming negligent of CVD and its important impact on the overall outcomes of patients who are being treated for cancer.

Clinical Practice and Research in Cardio-Oncology: Finding the "Rosetta Stone" for Establishing Program Excellence in Cardio-oncology.

The burgeoning field of cardio-oncology (C-O) is now necessary for the delivery of excellent care for patients with cancer. Many factors have contributed to this increasing population of cancer survivors or those being treated with novel and targeted cancer therapies. There is a tremendous need to provide outstanding cardiovascular (CV) care for these patients; however, current medical literature actually provides a paucity of guidance. C-O therefore provides a novel opportunity for clinical, translational, and basic research to advance patient care. This review aims to be a primer for cardio-oncologists on how to develop a vibrant and comprehensive C-O program, use practical tools to assist in the construction of C-O services, and to proactively incorporate translational and clinical research into the training of future leaders as well as enhance clinical care.

Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma.

PURPOSE: Cardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs. PATIENTS AND METHODS: Patients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography. Monitoring occurred over 18 months for development of CVAEs. RESULTS: Of 95 patients enrolled, 65 received carfilzomib and 30 received bortezomib, with median 25 months of follow-up. Sixty-four CVAEs occurred, with 55% grade 3 or greater in severity. CVAEs occurred in 51% of patients treated with carfilzomib and 17% of those treated with bortezomib (P = .002). Median time to first CVAE from treatment start was 31 days, and 86% occurred within the first 3 months. Patients receiving carfilzomib-based therapy with a baseline elevated BNP level higher than 100 pg/mL or N-terminal proBNP level higher than 125 pg/mL had increased risk for CVAE (odds ratio, 10.8; P < .001). Elevated natriuretic peptides occurring mid-first cycle of treatment with carfilzomib were associated with a substantially higher risk of CVAEs (odds ratio, 36.0; P < .001). Patients who experienced a CVAE had inferior progression-free survival (log-rank P = .01) and overall survival (log-rank P < .001). PI therapy was safely resumed in 89% of patients, although 41% required chemotherapy modifications. CONCLUSION: CVAEs are common during PI therapy for relapsed MM, especially with carfilzomib, particularly within the first 3 months of therapy. CVAEs were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of CVAEs; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.

Preparing the Cardiovascular Workforce to Care for Oncology Patients: JACC Review Topic of the Week.

Cardiovascular disease and cancer are the 2 main causes of death in the United States. They intersect on multiple levels, sharing common causal mechanisms and epidemiological risk factors. The growing prevalence and complexity of cardiovascular disease and cancer have resulted in the development of the discipline of cardio-oncology. Preparing the cardiovascular workforce for the care of a growing population of cancer patients is necessary to enhance the delivery of high-quality cardiovascular care for patients with cancer. The goal of this review is to present the dedicated efforts of the cardio-oncology community to meet the growing need for education and training of cardiovascular practitioners providing care to cancer patients and survivors. Integration in general cardiology training programs and the efforts of the stakeholder organizations serve as an example of how a multidimensional, innovative approach can address provider education and training needs in a relatively new discipline.

Long-term Survival After Treating Cardiac Metastasis With Radiation and Immune Therapy: A Case Report.

Cardiac metastases are a rare clinical entity and they generally portend a poor prognosis. Management is generally directed toward symptom control and maintaining cardiac function; however, long-term survival is rare. Here, we report a case of isolated metastatic urothelial cell carcinoma to the right ventricle that was functionally limiting the patient. The metastasis was successfully palliated for 17 months following radiation and immune therapy; however, disease progression in and around his heart ultimately led to a cardiac arrest.

Contrast-Enhanced Echocardiography Has the Greatest Impact in Patients with Reduced Ejection Fractions.

BACKGROUND: Contrast-enhanced echocardiography (CE) helps to improve image quality in patients with suboptimal acoustic windows. Despite current recommendations, contrast use remains low. The aim of this study was to identify populations that would benefit more from contrast use. METHODS: A total of 176 subjects (137 men; mean age, 60.8 ± 13.7 years) with technically difficult transthoracic echocardiographic studies who received clinically indicated intravenous contrast were prospectively studied. The impact on clinical decision making (including alterations in medical therapy, referral, imaging, or clinical procedures) was evaluated. RESULTS: The use of CE enabled biplane left ventricular (LV) ejection fraction measurement in 97.2% of studies and the interpretation of regional wall motion in 95% of studies. CE allowed definitive assessment of the presence or absence of LV thrombus in 99% of the cases. In the 174 patients whose ordering physicians could be reached at the time of image interpretation, changes in management occurred in 51% of subjects. There was no difference in the proportion of management changes between inpatients and outpatients (60.0% vs 48.1%, P = .225). Subjects with heart failure, cardiomyopathy, and arrhythmia had a higher proportion of changes (61.4% vs 44.2% [P = .031], 62.5% vs 45.0% [P = .028], and 72.0% vs 47.7% [P = .030], respectively). The proportion of management change after CE increased as pre-CE estimated ejection fraction decreased. Logistic regression showed that pre-CE estimated LV ejection fraction < 50% was the only significant predictor of change of management after contrast (P = .004). CONCLUSIONS: The use of CE has a significant impact on clinical decision making in patients with suboptimal acoustic windows, especially in those with depressed pre-CE LV ejection fractions.

Carfilzomib-Associated Cardiovascular Adverse Events: A Systematic Review and Meta-analysis.

IMPORTANCE: Cardiovascular adverse events (CVAE) with carfilzomib in patients with multiple myeloma can be potentially life-threatening and remain incompletely characterized. We performed the first systematic review and meta-analysis of carfilzomib-associated CVAE. OBJECTIVE: To determine the incidence of carfilzomib-associated CVAE and to compare the rates of carfilzomib CVAE among different doses and companion therapies. DATA SOURCES: PubMed, EMBASE, Web of Science, and clinicaltrials.gov were queried for the keywords "carfilzomib," "Kyprolis," and "PX-171" through January 1, 2017. STUDY SELECTION: Phase 1 to 3 prospective clinical trials of carfilzomib in patients with multiple myeloma with evaluable toxic effects data were eligible for meta-analysis. DATA EXTRACTION AND SYNTHESIS: Data were independently extracted by 2 reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Pooled incidence rates and relative risks (for randomized trials) and 95% confidence intervals were calculated using a random effects model. Subgroup analyses were performed to assess study-level characteristics associated with CVAE. MAIN OUTCOMES AND MEASURES: Cardiovascular adverse events were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grades 3 or higher AEs and study characteristics were recorded. RESULTS: A total of 514 studies were assessed for eligibility. Of those, 24 studies were eligible, including a total of 2594 patients with multiple myeloma. All-grade and grades 3 and higher CVAE were seen in 617 (18.1%) and 274 (8.2%), respectively. Phase 2 or 3 studies and carfilzomib doses of 45 mg/m2 or higher were associated with high-grade CVAE. Median age older than 65 years, prior myeloma therapies, and concurrent myeloma therapies were not associated with CVAE. For the 3 randomized clinical trials, the summary relative risk of all-grade and grade 3 or higher CVAE for patients receiving carfilzomib compared with noncarfilzomib-receiving control patients were 1.8 and 2.2, respectively. CONCLUSIONS AND RELEVANCE: Carfilzomib was associated with a significant incidence of CVAE, with higher rates seen with higher doses of carfilzomib. Phase 1 studies may be underdetecting CVAE. Future studies are needed to identify patients at high risk for CVAE, develop optimal monitoring strategies, and explore strategies to mitigate these risks.