Brown, Sherry‐Ann

Background Cardiovascular disease (CVD) is a leading cause of death in cancer survivors. Predicting CVD risk in this population remains challenging. Risk prediction models that use machine learning algorithms could provide an objective method for accurate risk prediction to facilitate the prevention and management of CVD in cancer survivors. We evaluated previously tested machine learning algorithms and logistic regression (regularized by machine learning methods), in addition to testing and validating newer, more complex machine learning algorithms, for CVD prediction in cancer survivors. Methods This multicenter study used a database of 3835 multiracial cancer survivors with 89 clinical, laboratory, and echocardiographic features over 20 years. Models were trained using repeated random and time‐split samples and tested on a separate cohort of 329 patients. Model performance was assessed using the area under the receiver operating characteristic curve. Results Regularized logistic regression achieved an area under the receiver operating characteristic curve of 0.845 (heart failure), 0.783 (atrial fibrillation), 0.792 (coronary artery disease), and 0.806 (composite CVD). These are comparable to 0.837 and 0.848 for heart failure, using Bayesian additive regression tree and random forest as more advanced machine learning models, respectively. De novo composite CVD (post‐cancer diagnosis) was also predicted with an area under the receiver operating characteristic curve of 0.826 using regularized logistic regression, compared with 0.735 and 0.802 using decision tree and random forest, respectively. Conclusions Regularized logistic regression and advanced machine learning models demonstrated similar predictive performance, with institutional transferability. These tools may support risk stratification and prevention strategies in cardio‐oncology using longitudinal data. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05377320.

BACKGROUND: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry. METHODS: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative. RESULTS: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment. CONCLUSIONS: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.

Background: Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. Methods: The myocardial infarction genes (MI-GENES) trial randomized participants aged 45-65 years who were at intermediate risk for CHD based on conventional risk factors and not on statins, to receive their conventional risk score (CRS) or their CRS plus a genetic risk score (GRS) based on 28 susceptibility variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys to assess information seeking (including internet use and accessing electronic health records (EHR)) were completed before and three and six months after risk disclosure. Information sharing parameters were assessed after risk disclosure. We assessed whether these behaviors differed by GRS disclosure, or by high (≥1.1) or low (<1.1) GRS. Adjustments were made for age, sex, family history of CHD, baseline CRS and GRS, and education. Results were reported as the mean difference (and standard error) in the score for each survey response between the GRS and CRS participants, with significance determined by regression analysis. Results: GRS participants accessed their EHR to obtain information related to their CHD risk more than CRS participants (0.14 ± 0.06, p=0.03). Overall internet use (0.61 ± 0.23, p=0.01), as well as internet use to seek information about heart disease (0.14 ± 0.06, p=0.02) and how genetic factors affect risk of having a heart attack (0.23 ± 0.07, p=0.002), was significantly higher in the GRS participants. GRS participants shared information about heart attack risk with others (0.35 ± 0.13, p=0.007), particularly family members (0.1 ± 0.04, p=0.02), (V4: 0.10 ± 0.05, p=0.05), and their primary care provider (V4: 0.15 ± 0.07, p=0.03) more than CRS participants. Internet use, EHR access, and information sharing did not differ significantly between the high and low GRS groups. Conclusions: Disclosure of GRS for CHD resulted in greater information seeking (including internet use and EHR access) and information sharing by study participants. Disclosure of genetic risk for CHD may help advance patient engagement in precision medicine.

Abstract Recent advances in treatment have transformed the management of cancer. Despite these advances, cardiovascular disease remains a leading cause of death in cancer survivors. Cardio-oncology has recently evolved as a subspecialty to prevent, diagnose, and manage cardiovascular side effects of antineoplastic therapy. An emphasis on optimal management of comorbidities and close attention to drug interactions are important in cardio-oncologic care. With interdisciplinary collaboration among oncologists, cardiologists, and pharmacists, there is potential to prevent and reduce drug-related toxicities of treatments. The cytochrome P450 (CYP450) family of enzymes and the P-glycoprotein (P-g) transporter play a crucial role in drug metabolism and drug resistance. Here we discuss the role of CYP450 and P-g in drug interactions in the field of cardio-oncology, provide an overview of the cardiotoxicity of a spectrum of cancer agents, highlight the role of precision medicine, and encourage a multidisciplinary treatment approach for patients with cancer.

Abstract BackgroundRe-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.ObjectivesTo 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.MethodsAn 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.Results1,415 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% (950/1,097) (p=<0.001). 95% of all groups supported more active leadership from medical professional societies.ConclusionsThese 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.Appendix: Link to the Survey: https://www.surveymonkey.com/r/C8ZDYNW

As many novel cancer therapies continue to emerge, the field of Cardio-Oncology (or onco-cardiology) has become crucial to prevent, monitor and treat cancer therapy-related cardiovascular toxicity. Furthermore, given the narrow therapeutic window of most cancer therapies, drug-drug interactions are prevalent in the cancer population. Consequently, there is an increased risk of affecting drug efficacy or predisposing individual patients to adverse side effects. Here we review the role of cytochrome P450 (CYP450) enzymes in the field of Cardio-Oncology. We highlight the importance of cardiac medications in preventive Cardio-Oncology for high-risk patients or in the management of cardiotoxicities during or following cancer treatment. Common interactions between Oncology and Cardiology drugs are catalogued, emphasizing the impact of differential metabolism of each substrate drug on unpredictable drug bioavailability and consequent inter-individual variability in treatment response or development of cardiovascular toxicity. This inter-individual variability in bioavailability and subsequent response can be further enhanced by genomic variants in CYP450, or by modifications of CYP450 gene, RNA or protein expression or function in various ‘omics’ related to precision medicine. Thus, we advocate for an individualized approach to each patient by a multidisciplinary team with clinical pharmacists evaluating a treatment plan tailored to a practice of precision Cardio-Oncology. This review may increase awareness of these key concepts in the rapidly evolving field of Cardio-Oncology.

This poem is a reflection on the risk of developing heart disease or cancer, and of the toll of cancer therapy on the heart, written as an inspiration to those working in the fields of oncology and cardiology and those affected by cancer, heart disease, or both.