Androgen Deprivation Therapy/Androgen Receptor Signaling Inhibitor Treatments for Prostate Cancer: Pathophysiology and Review of Effects on Cardiovascular Disease.

Androgen deprivation therapy is the cornerstone of systemic management for prostate cancer but is associated with multiple adverse effects that must be considered during treatment. These effects occur because of the profound hypogonadism that is induced from lack of testosterone or due to the medications used in the treatment or in combination with androgen receptor signaling inhibitors. This article critically reviews the associations between androgen deprivation therapy, androgen receptor signaling inhibitors, and cardiovascular complications such as prolonged QT interval, atrial fibrillation, heart failure, atherosclerosis, coronary heart disease, venous thromboembolism, and peripheral arterial occlusive disease. These unfavorable outcomes reinforce the need for regular cardiovascular screening of patients undergoing androgen deprivation for the management of prostate cancer.

Clonal Hematopoiesis and Inflammation in the VasculaturE (CHIVE): a prospective, longitudinal cohort and biorepository.

Clonal hematopoiesis (CH) is an age-associated phenomenon leading to increased risk of both hematologic malignancy and non-malignant organ dysfunction. Increasingly available genetic testing has made incidental discovery of CH clinically common, yet evidence-based guidelines and effective management strategies to prevent adverse CH health outcomes are lacking. To address this gap, the prospective CHIVE registry and biorepository was created to identify and monitor individuals at risk, support multidisciplinary CH clinics, and to refine standards of practice for CH risk mitigation. Data from the first 181 patients enrolled in this registry recapitulate the molecular epidemiology of CH from biobank scale retrospective studies, with DNMT3A, TET2, ASXL1, and TP53 as the most commonly mutated genes. CH patients had higher rates of end organ dysfunction, in particular chronic kidney disease (p=0.001). Among patients with CH, variant allele frequency was independently associated with presence of cytopenias (p=0.008) and progression to hematologic malignancy (p=0.010), while other common high-risk CH clone features were not clear. Notably, accumulation of multiple distinct high-risk clone features was also associated with cytopenias (p=0.013) and hematologic malignancy progression (p=0.004), supporting a recently published CH risk score. Surprisingly, ~30% of patients enrolled in CHIVE from CH clinics were adjudicated as not having CHIP, highlighting the need for molecular standards and purpose-built assays in this field. Maintenance of this well-annotated cohort and continued expansion of CHIVE to multiple institutions is underway and will be critical to understand how to thoughtfully care for this patient population.

Primary cardiac sarcoma: demographics, genomic study correlation, and survival benefits of surgery with adjuvant therapy in U.S. population.

BACKGROUND: Cardiac sarcomas are rare and aggressive tumors with little known about the demographics, genetics, or treatment outcomes. OBJECTIVES: The objectives of this study were to characterize the demographics, treatment modality, and survival associated with cardiac sarcomas and evaluate the potential for mutation-directed therapies. METHODS: All cases from 2000 to 2018 of cardiac sarcoma were extracted from the SEER database. Genomic comparison utilized The Cancer Genome Atlas (TCGA) database, as well as reviews and re-analysis of past applicable genomic studies. RESULTS: Cardiac sarcomas occurred most often in White patients, compared with national census data cardiac sarcomas occurred at a significantly higher rate in Asians. The majority of cases were undifferentiated (61.7%) and without distant metastases (71%). Surgery was the most common primary treatment modality and offered survival benefit (HR 0.391 (p = 0.001) that was most pronounced and sustained as compared to patients who received chemotherapy (HR 0.423 (p = 0.001) or radiation (HR 0.826 (p = 0.241) monotherapy. There was no difference in survival when stratified by race or sex; however, younger patients (< 50) had better survival. Genomics data on histologically undifferentiated cardiac sarcomas revealed a significant number were likely poorly differentiated pulmonary intimal sarcomas and angiosarcomas. CONCLUSIONS: Cardiac sarcoma is a rare disease with surgery continuing to be a cornerstone of therapy followed by traditional chemotherapy. Case studies have indicated the potential for therapies directed to specific genetic aberrations to improve survival for these patients and utilization of next-generation sequencing (NGS) will help improve both classification and these therapies for cardiac sarcoma patients.

Accuracy and Reliability of Chatbot Responses to Physician Questions.

Importance: Natural language processing tools, such as ChatGPT (generative pretrained transformer, hereafter referred to as chatbot), have the potential to radically enhance the accessibility of medical information for health professionals and patients. Assessing the safety and efficacy of these tools in answering physician-generated questions is critical to determining their suitability in clinical settings, facilitating complex decision-making, and optimizing health care efficiency. Objective: To assess the accuracy and comprehensiveness of chatbot-generated responses to physician-developed medical queries, highlighting the reliability and limitations of artificial intelligence-generated medical information. Design, Setting, and Participants: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes or no) or descriptive answers. The physicians then graded the chatbot-generated answers to these questions for accuracy (6-point Likert scale with 1 being completely incorrect and 6 being completely correct) and completeness (3-point Likert scale, with 1 being incomplete and 3 being complete plus additional context). Scores were summarized with descriptive statistics and compared using the Mann-Whitney U test or the Kruskal-Wallis test. The study (including data analysis) was conducted from January to May 2023. Main Outcomes and Measures: Accuracy, completeness, and consistency over time and between 2 different versions (GPT-3.5 and GPT-4) of chatbot-generated medical responses. Results: Across all questions (n = 284) generated by 33 physicians (31 faculty members and 2 recent graduates from residency or fellowship programs) across 17 specialties, the median accuracy score was 5.5 (IQR, 4.0-6.0) (between almost completely and complete correct) with a mean (SD) score of 4.8 (1.6) (between mostly and almost completely correct). The median completeness score was 3.0 (IQR, 2.0-3.0) (complete and comprehensive) with a mean (SD) score of 2.5 (0.7). For questions rated easy, medium, and hard, the median accuracy scores were 6.0 (IQR, 5.0-6.0), 5.5 (IQR, 5.0-6.0), and 5.0 (IQR, 4.0-6.0), respectively (mean [SD] scores were 5.0 [1.5], 4.7 [1.7], and 4.6 [1.6], respectively; P = .05). Accuracy scores for binary and descriptive questions were similar (median score, 6.0 [IQR, 4.0-6.0] vs 5.0 [IQR, 3.4-6.0]; mean [SD] score, 4.9 [1.6] vs 4.7 [1.6]; P = .07). Of 36 questions with scores of 1.0 to 2.0, 34 were requeried or regraded 8 to 17 days later with substantial improvement (median score 2.0 [IQR, 1.0-3.0] vs 4.0 [IQR, 2.0-5.3]; P < .01). A subset of questions, regardless of initial scores (version 3.5), were regenerated and rescored using version 4 with improvement (mean accuracy [SD] score, 5.2 [1.5] vs 5.7 [0.8]; median score, 6.0 [IQR, 5.0-6.0] for original and 6.0 [IQR, 6.0-6.0] for rescored; P = .002). Conclusions and Relevance: In this cross-sectional study, chatbot generated largely accurate information to diverse medical queries as judged by academic physician specialists with improvement over time, although it had important limitations. Further research and model development are needed to correct inaccuracies and for validation.

Artificial intelligence modelling to assess the risk of cardiovascular disease in oncology patients.

Aims: There are no comprehensive machine learning (ML) tools used by oncologists to assist with risk identification and referrals to cardio-oncology. This study applies ML algorithms to identify oncology patients at risk for cardiovascular disease for referrals to cardio-oncology and to generate risk scores to support quality of care. Methods and results: De-identified patient data were obtained from Vanderbilt University Medical Center. Patients with breast, kidney, and B-cell lymphoma cancers were targeted. Additionally, the study included patients who received immunotherapy drugs for treatment of melanoma, lung cancer, or kidney cancer. Random forest (RF) and artificial neural network (ANN) ML models were applied to analyse each cohort: A total of 20 023 records were analysed (breast cancer, 6299; B-cell lymphoma, 9227; kidney cancer, 2047; and immunotherapy for three covered cancers, 2450). Data were divided randomly into training (80%) and test (20%) data sets. Random forest and ANN performed over 90% for accuracy and area under the curve (AUC). All ANN models performed better than RF models and produced accurate referrals. Conclusion: Predictive models are ready for translation into oncology practice to identify and care for patients who are at risk of cardiovascular disease. The models are being integrated with electronic health record application as a report of patients who should be referred to cardio-oncology for monitoring and/or tailored treatments. Models operationally support cardio-oncology practice. Limited validation identified 86% of the lymphoma and 58% of the kidney cancer patients with major risk for cardiotoxicity who were not referred to cardio-oncology.

Assessing the Accuracy and Reliability of AI-Generated Medical Responses: An Evaluation of the Chat-GPT Model.

Background: Natural language processing models such as ChatGPT can generate text-based content and are poised to become a major information source in medicine and beyond. The accuracy and completeness of ChatGPT for medical queries is not known. Methods: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes/no) or descriptive answers. The physicians then graded ChatGPT-generated answers to these questions for accuracy (6-point Likert scale; range 1 - completely incorrect to 6 - completely correct) and completeness (3-point Likert scale; range 1 - incomplete to 3 - complete plus additional context). Scores were summarized with descriptive statistics and compared using Mann-Whitney U or Kruskal-Wallis testing. Results: Across all questions (n=284), median accuracy score was 5.5 (between almost completely and completely correct) with mean score of 4.8 (between mostly and almost completely correct). Median completeness score was 3 (complete and comprehensive) with mean score of 2.5. For questions rated easy, medium, and hard, median accuracy scores were 6, 5.5, and 5 (mean 5.0, 4.7, and 4.6; p=0.05). Accuracy scores for binary and descriptive questions were similar (median 6 vs. 5; mean 4.9 vs. 4.7; p=0.07). Of 36 questions with scores of 1-2, 34 were re-queried/re-graded 8-17 days later with substantial improvement (median 2 vs. 4; p<0.01). Conclusions: ChatGPT generated largely accurate information to diverse medical queries as judged by academic physician specialists although with important limitations. Further research and model development are needed to correct inaccuracies and for validation.

An Overview of Telehealth in the Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Telehealth enables the remote delivery of health care through telecommunication technologies and has substantially affected the evolving medical landscape. The COVID-19 pandemic accelerated the utilization of telehealth as health care professionals were forced to limit face-to-face in-person visits. It has been shown that information delivery, diagnosis, disease monitoring, and follow-up care can be conducted remotely, resulting in considerable changes specific to cardiovascular disease management. Despite increasing telehealth utilization, several factors such as technological infrastructure, reimbursement, and limited patient digital literacy can hinder the adoption of remote care. This scientific statement reviews definitions pertinent to telehealth discussions, summarizes the effect of telehealth utilization on cardiovascular and peripheral vascular disease care, and identifies obstacles to the adoption of telehealth that need to be addressed to improve health care accessibility and equity.

Differentiating pulmonary hypertension associated with protein kinase inhibitors.

Protein kinase inhibitors (PKIs) have been implicated in pulmonary vascular toxicities including risk factors for at least three of the five World Health Organization groups of pulmonary hypertension (PH). These toxicities include direct drug-induced pulmonary arterial hypertension, an increase in cardiomyopathies, and an increase in interstitial lung disease. On- and off-target toxicities are common within multitargeted PKIs leading to cardiopulmonary toxicities. This review highlights the incidence, possible mechanisms, and management strategies for each group of possible PKI-induced PH. Future identification and clarification of protein kinase pathways for both mechanisms of toxicity and pathophysiology for PH could lead to improvements in patient care in oncology and pulmonary vascular diseases.

Emerging cancer therapies and cardiovascular risk.

The cardiovascular (CV) toxicity profiles of traditional cancer therapies such as anthracyclines and radiation therapy are familiar to many cardiologists. With the development and widespread use of additional cancer therapeutics, CV toxicities related to these agents are becoming more common. Cardiovascular specialists are often integrated into the care team for individuals with cancer and knowledge of the CV toxicities of cancer therapeutics has become essential. In this review, we provide a clinically focused summary of the current data regarding CV toxicities of common cancer therapies and identify potential management strategies for the CV specialist.

Bleeding with vascular endothelial growth factor tyrosine kinase inhibitor: A network meta-analysis.

BACKGROUND: Targeted therapies like vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are the first-choice treatment in several types of cancers. We aim to determine the comparative risk of bleeding events associated with the VEGFR-TKIs through a network meta-analysis. METHODS: Published data search up to November 2018 reporting bleeding in cancer patients treated with VEGFR-TKIs was performed. The primary outcome was presence of hemorrhagic events at the end of the trial. Bleeding as a side-effect profile was examined for eleven VEGFR-TKIs (Apatinib, Brivanib, Cabozantinib, Lenvatinib, Motesanib, Nintedanib, Pazopanib, Regorafenib, Sorafenib, Sunitinib and Vandetanib). Network meta-analysis based on random effects model estimating Odds Ratio (OR) with 95 % confidence interval (CI), compared the risk of bleeding events among the VEGFR-TKIs with respect to placebo control conditions. RESULTS: Fifty Randomized Clinical Trials (RCTs) including 16,753 cancer patients were included in this analysis. Twenty studies compared VEGFR-TKIs with placebo, the remaining studies compared VEGFR-TKIs with the standard chemotherapeutic regimen. VEGFR-TKIs were associated with increased incidence of all-grade hemorrhagic events in comparison to control (standard chemotherapy and/or placebo) (OR = 1.79; 95 % CI 1.50-2.13, p-value <0.0001) and placebo (OR = 1.50; 95 % CI 1.16-1.93, p-value = 0.1). However, there was no difference in high-grade bleeding in patients treated with VEGFR-TKI in comparison to control (OR = 1.22; 95 % CI 0.87-1.71, p-value 0.74) or placebo alone (OR = 1.05; 95 % CI 0.65-1.70, p-value 0.73). Among individual VEGFR-TKIs, Sunitinib (OR = 3.31, 95 % CI 2.34-4.69) and Regorafenib (OR = 2.92, 95 % CI 1.50-5.71) were associated with higher risk of hemorrhagic events in comparison to placebo. CONCLUSION: VEGR-TKIs, particularly Sunitinib and Regorafenib appear to be associated with increased risk of bleeding incidence. TRIAL REGISTRATION NUMBER: PROSPERO CRD42017056406.

Cardiovascular Complications of Chimeric Antigen Receptor T-Cell Therapy: The Cytokine Release Syndrome and Associated Arrhythmias.

In recent years, cancer treatment has evolved, and new therapies have been introduced with significant improvement in prognosis. The immunotherapies stand out owing to their efficacy and remission rate. Chimeric antigen receptor (CAR) T-cell therapy is a part of this new era of therapies. Chimeric antigen receptor T-cell therapy is a form of adoptive cellular therapy that uses a genetically encoded CAR in modified human T cells to target specific tumor antigens in a nonconventional, non-major histocompatibility complex (MHC) protein presentation. Chimeric antigen receptor T-cell therapy successfully identifies tumor antigens and through activation of T cells destroys tumoral cells. It has been found to efficiently induce remission in patients who have been previously treated for B-cell malignancies and have persistent disease. As the use of this novel therapy increases, its potential side effects also have become more evident, including major complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokine release syndrome is a major systemic inflammatory process as a result of massive cytokine production by the proliferating and activated CAR T cells in which multiple interleukins and immune cells contribute to the inflammatory response. Cytokine release syndrome has been associated with cardiovascular life-threatening complications including hypotension, shock, tachycardia, arrhythmias, left ventricular dysfunction, heart failure, and cardiovascular death. Arrhythmias, among its major complications, vary from asymptomatic prolonged corrected QT interval (QTc) to supraventricular tachycardia, atrial fibrillation, flutter, and ventricular arrhythmias like Torsade de pointes. This article focuses on the cardiovascular complications and arrhythmias associated with CRS and CAR T-cell therapy.

Impact of appropriate use criteria for transesophageal echocardiograms on clinically meaningful care.

INTRODUCTION: The aim of this study was to evaluate appropriateness of transesophageal echocardiography (TEE) studies based on 2011 Appropriate Use Criteria (AUC) for Echocardiography and its impact on patient management. METHODS AND RESULTS: In a retrospective analysis of 100 inpatient TEEs, 85% of the TEEs ordered were determined to be appropriate, 9% were inappropriate, and 6% were uncertain. Inter-observer differences in the determination of AUC were seen in 24% of the studies, requiring a senior-level cardiologist to make the final determination of AUC score. The variance in interpretation by experts is concerning for how that might translate into differences in clinical practice. Of all TEEs, only 63% led to an active change in care, including changes in medications or procedures, while 37% did not. We found a statistically significant difference between cardiologists' and non-cardiologists' orders for TEE having an impact on patient's clinical care (41% vs 22%, respectively, P < 0.05) (Table ). While not statistically significant, a trend toward clinical change was observed in the appropriate vs inappropriate TEEs (70% vs 44%, respectively, P = 0.06). CONCLUSION: Ideally, the role of a diagnostic cardiovascular imaging test, such as a TEE, is to influence clinical care, if it is ordered appropriately on the right patient. While the AUC guides clinicians on the appropriate use of cardiovascular imaging, it is broadly written and offers room for interpretation to encompass variety of clinical scenarios. Clinical care paths that utilize AUC and standardize use of multidisciplinary institutional resources offer opportunity for optimal clinical impact and patient care.

Pathophysiology and Prevention of Heart Disease in Diabetes Mellitus.

Diabetes mellitus (DM) has become a public health problem worldwide, and it has large implications for cardiovascular disease (CVD). In this article, we discuss the etiology and pathophysiology of CVD in DM including the effects of abnormal glucose homeostasis, genetic factors, epigenetics, apoptosis, common pathophysiological mechanisms shared by both DM and CVD, and contributions of other comorbidities. We then cover the pathogenesis of both atherosclerotic disease and cardiomyopathy in relation to DM. Finally, we discuss the prevention of heart disease in DM with a focus on hypertension and dyslipidemia management, weight loss, lifestyle changes, antiplatelet therapy, and glycemic control.

Valvular Heart Disease in Cancer Patients: Etiology, Diagnosis, and Management.

OPINION STATEMENT: Cardiac valvular disease as consequence of radiation and chemotherapy during treatment for malignancy is growing in its awareness. While the overwhelming emphasis in this population has been on the monitoring and preservation of left ventricular systolic function, we are now developing a greater appreciation for the plethora of cardiac sequelae beyond this basic model. To this end many institutions across the country have developed cardio-oncology programs, which are collaborative practices between oncologists and cardiologists in order to minimize a patient's cardiovascular risk while allowing them to receive the necessary treatment for their cancer. These programs also help to recognize early nuanced treatment complications such as valvular heart disease, and provide consultation for the most appropriate course of action. In this article we will discuss the etiology, prevalence, diagnosis, and current treatment options of valvular heart disease as the result of chemotherapy and radiation.