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.

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.

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.

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.

Diabetes mellitus and hypertension: a dual threat.

PURPOSE OF REVIEW: The following is a review of the current concepts on the relationship between hypertension (HTN) and diabetes mellitus with a focus on the epidemiology and cardiovascular prognostic implications of coexistent HTN and diabetes mellitus, shared mechanisms underlying both conditions and pathophysiology of increased risk of cardiovascular disease, treatment of HTN in individuals with diabetes mellitus, and effects of anti-diabetic medications on blood pressure (BP). RECENT FINDINGS: Diabetes mellitus and HTN often coexist in the same individual. They share numerous risk factors and underlying pathophysiologic mechanisms, most important of which are insulin resistance and inappropriate activation of the rennin-angiotensin-aldosterone system. Recently updated guidelines recommend a BP goal of 140/90 mmHg in most individuals with diabetes mellitus. A new class of anti-diabetic medications, sodium-glucose co-transporter 2 inhibitors, has shown favorable effects on BP. SUMMARY: HTN affects the majority of individuals with diabetes mellitus. Coexistence of diabetes mellitus and HTN, especially if BP is not well controlled, dramatically increases the risk of morbidity and mortality from cardiovascular disease. BP control is an essential part of management of patients with diabetes mellitus, because it is one of the most effective ways to prevent vascular complications and death.

Platelet Inhibitors Reduce Rupture in a Mouse Model of Established Abdominal Aortic Aneurysm.

OBJECTIVE: Rupture of abdominal aortic aneurysms causes a high morbidity and mortality in the elderly population. Platelet-rich thrombi form on the surface of aneurysms and may contribute to disease progression. In this study, we used a pharmacological approach to examine a role of platelets in established aneurysms induced by angiotensin II infusion into hypercholesterolemic mice. APPROACH AND RESULTS: Administration of the platelet inhibitors aspirin or clopidogrel bisulfate to established abdominal aortic aneurysms dramatically reduced rupture. These platelet inhibitors reduced abdominal aortic platelet and macrophage recruitment resulting in decreased active matrix metalloproteinase-2 and matrix metalloproteinase-9. Platelet inhibitors also resulted in reduced plasma concentrations of platelet factor 4, cytokines, and components of the plasminogen activation system in mice. To determine the validity of these findings in human subjects, a cohort of aneurysm patients were retrospectively analyzed using developed and validated algorithms in the electronic medical record database at Vanderbilt University. Similar to mice, administration of aspirin or P2Y12 inhibitors was associated with reduced death among patients with abdominal aortic aneurysm. CONCLUSIONS: These results suggest that platelets contribute to abdominal aortic aneurysm progression and rupture.

Risk assessment and management of anthracycline and HER2 receptor inhibitor-induced cardiomyopathy.

With the advent and increased use of chemotherapeutic agents and radiation therapy, cancer survival rates have increased. With increased survival, both acute and chronic cardiotoxic adverse effects have emerged. The growing need for managing the treatment of individuals with chemotherapy-induced cardiotoxicity has led to the formation of cardio-oncology programs throughout the United States. These programs concentrate on many aspects of cardiac disease in the oncology patient. Of these, the cardiotoxic effects (particularly cardiomyopathy) of anthracyclines and HER2 receptor inhibitors are a large focus of cardio-oncology practice. Despite the increasing availability of these programs, no consensus guidelines have been established to provide a framework for treating these patients. This review describes the initial evaluation, risk assessment, and management of individuals receiving anthracycline and HER2 receptor inhibitor therapy for cardiomyopathy. These recommendations are supported by the current literature in this field.

The impact of mobile health interventions on chronic disease outcomes in developing countries: a systematic review.

INTRODUCTION: Rates of chronic diseases will continue to rise in developing countries unless effective and cost-effective interventions are implemented. This review aims to discuss the impact of mobile health (m-health) on chronic disease outcomes in low- and middle-income countries (LMIC). MATERIALS AND METHODS: Systematic literature searches were performed using CENTRAL, MEDLINE, EMBASE, and LILACS databases and gray literature. Scientific literature was searched to identify controlled studies evaluating cell phone voice and text message interventions to address chronic diseases in adults in low- or middle-income countries. Outcomes measured included morbidity, mortality, hospitalization rates, behavioral or lifestyle changes, process of care improvements, clinical outcomes, costs, patient-provider satisfaction, compliance, and health-related quality of life (HRQoL). RESULTS: From the 1,709 abstracts retrieved, 163 articles were selected for full text review, including 9 randomized controlled trials with 4,604 participants. Most of the studies addressed more than one outcome. Of the articles selected, six studied clinical outcomes, six studied processes of care, three examined healthcare costs, and two examined HRQoL. M-health positively impacted on chronic disease outcomes, improving attendance rates, clinical outcomes, and HRQoL, and was cost-effective. CONCLUSIONS: M-health is emerging as a promising tool to address access, coverage, and equity gaps in developing countries and low-resource settings. The results for m-health interventions showed a positive impact on chronic diseases in LMIC. However, a limiting factor of this review was the relatively small number of studies and patients enrolled, highlighting the need for more rigorous research in this area in developing countries.

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.

Clonal hematopoiesis and inflammation in the vasculature: CHIVE, a prospective, longitudinal clonal hematopoiesis cohort and biorepository.

ABSTRACT: Clonal hematopoiesis (CH) is an age-associated phenomenon leading to an increased risk of both hematologic malignancy and nonmalignant organ dysfunction. Increasingly available genetic testing has made the 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 (clonal hematopoiesis and inflammation in the vasculature) registry and biorepository was created to identify and monitor individuals at risk, support multidisciplinary CH clinics, and refine taxonomy and standards of practice for CH risk mitigation. Data from the first 181 patients enrolled in this prospective registry recapitulate the molecular epidemiology of CH from biobank-scale retrospective studies, with DNMT3A, TET2, ASXL1, and TP53 as the most commonly mutated genes. Blood counts across all hematopoietic lineages trended lower in patients with CH. In addition, patients with CH had higher rates of end organ dysfunction, in particular chronic kidney disease. Among patients with CH, variant allele frequency was independently associated with the presence of cytopenias and progression to hematologic malignancy, whereas other common high-risk CH clone features were not clear. Notably, accumulation of multiple distinct high-risk clone features was also associated with cytopenias and hematologic malignancy progression, supporting a recently published CH risk score. Surprisingly, ∼30% of patients enrolled in CHIVE from CH clinics were adjudicated as not having clonal hematopoiesis of indeterminate potential, 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 are underway and will be critical to understanding how to thoughtfully care for this patient population.

Short-term trends in heart failure-related hospitalizations in a high-risk state.

OBJECTIVES: We sought to determine whether there are signs of improvement in the rates of heart failure (HF) hospitalizations given the recent reports of improvement in national trends. METHODS: HF admissions data from the Tennessee Hospital Discharge Data System were analyzed. RESULTS: Hospitalization for primary diagnosis of HF (HFPD) in adults (aged 20 years old or older) decreased from 4.5% in 2006 to 4.2% in 2008. Similarly, age-adjusted HF hospitalization (per 10,000 population) declined by 19.1% (from 45.5 in 2006 to 36.8 in 2008). The age-adjusted rates remain higher among blacks than whites and higher among men than women. Notably, the rate ratio of black-to-white men ages 20 to 34 years admitted with HFPD increased from 8.5 in 2006 to 11.1 in 2008; similarly, the adjusted odds ratios for HFPD were 4.75 (95% confidence interval 3.29-6.86) and 5.61 (95% confidence interval 3.70-8.49), respectively. There was, however, a significant improvement in odds ratio for HF rates among young black women, as evidenced by a decrease from 4.60 to 3.97 (aged 20-34 years) and 4.21 to 3.12 (aged 35-44 years) between 2006 and 2008, respectively. Among patients aged 20 to 34 and 35 to 44 years, hypertension was the strongest independent predictor for HF. Diabetes and myocardial infarction emerged as predictors for HF among patients aged 35 years and older. CONCLUSIONS: The overall rate of HF hospitalization declined during the period surveyed, but the persistent disproportionate involvement of blacks with evidence of worsening among younger black men, requires close attention.

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.

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.

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.

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.