The Intersection of Prostate Cancer and Hypertension: a Call to Action.

OPINION STATEMENT: With improvements in treatment and survival from prostate cancer, comorbid cardiac conditions will significantly impact overall morbidity and mortality from prostate cancer. Hypertension is a well-established cardiovascular risk factor that increases the risk of heart failure, myocardial infarction, and stroke. Therapies used in the treatment of prostate cancer, including GnRH agonists, GnRH antagonists, enzalutamide, abiraterone, and others, can directly or indirectly increase the risk of hypertension. In this paper, we review the evidence available on the incidence and mechanism of hypertension in prostate cancer patients. In addition, we provide recommendations on the assessment, treatment, and future directions for hypertension management in the prostate cancer population. We propose an individualized goal for blood pressure in prostate cancer patients, balancing the target goal of 130/80 mmHg with common comorbidities of frailty, orthostatic symptoms, and imbalance in this population. The presence of additional comorbidities (myocardial infarction, heart failure, renal disease, diabetes) can assist in preference of anti-hypertensive drugs.

Ischemia and no obstructive coronary arteries (INOCA): A narrative review.

Myocardial ischemia with no obstructive coronary arteries (INOCA) is a chronic coronary syndrome condition that is increasingly being recognized as a substantial contributor to adverse cardiovascular mortality and outcomes, including myocardial infarction and heart failure with preserved ejection fraction (HFpEF). While INOCA occurs in both women and men, women are more likely to have the finding of INOCA and are more adversely impacted by angina, with recurrent hospitalizations and a lower quality of life with this condition. Abnormal epicardial coronary vascular function and coronary microvascular dysfunction (CMD) have been identified in a majority of INOCA patients on invasive coronary function testing. CMD can co-exist with obstructive epicardial coronary artery disease (CAD), diffuse non-obstructive epicardial CAD, and with coronary vasospasm. Epicardial vasospasm can also occur with normal coronary arteries that have no atherosclerotic plaque on intravascular imaging. While all predisposing factors are not clearly understood, cardiometabolic risk factors, and endothelium dependent and independent mechanisms that increase oxidative stress and inflammation are associated with microvascular injury, CMD and INOCA. Cardiac autonomic dysfunction has also been implicated in abnormal vasoreactivity and persistent symptoms. INOCA is under-recognized and under-diagnosed, partly due to the heterogenous patient populations and mechanisms. However, diagnostic testing methods are available to guide INOCA management. Treatment of INOCA is evolving, and focuses on cardiac risk factor control, improving ischemia, reducing atherosclerosis progression, and improving angina and quality of life. This review focuses on INOCA, relations to HFpEF, available diagnostics, current and investigational therapeutic strategies, and knowledge gaps in this condition.

Lactate Dehydrogenase B and Pyruvate Oxidation Pathway Associated With Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients: Result of a Multi-Omics Integrative Analysis.

Multiple myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), an irreversible proteasome inhibitor being used to treat relapsed and refractory MM, has been associated with cardiotoxicity, including heart failure. We hypothesized that a multi-omics approach integrating data from different omics would provide insights into the mechanisms of CFZ-related cardiovascular adverse events (CVAEs). Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with CVAEs and 6 with no CVAEs) at the University of Florida Health Cancer Center. These samples were evaluated in global metabolomic profiling, global proteomic profiling, and microRNA (miRNA) profiling. Integrative pathway analysis was performed to identify genes and pathways differentially expressed between patients with and without CVAEs. The proteomics analysis identified the up-regulation of lactate dehydrogenase B (LDHB) [fold change (FC) = 8.2, p = 0.01] in patients who experienced CVAEs. The metabolomics analysis identified lower plasma abundance of pyruvate (FC = 0.16, p = 0.0004) and higher abundance of lactate (FC = 2.4, p = 0.0001) in patients with CVAEs. Differential expression analysis of miRNAs profiling identified mir-146b to be up-regulatein (FC = 14, p = 0.046) in patients with CVAE. Pathway analysis suggested that the pyruvate fermentation to lactate pathway is associated with CFZ-CVAEs. In this pilot multi-omics integrative analysis, we observed the down-regulation of pyruvate and up-regulation of LDHB among patients who experienced CVAEs, suggesting the importance of the pyruvate oxidation pathway associated with mitochondrial dysfunction. Validation and further investigation in a larger independent cohort are warranted to better understand the mechanisms of CFZ-CVAEs.

Newly diagnosed cardiovascular disease in patients treated with immune checkpoint inhibitors: a retrospective analysis of patients at an academic tertiary care center.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center. METHODS: All patients with a cancer diagnosis who received any ICI treatment in the University of Florida's Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. RESULTS: Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55-4.95, p = 0.0006). CONCLUSIONS: This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.

Implementation of appropriate use criteria for cardiology tests and procedures: a systematic review and meta-analysis.

AIMS: The American College of Cardiology appropriate use criteria (AUC) provide clinicians with evidence-informed recommendations for cardiac care. Adopting AUC into clinical workflows may present challenges, and there may be specific implementation strategies that are effective in promoting effective use of AUC. We sought to assess the effect of implementing AUC in clinical practice. METHODS AND RESULTS: We conducted a meta-analysis of studies found through a systematic search of the MEDLINE, Web of Science, Cochrane, or CINAHL databases. Peer-reviewed manuscripts published after 2005 that reported on the implementation of AUC for a cardiovascular test or procedure were included. The main outcome was to determine if AUC implementation was associated with a reduction in inappropriate/rarely appropriate care. Of the 18 included studies, the majority used pre/post-cohort designs; few (n = 3) were randomized trials. Most studies used multiple strategies (n = 12, 66.7%). Education was the most common individual intervention strategy (n = 13, 72.2%), followed by audit and feedback (n = 8, 44.4%) and computerized physician order entry (n = 6, 33.3%). No studies reported on formal use of stakeholder engagement or 'nudges'. In meta-analysis, AUC implementation was associated with a reduction in inappropriate/rarely appropriate care (odds ratio 0.62, 95% confidence interval 0.49-0.78). Funnel plot suggests the possibility of publication bias. CONCLUSION: We found most published efforts to implement AUC observed reductions in inappropriate/rarely appropriate care. Studies rarely explored how or why the implementation strategy was effective. Because interventions were infrequently tested in isolation, it is difficult to make observations about their effectiveness as stand-alone strategies. STUDY REGISTRATION: PROSPERO 2018 CRD42018091602. Available from https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018091602.

Cardiometabolic risk factors and survival after cancer in the Women's Health Initiative.

BACKGROUND: Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer. METHODS: This study examined the association between prediagnosis cardiovascular health and total and cause-specific mortality among 12,076 postmenopausal women who developed local- or regional-stage invasive cancer in the Women's Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity-related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non-Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival. RESULTS: After a median follow-up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all-cause mortality (HR, 1.99; 95% CI, 1.73-2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88-5.57), cancer-specific mortality (HR, 1.37; 95% CI, 1.1-1.72), and other-cause mortality (HR, 2.14; 95% CI, 1.70-2.69). A higher waist circumference was associated with greater all-cause mortality (HR, 1.17; 95% CI, 1.06-1.30) and cancer-specific mortality (HR, 1.22; 95% CI, 1.04-1.42). CONCLUSIONS: Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all-cause, CVD, cancer-specific, and other-cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation. LAY SUMMARY: This study uses information from the Women's Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country. The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors. It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.

Template Design and Analysis: Integrating Informatics Solutions to Improve Clinical Documentation.

BACKGROUND: Electronic health record templates have served a variety of functions, such as improving documentation for reliable reporting of health care outcomes. Standardizing template documentation has been important for accurately capturing case workload and supporting quality improvement initiatives. METHODS: North Florida/South Georgia Veterans Health System consists of 2 Florida-based hospitals: Malcom Randall Veterans Affairs Medical Center (MRVAMC) in Gainesville, and Lake City Veterans Affairs Medical Center (LCVAMC). In the first quarter of fiscal year 2017, MRVAMC and LCVAMC had a below-average case severity index (CSI) of 0.76 and 0.81, respectively, compared with that of the 0.96 national average for the Veterans Health Administration (VHA). An innovative history and physical template design with embedded informatics tools was created to improve clinical documentation. RESULTS: Compliance with standardized history and physical medicine template use was monitored for about 1 year after standardized template implementation. Compliance improved from 43.2% in June 2018 to 89.9% in June 2019 at MRVAMC and increased from 48.2% in June 2018 to 96.9% in June 2019 at LCVAMC. CSI improved to 0.97 at MRVAMC and 1.07 at LCVAMC in the first quarter of fiscal year 2019, which exceeded the VHA national average of 0.89 during the same period. CONCLUSIONS: NF/SGVHS integrated informatics solutions within template design was associated with an increase in CSI via improved clinical documentation.

A rare case of synovial sarcoma presenting as abdominal pain.

Abdominal pain can arise from numerous sources, including those extra-abdominal. It is important to obtain additional imaging in the setting of clinical suspicion for malignancy.

Sex-Based Differences in Coronary and Structural Percutaneous Interventions.

In the current state of interventional cardiology, the ability to offer advanced therapies to patients who historically were not surgical candidates has grown exponentially in the last few decades. As therapies have expanded in complex coronary and structural interventions, the nuances of treating certain populations have emerged. In particular, the role of sex-based anatomic and outcome differences has been increasingly recognized. As guidelines for cardiovascular prevention and treatment for certain conditions may vary by sex, therapeutic interventions in the structural and percutaneous coronary areas may also vary. In this review, we aim to discuss these differences, the current literature available on these topics, and areas of focus for the future.

Sex differences in non-obstructive coronary artery disease.

Ischaemic heart disease is a leading cause of morbidity and mortality in both women and men. Compared with men, symptomatic women who are suspected of having myocardial ischaemia are more likely to have no obstructive coronary artery disease (CAD) on coronary angiography. Coronary vasomotor disorders and coronary microvascular dysfunction (CMD) have been increasingly recognized as important contributors to angina and adverse outcomes in patients with no obstructive CAD. CMD from functional and structural abnormalities in the microvasculature is associated with adverse cardiac events and mortality in both sexes. Women may be particularly susceptible to vasomotor disorders and CMD due to unique factors such as inflammation, mental stress, autonomic, and neuroendocrine dysfunction, which predispose to endothelial dysfunction and CMD. CMD can be detected with coronary reactivity testing and non-invasive imaging modalities; however, it remains underdiagnosed. This review focuses on sex differences in presentation, pathophysiologic risk factors, diagnostic testing, and prognosis of CMD.

Impact of Valve Size on Prosthesis-Patient Mismatch and Aortic Valve Gradient After Transcatheter versus Surgical Aortic Valve Replacement.

OBJECTIVE: Limited data is available about the effect of implanted valve size on prosthesis-patient mismatch (PPM) incidence and aortic gradient (AG) after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). We compared PPM incidence and postprocedural AG between TAVR and SAVR patients considering the impact of implanted valve size. METHODS: From March 20, 2012, to September 30, 2015, 563 consecutive patients underwent TAVR (n = 419) or isolated SAVR (n = 144). Postprocedural transthoracic echocardiography was obtained within 30 days; AG, effective orifice area (EOA), and EOA index were calculated. RESULTS: A total of 381 patients in TAVR group and 82 patients in SAVR group were included. Mean preoperative AG and mean aortic valve area were not significantly different between the 2 groups. Postprocedural AG was significantly lower in TAVR than SAVR group, 7.74 ± 5.39 versus 14.27 ± 8.16 (P < 0.001). Between patients who had TAVR and SAVR with a valve size ≤23 mm, SAVR patients were 3 times more likely to have greater than mild AG after the procedure, OR: 3.1 (95% CI, 1.1 to 8.9) (P < 0.001). PPM incidence was significantly higher in SAVR group than TAVR group, 44 (53.7%) versus 112 (29.4%), OR = 2.8 (95% CI, 1.7 to 4.5) (P < 0.001). The PPM incidence was also higher in SAVR group than TAVR group among those who had the procedures with a valve size ≤23 mm, 35 (64.8%) versus 56 (47.9%), OR = 2 (95% CI, 1.1 to 3.9) (P = 0.048). Postprocedural outcomes were comparable between the 2 groups. CONCLUSIONS: In comparison to SAVR, TAVR is associated with less PPM and lower AG, especially in patients receiving a valve size ≤23 mm.

Advances in small-molecule therapy for managing angina pectoris in the elderly.

Introduction: As our population ages, the prevalence of angina is growing, leading to increased morbidity and decreased quality of life. The management of angina in the elderly is challenging due to drug intolerance and/or drug resistance as well as frailty. Over the past decades, many new therapeutic small molecules have been investigated for the management of angina. Although none of these studies have specifically focused on the therapies for the elderly, they offer promising new avenues for the treatment of angina in the elderly. Areas covered: Herein, the authors provide a review of the recently published literature on the use of small-molecule therapies for angina management in the elderly and provide a brief overview of these therapies. Expert opinion: A variety of therapeutic classes of existing and newer small molecules are emerging for the management of angina in the elderly. An individualized approach to the management of angina in this growing population is critical for good outcomes. Many small molecules are in their initial stages of clinical use, and further research should be conducted on their utility, especially in the elderly.

Identifying Cancer Patients at Risk for Heart Failure Using Machine Learning Methods.

Cardiotoxicity related to cancer therapies has become a serious issue, diminishing cancer treatment outcomes and quality of life. Early detection of cancer patients at risk for cardiotoxicity before cardiotoxic treatments and providing preventive measures are potential solutions to improve cancer patients' quality of life. This study focuses on predicting the development of heart failure in cancer patients after cancer diagnoses using historical electronic health record (EHR) data. We examined four machine learning algorithms using 143,199 cancer patients from the University of Florida Health (UF Health) Integrated Data Repository (IDR). We identified a total number of 1,958 qualified cases and matched them to 15,488 controls by gender, age, race, and major cancer type. Two feature encoding strategies were compared to encode variables as machine learning features. The gradient boosting (GB) based model achieved the best AUC score of 0.9077 (with a sensitivity of 0.8520 and a specificity of 0.8138), outperforming other machine learning methods. We also looked into the subgroup of cancer patients with exposure to chemotherapy drugs and observed a lower specificity score (0.7089). The experimental results show that machine learning methods are able to capture clinical factors that are known to be associated with heart failure and that it is feasible to use machine learning methods to identify cancer patients at risk for cancer therapy-related heart failure.