Evaluation of Midodrine Utilization in Patients with Cancer and Heart Failure.

PURPOSE: The purpose of this study was to evaluate safety and cardiovascular outcomes as well as overall survival of cancer patients with concomitant heart failure (HF) treated with midodrine for hypotension. METHODS: Adult patients diagnosed with cancer and HF who were treated with midodrine at a tertiary cancer center from 03/2013 to 08/2021 were identified. Demographic and clinical parameters were collected retrospectively. RESULTS: A total of 85 patients were included with a median age of 68 years (IQR: 60, 74; 33% female and 85% White). Of those, 31% had HFpEF (EF ≥ 50%), 42% HF with mildly reduced EF (HFmrEF; EF 41-49%), and 27% HFrEF (EF ≤ 40%). The most common indication for midodrine use was orthostatic hypotension (49%). Midodrine was continued for at least one month in 57% of the patients. Supine hypertension was the only side effect reported in 6% of patients. No statistically significant changes in NYHA class, guideline-directed medical therapy, cardiac biomarkers (NT-proBNP or troponin T), echocardiographic findings or cardiovascular hospitalizations were observed between patients who continued treatment with midodrine compared to those who stopped using midodrine over a median follow-up of 38 months. In the multivariable cox regression analysis, continuation of midodrine, compared to discontinuation, and use of midodrine for orthostatic hypotension, as opposed to other causes of hypotension, were not associated with an increased risk of mortality (HR 0.41, 95% CI 0.24-0.69, p < .0001; HR 0.34, 95% CI 0.18-0.64, p < .001, respectively). In contrast, elevated creatinine (> 1.3 for males and > 1.1 for females) was associated with an increased risk of mortality (HR 1.83, 95% CI 1.07-3.14). LVEF was not significantly associated with lower or higher risk of mortality. CONCLUSIONS: In our study, midodrine use in patients with cancer and HF was not associated with significant adverse effects, worse cardiovascular outcomes, or increased risk of mortality. Larger, prospective studies are needed to confirm these findings.

Geographical Differences in Cardiovascular Comorbidities and Outcomes of COVID-19 Hospitalized Patients in the USA.

INTRODUCTION: Cardiovascular comorbidities may predispose to adverse outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). However, across the USA, the burden of cardiovascular comorbidities varies significantly. Whether clinical outcomes of hospitalized patients with COVID-19 differ between regions has not yet been studied systematically. Here, we report differences in underlying cardiovascular comorbidities and clinical outcomes of patients hospitalized with COVID-19 in Texas and in New York state. METHODS: We established a multicenter retrospective registry including patients hospitalized with COVID-19 between March 15 and July 12, 2020. Demographic and clinical data were manually retrieved from electronic medical records. We focused on the following outcomes: mortality, need for pharmacologic circulatory support, need for mechanical ventilation, and need for hemodialysis. Univariate and multivariate logistic regression analyses were performed. RESULTS: Patients in the Texas cohort (n = 296) were younger (57 vs. 63 years, p value <0.001), they had a higher BMI (30.3 kg/m2 vs. 28.5 kg/m2, p = 0.015), and they had higher rates of diabetes mellitus (41 vs. 30%; p = 0.014). In contrast, patients in the New York state cohort (n = 218) had higher rates of coronary artery disease (19 vs. 10%, p = 0.005) and atrial fibrillation (11 vs. 5%, p = 0.012). Pharmacologic circulatory support, mechanical ventilation, and hemodialysis were more frequent in the Texas cohort (21 vs. 13%, p = 0.020; 30 vs. 12%, p < 0.001; and 11 vs. 5%, p = 0.009, respectively). In-hospital mortality was similar between the 2 cohorts (16 vs. 18%, p = 0.469). After adjusting for differences in underlying comorbidities, only the use of mechanical ventilation remained significantly higher in the participating Texas hospitals (odds ratios [95% CI]: 3.88 [1.23, 12.24]). Median time to pharmacologic circulatory support was 8 days (interquartile range: 2, 13.8) in the Texas cohort compared to 1 day (0, 3) in the New York state cohort, while median time to in-hospital mortality was 16 days (10, 25.5) and 7 days (4, 14), respectively (both p < 0.001). In-hospital mortality was higher in the late versus the early study phase in the New York state cohort (24 vs. 14%, p = 0.050), while it was similar between the 2 phases in the Texas cohort (16 vs. 15%, p = 0.741). CONCLUSIONS: Geographical differences, including practice pattern variations and the impact of disease burden on provision of health care, are important for the evaluation of COVID-19 outcomes. Unadjusted data may cause bias affecting future regulatory policies and proper allocation of resources.

Prostate Cancer Therapy Cardiotoxicity Map (PROXMAP) for Advanced Disease States: A Systematic Review and Network Meta-analysis with Bayesian Modeling of Treatment Histories.

BACKGROUND AND OBJECTIVE: Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies. METHODS: We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024. Network meta-analyses of first-line mHSPC, M0CRPC, and mCRPC therapies were constructed for the five cardiotoxicity metrics defined by the International Cardio-Oncology Society: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Additional Bayesian network meta-analyses also accounted for prior treatment history. KEY FINDINGS AND LIMITATIONS: Thirteen RCTs (16 292 patients) were included. For mHSPC, androgen deprivation therapy (ADT) plus docetaxel (DTX) plus abiraterone acetate (AA) with prednisone (P) demonstrated a significant increase in hypertension and arrhythmias versus ADT + DTX (risk ratio [RR] 2.85, 95% confidence interval [CI] 1.67-4.89, and RR 2.01, 95% CI 1.17-3.44, respectively); however, no corresponding differences were observed between ADT + DTX plus darolutamide (DAR) and ADT + DTX (RR 1.55, 95% CI 0.73-3.30, and RR 0.94, 95% CI 0.63-1.40, respectively). For mCRPC assuming a history of mHSPC treatment, ADT + AA + P plus olaparib (OLA) demonstrated a statistically significant decrease in hypertension versus ADT + AA + P (RR 0.20, 95% CI 0.16-0.26). M0CRPC results were unremarkable. CONCLUSIONS AND CLINICAL IMPLICATIONS: For mHSPC, ADT + DTX + DAR demonstrates less cardiotoxicity than ADT + DTX + AA + P due to a lower risk of hypertension and arrhythmias from decreased mineralocorticoid excess. In addition, OLA counterintuitively offers decreased hypertension when superimposed on ADT + AA + P for mCRPC treatment after prior androgen deprivation from mHSPC therapy.