From chest pain to coronary functional testing: Clinical and economic impact of coronary microvascular dysfunction.

BACKGROUND: Coronary functional testing to formally diagnose coronary microvascular dysfunction (CMD) reduces cardiovascular events and alleviates angina. This study aims to investigate the extensive and complex journey that patients with CMD undergo, from the onset of chest pain to eventual diagnosis. METHODS: Data from the Coronary Microvascular Disease Registry (CMDR) were analyzed, including information on the date of first documentation of chest pain, number of non-invasive and invasive tests the patient underwent, emergency department visits, and hospitalizations. In addition, we estimated the total cost per patient. A total of 61 patients with CMD diagnosis were included in this analysis. RESULTS: Most patients in our cohort were older than 50 years of age. The median time from initial chest pain symptoms to diagnosis was 0.62 (interquartile range [IQR]: 0.06-2.96) years. During this period, patients visited the emergency department a median of 1.0 (IQR: 0.0-2.0) times. Diagnostic tests included 3.0 (IQR: 2.0-6.0) electrocardiograms, 3.0 (IQR: 0.0-6.0) high-sensitivity troponin tests, and 1.0 (IQR: 1.0-2.0) echocardiograms. Prior to diagnosis of CMD, 13 (21.3 %) patients had left heart catheterization without coronary functional testing. Non-invasive testing for ischemia was conducted in 43 (70.5 %) patients. Alternative non-cardiac diagnoses were given to 11 (18.0 %) patients during the diagnostic process, with referrals made to gastroenterology for 16 (26.2 %) and pulmonology for 10 (16.4 %) patients. The cost was almost $2000/patient. CONCLUSION: Timely identification of CMD offers promising opportunities for prompt symptom alleviation, accompanied by reduced visits to the emergency department, cardiovascular testing, invasive medical procedures, and consequently reduced healthcare expenses.

Coronary microvascular dysfunction assessment: A comparative analysis of procedural aspects.

BACKGROUND: Full adoption of coronary microvascular dysfunction (CMD) assessment faces challenges due to its invasive nature and concerns about prolonged procedure time and increased contrast and/or radiation exposure. We compared procedural aspects of CMD invasive assessment to diagnostic left heart catheterization (DLHC) in patients with chest pain who were not found to have obstructive coronary artery disease. METHODS: A total of 227 patients in the Coronary Microvascular Disease Registry were compared to 1592 patients who underwent DLHC from August 2021 to November 2023. The two cohorts were compared using propensity-score matching; primary outcomes were fluoroscopy time and total contrast use. RESULTS: The participants' mean age was 64.1 ± 12.6 years. CMD-assessed patients were more likely to be female (66.5% vs. 45.2%, p < 0.001) and have hypertension (80.2% vs. 44.5%, p < 0.001), history of stroke (11.9% vs. 6.3%, p = 0.002), and history of myocardial infarction (20.3% vs. 7.7%, p < 0.001). CMD assessment was safe, without any reported adverse outcomes. A propensity-matched analysis showed that patients who underwent CMD assessment had slightly higher median contrast exposure (50 vs. 40 mL, p < 0.001), and slightly longer fluoroscopy time (6.9 vs. 4.7 min, p < 0.001). However, there was no difference in radiation dose (209.3 vs. 219 mGy, p = 0.58) and overall procedure time (31 vs. 29 min, p = 0.37). CONCLUSION: Compared to DLHC, CMD assessment is safe and requires only slightly additional contrast use (10 mL) and slightly longer fluoroscopy time (2 min) without clinical implications. These findings emphasize the favorable safety and feasibility of invasive CMD assessment.

Bringing CAR T cell therapy trials to underserved populations.

There is a critical need for equitable access to cell therapies in cancer treatment, particularly within public safety-net healthcare systems that serve minority and socioeconomically disadvantaged populations. We discuss how the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine is piloting a cell therapy program aimed at addressing cancer care disparities and has the potential to serve as a national model for enhancing health equity in cancer care.

Race, Ethnicity, and Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative, Node-Negative Breast Cancer in the Randomized TAILORx Trial.

BACKGROUND: Black race is associated with worse outcomes in early breast cancer. We evaluated clinicopathologic characteristics, the 21-gene recurrence score (RS), treatment delivered, and clinical outcomes by race and ethnicity among women who participated in the Trial Assigning Individualized Options for Treatment. METHODS: The association between clinical outcomes and race (White, Black, Asian, other or unknown) and ethnicity (Hispanic vs non-Hispanic) was examined using proportional hazards models. All P values are 2-sided. RESULTS: Of 9719 eligible women with hormone receptor-positive, HER2-negative, node-negative breast cancer, there were 8189 (84.3%) Whites, 693 (7.1%) Blacks, 405 (4.2%) Asians, and 432 (4.4%) with other or unknown race. Regarding ethnicity, 889 (9.1%) were Hispanic. There were no substantial differences in RS or ESR1, PGR, or HER2 RNA expression by race or ethnicity. After adjustment for other covariates, compared with White race, Black race was associated with higher distant recurrence rates (hazard ratio [HR] = 1.60, 95% confidence intervals [CI] = 1.07 to 2.41) and worse overall survival in the RS 11-25 cohort (HR = 1.51, 95% CI = 1.06 to 2.15) and entire population (HR = 1.41, 95% CI = 1.05 to 1.90). Hispanic ethnicity and Asian race were associated with better outcomes. There was no evidence of chemotherapy benefit for any racial or ethnic group in those with a RS of 11-25. CONCLUSIONS: Black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy in the Trial Assigning Individualized Options for Treatment. Similar to Whites, Black women did not benefit from adjuvant chemotherapy if the 21-gene RS was 11-25. Further research is required to elucidate the basis for this racial disparity in prognosis.

Assessment of Individual versus Composite Endpoints of Acute Graft-versus-Host Disease in Determining Long-Term Survival after Allogeneic Transplantation.

The overall composite of graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS), defined as survival free of grade III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic immunosuppressive therapy (IST), or relapse, has emerged as a useful composite in clinical trials and to capture clinically meaningful events that impact quantity and quality of survival after allogeneic hematopoietic cell transplantation (HCT). We reviewed 565 consecutive patients aged ≥18 years undergoing HCT for hematologic malignancy to analyze how baseline incidence, specifics of clinical definitions, and proposed reductions in any one individual event may dynamically alter the overall performance of the composite To determine the relative impact of each GRFS event (excluding death), we accounted for competing risks using Fine and Gray methods, and correlated each event with overall survival (OS) using Kaplan-Meier methods. The consequences of modulating individual or composite endpoints on OS, such as hypothesized reductions of events of an HCT interventional trial, were examined using Monte Carlo simulations. The median age of the cohort was 54 years (range, 18 to 73 years). The majority of patients received HLA-matched unrelated donor HCT (53%), consisting of peripheral blood stem cell grafts (90%) after myeloablative conditioning (68%). Relapse conferred the greatest risk for death (hazard ratio [HR], 7.89; 95% confidence interval [CI], 5.83 to 10.69), followed by grade III-IV aGVHD (HR, 6.16; 95% CI, 4.42 to 8.56) and cGVHD requiring IST (HR, 1.69; 95% CI, 1.16 to 2.46). The overall GRFS composite correlated with an HR of 4.81 (95% CI, 3.61 to 6.41), which was lower compared with either relapse or grade III-IV aGVHD. Statistical simulations found that modulating the combined risk of both relapse and grade III-IV aGVHD predicted the greatest change in 5-year OS. These simulations suggest that GRFS as currently defined may be less optimal for correlating with OS, and further refinement of composite endpoints is needed. Nonetheless, composite endpoints may be particularly helpful in mitigating potential difficulties in interpretation when competing risks are present, most commonly seen in HCT studies.