Cardiology Encounters for Underrepresented Racial and Ethnic Groups with Human Immunodeficiency Virus and Borderline Cardiovascular Disease Risk.

BACKGROUND: Underrepresented racial and ethnic groups (UREGs) with HIV have a higher risk of cardiovascular disease (CVD) compared with the general population. Referral to a cardiovascular specialist improves CVD risk factor management in high-risk individuals. However, patient and provider factors impacting the likelihood of UREGs with HIV to have an encounter with a cardiologist are unknown. METHODS: We evaluated a cohort of UREGs with HIV and borderline CVD risk (10-year risk ≥ 5% by the pooled cohort equations or ≥ 7.5% by Framingham risk score). Participants received HIV-related care from 2014-2020 at four academic medical centers in the United States (U.S.). Adjusted Cox proportional hazards regression was used to estimate the association of patient and provider characteristics with time to first ambulatory cardiology encounter. RESULTS: A total of 2,039 people with HIV (PWH) and borderline CVD risk were identified. The median age was 45 years (IQR: 36-50); 52% were female; and 94% were Black. Of these participants, 283 (14%) had an ambulatory visit with a cardiologist (17% of women vs. 11% of men, p < .001). In fully adjusted models, older age, higher body mass index (BMI), atrial fibrillation, multimorbidity, urban residence, and no recent insurance were associated with a greater likelihood of an encounter with a cardiologist. CONCLUSION: In UREGs with HIV and borderline CVD risk, the strongest determinants of a cardiology encounter were diagnosed CVD, insurance type, and urban residence. Future research is needed to determine the extent to which these encounters impact CVD care practices and outcomes in this population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04025125.

Electronic health record characterization and outcomes of heart failure with preserved ejection fraction.

BACKGROUND: Electronic health record (EHR)-based identification of heart failure with preserved ejection fraction (HFpEF) in the clinical setting may facilitate screening for clinical trials by improving the understanding of its epidemiology and outcomes; yet, previous data have yielded variable results. We sought to characterize groups identified with HFpEF by different EHR screening strategies and their associated long-term outcomes across a large and diverse population. METHODS: We retrospectively analyzed 116,499 consecutive patients from an academic referral center who underwent echocardiography, and 9,263 patients who underwent echocardiography within 6 months of right heart catheterization (RHC), between 2008 and 2018. EHR-based screening strategies identified patients with HFpEF using 1) International Classification of Diseases (ICD)-9/10 codes, 2) H2FpEF score ≥6 and ejection fraction (EF) ≥50%, or 3) RHC wedge pressure ≥15 mmHg and EF ≥50%, when available. Primary outcomes were 1) cumulative incident heart failure hospitalization (HFH), and 2) death, over 10 years. RESULTS: There were 33,461 (29%) patients who met either ICD or H2FpEF-HFpEF definition, of whom 5,310 (16%) met both criteria. Compared to ICD-HFpEF, patients with H2FpEF-HFpEF were more likely older (median age 72 vs 67), White (78% vs 64%), and had atrial fibrillation (97% vs 41%). Among those also with RHC, 6,353 (69%) patients met any HFpEF criteria, of whom only 783 (12%) satisfied all three criteria. Female sex was more common among RHC-HFpEF (55%) compared to other methods (H2FpEF-HFpEF, 47%; ICD-HFpEF, 43%). Atrial fibrillation was substantially higher among HFpEF identified by the H2FpEF score (97%) compared to other methods (49% for ICD and 47% for RHC). Across HFpEF screening methods, 10-year cumulative incidence rates for HFH was 32% to 45% for echocardiography only and 43% to 52% for echocardiography and RHC populations; 10-year risk of death was 54% to 56% for echocardiography only and 52% to 57% for echocardiography and RHC populations. CONCLUSIONS: Different EHR-based HFpEF definitions identified cohorts with modest overlap and varying baseline characteristics. Yet, long-term risk for HFH and death were similarly high for cohorts identified among both populations undergoing echocardiography only or echocardiography and RHC. These data aid in identifying relevant subgroups in clinical trials of HFpEF.

Optimizing regional infusion treatment strategies for melanoma of the extremities.

The incidence of malignant melanoma is increasing faster than any other cancer. In cases of recurrent melanoma confined to the extremities, hyperthermic isolated limb perfusion and isolated limb infusion provide a way to isolate the extremity and deliver a dose of chemotherapy several orders of magnitude higher than would be tolerated systemically. Although complete response rates of up to 80% for hyperthermic isolated limb perfusion and 44% for isolated limb infusion have been observed, there is still room for improvement and standardization in these two procedures in an attempt to optimize response while minimizing toxicity. Currently, new chemotherapy agents and small-molecule inhibitors are being investigated as a means of overcoming chemoresistance and improving response rates. In patients with advanced cutaneous disease confined to the extremities, evaluation of these new therapies can be very informative, as tissue acquisition at multiple treatment time points is easy owing to the superficial and multifocal nature of the disease. Through studying the biomolecular and genetic alterations in tumor tissue in response to these new therapies, genetically customized treatment regimens in which tumor resistance and sensitivity is predicted and treatment strategy is optimized before treatment begins may soon be available. Progress in regional therapy will prove not only beneficial for patients with disease confined to an extremity, but may also provide insight into developing novel treatment strategies for patients with systemic disease for whom current disease management options are poor.

A phase 1 study of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with locally advanced in-transit malignant melanoma.

BACKGROUND: Isolated limb infusion with melphalan is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximately 30% complete response (CR) rate. ADH-1 is a cyclic pentapeptide that disrupts N-cadherin adhesion complexes and when given systemically in a preclinical model of regional melphalan therapy demonstrated synergistic antitumor activity. A phase 1 dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with in-transit extremity melanoma was performed. METHODS: Dose escalation cohorts of 3 patients each received 1000, 2000, and 4000 mg (10 patients) of ADH-1 administered intravenously on Days 1 and 8 with standard dose melphalan via isolated limb infusion on Day 1. N-cadherin immunohistochemistry staining and quantitative polymerase chain reaction analysis were performed on pretreatment tumor. Response was defined at 3 months using modified Response Evaluation Criteria in Solid Tumors. RESULTS: Sixteen patients have been treated with no observed dose-limiting toxicities. Common treatment-related grade 1 or 2 toxicities included skin/dermatologic (n=14) and pain (n=12). Grade 3 toxicities included shortness of breath (n=1), hypertension (n=1), serologic toxicities (n=4), and 1 grade 4 creatine phosphokinase elevation. In-field responses included 8 CRs, 2 partial responses, 1 stable disease, and 5 progressive diseases. Pharmacokinetic analysis demonstrated increasing ADH-1 concentrations at each dose and minimal variability in melphalan drug levels. CONCLUSIONS: Systemic ADH-1 at a dose of 4000 mg on Days 1 and 8 in combination with melphalan via isolated limb infusion is a well-tolerated, novel targeted therapy approach to regionally advanced melanoma. The number of CRs exceeded expectations, suggesting that targeting N-cadherin may be a new strategy for overcoming melanoma chemoresistance.

Isolated limb infusion for in-transit malignant melanoma of the extremity: a well-tolerated but less effective alternative to hyperthermic isolated limb perfusion.

BACKGROUND: Isolated limb infusion (ILI) is a recently described minimally invasive technique developed in Australia for delivering regional chemotherapy. This study examined the efficacy and toxicity of ILI, compared to hyperthermic isolated limb perfusion (HILP), in treating extremity in-transit melanoma. METHODS: Variables from a prospective single institution database of 120 regionally treated melanoma patients (1995-2007) were compared using chi-square analysis. This included 61 consecutive ILI treatments in 58 patients and 59 HILP treatments in 54 patients. Response was defined at 3 months using the response evaluation criteria in solid tumors (RECIST). ILI was performed using melphalan (LPAM) and dactinomycin for 30 min after limb temperature reached 37 degrees C. HILP was performed using LPAM for 60 min after limb temperature reached 38.5 degrees C. RESULTS: For ILI (n = 61), the complete response (CR) rate was 30%, the partial response (PR) rate was 14%, and there was no response (NR) in 56% of patients. The median duration of CR was 12 months and 18% of patients experienced (grade >or=3) toxicity. HILP (n = 59) was associated with a better (P < 0.001) response rate (CR 57%, PR 31%, and NR 12%) however, more patients (32%) experienced grade >or=3 toxicity (P = 0.037). The dose of LPAM was corrected for ideal body weight (IBW) in 40 out of 61 ILI procedures, and 13 of 59 HILP procedures. This dosing modification was associated with decreased toxicity (P = 0.024) without diminishing response. CONCLUSION: ILI was found to be a well-tolerated alternative to HILP. While ILI does not appear to be as effective as HILP, it does seem to be associated with less morbidity.