Center-level self-study identifies opportunities to advance equity in cystic fibrosis clinical trial participation.

Clinical trials are a necessary tool for evaluating the effectiveness of newly developed treatments and interventions for cystic fibrosis (CF). Prior work demonstrated a proportional underrepresentation of people with CF (pwCF) identifying as part of a minoritized racial or ethnic group in clinical trials. In order to establish a baseline for improvement efforts, we undertook a center-level self-study to evaluate if the racial and ethnic backgrounds of pwCF participating in clinical trials at our CF Center in New York City reflect our overall patient diversity (N = 200; 55 pwCF identifying as part of a minoritized racial or ethnic group and 145 pwCF identifying as non-Hispanic White). A smaller proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a clinical trial as compared to pwCF identifying as non-Hispanic White (21.8% vs. 35.9%, P = 0.06). A similar trend was present for pharmaceutical clinical trials (9.1% vs. 16.6%, P = 0.3). When limiting the study population to the pwCF most likely to be eligible for a CF pharmaceutical clinical trial, a larger proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a pharmaceutical clinical trial as compared to pwCF identifying as non-Hispanic White (36.4% vs. 19.6%, P = 0.2). No pwCF identifying as part of a minoritized racial or ethnic group participated in an offsite clinical trial. Efforts to improve the racial and ethnic diversity of pwCF in clinical trials, both onsite and offsite, will require a shift in how recruitment opportunities are identified and communicated to pwCF.

Prediction of patient outcomes through social determinants of health: The Pulmonary Hypertension Association Registry (PHAR) evaluation.

Outcomes of patients with pulmonary arterial hypertension (PAH) may be associated with social determinants of health (SDOH) and other baseline patient characteristics. At present, there is no prognostic model to predict important patient outcomes in PAH based on SDOH. Utilizing information from the Pulmonary Hypertension Association Registry (PHAR), we derive a model (PHAR Evaluation or PHARE) to predict an important composite patient outcomes based on SDOH and other patient characteristics. Baseline data regarding SDOH from adult patients with PAH enrolled in the PHAR between 2015 and March 23, 2020, were included for analysis. We performed repeated measures logistic regression modeling with dichotomous outcome data (0 for no events, 1 for one or more events) to derive the PHARE. Here, 1275 consecutive adult patients enrolled in the PHAR from 47 participating centers were included. Variables included in our model are race, gender, ethnicity, household income, level of education, age, body mass index, drug use, alcohol use, marital status, and type of health insurance. Interaction effect between variables was analyzed and several interactions were also included in the PHARE. The PHARE shows a c-statistic of 0.608 (p < 0.0001) with 95% confidence intervals (0.583, 0.632). Using SDOH and baseline characteristics from the PHAR, the PHARE correlates with our composite patient outcome. Further work evaluating the role of SDOH in prognostic modeling of PAH is indicated.

Assessment of late-term progression of cardiac allograft vasculopathy in patients with orthotopic heart transplantation using quantitative cardiac 82Rb PET.

The risk stratification and long-term survival of patients with orthotopic heart transplantation (OHT) is impacted by the complication of cardiac allograft vasculopathy (CAV). This study evaluates changes in myocardial blood flow (MBF) and myocardial coronary flow reserve (CFR) in a group of long-term OHT patients using quantitative cardiac 82Rb-positron emission tomography (PET). Twenty patients (7 females and 13 males, mean age = 72.7 ± 12.2 years with CAV and 62.9 ± 7.2 years without CAV and post-OHT mean time = 13.9 years), were evaluated retrospectively using dynamic cardiac 82Rb-PET at rest and regadenoson-induced stress. The patients also underwent selective coronary angiography (SCA) for diagnosis and risk stratification. CAV was diagnosed based on SCA findings and maximal intimal thickness greater than 0.5 mm, as defined by International Society of Heart and Lung Transplantation (ISHLT). Global and regional MBFs were estimated in three vascular territories using the standard 1-tissue compartment model for dynamic 82Rb-PET. The myocardial CFR was also calculated as the ratio of peak stress MBF to rest MBF. Among twenty patients, seven had CAV in, at least, one major coronary artery (ISHLT CAV grade 1 or higher) while 13 patients did not have CAV (NonCAV). Mean rate-pressure products (RPP) at rest were significantly elevated in CAV patients compared to those without CAV (P = 0.002) but it was insignificant at stress (P = NS). There was no significant difference in the stress MBFs between CAV and NonCAV patients (P = NS). However, the difference in RPP-normalized stress MBFs was significant (P = 0.045), while RPP-normalized MBFs at rest was not significant (P = NS). Both CFR and RPP-normalized CFR were significantly lower in CAV compared to NonCAV patients (P < 0.001). There were significant correlations between MBFs and RPPs at rest for both CAV (ρ = 0.764, P = 0.047) and NonCAV patients (ρ = 0.641, P = 0.017), while there were no correlations at stress for CAV (ρ = 0.232, P = NS) and NonCAV patients (ρ = 0.068, P = NS). This study indicates that the resting MBF is higher in late-term post-OHT patients. The high resting MBF and reduced CFR suggest an unprecedented demand of blood flow and blunted response to stress due to impaired vasodilatory capacity that is exacerbated by the presence of CAV.

Echocardiographic assessment of pulmonary arterial capacitance predicts mortality in pulmonary hypertension.

BACKGROUND: Pulmonary arterial capacitance (PAC) is one of the strongest predictors of clinical outcomes in patients with pulmonary hypertension (PH). We examined the value of an echocardiographic surrogate for PAC (ePAC) as a predictor of mortality in patients with PH. METHODS: We performed a retrospective study of 302 patients with PH managed at a PH comprehensive care center over a cumulative follow-up time of 858 patient-years. Charts from 2004 to 2018 were reviewed to identify patients in whom a right heart catheterization (RHC) was performed within two months of an echocardiogram. Standard invasive, non-invasive, functional, and biochemical prognostic markers were extracted from the time of RHC. The primary outcome was all-cause mortality. Cox proportional hazards models were used to model the time from RHC to the primary outcome or last medical contact. RESULTS: Variables associated with all-cause mortality included ePAC [standardized hazard ratio (HR) 0.68, 95% CI 0.48-0.98, p = 0.036], RHC-PAC (HR 0.68, 95% CI 0.48-0.96, p = 0.027), echocardiographic pulmonary vascular resistance (HR 1.29, 95% CI 1.05-1.60, p = 0.017), six-minute walk distance (HR 0.43, 95% CI 0.23-0.82, p = 0.01), and B-type natriuretic peptide (HR 1.29, 95% CI 1.03-1.62, p = 0.027). In multivariable-adjusted Cox analysis, ePAC predicted all-cause mortality independently of age, gender, and multiple comorbidities. There was a graded and stepwise association between low (<0.15 cm/mmHg), medium (0.15-0.25 cm/mmHg), and high (>0.25 cm/mmHg) tertiles of ePAC and all-cause mortality. CONCLUSIONS: We have demonstrated that ePAC is a readily available echocardiographic marker that independently predicts mortality in PH, and have provided clinically relevant ranges by which to risk-stratify patients and predict mortality.