Levine, Deborah J.

Background Medication nonadherence has been associated with poor outcomes in transplant recipients yet identifying these behaviors pre-transplant remains challenging. The simplified medication adherence questionnaire (SMAQ) is a brief, reliable instrument to assess medication adherence. The aim of this study was to perform SMAQ testing on thoracic organ candidates and examine correlations between these scores and individual patient factors predicting medication nonadherence. Methods Consenting waitlisted lung, heart, and heart-lung transplant candidates from six thoracic transplant centers were mailed a survey that included demographic information and the Simplified Medication Adherence Questionnaire (SMAQ). Univariate logistic regression analysis was performed to assess association between pre-transplant medication adherence and demographic characteristics, psychosocial factors, and mortality. Results Among 298 participants, 60.7% were medication nonadherent. Nonadherence was associated with some college education (OR: 1.73; CI: 1.06, 2.81), lower positive affect (OR: 0.95; CI: 0.92, 0.99), and higher uncertainty (OR: 1.02; CI: 1.01, 1.04). Higher positivity ratio predicted adherence. Conclusion Identifiable patient-specific characteristics associated with medication nonadherence can be screened for during thoracic transplant evaluation. Interventions aimed at improving these factors during the pre-transplant period may improve clinical post-transplant outcomes, however, larger studies are needed to validate these findings.

ABSTRACTLung transplantation is indicated for selected patients with advanced pulmonary arterial hypertension (PAH). We used a modified Delphi process to develop recommendations on care of patients with PAH undergoing lung transplantation. This Delphi panel was recruited from the Pulmonary Vascular Research Institute's Innovative Drug Discovery Initiative ‐ Lung Transplantation Workstream, consisting of clinical and research experts in PAH and lung transplantation. In this process, 29 panelists were given open‐ended questions, querying topics related to lung transplantation in PAH. A steering group converted the responses into discrete statements. Panelists then rated agreement using a Likert scale in two further survey rounds: −5 (strongly disagree) to 5 (strongly agree). Consensus was defined as mean ≥ 2.5 or ≤ −2.5, with a standard deviation not crossing zero. Consensus was reached on 141 of 223 statements. Notable areas of consensus were for early discussions about transplantation, and agreement with previously published referral and listing criteria. There was agreement that lung transplantation could be offered in sick candidates, including those with concurrent renal or hepatic insufficiency. Bilateral lung transplantation was considered the procedure of choice for most patients, with rare indications for heart‐lung transplantation. Consensus on bridging strategies included use of veno‐arterial extracorporeal membrane oxygenation and preemptive awake cannulation in those with severe right ventricular dysfunction. Consensus was also achieved on intraoperative use of invasive hemodynamic monitoring, and prolonged postoperative circulatory support guided by hemodynamic response and echocardiography. Patients with PAH undergoing transplantation require specialized management, which differs somewhat from other candidates.

Background Inhaled treprostinil (iTre) is the only treatment approved for pulmonary hypertension due to interstitial lung disease (PH-ILD) to improve exercise capacity. This post hoc analysis evaluated clinical worsening and PH-ILD exacerbations from the 16-week INCREASE study and change in 6-minute walking distance (6MWD) in the INCREASE open-label extension (OLE) in patients with less severe haemodynamics. Methods Patients were stratified by baseline pulmonary vascular resistance (PVR) of <4 Wood units (WU) versus ≥4 WU and ≤5 WU versus >5 WU. Exacerbations of underlying lung disease, clinical worsening and change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in INCREASE were evaluated. For the OLE, patients previously assigned to placebo were considered to have a 16-week treatment delay. 6MWD and clinical events in the OLE were evaluated by PVR subgroup. Results Of the 326 patients enrolled in INCREASE, patients with less severe haemodynamics receiving iTre had fewer exacerbations of underlying lung disease and clinical worsening events. This was supported by the Bayesian analysis of the risk of disease progression (HR<1), and significant decreases in NT-proBNP levels. In the OLE, patients without a treatment delay had improved exercise capacity after 1-year compared with those with a 16-week treatment delay (22.1 m vs −10.3 m). Patients with a PVR of ≤5 WU without a treatment delay had a change of 5.5 m compared with −8.2 m for those with a treatment delay. Patients without a treatment delay had a prolonged time to hospitalisation, lung disease exacerbation and death. Conclusion Treatment with iTre led to consistent benefits in clinical outcomes in patients with PH-ILD and less severe haemodynamics. Earlier treatment in less severe PH-ILD may lead to better exercise capacity long-term, however, the subgroup analyses in this post hoc study were underpowered and confirmation of these findings is needed.

AbstractBackgroundDecisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleic acid test‐positive (NAT+) donors must balance risk of donor‐derived transmission events (DDTE) with the scarcity of available organs.MethodsOrgan Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS‐CoV‐2 NAT+ and NAT– donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee.ResultsFrom May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT– donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT– donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30‐day mortality, and 30‐day graft loss were similar for all organ types. No SARS‐CoV‐2 DDTE occurred in this interval.ConclusionsTransplantation of SARS‐CoV‐2 NAT+ donor organs appears safe for short‐term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes. image

AbstractBackgroundResilience represents the capacity to adapt to adversity. Resilience can improve following behavioral interventions. We examined lung transplant candidates’ resilience as a novel predictor using the Connor‐Davidson Resilience Scale (RISC‐10).MethodsWaitlisted candidates at six centers were mailed questionnaires from 9/16/2015 to 10/1/2019. Follow‐up surveys were collected annually and post‐transplant. Outcomes were recorded through February 17, 2020. Primary outcome was pre‐transplant death/delisting. Analyses included t test or chi‐square for group comparisons, Pearson's correlation coefficients for strength of relationships, and Cox proportional‐hazard models to evaluate associations with outcomes, adjusting for age, sex, and mood.ResultsParticipation was 55.3% (N = 199). Baseline RISC‐10 averaged 32.0 ± 5.6 and did not differ by demographics, primary transplant diagnosis, or disease severity markers. RISC‐10 did not correlate to the commonly utilized Psychosocial Assessment of Candidates for Transplant [PACT] or Stanford Integrated Psychosocial Assessment for Transplantation [SIPAT] tools. Scores < 26.3 (representing > 1 standard deviation below population average) occurred in 16% and were associated with pre‐transplant death or delisting, adjusted Hazard Ratio of 2.60 (95% Confidence Interval 1.23‐5.77; P = .01).ConclusionOne in six lung candidates had low resilience, predicting increased pre‐transplant death/delisting. RISC‐10 did not correlate with PACT or SIPAT; resilience may represent a novel risk factor.

Background: We examined the association of adult lung transplant candidates’ self-reported affect with transplant-related outcomes, evaluating whether a positive (vs negative) frame of mind might be protective. Method: Consenting waitlisted candidates from 6 centers completed the questionnaires including the Positive and Negative Affect Schedule annually and posttransplant. Univariate logistic regression analysis was performed to determine the association of baseline affect with outcomes of death or delisting. Models were subsequently adjusted for age, marital status, and education. Results: Questionnaires were completed by 169 candidates (77.9% participation). Mean positive affect, negative affect, and positive-to-negative affect ratio (positivity ratio) were similar to expected norms. The scores of the questionnaire did not change significantly over time. Fifteen (8.9%) waitlisted participants died. Candidates who died while waiting had lower positivity ratios compared to those who survived (1.82 vs 2.45; P = .02). A more negative affect was associated with increased death on the waiting list (adjusted odds ratio [OR] 1.10; P = .021). Conversely, a higher positivity ratio was associated with decreased death while waiting (adjusted OR: 0.45; P = .027). Conclusion: Negative affect may represent a novel risk factor for death on the waitlist. Enhancing positive affect may represent a useful target for psychological optimization in lung transplant candidates.

Section editor's note: Welcome to a new section in Advances titled “Pulmonary Hypertension Grand Rounds” (PHGR), which we are introducing in this issue. With this addition, Advances offers a unique opportunity for trainees and junior faculty interested in pulmonary hypertension (PH). This section will highlight cases with literature reviews written by young clinicians and researchers in PH. PHGR was created to use patient cases to integrate individual clinical expertise with the best available evidence from the literature to enable the best decisions for patients. As with the rest of the journal, our audience continues to be physicians, researchers, nurses, students, residents, and fellows interested in both the care of individual patients and the advances in our field. We welcome comments about the section and inquiries regarding submitting a case for publication. Please direct inquiries to advancesgrandrounds@PHAssociation.org

Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory‐related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to characterize respiratory‐related adverse events (AEs) associated with current or recent treatment with inhaled treprostinil and to compare the incidence of respiratory‐related AEs in PAH patients treated with inhaled treprostinil with that in patients treated with other Food and Drug Administration (FDA)–approved PAH therapies. This was a long‐term, prospective, observational study. All respiratory‐related AEs were recorded during the study. The number of PAH patients enrolled was 1,333, 666 treated with inhaled treprostinil and 667 controls (treated with an FDA‐approved PAH therapy other than inhaled treprostinil), for a total of 958 and 1,094 patient‐years of exposure, respectively. In the inhaled‐treprostinil group, 1,281 respiratory‐related AEs were reported in 403 patients (61%), and in the control group, 1,295 respiratory‐related AEs were reported in 388 patients (58%). Cough, throat irritation, nasal discomfort, and hemoptysis were the most common respiratory‐related AEs (occurring in ≥2% of patients in either treatment group) that demonstrated a higher number of events per patient‐year of exposure in the inhaled‐treprostinil group than in the control group (risk ratio [95% confidence interval]: 1.487 [1.172–1.887], 3.777 [2.050–6.956], 2.039 [1.072–3.879], and 1.957 [1.024–3.741], respectively). Overall, inhaled treprostinil was well tolerated by PAH patients in routine clinical care, with respiratory‐related AEs consistent with the known safety profile (trial registration: clinicaltrials.gov identifier: NCT01266265).