BACKGROUND Historically, there is perceived pressure to achieve therapeutic levels of tacrolimus quickly after heart transplant (HT). We evaluated the association between time within therapeutic tacrolimus range and time to therapeutic trough and rejection in the 30 days following HT. METHODS This is a single-center retrospective cohort study of consecutive adult HT patients receiving immunosuppression. Goal trough tacrolimus levels were 10-15 ng/ml. Surveillance endomyocardial biopsies were performed weekly for 4 weeks. Outcomes included the effect of time to and timein-therapeutic tacrolimus range (Rosendaal method) on 30-day clinical rejection, 1R/1B, and 2R or higher histologic occurrences. RESULTS We reviewed 67 HT patients (median age 58.8 yrs). For clinical rejection versus no-rejection groups, the median (25th, 75th percentile) time to therapeutic tacrolimus levels was 9.5 (8, 12.3) days versus 9.0 (7, 13) days (p=0.623). The median time-in-therapeutic tacrolimus range was 34.1% (23.2, 42.2) versus 36.2% (19.9, 51.2), respectively (p=0.512). Similarly, we observed no significant differences in time to and time-in-therapeutic tacrolimus range in patients who developed grade 1R/1B (p=0.650 and p=0.725) or grade 2R or higher histology (p=0.632 and p=0.933). CONCLUSIONS Our small single-center analysis suggests that neither time to nor time in therapeutic tacrolimus range predicted acute rejection within 30 days of HT.
Right-sided heart failure is the most common cause of death in pulmonary hypertension (PH). Echocardiographic measurements of right atrial (RA) size are associated with worse outcome in PH, however the association between RA function and death in PH has not been well-described. 160 PH patients (World Health Organization groups 1-5) underwent cardiac magnetic resonance imaging (cMRI) and right heart catheterization (RHC) within 6 weeks of each other at a tertiary care academic medical center in the United States. We measured cMRI RA maximum and minimum volumes indexed to body surface area and calculated RA emptying fraction (RAEF). We evaluated the relationship between RAEF and clinical variables with death using Cox proportional hazard models. 57 deaths occurred during a median follow-up of 3.5 years (36 % died overall, 10 % per year). RAEF was directly correlated in univariate analyses with right ventricular (RV) ejection fraction, left ventricular (LV) ejection fraction, LV size, cardiac index, absence of tricuspid and pulmonic regurgitation, absence of pericardial effusion, estimated glomerular filtration rate, 6-minute walk distance, and pulmonary arterial oxygen saturation, whereas it was inversely correlated with death, BNP, heart rate, mean RA pressure, mean PA pressure, pulmonary and systemic vascular resistance, RV size, and RA size. Using multivariate analyses, RAEF had a robust inverse association with death after adjusting for measured risk factors (HR per 5 % change in RAEF: 0.83 [95 % CI 0.73-0.94], p = 0.003). In PH patients, decreased RAEF by cMRI is independently associated with worse survival after adjustment for other risk factors.
The specific role of selexipag for managing PAH patients is unclear because of its modest efficacy, lack of mortality reduction, and cost similar to intravenous prostacyclins. Additional clinical trials exploring combination therapy as well as its role in other types of pulmonary hypertension are needed.
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