ABSTRACT
BACKGROUND: Cardiac sarcoidosis (CS) is a progressive inflammatory cardiomyopathy that can lead to heart failure, arrhythmia, and death. There is limited data on Orthotopic Heart Transplantation (OHT) outcomes in patients with CS. Here we examine outcomes in patients with CS who have undergone OHT at centers throughout the United States from 1987 to 2019. METHODS: This was an analysis of 63,947 adult patients undergoing OHT captured in the United Network for Organ Sharing (UNOS) registry. Patients were characterized as cardiac sarcoidosis (CS) or Non-CS. Baseline characteristics were compared using chi-square and Kruskal-Wallis Tests. Outcomes of interest included primary graft failure, patient survival, treated graft rejection, hospitalization for infection, and post-transplant malignancy. RESULTS: During the study period 227 patients with CS underwent OHT. Patients with CS were younger, had higher proportion of non-white patients, and received transplants at more urgent statuses. After multivariable modeling there was no difference in survival (HR 0.86, CI 0.59-1.3, p = 0.446) or graft failure (HR 0.849, CI 0.58-1.23, p = 0.394) between patients with CS and Non-CS. Patients with CS had lower odds of rejection (OR 0.558, CI 0.315- 0.985, p = 0.0444). Patients with CS had similar odds of hospitalization for infection and post-transplant malignancy, as Non-CS patients. CONCLUSIONS: Patients with CS and Non-CS had similar post OHT survival, odds of graft failure, hospitalizations for infection, and post-transplant malignancy. Results of this study confirm the role of heart transplantation as a viable option for patients with CS.
Subject(s)
Cardiomyopathies/surgery , Heart Transplantation , Sarcoidosis/surgery , Female , Humans , Male , Middle Aged , Treatment Outcome , United StatesABSTRACT
BACKGROUND: Dietary intake of the soy isoflavone genistein is associated with reduced severity of asthma, but the mechanisms responsible for this effect are unknown. OBJECTIVE: To determine whether genistein blocks eosinophil leukotriene C(4) (LTC(4)) synthesis and to evaluate the mechanism of this effect, and to assess the impact of a 4-week period of soy isoflavone dietary supplementation on indices of eosinophilic inflammation in asthma patients. METHODS: Human peripheral blood eosinophils were stimulated in the absence and presence of genistein, and LTC(4) synthesis was measured. 5-lipoxygenase (5-LO) nuclear membrane translocation was assessed by confocal immunofluorescence microscopy. Mitogen-activated protein (MAP) kinase activation was determined by immunoblot. Human subjects with mild-to-moderate persistent asthma and minimal or no soy intake were given a soy isoflavone supplement (100 mg/day) for 4 weeks. The fraction of exhaled nitric oxide (FE(NO)) and ex vivo eosinophil LTC(4) production were assessed before and after the soy isoflavone treatment period. RESULTS: Genistein inhibited eosinophil LTC(4) synthesis (IC(50) 80 nm), blocked phosphorylation of p38 MAP kinase and its downstream target MAPKAP-2, and reduced translocation of 5-LO to the nuclear membrane. In patients with asthma, following 4 weeks of dietary soy isoflavone supplementation, ex vivo eosinophil LTC(4) synthesis decreased by 33% (N=11, P=0.02) and FE(NO) decreased by 18% (N=13, P=0.03). CONCLUSION: At physiologically relevant concentrations, genistein inhibits eosinophil LTC(4) synthesis in vitro, probably by blocking p38- and MAPKAP-2-dependent activation of 5-LO. In asthma patients, dietary soy isoflavone supplementation reduces eosinophil LTC(4) synthesis and eosinophilic airway inflammation. These results support a potential role for soy isoflavones in the treatment of asthma.
