Background

We investigated the myocardial perfusion differences and changes in immune cell response in heart-transplant patients with nonspecific graft dysfunction (NGD) compared to cardiac allograft vasculopathy (CAV) patients and normal heart-transplant patients.

Methods and Results

We prospectively studied 17 heart-transplant patients (59.8±14.1 years, 78% male) from January to June 2016. Regadenoson stress cardiac MRI was performed in the patients and peripheral blood obtained contemporaneously to isolate peripheral blood mononuclear cells (PBMCs). Stress myocardial perfusion showed significantly decreased myocardial perfusion using maximum upslope method in NGD and CAV patients compared to normal heart-transplant patients. Myocardial scar by late gadolinium enhancement also was significantly increased in nonspecific graft dysfunction patients compared to normal. Evaluation of PBMCs by flow cytometry showed a trend towards increased activated HLA-DR + T cells in NGD patients compared to normal. Clinical outcomes for cardiac hospitalization, allograft loss/retransplant, death were assessed at 8 years.

Conclusions

NGD shows decreased stress myocardial perfusion by cardiac MRI and a trend towards increased activated T cells in PBMCs, suggestive of an immune-mediated cause for allograft dysfunction.

Rationale

OSA has been associated with reduced exercise capacity. Endothelial dysfunction and exercise-induced pulmonary hypertension (ePH) may be mediators of this impairment. We hypothesized that OSA severity would be associated with impaired exercise performance, endothelial dysfunction, and ePH.

Methods

Subjects with untreated OSA were recruited. Subjects underwent endothelial function, and cardiopulmonary exercise testing with an echocardiogram immediately before and following exercise.

Results

22 subjects were recruited with mean age 56 ± 8 years, 74 % male, BMI 29 ± 3 kg/m², and AHI 22 ± 12 events/hr. Peak V˙O₂ did not differ from normal (99.7 ± 17.3 % predicted; p = 0.93). There was no significant association between OSA severity (as AHI, ODI) and exercise capacity, endothelial function, or pulmonary artery pressure. However, ODI, marker of RV diastolic dysfunction, and BMI together explained 59.3 % of the variability of exercise performance (p < 0.001) via our exploratory analyses.

Conclusions

Exercise capacity was not impaired in this OSA cohort. Further work is needed to elucidate mechanisms linking sleep apnea, obesity, endothelial dysfunction and exercise impairment.