Cardiopulmonary, biomarkers, and vascular responses to acute hypoxia following cardiac transplantation.

Previous studies have suggested good adaptation of cardiac transplant (CTx) recipients to exposure to a high altitude. No studies have investigated the cardiopulmonary and biomarker responses to acute hypoxic challenges following CTx. Thirty-six CTx recipients and 17 age-matched healthy controls (HC) were recruited. Sixteen (16) patients (42%) had cardiac allograft vasculopathy (CAV). Cardiopulmonary responses to maximal and submaximal exercise at 21% O2 , 20-minutes hypoxia (11.5% O2 ), and following a 10-minute exposure to 11.5% O2 using 30% of peak power output were completed. Vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), suppression of tumorigenicity 2 (ST2) were measured at baseline and at peak stress. Endothelial peripheral function was assessed using near-infrared spectroscopy. Compared with HC, CTx presented a lesser O2 desaturation both at rest (-19.4 ± 6.8 [CTx] vs -24.2 ± 6.0% O2 [HC], P < 0.05) and following exercise (-23.2 ± 4.9 [CTx] vs -26.2 ± 4.7% O2 [HC], P < 0.05). CTx patients exhibited a significant decrease in peak oxygen uptake. IL-6 and VEGF levels were significantly higher in CTx recipients in basal conditions but did not change in response to acute stress. CTx patients exhibit a favorable ventilatory and overall response to hypoxic stress. These data provide further insights on the good adaptability of CTx to exposure to high altitude.

Myocardial Vascular Function Assessed by Dynamic Oxygenation-sensitive Cardiac Magnetic Resonance Imaging Long-term Following Cardiac Transplantation.

BACKGROUND: Coronary vascular function is related to adverse outcomes following cardiac transplantation (CTx) in patients with or without cardiac allograft vasculopathy (CAV). The noninvasive assessment of the myocardial vascular response using oxygenation-sensitive cardiac magnetic resonance (OS-CMR has not been investigated in stable long-term CTx recipients). METHODS: CTx patients were prospectively recruited to complete a CMR study with a breathing maneuver of hyperventilation followed by a voluntary apnea. Changes in OS-sensitive signal intensity reflecting the myocardial oxygenation response were monitored and expressed as % change in response to these breathing maneuvers. Myocardial injury was further investigated with T2-weighted imaging, native and postcontrast T1 measurements, extracellular volume measurements, and late gadolinium enhancement. RESULTS: Forty-six CTx patients with (n = 23) and without (n = 23) CAV, along with 25 healthy controls (HC), were enrolled. The OS response was significantly attenuated in CTx compared with HC at the 30-second time-point into the breath-hold (2.63% ± 4.16% versus 6.40% ± 5.96%; P = 0.010). Compared with HC, OS response was lower in CTx without CAV (2.62% ± 4.60%; P < 0.05), while this response was further attenuated in patients with severe CAV (grades 2-3, -2.24% ± 3.65%). An inverse correlation was observed between OS-CMR, ventricular volumes, and diffuse fibrosis measured by extracellular volume mapping. CONCLUSIONS: In heart transplant patients, myocardial oxygenation is impaired even in the absence of CAV suggesting microvascular dysfunction. These abnormalities can be identified by oxygenation-sensitive CMR using simple breathing maneuvers.

Temporal Changes on the Risks and Complications of Posttransplantion Diabetes Mellitus Following Cardiac Transplantation.

BACKGROUND: Recent changes in the demographic of cardiac donors and recipients have modulated the rate and risk, associated with posttransplant diabetes mellitus (PTDM). We investigated the secular trends of the risk of PTDM at 1 year and 3 years after transplantation over 30 years and explored its effect on major outcomes. METHODS: Three hundred and three nondiabetic patients were followed for a minimum of 36 months, after a first cardiac transplantation performed between 1983 and 2011. Based on the year of their transplantation, the patients were divided into 3 eras: (1983-1992 [era 1], 1993-2002 [era 2], and 2003-2011 [era 3]). RESULTS: In eras 1, 2, and 3, the proportions of patients with PTDM at 1 versus 3 years were 23% versus 39%, 21% versus 26%, and 33% versus 38%, respectively. Independent risk factors predicting PTDM at one year were recipient's age, duration of cold ischemic time, treatment with furosemide, and tacrolimus. There was a trend for overall survival being worse for patients with PTDM in comparison to patients without PTDM (p = 0.08). Patients with PTDM exhibited a significantly higher rate of renal failure over a median follow-up of 10 years (p = 0.03). CONCLUSION: The development of PTDM following cardiac transplantation approaches 40% at 3 years and has not significantly changed over thirty years. The presence of PTDM is weakly associated with an increased mortality and is significantly associated with a worsening in renal function long-term following cardiac transplantation.