Invasive haemodynamics in de novo everolimus vs. calcineurin inhibitor heart transplant recipients

• Aims: Invasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)-based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow-up after HTx in a sub-study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI-based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise. Methods and results: Ninety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre-HTx to the first follow-up at 7–11 weeks post-HTx and thereafter remained unchanged up to 3 years of follow-up. During follow-up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post-capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≥ 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7–11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy-proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy-proven treated acute rejections were not associated with altered haemodynamics. Conclusions: De novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy-proven treated rejections.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Nyckelord

Calcineurin inhibitor

Everolimus

Exercise

Haemodynamics

Heart transplantation

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)