Long-term prognostic value of elevated heart rate one year after heart transplantation.

BACKGROUND: Elevated heart rate (HR) is associated with adverse cardiovascular outcome in the general population and in patients with cardiovascular disease. Elevated HR due to graft denervation is often found in heart transplantation (HTx) patients; the effect on graft survival and vasculopathy is unclear. Thus, the aim of this study was to evaluate the role of elevated HR at 12 months post-HTx and its power to predict HTx long-term outcome. METHODS: We evaluated retrospectively a prospective database of 312 patients undergoing HTx at two centers. HR was registered at 12 months post-HTx. The median HR was used as a cutoff point. Cox regression analysis was performed with variables known to be clinically relevant to mortality and those selected from the univariate analysis. RESULTS: During a mean follow-up of 5.5 ± 2.8 years there were 58 deaths (19%). Patients with a HR ≥ 90 bpm (median HR) at 12 months had an increased risk for all-cause mortality (Hazard Ratio=2.4, 95% CI 1.2 to 4.5, p=0.009) and mortality related to coronary allograft vasculopathy (CAV) (Hazard Ratio=3.0, 95% CI 1.25-7.14, p=0.01). Multivariate analysis showed that a HR ≥ 90 bpm independently predicted mortality (HR 3.2, 95% CI 1.4-7.1, p=0.004). CONCLUSIONS: Elevated HR measured at 12 months after HTx is an independent predictor of all-cause mortality in HTx recipients. A HR ≥ 90 bpm identifies a group of patients at high risk of death and CAV-related mortality at mid- to long-term.

Bosentan in heart transplantation candidates with severe pulmonary hypertension: efficacy, safety and outcome after transplantation.

BACKGROUND: Increased pulmonary vascular resistance (PVR) is associated with increased right ventricular failure and mortality after heart transplantation. METHODS: In this prospective study, 22 patients considered high-risk candidates for heart transplantation because of severe pulmonary hypertension (PVR = 6 ± 2 Wood units; transpulmonary gradient 22 ± 7 mmHg), received bosentan 125 mg bid. Right heart catheterization was repeated after four months (n = 22) and 12 months (n = 9). Eleven patients who declined participation in the study were considered as control group. RESULTS: After four months, PVR decreased by 38% in patients receiving bosentan (n = 22), while it increased by 25% in the control group (p = 0.001). Those patients who received bosentan for 12 months (n = 9), experienced a 60% reduction in PVR compared to baseline (p = 0.003). Only three patients (14%) had no hemodynamic improvement with bosentan. After bosentan therapy, 14 patients (64%) underwent heart transplantation. Patients with high PVR who received bosentan showed a trend toward better one-yr survival after transplantation than patients with PVR ≤ 2.5 Wood units transplanted in the same period of time (93% vs. 83%). CONCLUSIONS: In patients considered high-risk candidates for heart transplantation because of high PVR, therapy with bosentan is associated with a significant reduction in PVR and a good outcome after transplantation.

Assessment of peripheral endothelial-dependent vasodilatation within the first year after heart transplantation.

BACKGROUND: Peripheral endothelial dysfunction (ED) has been found in patients with severe heart failure. Whether ED improves after heart transplantation (HTx) is still a matter of controversy. METHODS: Forearm endothelium-dependent vasoreactivity was assessed in 40 patients after HTx. Flow-mediated vasodilatation (FMD) was measured by high-resolution brachial artery ultrasound to assess endothelial function at 1, 6, and 12 months after HTx. Cardiac allograft vasculopathy (CAV) was assessed by coronary angiography at 1 and 12 months and by intravascular ultrasound (IVUS) at 1 year. RESULTS: Mean FMD at 1 month was 1.9% +/- 2.6%, improving to 3.3% +/- 3.2% at 6 months (p < 0.005) and to 5.1% +/- 3.4% at 1 year (p < 0.0001). FMD was significantly impaired in 33 patients (82%) at 1 month, in 27 (67%) at 6 months, and in 19 (47%) at 1 year after HTx. CAV was diagnosed by IVUS in 19 patients (63%) at 1 year. Patients without peripheral ED at 1 month had lower incidence of increased intimal thickness of 0.5 mm or more at 1 year after HTx (20% vs 75%, p < 0.01). CONCLUSIONS: Impairment of peripheral FMD was highly prevalent soon after HTx and was present in nearly 50% of patients at 1 year. Patients without peripheral ED at 1 month were associated with lower probability of CAV. Although more studies are needed, the evaluation of peripheral endothelial function at 1 month after HTx could be potentially useful to identify patients at lower risk of CAV.

Initial experience with bosentan therapy in patients considered ineligible for heart transplantation because of severe pulmonary hypertension.

BACKGROUND: Pre-operative elevated pulmonary vascular resistance (PVR) has been associated with increased right ventricular failure and mortality after heart transplantation. The aim of this study was to assess the efficacy of bosentan, an oral endothelin-receptor antagonist, to reduce PVR in patients considered ineligible for heart transplantation because of severe pulmonary hypertension. METHODS: Seven patients with end-stage congestive heart failure and considered ineligible for heart transplantation because of severe pulmonary hypertension (PVR>2.5 Wood units after nitroprusside infusion) were included in the study. They received bosentan 62.5 mg b.i.d. for four wk and 125 mg b.i.d. thereafter. Right heart catheterization was repeated after six wk of therapy. RESULTS: After six wk of bosentan therapy, there was a significant decrease in PVR (6.0 +/- 2 vs. 3.8 +/- 2 Wood units, before vs. after bosentan; p = 0.02), in PVR during nitroprusside infusion (3.3 +/- 1 vs. 2.1 +/- 1 Wood units, before vs. after bosentan; p = 0.02) and in diastolic pulmonary artery pressure (33 +/- 7 vs. 23 +/- 7 mmHg, before vs. after bosentan; p = 0.04). No significant adverse events were observed. After bosentan therapy, five patients had PVR