Pulmonary hypertension in heart transplantation: Discrepant prognostic impact of pre-operative compared with 1-year post-operative right heart hemodynamics
The prognostic impact of pulmonary hypertension (PH) before and after heart transplantation (HTx) is debated. We investigated: (i) the significance of pre-operative reversible PH on post-operative survival; (ii) the value of recatheterization while on the waiting list; (iii) the evolution of right heart hemodynamics (RHH) after HTx; and (iv) the prognostic impact of PH at 1 year after HTx.
We reviewed the records of 500 HTx recipients transplanted between 1983 and 2007. Pre-operatively, a non-PH group (Group 1, n = 365) fulfilled directly our RHH criteria for HTx, while a PH group (Group 2, n = 135) was accepted after reversibility of PH by acute vasodilatory testing. Recatheterization was performed every third month while on the waiting list and repeatedly after transplantation.
With a follow-up of 6.8 +/- 5.1 years and a 50% survival rate of 12.1 +/- 5.4 years, our main findings were as follows: (i) Patients with reversible PH on vasodilatory testing had a survival rate similar to that of patients without PH (11.7 +/- 0.8 vs 12.1 +/- 0.5 years, p = 0.80). (ii) Pre-operative recatheterization was of limited value as RHH remained stable. Five percent of patients died while on the waiting list and 2 improved clinically and were removed. (iii) Mean pulmonary artery pressure (MAP) was reduced from 28 +/- 9 and 40 +/- 8 mm Hg pre-operatively to 21 +/- 7 and 24 +/- 6 mm Hg after 2 weeks and 16 +/- 7 and 18 +/- 8 mm Hg at 3 years in Groups 1 and 2, respectively. (iv) Recipients with MAP >20 mm Hg at 1 year post-HTx had significantly lower survival than those with MAP <or=20 mm Hg (11.5 +/- 0.7 vs 15.6 +/- 0.6 years, p < 0.001).
Elevated pulmonary pressure 1 year after HTx provides significant prognostic information regarding long-term outcome, whereas pre-operative reversible PH in this group does not influence survival.
Available from: Cristiano Amarelli
- "Finally, reversal of PH was definitively achieved by the third post-operative month. Such results are again in accordance with those previously published by these authors and others and should be read in the light of the negative prognostic value that persistent PH exerts on long term survival after transplantation, as well as the suggestion that persistence of the sildenafil effect on the pulmonary circulation beyond an acute vasomotor effect might be due to pulmonary vascular remodelling : an hypothesis never tested in humans. "
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ABSTRACT: Unresponsive pulmonary hypertension (PH) may contraindicate heart transplant since it implies poor early outcomes. The present study reports the effectiveness of oral perioperative sildenafil in allowing heart transplant candidacy and surgery in a selected group of patients initially deemed ineligible because of PH.
Between May 2005 and December 2009, 31 consecutive patients (5 females, 9 with a history of idiopatic cardiomyopathy and 16 with a history of coronary artery disease, 10 with previous sternotomies, 71.42 ± 27.69 ml/min/m(2) mean preoperative epidermal growth factor receptor) were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12-week trial, RHC disclosed PH reversibility (mean pulmonary vascular resistance index: 9.57 ± 4.07 WU, mean transpulmonary gradient 14.47 ± 5.66 mmHg and mean systolic pulmonary artery pressure: 68.96 ± 15.15 mmHg), allowing listing despite a higher risk for early post-transplant RV failure. Transplant protocol included donor/recipient size matching ≥0.8 and inhaled nitric oxide in the early postoperative period followed by reinstitution of oral sildenafil.
All patients underwent heart transplantation. Mean overall graft ischaemic time was 179 ± 47min; mean donor recipient weight ratio was 1.04 ± 0.17. Right ventricular failure developed in three patients (9.6%) and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary haemodynamic profile normalization within the third postoperative month allowing weaning from sildenafil in the 30 hospital survivors. One-year RHC confirmed PH reversal (n = 29 patients, all who survived up to 1year).
This pilot prospective uncontrolled trial suggests that oral sildenafil is effective in allowing candidacy, safe transplantation and postoperative pulmonary profile normalization in potential recipients initially disqualified because of PH.
Available from: Armin Zittermann
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ABSTRACT: In heart failure (HF) patients, pulmonary hypertension (PH) is associated with a poor prognosis. We assessed whether low dose treatment with the dual endothelin-1 receptor antagonist bosentan is associated with improved hemodynamics and clinical outcome in these patients.
We performed a retrospective data analysis in 82 end-stage heart failure patients on the waiting list for cardiac transplantation since January 2006. All patients had pulmonary arterial pressure >35 mmHg, pulmonary vascular resistance >240 dyn × s × cm-5, and/or a transpulmonary gradient (TPG) >15 mmHg. Fifty-four patients received a median dose of 125 mg bid bosentan (BOS group), and 28 patients received standard medical treatment (CON group). Data were assessed until June 2009.
Hemodynamic parameters improved significantly in the BOS group but remained unchanged in the CON group. The percentage of patients who fell below the thresholds of PAP, PVR, and TPG for cardiac transplantation increased significantly by 20.3%, 34.5%, and 20.8%, respectively (p = 0.007-0.013) in the BOS group, but did not change significantly in the CON group. One-year survival on the waiting list was approximately 20% higher in the BOS group than in the CON group (p = 0.020). Bosentan treatment remained an independent predictor of reduced mortality risk on the waiting list after propensity score adjustment (relative risk = 0.107; 95% CI: 0.013-0.869; p = 0.036).
Treatment with the endothelin-1 antagonist bosentan is associated with improvements in hemodynamics and clinical outcome in end-stage heart failure patients with PH. If these results can be confirmed by randomized controlled trials, bosentan may represent a treatment option in these patients.
Available from: Petr Nemec
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To determine the effect of pre-existing pulmonary hypertension (PHT) on early hemodynamics, morbidity and mortality after heart transplantation (HTx).
Data were prospectively collected from 149 patients, who underwent HTx between January 2000 and December 2007. The subjects were divided into 3 groups: Group A (n=84) without PTH, group B (n=50) with mild to moderate PTH and group C (n=15) with severe PTH. We studied hemodynamic profile, tricuspid valve regurgitation (TR), incidence of acute cellular rejections (AR), infections, duration of hospitalization, 30-day mortality and a long-term survival.
Baseline characteristics were similar in all groups. Using vasodilator treatment PVR was successfully brought down to normal range 2.5 ± 0.6 Wood' units (WU) on the day 1 following the surgery in all groups. Over 80% of patients were treated in Group C, 32% in Group A and 46% in Group B. There was no significant difference in the severity of TR among the 3 groups early after HTx (severe TR was observed in 46%, 54%, 33%, respectively). There was no significant difference in incidence of AR (G ≥ 2 Banff classification) (23%, 23%, 33%, respectively), infections (28%, 32%, 33%, respectively) or duration of hospitalization (30, 30, 28 days, respectively). There was no correlation between pre-transplant PHT and 30-day mortality or a long-term survival.
In our cohort, PHT dropped very quickly after HTx, and was not associated with acute right heart failure following the surgery. Reversible PTH does not have a negative impact on short- or long-term survival after HTx.
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