Baseline pulmonary hypertension in heart transplant recipients: 9 years of experience at Almazov National Medical Research Centre

Objective: to assess the impact of baseline pulmonary hypertension (PH) on early and long-term outcomes following heart transplantation (HT). Materials and methods. From January 2010 to December 2018, 112 HTs were carried out. Based on right heart catheterization results, all recipients were divided into 2 groups: Group 1 with PH (n = 76; mean pulmonary arterial pressure (mPAP) ≥25 mm Hg), Group 2 – without PH (n = 36; MPAP <25 mm Hg). The average age of Group 1 patients was 46.4 ± 14.9 years, baseline pulmonary vascular resistance (PVR) was 3.5 ± 1.5 Wood units, PVR after reversion test (nitric oxide – 80 ppm, iloprost 20 μg) – 2.8 ± 1.0 Wood units, systolic PAP (sPAP) – 50.1 ± 13.4 mm Hg. The average age in Group 2 was 47.3 ± 12.2 years, baseline PVR – 2.1 ± 0.8 Wood units, sPAP – 27.4 ± 5.3 mm Hg. The dynamics in indicators of early postoperative period (duration of mechanical ventilatory support, use of vasodilators and inotropic support and the length of stay in intensive care unit (ICU), 30-day mortality) and long-term post-HT echocardiography results were assessed. Results. Due to acute right-ventricular failure (RVF) developing after heart transplantation, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was done in 8 patients (11%) from Group 1 and one patient (3%) from Group 2. Presence of PH did not affect duration of mechanical ventilatory support, inotropic support, and length of stay in ICU. Levosimendan therapy in the early postoperative period was more often performed in Group 1 (n = 29) than in Group 2 (n = 6) (p = 0.048). Nitric oxide inhalation was also more often administered in Group 1 (n = 54); Group 2 (n = 7), (p = 0.003). Sildenafil therapy after HT was comparable in both groups Group 1 (n = 25); Group 2 (n = 6), (p = 0.048). In early post-HT stages, 14 patients died, 30-day mortality was comparable in both groups (p = 0.12). Six months after HT, no differences were found in the sPAP (p = 0.21) and PVR (p = 0.07) levels. Conclusion. Patients with baseline PH after HT have a more severe early postoperative period, including a higher RVF incidence, with the need for ECMO implantation. A PVR level >3.5 Wood units is not a threshold for HT. Patients with baseline PVR >3.5 Wood units following HT show comparable results with patients without baseline PH. This allows such patients (baseline PVR >3.5 Wood units) to be considered for inclusion in the heart transplant waiting list. In addition, 30-day mortality and duration of mechanical ventilatory support after HT in patients with and without baseline PH did not differ. Regardless of the baseline level of sPAP and PVR, all patients showed improvement in these parameters after HT. Six months after HT, no differences were found in sPAP and PVR levels in the patients, regardless of whether there was baseline PH or not.

heart transplantation, heart failure, pulmonary hypertension, PH, pulmonary artery pressure, PAP, pulmonary vascular resistance, PVR, vasodilators

1. Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A et al. 2015 ESC/ERC Guidelines for the diagnosis and treatment of pulmonary hypertension, European Society of Cardiology / European Respiratory Society. Eur Heart J. 2016; 37: 67–119. doi: 10.1093/eurheartj/ehv317.

2. Roldan C. The ultimate echo guide. Lippincott Williams and Wilkins, 2005. PMCID: PMC2650657.

3. Delgado JF, Gomez-Sanchez MA, Saenz de la Calzada C, Sanchez V, Escribano SV, Hernandez-Afonso et al. Impact of mild pulmonary hypertension on mortality and pulmonary artery pressure profile after heart transplantation. Journal of Heart Lung Transplantation. 2001; 20: 942–948. PMID: 11557188. doi: 10.1016/s10532498(01)00286-8.

4. Deng MC, Gradaus R, Hammel D, Weyand M., Gunther F, Kerber S et al. Heart Transplant candidates at high risk can be identified at the time of initial evaluation. Transplantat International. 1996; 9 (1): 38–45. PMID: 8748409. doi: 10.1007/bf00336810.

5. Ross H, Hendry P, Dipchand A, Giannetti N, Hirsch G, Isaac D et al. Canadian Cardiovascular Society Consensus Conference on cardiac transplantation. Canadian Journal of Cardiology. 2003; 19: 620–654. PMCID: PMC2706756.

6. Kettner A, Dorazilova Z, Netuka I, Maly J, Al-hiti H, Melenovsky V et al. Is severe pulmonary hypertension a contraindication for orthotopic heart transplantation? Not any more. Physiol Res. 2011; 60 (5): 769–775. PMID: 21812520.

7. Klotz S, Wenzelburger F, Stypmann J, Welp H, Drees G, Schmid C et al. Reversible pulmonary hypertension in heart transplant candidates: to transplant or not to transplant. The annals of thoracic surgery. 2006; 82 (5): 1770–1773. doi: 10.1016/j.athoracsur.2006.05.114.

8. Hill NS, Roberts KR, Preston IR. Postoperative Pulmonary Hypertension: Etiology and Treatment of a Dangerous Complication. Respiratory Care. 2009; 54 (7): 958–968. PMID: 19558745.

9. Follath F, Cleland JG, Just H, Papp JG, Scholz H, Peuhkurinen K et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe lowoutput heart failure (the LIDO study): a randomized double-blind trial. Lancet. 2002; 360 (9328): 196–202. PMID: 12133653.

10. Mogollon Jimenez MV, Escoresca Prtega AM, Cabeza Letran ML, Hinojosa Perez R, Galle EL, Sobrino Marquez JM et al. Correlation of Echocardiographic and Hemodynamic Parameters in Pulmonary Hypertension Assessment Prior to Heart Transplantation. Transplantation Proceedings. 2008; 40: 3023–3024. doi: 10.1016/j.transproceed.2008.09.044.

11. Zeng Z, Jiang Z, Wang CS, Luo H, Huang YF, Jin XH. Preoperative Evaluation Improves the Outcome in Heart Transplant Recipients With Pulmonary Hypertension Retrospective Analysis of 106 Cases. Transplantation Proceedings by ELSEVIER. 2010; 42: 3708–3710. doi: 10.1016/j.transproceed.2010.08.067.

12. Klotz S, Deng MC, Hanafy D, Schmid C, Stypmann J, Schmidt C et al. Reversible pulmonary hypertension in heart transplant candidates – pretransplant evalution and outcome after orthotopic heart transplantation. The European Journal of Heart Failure. 2003; 5: 645–653. doi: 10.1016/S1388-9842(03)00059-X.

13. Drakos SG, Kfoure AG, Gilbert EM, Horne BD, Long JW, Strangham JC et al. Effect of reversible pulmonary hypertension on outcomes after heart transplantation. The Journal of Heart and Lung Transplantation. 2007; 26 (4): 319–323. doi: 10.1016/j.healun.2007.01.012.

14. Gude E, Simonsen S, Geiran OR, Fiane AE, Gullestad L, Arora S et al. Pulmonary hypertension in heart transplantation: Discrepant prognostic impact of pre-operative compared with 1-year post-operative right heart hemodynamics. The Journal of Heart and Lung Transplantation. 2010; 29 (2): 216–223. doi: 10.1016/j.healun.2009.08.021.

15. Lindelow B, Andersson B, Waagstein F, Bergh CH. High and low pulmonary vascular resistance in heart transplant candidates. A 5-year follow-up after heart transplantation shows continuous reduction in resistance and no difference in complication rate. European Heart Journal. 1999; 20: 148–156. PMID: 10099912.

16. Kitamura S, Nakatani T, Kato T, Yanase M, Kobayashi J, Nakajima H et al. Hemodynamic and Echocardiographic Evaluation of Orthotopic Heart Transplantation with the modified bicaval anastomosis technique. Circulation Journal. 2009; 73 (7): 1235–1239. PMID: 19398842. doi: 10.1253/circj.cj-08-1098.

17. Bautin AE, Yakovlev AS, Zayashnikov SV, Tashkhanov DM, Marichev AO, Fedotov PA et al. Comparison of hemodynamic effects of inhalatory iloprost and nitroc oxide in patients with sever left ventricle dysfunction. Russ J Cardiol. 2017, 12 (152): 97–103. doi: 10.15829/1560-4071-2017-12-97-103.

18. Bortsova MA, Bautin AE, Yakovlev AS, Fedotov PA, Sazonova YuV, Marichev AO et al. On the possibility to increase sensitivity of diagnostic tests for fixed pulmonary hypertension in heart transplant candidates. Almanac of Clinical Medicine. 2019; 47 (3): 212–220. doi: 10.18786/2072-0505-2019-47-030.

19. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasckaran K et al. Guidelines for the Echocardiographic Assessment of the Right Heart in Adults: A report from the American society of echocardiography. Endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. Journal American Society of Echocardiology. 2010; 23: 685–713. PMID: 20620859. doi: 110.1016/j.echo.2010.05.010.

20. Wong RC, Abrahams Z, Hanna M, Pangrace J, Gonzalez-Stawinski G, Starling R et al. Tricuspid Regurgitation after Cardiac Transplantation: An Old Problem Revisited. Journal of Heart and Lung Transplantation. 2008; 27 (3): 247–252. doi: 10.1016/j.healun.2007.12.011.

21. Barst RJ, Galle N, Naelje R, Simonneau G, Jeffs R, Arneson C et al. Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil. European Respiratory Journal. 2006; 28: 11951203. doi: 10.1183/09031936.06.00044406.

22. Shemakin SY, Khalilulin TA, Fedoseeva AA. Tricuspid valve dysfunction after orthotopic heart transplantation. Russian Journal of Transplantology and Artificial Organs. 2009; 11 (2): 21–34.

23. Mogollon MV, Galle EL, Perez RH, Aviles AH, Sobrino Marquez JM, Rodriguez NR et al. Prognosis after Heart Transplant in Patients with Pulmonary Hypertension Secondary to Cardiopathy. Transplantation Proceedings. 2008; 40: 3031–3033. doi: 10.1016/j.transproceed.2008.09.051.

24. Ghio S, Crimi G, Pica S, Temporelli PL, Boffini M, Rinaldi M et al. Persistent abnormalities in pulmonary arterial compliance after heart transplantation in patients with combined post-capillary and pre-capillary pulmonary hypertension. Plos One. 2017; 13 (12): 1–10. doi: 10.1371/journal.pone.0188383.

25. Al-Hiti H, Melenovsky V, Syrovatka P, Kettner J, Malek I, Kautzner J. Sildenafil is more selective pulmonary vasodilator than Prostaglandin E1 in Patients with Pulmonary Hypertension Due to Heart Failure. Physiol Res. 2011; 60: 303–308. ISSN 1802-9973.

26. Seferian A, Simonneau G. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow? European Respiratory Revision. 2013; 22: 217–226. doi: 10.1183/09059180.00001713.