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Journal Article

Comparison of drugs for pulmonary hypertension reversibility testing: A meta-analysis

Maya Guglin, Shabnam Mehra and Thomas J. Mason
Pulmonary Circulation
Vol. 3, No. 2 (April 2013), pp. 406-413
DOI: 10.4103/2045-8932.113180
Stable URL:
Page Count: 8
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AbstractMultiple drugs are used for reversibility testing of pulmonary hypertension (PH) in advanced heart failure (HF), especially in the process of heart transplant evaluation. Effects of these drugs were never systematically compared. The aim of this meta-analysis was to compare hemodynamic effects of different drugs. We identified 20 prospective studies reporting hemodynamic variables before and after acute pharmacologic testing for PH reversibility in patients with advanced HF. The data from individual studies were grouped by an outcome measure and analyzed. A mixed model meta-analysis was performed using SAS to give weighted mean effect of pre- and post-test change and inverse variance. The mean effects were weighted by the published sample size. Prostacyclin, inhaled or intravenous, and prostaglandin E1 (PGE1) had the most potent effect on pulmonary vascular resistance (PVR). Sodium nitroprusside and nitroglycerin decreased pulmonary capillary wedge pressure (PCWP), and mean pulmonary arterial pressure (MPAP) better than other drugs. Sildenafil provided overall good hemodynamic outcomes but was not the strongest drug with regard to any particular outcome. PCWP, MPAP, and systolic pulmonary arterial pressure respond better to nitroglycerin and sodium nitroprusside than to other drugs in the setting of reversibility testing. Prostacyclin and PGE1 are superior to other drugs in their acute effects on PVR.

Notes and References

This item contains 37 references.

  • 1.
    ['Erickson KW, Costanzo-Nordin MR, O’Sullivan EJ, Johnson MR, Zucker MJ, Pifarré R, et al. Influence of preoperative transpulmonary gradient on late mortality after orthotopic heart transplantation. J Heart Transplant 1990;9:526–37.']
  • 2.
    ['Chen JM, Levin HR, Michler RE, Prusmack CJ, Rose EA, Aaronson KD. Reevaluating the significance of pulmonary hypertension before cardiac transplantation: Determination of optimal thresholds and quantification of the effect of reversibility on perioperative mortality. J Thorac Cardiovasc Surg 1997;114:627–34.']
  • 3.
    ['Mehra MR, Kobashigawa J, Starling R, Russell S, Uber PA, Parameshwar J, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates-2006. J Heart Lung Transplant 2006;25:1024–42.']
  • 4.
    ['O’Dell KM, Kalus JS, Kucukarslan S, Czerska B. Nesiritide for secondary pulmonary hypertension in patients with end-stage heart failure. Am J Health Syst Pharm 2005;62:606–9.']
  • 5.
    ['Sablotzki A, Starzmann W, Scheubel R, Grond S, Czeslick EG. Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates. Can J Anaesth 2005;52:1076–82.']
  • 6.
    ['Braun S, Schrötter H, Schmeisser A, Strasser RH. Evaluation of pulmonary vascular response to inhaled iloprost in heart transplant candidates with pulmonary venous hypertension. Int J Cardiol 2007;115:67–72.']
  • 7.
    ['Wasler A, Iberer F, Tscheliessnigg KH, Auer T, Petutschnigg B. Prostaglandin E1 in the pretransplantation period in patients with pulmonary hypertension. J Heart Lung Transplant 1993;12:884.']
  • 8.
    ['Alaeddini J, Uber PA, Park MH, Scott RL, Ventura HO, Mehra MR. Efficacy and safety of sildenafil in the evaluation of pulmonary hypertension in severe heart failure. Am J Cardiol 2004;94:1475–7.']
  • 9.
    ['Angel Gómez-Sánchez M, Saenz De La Calzada C, Escribano Subias P, Francisco Delgado Jiménez J, Lázaro Salvador M, Albarrán González A, et al. Pilot assessment of the response of several pulmonary hemodynamic variables to sublingual sildenafil in candidates for heart transplantation. Eur J Heart Fail 2004;6:615–7.']
  • 10.
    ['Lepore JJ, Maroo A, Bigatello LM, Dec GW, Zapol WM, Bloch KD. Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary hypertension: Combined administration with inhaled nitric oxide. Chest 2005;127:1647–53.']
  • 11.
    ['Haraldsson A, Kieler-Jensen N, Nathorst-Westfelt U, Bergh CH, Ricksten SE. Comparison of inhaled nitric oxide and inhaled aerosolized prostacyclin in the evaluation of heart transplant candidates with elevated pulmonary vascular resistance. Chest 1998;114:780–6.']
  • 12.
    ['Lepore JJ, Dec GW, Zapol WM, Bloch KD, Semigran MJ. Combined administration of intravenous dipyridamole and inhaled nitric oxide to assess reversibility of pulmonary arterial hypertension in potential cardiac transplant recipients. J Heart Lung Transplant 2005;24:1950–6.']
  • 13.
    ['Loh E, Stamler JS, Hare JM, Loscalzo J, Colucci WS. Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction. Circulation 1994;90:2780–5.']
  • 14.
    ['Mahajan A, Shabanie A, Varshney SM, Marijic J, Sopher MJ. Inhaled nitric oxide in the preoperative evaluation of pulmonary hypertension in heart transplant candidates. J Cardiothorac Vasc Anesth 2007;21:51–6.']
  • 15.
    ['Pagano D, Townend JN, Horton R, Smith C, Clutton-Brock T, Bonser RS. A comparison of inhaled nitric oxide with intravenous vasodilators in the assessment of pulmonary haemodynamics prior to cardiac transplantation. Eur J Cardiothorac Surg 1996;10:1120–6.']
  • 16.
    ['Pamboukian SV, Carere RG, Webb JG, Cook RC, D’yachkova Y, Abel JG, et al. The use of milrinone in pre-transplant assessment of patients with congestive heart failure and pulmonary hypertension. J Heart Lung Transplant 1999;18:367–71.']
  • 17.
    ['Sablotzki A, Hentschel T, Gruenig E, Schubert S, Friedrich I, Mühling J, et al. Hemodynamic effects of inhaled aerosolized iloprost and inhaled nitric oxide in heart transplant candidates with elevated pulmonary vascular resistance. Eur J Cardiothorac Surg 2002;22:746–52.']
  • 18.
    ['Radovancevic B, Vrtovec B, Thomas CD, Croitoru M, Myers TJ, Radovancevic R, et al. Nitric oxide versus prostaglandin E1 for reduction of pulmonary hypertension in heart transplant candidates. J Heart Lung Transplant 2005;24:690–5.']
  • 19.
    ['Semigran MJ, Cockrill BA, Kacmarek R, Thompson BT, Zapol WM, Dec GW, et al. Hemodynamic effects of inhaled nitric oxide in heart failure. J Am Coll Cardiol 1994;24:982–8.']
  • 20.
    ['von Scheidt W, Costard-Jaeckle A, Stempfle HU, Deng MC, Schwaab B, Haaff B, et al. Prostaglandin E1 testing in heart failure-associated pulmonary hypertension enables transplantation: The PROPHET study. J Heart Lung Transplant 2006;25:1070–6.']
  • 21.
    ['Freitas Jr AF, Bacal F, Oliveira Jr Jde L, Santos RH, Moreira LF, Silva CP, et al. Impact of sublingual sildenafil on pulmonary hypertension in patients with heart failure. Arq Bras Cardiol 2009;92:116–26.']
  • 22.
    ['Kieler-Jensen N, Ricksten SE, Stenqvist O, Bergh CH, Lindelöv B, Wennmalm A, et al. Inhaled nitric oxide in the evaluation of heart transplant candidates with elevated pulmonary vascular resistance. J Heart Lung Transplant 1994;13:366–75.']
  • 23.
    ['Fojón S, Fernández-González C, Sánchez-Andrade J, López-Pérez JM, Hermida LF, Rodríguez JA, et al. Inhaled nitric oxide through a noninvasive ventilation device to assess reversibility of pulmonary hypertension in selecting recipients for heart transplant. Transplant Proc 2005;37: 4028–30.']
  • 24.
    ['Murali S, Uretsky BF, Armitage JM, Tokarczyk TR, Betschart AR, Kormos RL. Utility of prostaglandin E1 in the pretransplantation evaluation of heart failure patients with significant pulmonary hypertension. J Heart Lung Transplant 1992;11:716–23.']
  • 25.
    ['Murali S, Uretsky BF, Reddy PS, Tokarczyk TR, Betschart AR. Reversibility of pulmonary hypertension in congestive heart failure patients evaluated for cardiac transplantation: Comparative effects of various pharmacologic agents. Am Heart J 1991;122:1375–81.']
  • 26.
    ['Givertz MM, Hare JM, Loh E, Gauthier DF, Colucci WS. Effect of bolus milrinone on hemodynamic variables and pulmonary vascular resistance in patients with severe left ventricular dysfunction: A rapid test for reversibility of pulmonary hypertension. J Am Coll Cardiol 1996;28:1775–80.']
  • 27.
    ['Weston MW, Isaac BF, Crain C. The use of inhaled prostacyclin in nitroprusside-resistant pulmonary artery hypertension. J Heart Lung Transplant 2001;20:1340–4.']
  • 28.
    ['Kieler-Jensen N, Lundin S, Ricksten SE. Vasodilator therapy after heart transplantation: Effects of inhaled nitric oxide and intravenous prostacyclin, prostaglandin E1, and sodium nitroprusside. J Heart Lung Transplant 1995;14:436–43.']
  • 29.
    ['Haraldsson s A, Kieler-Jensen N, Ricksten SE. The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension. Anesth Analg 2001;93:1439–45.']
  • 30.
    ['Kieler-Jensen N, Houltz E, Ricksten SE. A comparison of prostacyclin and sodium nitroprusside for the treatment of heart failure after cardiac surgery. J Cardiothorac Vasc Anesth 1995;9:641–6.']
  • 31.
    ['Bocchi EA, Bacal F, Auler Júnior JO, Carmone MJ, Bellotti G, Pileggi F. Inhaled nitric oxide leading to pulmonary edema in stable severe heart failure. Am J Cardiol 1994;74:70–2.']
  • 32.
    ['Khan TA, Schnickel G, Ross D, Bastani S, Laks H, Esmailian F, et al. A prospective, randomized, crossover pilot study of inhaled nitric oxide versus inhaled prostacyclin in heart transplant and lung transplant recipients. J Thorac Cardiovasc Surg 2009;138:1417–24.']
  • 33.
    ['Kieler-Jensen N, Milocco I, Ricksten SE. Pulmonary vasodilation after heart transplantation. A comparison among prostacyclin, sodium nitroprusside, and nitroglycerin on right ventricular function and pulmonary selectivity. J Heart Lung Transplant 1993;12:179–84.']
  • 34.
    ['Torres Macho J, Delgado Jimenez JF, Sanz Salvo J, Gonzalez Mansilla A, Sanchez Sanchez V, Gamez Diez S, et al. Effect of different pharmacologic agents to reverse severe pulmonary hypertension among end-stage heart failure patients. Transplant Proc 2009;41:2477–9.']
  • 35.
    ['Costard-Jackle A, Fowler MB. Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: Testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group. J Am Coll Cardiol 1992;19:48–54.']
  • 36.
    ['Klote S, Wenzelburger F, Stypmann J, Welp H, Drees G, Schmid C. Reversible pulmonary hypertension in heart transplant candidates: To transplant or not to transplant. Ann Thorac Surg 2006;82:1770–3.']
  • 37.
    ['Califf RM, Adams KF, McKenna WJ, Gheorghiade M, Uretsky BF, McNulty SE, et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST). Am Heart J 1997;134:44–54.']