Advertisement

Pediatric Cardiology

, Volume 34, Issue 1, pp 129–134 | Cite as

Sildenafil and Ventriculo-Arterial Coupling in Fontan-Palliated Patients: A Noninvasive Echocardiographic Assessment

  • Reza ShabanianEmail author
  • Leila Shahbaznejad
  • Anahita Razaghian
  • Abdolrazagh Kiani
  • Mitra Rahimzadeh
  • Soroush Seifirad
  • Armen Kocharian
  • Jami Shakibi Gilani
  • Mohammad Ali Navabi
Original Article

Abstract

The fundamental role of pulmonary vascular resistance in the Fontan circulation is obvious. Medications decreasing this resistance may have an impact on the fate of this population. Hence, we assessed noninvasively the effect of oral sildenafil on the ventriculo-arterial coupling in patients with Fontan circulation. In a single-center, prospective case series study, 23 patients with fenestrated extracardiac total cavopulmonary connection age 12–31 years were enrolled in this study. Clinical characteristics and echocardiographic examination were performed before and after a 1 week course of sildenafil at 0.5 mg/kg every 8 h. Sildenafil had no effect on heart rate and blood pressure. However, oxygen saturation was significantly increased with sildenafil (87.6 ± 4.3 vs. 90.1 ± 3.6; P < 0.0001). The calculated noninvasive ventricular end-systolic elastance (Ees) was greater after sildenafil compared with the pre-sildenafil values (1.59 ± 0.17 vs. 1.72 ± 0.27 mm Hg/ml; P = 0.001). Moreover, significant decreases in arterial elastance (Ea) (1.62 ± 0.53 vs. 1.36 ± 0.43 mm Hg/ml; P < 0.0001), ventricular end-diastolic elastance (Eed) (0.05 ± 0.021 vs. 0.04 ± 0.013; P = 0.002), and, finally, ventriculo-arterial coupling index (0.99 ± 0.26 vs. 0.76 ± 0.15; P < 0.0001) were found after sildenafil administration. The intolerable side effects that led to stopping the sildenafil occurred only in one (4 %) patient. Sildenafil has increased ventricular systolic elastance and improved ventriculo-arterial coupling in patients palliated with Fontan circulation. Short-term sildenafil was well tolerated in most of the patients with only minor side effects.

Keywords

Elastance Fontan Sildenafil Ventriculo-arterial coupling 

References

  1. 1.
    Blum A (2009) Treating heart failure with sildenafil. Congest Heart Fail 15:181–185PubMedCrossRefGoogle Scholar
  2. 2.
    Chen CH, Nakayama M, Nevo E, Fetics BJ, Maughan WL, Kass DA (1998) Coupled systolic-ventricular and vascular stiffening with age implications for pressure regulation and cardiac reserve in the elderly. J Am Coll Cardiol 32:1221–1227PubMedCrossRefGoogle Scholar
  3. 3.
    Chen CH, Fetics B, Nevo E, Rochitte CE, Chiou KR, Ding PA et al (2001) Noninvasive single-beat determination of left ventricular end-systolic elastance in humans. J Am Coll Cardiol 38:2028–2034PubMedCrossRefGoogle Scholar
  4. 4.
    Cremers B, Scheler M, Maack C, Wendler O, Schäfers HJ, Südkamp M et al (2003) Effects of sildenafil (Viagra) on human myocardial contractility, in vitro arrhythmias, and tension of internal mammaria arteries and saphenous veins. J Cardiovasc Pharmacol 41:734–743PubMedCrossRefGoogle Scholar
  5. 5.
    Dasi LP, Krishnankuttyrema R, Kitajima HD, Pekkan K, Sundareswaran KS, Fogel M et al (2009) Fontan hemodynamics: importance of pulmonary artery diameter. J Thorac Cardiovasc Surg 137:560–564PubMedCrossRefGoogle Scholar
  6. 6.
    de Leval MR (2002) The Fontan circulation: a challenge to William Harvey? Nat Clin Pract Cardiovasc Med 2:202–208CrossRefGoogle Scholar
  7. 7.
    Feldman MD, Pak PH, Wu CC, Haber HL, Heesch CM, Bergin JD et al (1996) Acute cardiovascular effects of OPC-18790 in patients with congestive heart failure. Time- and dose-dependence analysis based on pressure-volume relations. Circulation 93:474–483PubMedCrossRefGoogle Scholar
  8. 8.
    Gewillig M, Brown SC, Eyskens B, Heying R, Ganame J, Budts W et al (2010) The Fontan circulation: who controls cardiac output? Interact Cardiovasc Thorac Surg 10:428–433PubMedCrossRefGoogle Scholar
  9. 9.
    Giardini A, Balducci A, Specchia S, Gargiulo G, Bonvicini M, Picchio FM (2008) Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. Eur Heart J 29:1681–1687PubMedCrossRefGoogle Scholar
  10. 10.
    Goldberg DJ, French B, McBride MG, Marino BS, Mirarchi N, Hanna BD et al (2011) Impact of oral sildenafil on exercise performance in children and young adults after the Fontan operation: a randomized, double-blind, placebo-controlled, crossover trial. Circulation 123:1185–1193PubMedCrossRefGoogle Scholar
  11. 11.
    Goldberg DJ, French B, Szwast AL, McBride MG, Marino BS, Mirarchi N et al (2012) Impact of Sildenafil on echocardiographic indices of myocardial performance after the Fontan operation. Pediatr Cardiol 33(5):689–696PubMedCrossRefGoogle Scholar
  12. 12.
    Haseyama K, Satomi G, Yasukochi S, Matsui H, Harada Y, Uchita S (2006) Pulmonary vasodilation therapy with sildenafil citrate in a patient with plastic bronchitis after the Fontan procedure for hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 132:1232–1233PubMedCrossRefGoogle Scholar
  13. 13.
    Hiraishi S, DiSessa TG, Jarmakani JM, Nakanishi T, Isabel-Jones JB, Friedman WF (1982) Two-dimensional echocardiographic assessment of right ventricular volume in children with congenital heart disease. Am J Cardiol 50:1368–1375PubMedCrossRefGoogle Scholar
  14. 14.
    Kelley JR, Mack GW, Fahey JT (1995) Diminished venous capacitance in patients with univentricular hearts after the Fontan operation. Am J Cardiol 76:158–163PubMedCrossRefGoogle Scholar
  15. 15.
    Lepore JJ, Maroo A, Bigatello LM, Dec GW, Zapol WM, Bloch KD et al (2005) Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary hypertension: combined administration with inhaled nitric oxide. Chest 127:1647–1653PubMedCrossRefGoogle Scholar
  16. 16.
    Magosso E, Cavalcanti S, Ursino M (2002) Theoretical analysis of rest and exercise hemodynamics with total cavopulmonary connection. Am J Physiol 282:H1018–H1034Google Scholar
  17. 17.
    Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S (2002) Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation 105:2398–2403PubMedCrossRefGoogle Scholar
  18. 18.
    Nagendran J, Archer SL, Soliman D, Gurtu V, Moudgil R, Haromy A et al (2007) Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation 116:238–248PubMedCrossRefGoogle Scholar
  19. 19.
    Nogaki M, Senzaki H, Masutani S, Kobayashi J, Kobayashi T, Sasaki N et al (2000) Ventricular energetics in Fontan circulation: evaluation with a theoretical model. Pediatr Int 42:651–657PubMedCrossRefGoogle Scholar
  20. 20.
    Ovroutski S, Ewert P, Alexi-Meskishvili V, Hölscher K, Miera O, Peters B et al (2009) Absence of pulmonary artery growth after Fontan operation and its possible impact on late outcome. Ann Thorac Surg 87:826–831PubMedCrossRefGoogle Scholar
  21. 21.
    Pak PH, Maughan WLM, Baughman KL, Kieval RS, Kass DA (1998) Mechanisms of acute mechanical benefit from VDD pacing in hypertrophic heart disease. Circulation 98:242–248PubMedCrossRefGoogle Scholar
  22. 22.
    Redington AN (2006) The physiology of the Fontan circulation. Prog Pediatr Cardiol 22:179–186CrossRefGoogle Scholar
  23. 23.
    Senzaki H, Smith CJ, Juang GJ, Isoda T, Mayer SP, Ohler A et al (2001) Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J 15:1718–1726PubMedCrossRefGoogle Scholar
  24. 24.
    Senzaki H, Masutani S, Ishido H, Kobayashi J, Kobayashi T, Sasaki N et al (2002) Ventricular afterload and ventricular work in Fontan circulation. Comparison with normal two-ventricle circulation and single ventricle circulation with Blalock-Taussig shunts. Circulation 105:2885–2892PubMedCrossRefGoogle Scholar
  25. 25.
    Shekerdemian LS, Bush A, Shore DF, Lincoln C, Redington AN (1997) Cardiopulmonary interactions after Fontan operations. Circulation 96:3934–3942PubMedCrossRefGoogle Scholar
  26. 26.
    Starling MR (1993) Left ventricular-arterial coupling relations in the normal human heart. Am Heart J 125:1659–1666PubMedCrossRefGoogle Scholar
  27. 27.
    Szabó G, Bährle S (2005) Contractility-afterload mismatch after the Fontan operation. Cardiol Young 15(Suppl 3):35–38PubMedCrossRefGoogle Scholar
  28. 28.
    Szabó G, Buhmann V, Graf A, Melnitschuk S, Bährle S, Vahl CF et al (2003) Ventricular energetics after the Fontan operation: contractility-afterload mismatch. J Thorac Cardiovasc Surg 125:1061–1091PubMedCrossRefGoogle Scholar
  29. 29.
    Tanoue Y, Sese A, Ueno Y, Joh K, Hijii T (2001) Bidirectional Glenn procedure improves the mechanical efficiency of a total cavopulmonary connection in high-risk Fontan candidates. Circulation 103:2176–2180PubMedCrossRefGoogle Scholar
  30. 30.
    Thadani U, Parker JO (1978) Hemodynamics at rest and during supine and sitting bicycle exercise in normal subjects. Am J Cardiol 41:52–59PubMedCrossRefGoogle Scholar
  31. 31.
    Uzun O, Wong JK, Bhole V, Stumper O (2006) Resolution of protein-losing enteropathy and normalization of mesenteric Doppler flow with sildenafil after Fontan. Ann Thorac Surg 82:e39–e40PubMedCrossRefGoogle Scholar
  32. 32.
    Yano M, Kohno M, Konishi M, Obayashi M, Kobayashi S, Seki K et al (1997) Effect of aortic impedance on preload-afterload mismatch in canine hearts in situ. Basic Res Cardiol 92:115–122PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Reza Shabanian
    • 1
    Email author
  • Leila Shahbaznejad
    • 1
  • Anahita Razaghian
    • 1
  • Abdolrazagh Kiani
    • 1
  • Mitra Rahimzadeh
    • 2
  • Soroush Seifirad
    • 1
  • Armen Kocharian
    • 1
  • Jami Shakibi Gilani
    • 3
  • Mohammad Ali Navabi
    • 1
  1. 1.Department of Pediatric Cardiology, Children’s Medical CenterTehran University of Medical SciencesTehranIran
  2. 2.Department of BiostatisticsAlborz University Medical SciencesTehranIran
  3. 3.Department of Pediatric CardiologyDay General HospitalTehranIran

Personalised recommendations