Skip to main content
Log in

Impact of Sildenafil on Echocardiographic Indices of Myocardial Performance After the Fontan Operation

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

The objective of this study was describe the impact of sildenafil on echocardiographic measures of myocardial performance in children and young adults with a functional single-ventricle physiology late after Fontan surgery. A double-blind, placebo-controlled, crossover trial was conducted in children and young adults after the Fontan operation at a single pediatric center. Subjects were randomized to receive placebo or sildenafil (20 mg tid) for 6 weeks. After a 6-week washout period, subjects were crossed for an additional 6 weeks. Each subject underwent an echocardiogram at the start and finish of each phase. A total of 27 subjects completed study testing at a mean age of 14.9 years and a mean time from Fontan surgery of 11.3 years. After sildenafil, subjects demonstrated improvement in their myocardial performance index (MPI; −0.051; 95% CI −0.095, −0.0077; p 0.02) and in the product of the velocity time integral (VTI) of the dominant outflow tract and the heart rate (HR; 110 cm × bpm; 95% CI 7.5, 220; p = 0.04). Measures of diastolic performance, including inflow velocities, myocardial velocities, and the ratio of blood pool velocity to myocardial velocity during passive inflow, did not change. In this cohort, there were significant improvements in both the MPI and the product of the VTI × HR after 6 weeks of treatment with sildenafil. These findings suggest that sildenafil may be a useful therapy to improve or maintain ventricular performance in select patients after the Fontan operation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Anderson PA, Sleeper LA, Mahony L, Colan SD, Atz AM, Breitbart RE et al (2008) Contemporary outcomes after the Fontan procedure: a Pediatric Heart Network multicenter study. J Am Coll Cardiol 52:85–98

    Article  PubMed  Google Scholar 

  2. Behling A, Rohde LE, Colombo FC, Goldraich LA, Stein R, Clausell N (2008) Effects of 5′-phosphodiesterase four-week long inhibition with sildenafil in patients with chronic heart failure: a double-blind, placebo-controlled clinical trial. J Card Fail 14:189–197

    Article  PubMed  CAS  Google Scholar 

  3. Caldas MC, Meira ZA, Barbosa MM (2008) Evaluation of 107 patients with sickle cell anemia through tissue Doppler and myocardial performance index. J Am Soc Echocardiogr 21:1163–1167

    Article  PubMed  Google Scholar 

  4. Canter CE, Shaddy RE, Bernstein D, Hsu DT, Chrisant MR, Kirklin JK et al (2007) Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology, Cardiovascular Nursing, and Cardiovascular Surgery and Anesthesia; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 115:658–676

    Article  PubMed  Google Scholar 

  5. Cheung EW, Lam WW, Cheung SC, Cheung YF (2008) Functional implications of the right ventricular myocardial performance index in patients after surgical repair of tetralogy of Fallot. Heart Vessels 23:112–117

    Article  PubMed  Google Scholar 

  6. Diller GP, Giardini A, Dimopoulos K, Gargiulo G, Muller J, Derrick G et al (2010) Predictors of morbidity and mortality in contemporary Fontan patients: results from a multicenter study including cardiopulmonary exercise testing in 321 patients. Eur Heart J 31(24):3073–3083

    Article  PubMed  Google Scholar 

  7. Fontan F, Baudet E (1971) Surgical repair of tricuspid atresia. Thorax 26:240–248

    Article  PubMed  CAS  Google Scholar 

  8. 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 123:1185–1193

    Article  PubMed  CAS  Google Scholar 

  9. Guazzi M, Vicenzi M, Arena R, Guazzi MD (2011) PDE5-inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry and clinical status in patients with stable systolic heart failure: results of a 1-year prospective, randomized, placebo-controlled study. Circ Heart Fail 4(1):8–17

    Article  PubMed  CAS  Google Scholar 

  10. Jenkins PC, Chinnock RE, Jenkins KJ, Mahle WT, Mulla N, Sharkey AM et al (2008) Decreased exercise performance with age in children with hypoplastic left heart syndrome. J Pediatr 152:507–512

    Article  PubMed  Google Scholar 

  11. Kenward MG, Roger JH (2010) The use of baseline covariates in crossover studies. Biostatistics 11:1–17

    Article  PubMed  Google Scholar 

  12. Klimes K, Ovroutski S, Abdul-Khaliq H, Ewert P, Alexi-Meskishvili V, Kuehne T et al (2009) Exercise capacity reflects ventricular function in patients having the Fontan circulation. Cardiol Young 19(4):340–345

    Article  PubMed  Google Scholar 

  13. Kreutzer G, Galindez E, Bono H, De Palma C, Laura JP (1973) An operation for the correction of tricuspid atresia. J Thorac Cardiovasc Surg 66:613–621

    PubMed  CAS  Google Scholar 

  14. Lai WW, Geva T, Shirali GS, Frommelt PC, Humes RA, Brook MM et al (2006) Guidelines and standards for performance of a pediatric echocardiogram: a report from the Task Force of the Pediatric Council of the American Society of Echocardiography. J Am Soc Echocardiogr 19:1413–1430

    Article  PubMed  Google Scholar 

  15. Morner S, Lindqvist P, Waldenstrom A, Kazzam E (2008) Right ventricular dysfunction in hypertrophic cardiomyopathy as evidenced by the myocardial performance index. Int J Cardiol 124:57–63

    Article  PubMed  Google Scholar 

  16. Nagayama T, Hsu S, Zhang M, Koitabashi N, Bedja D, Gabrielson KL et al (2009) Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. J Am Coll Cardiol 53:207–215

    Article  PubMed  CAS  Google Scholar 

  17. 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 116:238–248

    Article  PubMed  CAS  Google Scholar 

  18. Patel N, Mills JF, Cheung MM (2009) Use of the myocardial performance index to assess right ventricular function in infants with pulmonary hypertension. Pediatr Cardiol 30:133–137

    Article  PubMed  Google Scholar 

  19. Pokreisz P, Vandenwijngaert S, Bito V, Van den Bergh A, Lenaerts I, Busch C et al (2009) Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice. Circulation 119:408–416

    Article  PubMed  CAS  Google Scholar 

  20. Rychik J (2010) Forty years of the Fontan operation: a failed strategy. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 13:96–100

    Article  PubMed  Google Scholar 

  21. Sarkar H, Siddique MA, Haque KM, Ahmed CM, Mahmood M, Bhattacharjee B et al (2008) Evaluation of left ventricular global function using Doppler myocardial performance index in patients with systemic hypertension. Mymensingh Med J 17(Suppl):S65–S71

    PubMed  CAS  Google Scholar 

  22. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER et al (2005) Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11:214–222

    Article  PubMed  CAS  Google Scholar 

  23. Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ et al (1995) New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function: a study in normals and dilated cardiomyopathy. J Cardiol 26:357–366

    PubMed  CAS  Google Scholar 

  24. Tweddell JS, Nersesian M, Mussatto KA, Nugent M, Simpson P, Mitchell ME et al (2009) Fontan palliation in the modern era: factors impacting mortality and morbidity. Ann Thorac Surg 88:1291–1299

    Article  PubMed  Google Scholar 

  25. Zhang YQ, Sun K, Zhu SL, Wu LP, Chen GZ, Zhang ZF et al (2008) Doppler myocardial performance index in assessment of ventricular function in children with single ventricles. World J Pediatr 4:109–113

    Article  PubMed  Google Scholar 

  26. Zhang M, Takimoto E, Hsu S, Lee DI, Nagayama T, Danner T et al (2010) Myocardial remodeling is controlled by myocyte-targeted gene regulation of phosphodiesterase type 5. J Am Coll Cardiol 56:2021–2030

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Erin Davis, Anysia Fedec, the staff of the Echocardiography Laboratory, and the staff of the Investigational Pharmacy at The Children’s Hospital of Philadelphia for their assistance and contributions to this work. This study was supported by grants from the The Mark H. and Blanche M. Harrington Family Foundation and from Big Hearts to Little Hearts. D. J. G. received support from NIH T32 Grant no. HL07915.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David J. Goldberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goldberg, D.J., French, B., Szwast, A.L. et al. Impact of Sildenafil on Echocardiographic Indices of Myocardial Performance After the Fontan Operation. Pediatr Cardiol 33, 689–696 (2012). https://doi.org/10.1007/s00246-012-0196-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-012-0196-9

Keywords

Navigation