Document Type : Original Article(s)


1 Professor, Department of Pediatric Cardiology, Pediatric Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

2 Pediatric Cardiology Fellow, Pediatric Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Epidemiology, Esfarayen School of Medical Sciences, Esfarayen, Iran


BACKGROUND: Tetralogy of Fallot (TOF) is one of the most common cyanotic congenital heart diseases (CHD) in children. Various surgical procedures including palliative shunts and TOF total correction (TFTC) were done with some complications, of which, the most common is pulmonary valve regurgitation (PR). Tadalafil is a phosphodiesterase 5 inhibitor which reduces pulmonary vascular resistance, and improves right ventricular function and vascular endothelium, and may have some beneficial effects after TFTC.METHODS: We studied 18 patients with TOF and PR, with some impaired right ventricular function after TFTC. Tadalafil tablets at a dose of 1 mg per kg (maximum 40 mg) per day as a single dose was administered orally for 8 weeks. In all patients, before and after taking tadalafil, functional class assessment, electrocardiography (ECG) changes, some echocardiographic and endothelial function parameters [flow-mediated dilation (FMD) and intima-media thickness (IMT) of carotid artery], and exercise test were determined.RESULTS: The patient’s mean age was 10.11 ± 4.03 years, and the mean age of operation was 2.52 ± 1.12 years. The effect of tadalafil on different echocardiographic parameters and also on tricuspid valve regurgitation (TR) and PR severity and gradient was not significant. Moreover, it had no effects on QRS duration. Tadalafil had a significant effect on improving FMD and exercise test (P = 0.01). The effect of tadalafil on echocardiographic parameters, carotid artery IMT, and ECG parameters was not significant (P > 0.05). Tadalafil was tolerated well, and the most common side effects were headache and myalgia.CONCLUSION: This study showed that tadalafil is a safe and well-tolerated drug. It might improve exercise performance, endothelial function, and functional class, and possibly could allow patients a longer period of well-being and could possibly delay the need for pulmonary valve replacement (PVR).


  1. Luijnenburg SE, Helbing WA, Moelker A, Kroft LJ, Groenink M, Roos-Hesselink JW, et al. 5-year serial follow-up of clinical condition and ventricular function in patients after repair of tetralogy of Fallot. Int J Cardiol 2013; 169(6): 439-44.
  2. Allen HD. Moss and Adams' heart disease in infants, children, and adolescents: Including the fetus and young adult. Alphen Aan Den Rijn, Netherlands: Wolters Kluwer; 2016. p. 969-78
  3. Promphan W, Wonglikhitpanya T, Katanyuwong P, Siripornpitak S. A comparative study: Right ventricular assessment in post-repaired tetralogy of Fallot patients by echocardiogram with cardiac magnetic resonance imaging. J Med Assoc Thai 2014; 97(Suppl 6): S232-S238.
  4. Affuso F, Palmieri EA, Di Conza P, Guardasole V, Fazio S. Tadalafil improves quality of life and exercise tolerance in idiopathic pulmonary arterial hypertension. Int J Cardiol 2006; 108(3): 429-31.
  5. Croxtall JD, Lyseng-Williamson KA. Tadalafil: In pulmonary arterial hypertension. Drugs 2010; 70(4): 479-88.
  6. Jackson KW, Butts RJ, Svenson AJ, McQuinn TC, Atz AM. Response to a single dose of sildenafil in single-ventricle patients: An echocardiographic evaluation. Pediatr Cardiol 2013; 34(7): 1739-42.
  7. Rosano GM, Aversa A, Vitale C, Fabbri A, Fini M, Spera G. Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol 2005; 47(2): 214-20.
  8. Takatsuki S, Calderbank M, Ivy DD. Initial experience with tadalafil in pediatric pulmonary arterial hypertension. Pediatr Cardiol 2012; 33(5): 683-8.
  9. Sabri MR, Beheshtian E. Comparison of the therapeutic and side effects of tadalafil and sildenafil in children and adolescents with pulmonary arterial hypertension. Pediatr Cardiol 2014; 35(4): 699-704.
  10. Sabri MR, Zolfi-Gol A, Ahmadi A, Haghjooy-Javanmard S. Effect of tadalafil on myocardial and endothelial function and exercise performance after modified fontan operation. Pediatr Cardiol 2016; 37(1): 55-61.
  11. Eidem BW, O'Leary PW, Cetta F. Echocardiography in pediatric and adult congenital heart disease. Alphen Aan Den Rijn, Netherlands: Wolters Kluwer Health; 2014. p. 666-72.
  12. Meyer AA, Kundt G, Steiner M, Schuff-Werner P, Kienast W. Impaired flow-mediated vasodilation, carotid artery intima-media thickening, and elevated endothelial plasma markers in obese children: The impact of cardiovascular risk factors. Pediatrics 2006; 117(5): 1560-7.
  13. Jackson G. Hemodynamic and exercise effects of phosphodiesterase 5 inhibitors. Am J Cardiol 2005; 96(12B): 32M-6M.
  14. Galie N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation 2009; 119(22): 2894-903.
  15. Forgue ST, Patterson BE, Bedding AW, Payne CD, Phillips DL, Wrishko RE, et al. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol 2006; 61(3): 280-8.
  16. Magee AG, Makhecha S, Bentley S. Risk-benefit considerations when prescribing phosphodiesterase-5 inhibitors in children. Expert Opin Drug Saf 2015; 14(5): 633-42.