The Cardiopulmonary Effect of Inhaled Beta-2-agonists on Adult Patients Born With Ventricular Septum Defects.

Summary

The overall objective for this study is to test whether β2-agonists will affect the cardiopulmonary capacity of VSD-operated patients compared with un-operated VSD-patients and healthy age- and gender-matched controls.

Timeline

Start

2016-10-15

Primary completion

2017-07-01

Completion

2018-01-01

Outcome

Missed primary endpoint

paper Salbutamol had no effect on peak oxygen uptake compared with placebo, 46.8±1.3 mL/kg/min versus 46.6±1.2 mL/kg/min, p=0.64. PMID 30233808 ↗

Publications

• Background Dolk H, Loane M, Garne E; European Surveillance of Congenital Anomalies (EUROCAT) Working Group. Congenital heart defects in Europe: prevalence and perinatal mortality, 2000 to 2005. Circulation. 2011 Mar 1;123(8):841-9. doi: 10.1161/CIRCULATIONAHA.110.958405. Epub 2011 Feb 14.
• Background Warnes CA, Liberthson R, Danielson GK, Dore A, Harris L, Hoffman JI, Somerville J, Williams RG, Webb GD. Task force 1: the changing profile of congenital heart disease in adult life. J Am Coll Cardiol. 2001 Apr;37(5):1170-5. doi: 10.1016/s0735-1097(01)01272-4. No abstract available.
• Background van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, Roos-Hesselink JW. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011 Nov 15;58(21):2241-7. doi: 10.1016/j.jacc.2011.08.025.
• Background Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital heart disease in the general population: changing prevalence and age distribution. Circulation. 2007 Jan 16;115(2):163-72. doi: 10.1161/CIRCULATIONAHA.106.627224. Epub 2007 Jan 8.
• Background Penny DJ, Vick GW 3rd. Ventricular septal defect. Lancet. 2011 Mar 26;377(9771):1103-12. doi: 10.1016/S0140-6736(10)61339-6. Epub 2011 Feb 23.
• Background Bol-Raap G, Weerheim J, Kappetein AP, Witsenburg M, Bogers AJ. Follow-up after surgical closure of congenital ventricular septal defect. Eur J Cardiothorac Surg. 2003 Oct;24(4):511-5. doi: 10.1016/s1010-7940(03)00430-5.
• Background Roos-Hesselink JW, Meijboom FJ, Spitaels SE, Van Domburg R, Van Rijen EH, Utens EM, Bogers AJ, Simoons ML. Outcome of patients after surgical closure of ventricular septal defect at young age: longitudinal follow-up of 22-34 years. Eur Heart J. 2004 Jun;25(12):1057-62. doi: 10.1016/j.ehj.2004.04.012.
• Background Menting ME, Cuypers JA, Opic P, Utens EM, Witsenburg M, van den Bosch AE, van Domburg RT, Meijboom FJ, Boersma E, Bogers AJ, Roos-Hesselink JW. The unnatural history of the ventricular septal defect: outcome up to 40 years after surgical closure. J Am Coll Cardiol. 2015 May 12;65(18):1941-51. doi: 10.1016/j.jacc.2015.02.055.
• Background Heiberg J, Laustsen S, Petersen AK, Hjortdal VE. Reduced long-term exercise capacity in young adults operated for ventricular septal defect. Cardiol Young. 2015 Feb;25(2):281-7. doi: 10.1017/S1047951113002084. Epub 2013 Nov 21.
• Background Heiberg J, Schmidt MR, Redington A, Hjortdal VE. Disrupted right ventricular force-frequency relationships in adults operated for ventricular septal defect as toddlers: abnormal peak force predicts peak oxygen uptake during exercise. Int J Cardiol. 2014 Dec 20;177(3):918-24. doi: 10.1016/j.ijcard.2014.10.009. Epub 2014 Oct 28.
• Background Heiberg J, Petersen AK, Laustsen S, Hjortdal VE. Abnormal ventilatory response to exercise in young adults operated for ventricular septal defect in early childhood: A long-term follow-up. Int J Cardiol. 2015 Sep 1;194:2-6. doi: 10.1016/j.ijcard.2015.05.071. Epub 2015 May 15.
• Background Heiberg J, Ringgaard S, Schmidt MR, Redington A, Hjortdal VE. Structural and functional alterations of the right ventricle are common in adults operated for ventricular septal defect as toddlers. Eur Heart J Cardiovasc Imaging. 2015 May;16(5):483-9. doi: 10.1093/ehjci/jeu292. Epub 2014 Dec 31.
• Background Meijboom F, Szatmari A, Utens E, Deckers JW, Roelandt JR, Bos E, Hess J. Long-term follow-up after surgical closure of ventricular septal defect in infancy and childhood. J Am Coll Cardiol. 1994 Nov 1;24(5):1358-64. doi: 10.1016/0735-1097(94)90120-1.
• Background Norozi K, Gravenhorst V, Hobbiebrunken E, Wessel A. Normality of cardiopulmonary capacity in children operated on to correct congenital heart defects. Arch Pediatr Adolesc Med. 2005 Nov;159(11):1063-8. doi: 10.1001/archpedi.159.11.1063.
• Background Binkhorst M, van de Belt T, de Hoog M, van Dijk A, Schokking M, Hopman M. Exercise capacity and participation of children with a ventricular septal defect. Am J Cardiol. 2008 Oct 15;102(8):1079-84. doi: 10.1016/j.amjcard.2008.05.063. Epub 2008 Jul 26.
• Background Hovels-Gurich HH, Konrad K, Skorzenski D, Nacken C, Minkenberg R, Messmer BJ, Seghaye MC. Long-term neurodevelopmental outcome and exercise capacity after corrective surgery for tetralogy of Fallot or ventricular septal defect in infancy. Ann Thorac Surg. 2006 Mar;81(3):958-66. doi: 10.1016/j.athoracsur.2005.09.010.
• Background Cumming GR. Maximal exercise capacity of children with heart defects. Am J Cardiol. 1981 Jun;47(6):1381. doi: 10.1016/0002-9149(81)90273-3. No abstract available.
• Background Otterstad JE, Simonsen S, Erikssen J. Hemodynamic findings at rest and during mild supine exercise in adults with isolated, uncomplicated ventricular septal defects. Circulation. 1985 Apr;71(4):650-62. doi: 10.1161/01.cir.71.4.650.
• Background Pieroni DR, Nishimura RA, Bierman FZ, Colan SD, Kaufman S, Sanders SP, Seward JB, Tajik AJ, Wiggins JW, Zahka KG. Second natural history study of congenital heart defects. Ventricular septal defect: echocardiography. Circulation. 1993 Feb;87(2 Suppl):I80-8.
• Background Reybrouck T, Rogers R, Weymans M, Dumoulin M, Vanhove M, Daenen W, Van der Hauwaert L, Gewillig M. Serial cardiorespiratory exercise testing in patients with congenital heart disease. Eur J Pediatr. 1995 Oct;154(10):801-6. doi: 10.1007/BF01959785.
• Background Perrault H, Drblik SP, Montigny M, Davignon A, Lamarre A, Chartrand C, Stanley P. Comparison of cardiovascular adjustments to exercise in adolescents 8 to 15 years of age after correction of tetralogy of fallot, ventricular septal defect or atrial septal defect. Am J Cardiol. 1989 Jul 15;64(3):213-7. doi: 10.1016/0002-9149(89)90460-8.
• Background Norozi K, Wessel A, Alpers V, Arnhold JO, Binder L, Geyer S, Zoege M, Buchhorn R. Chronotropic incompetence in adolescents and adults with congenital heart disease after cardiac surgery. J Card Fail. 2007 May;13(4):263-8. doi: 10.1016/j.cardfail.2006.12.002.
• Background Ohuchi H, Watanabe K, Kishiki K, Wakisaka Y, Echigo S. Heart rate dynamics during and after exercise in postoperative congenital heart disease patients. Their relation to cardiac autonomic nervous activity and intrinsic sinus node dysfunction. Am Heart J. 2007 Jul;154(1):165-71. doi: 10.1016/j.ahj.2007.03.031.
• Background Sulc J, Samanek M, Zapletal A, Voriskova M, Hucin B, Skovranek J. Lung function in VSD patients after corrective heart surgery. Pediatr Cardiol. 1996 Jan-Feb;17(1):1-6. doi: 10.1007/BF02505804.
• Background Baker JG. The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors. Br J Pharmacol. 2010 Jul;160(5):1048-61. doi: 10.1111/j.1476-5381.2010.00754.x.
• Background Lehmann S, Bakke PS, Eide GE, Gulsvik A. Bronchodilator response to adrenergic beta2-agonists: relationship to symptoms in an adult community. Respir Med. 2007 Jun;101(6):1183-90. doi: 10.1016/j.rmed.2006.11.007. Epub 2006 Dec 22.
• Background Kindermann W. Do inhaled beta(2)-agonists have an ergogenic potential in non-asthmatic competitive athletes? Sports Med. 2007;37(2):95-102. doi: 10.2165/00007256-200737020-00001.
• Background Pluim BM, de Hon O, Staal JB, Limpens J, Kuipers H, Overbeek SE, Zwinderman AH, Scholten RJ. beta(2)-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials. Sports Med. 2011 Jan 1;41(1):39-57. doi: 10.2165/11537540-000000000-00000.
• Background Morton AR, Joyce K, Papalia SM, Carroll NG, Fitch KD. Is salmeterol ergogenic? Clin J Sport Med. 1996 Oct;6(4):220-5. doi: 10.1097/00042752-199610000-00003.
• Background Vik-Mo H, Halvorsen FJ, Thorsen E, Walde NH, Rosland GA. Improved cardiac performance by salbutamol, a selective beta 2-agonist, in chronic cor pulmonale. J Cardiovasc Pharmacol. 1987 Feb;9(2):129-34. doi: 10.1097/00005344-198702000-00001.
• Eckerstrom F, Rex CE, Maagaard M, Rubak S, Hjortdal VE, Heiberg J. Exercise performance after salbutamol inhalation in non-asthmatic, non-athlete individuals: a randomised, controlled, cross-over trial. BMJ Open Sport Exerc Med. 2018 Aug 30;4(1):e000397. doi: 10.1136/bmjsem-2018-000397. eCollection 2018.

Drugs

Indications