Clinical trial NCT01607983: Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
Official title: The Effect of Selective Pulmonary Vasodilation on Ventricular Afterload and Ventricular-arterial Coupling in Patients With Fontan Physiology and Validation of Echocardiographic Measures of Systolic and Diastolic Function.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Congenital Heart Disease
Fontan
Keywords: nitric oxide
ventricular-arterial coupling
congenital heart disease
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2012-05-30
Enrollment: 0
Sex: ALL
Minimum age (years): 4
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study involves documenting the effects of inhaled nitric oxide upon ventricular-arterial coupling in patients with congenital heart disease and passive pulmonary blood flow. Consenting patients undergoing a clinically-indicated cardiac catheterization will be given inhaled nitric oxide for 10 minutes while intraventricular pressure-volume analysis will be make via conduction catheters.

Detailed description: Patients with complex congenital heart disease and single ventricle physiology typically undergo a staged surgical palliation to a situation where the single ventricle is recruited as the systemic pumping chamber and some (following a Glenn surgery) or all (following a Fontan surgery) systemic venous return flows passively to the lungs. While this physiology eliminates ventricular volume loading and normalizes systemic arterial oxygen saturations, there remain a number of physiologic burdens that limit functional capacity and life expectancy. Evidence suggests that this surgical imposition of the systemic and pulmonary vascular beds in series results in ventricular loading conditions that adversely affect ventricular function. At present, there exist limited means by which to mitigate these burdens, however, new therapies directed at reducing total pulmonary resistance may favorably affect patients with this physiology by reducing systemic venous pressures and improving both ventricular preload and afterload. One such therapy is inhaled nitric oxide (iNO), which is a selective pulmonary vasodilator that has been shown to reduce total pulmonary resistance and improve systemic venous pressures in this patient population. However limited data exist regarding the affects of pulmonary vasodilators like iNO on ventricular loading and ventricular-arterial coupling. This study proposes to assess the effects of pulmonary vasodilator therapy upon ventricular loading and ventricular-arterial coupling in single ventricle patients with passive pulmonary blood flow presenting for elective cardiac catheterization. The study components include obtaining routine (they would be obtained as a part of the clinically-indicated catheterization) hemodynamic measurements with hi-fidelity catheters rather than standard fluid-filled catheters, as well as simultaneous additional measurements with the same catheters at rest and during administration of iNO.

Eligibility criteria: Inclusion Criteria:

* All consecutive patients with single ventricle hearts having passive pulmonary blood flow presenting to the cardiac catheterization laboratory for clinically indicated cardiac catheterization.

Exclusion Criteria:

* Patients with coarctation of the aorta or known bilateral femoral arterial obstruction
* Patients with known severe systemic venous/Fontan obstruction
* Patients already receiving sildenafil or other vasodilator therapy

Primary outcomes:
measure: Effective arterial elastance (Ea)
timeFrame: Acute, approximately 10-15 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Jeffery Meadows, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Senzaki H, Masutani S, Kobayashi J, Kobayashi T, Sasaki N, Asano H, Kyo S, Yokote Y, Ishizawa A. Ventricular afterload and ventricular work in fontan circulation: comparison with normal two-ventricle circulation and single-ventricle circulation with blalock-taussig shunts. Circulation. 2002 Jun 18;105(24):2885-92. doi: 10.1161/01.cir.0000018621.96210.72.
citation: Szabo G, Buhmann V, Graf A, Melnitschuk S, Bahrle S, Vahl CF, Hagl S. Ventricular energetics after the Fontan operation: contractility-afterload mismatch. J Thorac Cardiovasc Surg. 2003 May;125(5):1061-9. doi: 10.1067/mtc.2003.405.
citation: Tanoue Y, Sese A, Imoto Y, Joh K. Ventricular mechanics in the bidirectional glenn procedure and total cavopulmonary connection. Ann Thorac Surg. 2003 Aug;76(2):562-6. doi: 10.1016/s0003-4975(03)00467-3.
citation: Senzaki H, Masutani S, Ishido H, Taketazu M, Kobayashi T, Sasaki N, Asano H, Katogi T, Kyo S, Yokote Y. Cardiac rest and reserve function in patients with Fontan circulation. J Am Coll Cardiol. 2006 Jun 20;47(12):2528-35. doi: 10.1016/j.jacc.2006.03.022. Epub 2006 May 30.
citation: Cai J, Su Z, Shi Z, Zhou Y, Xu Z, Xu Z, Yang Y. Nitric oxide and milrinone: combined effect on pulmonary circulation after Fontan-type procedure: a prospective, randomized study. Ann Thorac Surg. 2008 Sep;86(3):882-8; discussion 882-8. doi: 10.1016/j.athoracsur.2008.05.014.