Sildenafil in Pulmonary Hypertension Secondary to Unilateral Agenesis of. Pulmonary Artery. M.A. Hamdan,1 R.M. Abu-Sulaiman,1 H.K. Najm2. 1Section of ...
Pediatr Cardiol 27:279–281, 2006 DOI: 10.1007/s00246-005-1100-7
Sildenafil in Pulmonary Hypertension Secondary to Unilateral Agenesis of Pulmonary Artery M.A. Hamdan,1 R.M. Abu-Sulaiman,1 H.K. Najm2 1 Section of Pediatric Cardiology, King Abdulaziz Cardiac Center, King Fahad National Guard Hospital, Riyadh, Saudi Arabia 2
Section of Cardiovascular Surgery, King Abdulaziz Cardiac Center, King Fahad National Guard Hospital, Riyadh, Saudi Arabia
Abstract. Unilateral agenesis of the pulmonary artery (PA) is a rare anomaly that can lead to pulmonary hypertension (PHTN). We report the case of a 10-month-old female with agenesis of the left PA, ventricular septal defect, and patent ductus arteriosus who developed PHTN precluding surgical repair. The use of sildenafil decreased PA pressure and normalized pulmonary vascular resistance, after which surgery was successfully performed. Key words: Sildenafil — Pulmonary hypertension — Pulmonary artery agensis
Case Report A 10-month-old female presented to our institution with a 4-month history of progressive tachypnea, poor weight gain, and cardiac murmur. On examination, her weight was 5.8 kg, room air saturation was 96%, and blood pressure was 85/45 mmHg. She had mild tachypnea, normal first and accentuated second heart sound, palpable thrill, and grade 4/6 pansystolic murmur all over the precordium. Her electrocardiogram showed biventricular hypertrophy, whereas echocardiogram showed an 8-mm nonrestrictive perimembranous ventricular septal defect, together with a 3-mm nonrestrictive patent ductus arteriosus and right aortic arch. Her tricuspid valve regurgitation Doppler velocity predicted pulmonary artery (PA) systolic pressure of 75 mmHg at 90% of systemic pressure. Computed tomography of the chest showed absent left PA and hyoplasia of the left lung, which had no perfusion by lung perfusion scan. Cardiac catheterization under general anesthesia confirmed the absence of the left PA by main PA angiography (Fig. 1), as well as by reverse pulmonary wedge angiography. PA pressure on room air was near systemic, with indexed pulmonary
Correspondence to: M.A. Hamdan, Tawam Hospital, P.O. Box 15258, Al Ain, Abu Dhabi, UAE, email: mhamdan@tawam-hosp. gov.ae
vascular resistence (PVR) of 10.7 Woods units, decreasing to 6 woods units on 100% oxygen (Fig. 2). Her pulmonary-to-systemic flow ratio was 1.3 on room air, increasing to 1.5 on 1 00% oxygen (Fig. 3). A trial of oral phenoxybenzamine (Dibezyline, WellSpring) was started before surgical repair of the cardiac defects was contemplated. Phenoxybenzamine was started at 0.25 increasing to 1 mg/kg/day in three divided doses over 10 days, and it was continued for 2 weeks. Repeat echocardiograms failed to show any change in PA pressure, which persisted at near-systemic level. Phenoxybenzamine was thus discontinued, the patient was rehospitalized, and parental consent to use oral sildenafil (Viagra, Pfizer) was obtained. Sildenafil was started at 1 mg/kg/day in three divided doses and increased to a maximum of 4 mg/kg/day in four divided doses over 1 week. Systemic blood pressure, saturation, and PA pressure were monitored. Elective cardiac catheterization under general anesthesia 5 weeks after starting sildenafil showed indexed PVR on room air of 2.9 Woods units and systemic-to-pulmonary flow ratio of 1.8. On 100% oxygen, the PVR declined to 1.0 Woods unit, and the flow ratio increased to 3.7 (Figs. 2 and 3). The patient underwent successful surgical closure of the ventricular septal defect, and ligation of the patent ductus arteriosus on the next day, without significant perioperative complications, and was extubated on postoperative day 2. Intraoperatively, no significant distal PA branches were found. Oral sildenafil was restarted on postoperative day 2 at the previous maximal dose and weaned over 1 week before it was discontinued. Follow-up echocardiogram before discharge showed no residual shunts and PA pressure of 40 mmHg (compared to systemic blood pressure of 100/60), which persisted at 3-month follow-up.
Discussion Unilateral agenesis of the PA is found in 0.5 % of patients undergoing cardiac catheterization [6]. It occurs when either the right or left PA arises from the systemic side of a homolateral ductus arteriosus rather than from the pulmonary trunk. When the ductus closes, the PA obliterates [6, 7]. This can occur in isolation or in association with congenital heart disease, the most common of which is tetralogy
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Fig. 1. Frontal projection with cranial angulation of main pulmonary artery angiography. The left pulmonary artery is absent. Neither the descending aorta nor the patent ductus arteriosus is visualized in this angiogram.
Fig. 2. Change of pulmonary and systemic vascular resistance indexed to body surface area before (pre) and after (post) use of sildenafil on 21% and 100% oxygen. PVRI, pulmonary vascular resistance indexed to body surface area; SVRI, systemic vascular resistance indexed to body surface area.
of Fallot, and ventricular septal defect [7, 10]. If left untreated, pulmonary hypertension (PHTN) can develop [3, 10]. Distal intrapericardial or hilar branches of the PA can be found at angiography or surgical exploration [3, 7, 10]. Reanastomosis to the main PA early in life, before these branches involute, can promote lung growth, reverse PHTN, and avoid later complications [3, 7, 10]. In our patient, late presentation and PHTN precluded early surgical exploration of a viable left PA remnant that could be reanastomosed to the main PA; therefore, sildenafil was used. Sildenafil is a selective inhibitor of 5-phosphodiesterase enzyme. Once inhibited, its target substance, cyclic guanylate monophosphate, increases in the pulmonary vascular bed promoting nitric oxidemediated vasodilation. Sildenafil has a proven ther-
apeutic benefit in adults with PHTN of different etiologies [4, 5, 8]. It lowers PA pressure and PVR, and it improves cardiac output, exercise tolerance, and functional capacity [4, 5, 8]. The experience in children is limited to case reports and small patient series. Abrams et al. [1] reported its use in a 4-year-old child with primary PHTN failing treatment with nitric oxide and prostacyclin. Sildenafil improved right ventricular hypertension and function, exercise tolerance, and saturation within 4 weeks of its use. Similar results were also reported in children with both primary and secondary PHTN, including postoperative PHTN [2, 4, 9]. The use of sildenafil in PHTN secondary to unilateral agenesis of PA has not been previously reported. The etiology of PHTN, which occurs
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Fig. 3. Change of pulmonary and systemic blood flow before (pre) and after (post) use of sildenafil on 21% and 100% oxygen. Qp, pulmonary blood blood flow. Qs, systemic blood flow.
in 44% of such patients, is unknown, but it may be related to exaggerated pulmonary vasoconstriction in response to hypoxia in the healthy lung or hypoplasia of pulmonary vasculature in the affected lung [10]. The use of sildenafil in our patient normalized her PVR, increased reactivity of the pulmonary vascular bed in response to 100% oxygen, and improved the cardiac output, as was documented at cardiac catheterization (Figs. 2 and 3). This allowed safe surgical repair of cardiac defects and reversed PHTN, despite the involution of the distal PA branches. Conclusion Sildenafil may reverse PHTN secondary to PA agenesis. It may provide an alternative when PA reanastomosis is not feasible or when surgery is contemplated. References 1. Abrams D, Schulze-Neick I, Magee AG (2000) Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Heart 84:e4
2. Carroll WD, Dhillon R (2003) Sildenafil as a treatment for pulmonary hypertension. Arch Dis Child 88:827–828 3. Imanaka K, Shimizu S, Matsumoto J, et al. (1998) Unilateral absence of pulmonary artery and ventricular septal defect in an infant. Ann Thorac Surg 66:251–252 4. Kothari SS, Duggal B (2002) Chronic oral sildenafil therapy in severe plulmonary artery hypertension. Indian Heart J 54:404– 408 5. Michelakis E, Tymchak W, Lien D, et al. (2002) Oral sildenafil is an effective and specific pulmonary vasodilator in patients with Pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation 105:2398–2403 6. Pfefferkorn JR, Loser H, Pech G, Toussaint R, Hilgenberg F (1982) Absent pulmonary artery: a hint to its embryogenesis. Pediatr Cardiol 3:283–286 7. Presbitero P, Bull C, Haworth SG, De Leval MR (1984) Absent or occult pulmonary artery. Br Heart J 52:178–185 8. Sastry BK, Narasimhan C, Reddy NK, Raju BS (2004) Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol 43:1149–1153 9. Stocker C, Penny DJ, Brizard CP, et al. (2003) Intravenous sildenafil and inhaled nitric oxide; a randomised trial in infants after cardiac surgery. Intensive Care Med 29: 1996–2003 10. Ten Harkel AD, Blom NA, Ottenkamp J (2002) Isolated unilateral absence of a pulmonary artery: a case report and review of the literature. Chest 122:1471–1477
