Ann Thorac Surg 2006;81:1505-1507
© 2006 The Society of Thoracic Surgeons
Case report
Heterotopic Heart Transplant Combined With Postoperative Sildenafil Use for the Treatment of Restrictive Cardiomyopathy
Abdulaziz Al-Khaldi, MD
a
,
b
,
Bruce A. Reitz, MD
a
,
b
,
*
,
Henry Zhu, MD
a
,
b
,
David Rosenthal, MD
a
,
b
a Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, California
b Department of Pediatric Cardiology, Stanford University Medical Center, Stanford, California
Accepted for publication February 23, 2005.
* Address correspondence to Dr Reitz, Falk Cardiovascular Research Center, 300 Pasteur Dr, Stanford University, Stanford, CA 94305-5407 (Email: breitz{at}stanford.edu).
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Abstract
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We report successful management of a 22-month-old child with restrictive cardiomyopathy and severe pulmonary hypertension using the heterotopic heart transplant technique. Additional lessons learned from postoperative management, including the novel use of Sildenafil (Viagra, Pfizer, NY) for controlling pulmonary arterial pressure are described.
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Introduction
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Young children with advanced cardiomyopathy and fixed-severe pulmonary hypertension (PHT) are not candidates for orthotopic heart transplant. Heterotopic heart transplant (HHT) is an option, but immediate post-transplant management can be complicated by pulmonary hypertensive crisis requiring prolonged cardiovascular support. Sildenafil can be used to control pulmonary artery pressure (PAP) in a post-cardiopulmonary bypass setting, which helps early extubation and weaning of support.
A 22-month-old Hispanic female baby was diagnosed with idiopathic restrictive cardiomyopathy at the age of 6 months and was referred to our center due to progressive clinical deterioration. Her heart catheterization documented supra-systemic PAP 109/55/76 mm Hg with aortic pressure 76/51/63 mm Hg and elevated pulmonary vascular resistance (PVR) of 17.4 Wood units that was reduced to 5.7 Wood units with nitric oxide (NO) and oxygen challenge. She was listed for HHT. The donor was an 18-month-old female. The donor-recipient's weight ratio was 1.44. Figure 1A shows the transplant technique. The donor's inferior vena caval orifice and the right-sided pulmonary veins were oversewn, while the left-sided pulmonary veins were joined together making a single cuff. Using systemic hypothermia with fibrillatory arrest, the recipient's left atrium was opened through a right-sided vertical atriotomy; then it was anastomosed to the donor's left atrial cuff. The donor's superior vena cava was connected end-to-side to the lateral wall of the recipient's right atrium. The donor's aorta was anastomosed end-to-side to the recipient's mid-ascending aorta. A segment of the donor's descending aorta was used to connect the donor's and the recipient's main pulmonary arteries (Fig 1A). The ischemic time of the donor's heart was 159 minutes. During the period of reperfusion, we started NO (20 ppm) and a milrinone infusion (0.5 mcg/kg/min). Initially, the PAP was equal to the systemic pressure, but then it declined to two thirds of the systemic pressure within the next 20 minutes. The patient was easily weaned from cardiopulmonary bypass, and the chest was closed with no hemodynamic compromise. Postoperatively, aggressive diuresis was started. Immunosuppression was not different from our standard protocol. As is customary, the two hearts had independent sinus rhythm (Fig 1B). Transthoracic echocardiogram showed good function of the donor left ventricle, whereas the recipient right ventricle maintained the major amount of flow to the lungs. The patient was kept intubated and sedated on NO (40 ppm) and milrinone to lower the PAP, which remained two thirds of the systemic pressure, despite all these measures. On postoperative day 4, a trial to slowly wean the NO failed with rapid elevation of the PAP to systemic levels associated with clinical evidence of worsening systemic perfusion. We decided to start the patient on Sildenafil (Viagra, Pfizer, NY) (0.4 mg/kg every 6 hours). Another attempt to wean the patient off the NO was done 24 hours after starting the Sildenafil, and it was now possible to completely withdraw the NO within the next 48 hours without an increase in PAP, which remained at two-thirds systemic with excellent systemic blood flow as clinically assessed. This dose of Sildenafil was well tolerated with no systemic hypotension. The PAP continued to drop to half of the systemic blood pressure after 4 days of Sildenafil therapy, despite weaning the milrinone infusion. A heart catheterization was done 2 weeks postoperatively and showed that the PAP was less than 50% of the systemic arterial pressure (PAP = 38/18/27) while continuing the Sildenafil.
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Fig 1. (A) Schematic drawing of the heterotopic heart transplant. Not shown in the drawing is the connection of the donor and native left atria. (B) Chest roentgenogram showing the donor heart shadow with the apex directed to the right. (C) Electrocardiogram record showing the asynchronous QRS complexes of the native and donor hearts.
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The patient's respiratory status was complicated by partial right upper and middle lobes collapse. She required nasal continuous positive airway pressure ventilation for 8 days followed by gradual weaning with no clinical or radiologic evidence of recurrence of lung collapse. The rest of her postoperative course was unremarkable with excellent progress and recovery. She was discharged home in stable condition 33 days after her surgery.
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Comment
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In 1974, Christian Bernard (Cape Town, South Africa) reported the early clinical experience with HHT as a left ventricular bypass [1]. The concept of having the native and donor hearts side-by-side assisting each other was appealing in the early era of heart transplant when the incidence of early graft failure due to poor preservation, PHT, or rejection was high. Currently, there are two potential indications for HHT: (1) patients with high and fixed PHT in which the untrained donor right ventricle will not be able to overcome the high PVR with subsequent right heart failure, and (2) significant donor-recipient size mismatch with the smaller donor being used for a larger recipient. Enthusiasm toward HHT generally disappeared in the last 2 decades as more studies showed better survival with orthotopic heart transplant [2–4] and more potential complications with HHT including pulmonary complications due to compression of right middle and lower lung lobes [4, 5], systemic thromboembolism due to reduced flow through the native left ventricle with increased risk of clot formation [5], development of mitral and tricuspid regurgitation in the native heart [3], malignant ventricular arrhythmias, and recurrence of angina in the native heart in patients with ischemic cardiomyopathy [2, 5].
Nevertheless, HHT is a promising therapeutic option for restrictive cardiomyopathy in infants and young children. The natural history of idiopathic restrictive cardiomyopathy is characterized by rapid deterioration with early development of severe PHT that makes orthotopic heart transplant risky and a contraindicated procedure in many cases. The only other available surgical option is combined heart-lung transplant, which has a lower survival compared with isolated heart transplant due to the development of bronchiolitis obliterans, in addition to the limited availability of suitable heart-lung block donors in this age group.
After HHT, the relief of the native left atrial hypertension results in gradual reduction of the PHT with time (as early as 3 months to 2 years) [6]. In our patient, the early postoperative management was greatly facilitated by the use of Sildenafil, which reduced the PAP and controlled the reactivity of the pulmonary vascular bed, allowing early weaning of NO, milrinone, and sedation with no significant effect on systemic blood pressure. Sildenafil is a phosphodiesterase-5 inhibitor that decreases the breakdown of intracellular cyclic guanosine monophosphate resulting in vascular smooth muscle relaxation [7]. Sildenafil has an acute pulmonary vasodilator effect [8]. Lyons and colleagues [9] showed that Sildenafil is effective in relieving post-cardiopulmonary bypass PHT in a neonatal piglets model. Keller and colleagues [10] successfully used Sildenafil to control severe PHT and weaned NO in an infant with congenital diaphragmatic hernia. Until the time of writing this article, we believe that this is the first description in the literature for the use of Sildenafil in the management of post-heart transplant PHT.
In conclusion, HHT is a viable option for young children with end-stage cardiomyopathy and severe PHT. The use of Sildenafil for control of post-transplant PHT is a novel and promising strategy that is also probably worth trying in other clinical situations with post-cardiac surgery PHT.
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References
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- Lyons JM, Duffy JY, Wagner CJ, et al. Sildenafil citrate alleviates pulmonary hypertension after hypoxia and reoxygenation with cardiopulmonary bypass J Am Coll Surg 2004;199:607-614.[Medline]
- Keller RL, Hamrick SE, Kitterman JA, et al. Treatment of rebound and chronic pulmonary hypertension with oral Sildenafil in an infant with congenital diaphragmatic hernia Pediatr Crit Care Med 2004;5:184-187.[Medline]
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Abstract
Introduction
