Introduction
Williams syndrome is characterised by a 7q11.23 gene deletion affecting the elastin gene, leading to distinctive facies, connective tissue abnormalities, and cardiovascular disease. Reference Morris, Adam, Feldman and Mirzaa1 Cardiac manifestations include supravalvular aortic stenosis and stenosis of peripheral pulmonary and systemic arteries, which can lead to ischaemic cardiomyopathy, myocardial infarction, and lethal arrythmias. Coronary artery anomalies are present in up to 9% of patients, increasing to 45% if supravalvular aortic stenosis is present. Reference Staudt and Eagle2
We describe the first long-term follow-up of a patient with Williams syndrome who underwent heart transplantation for acute decompensated heart failure. This paper lends to the discussion on transplanting those with Williams syndrome and may guide future management.
Materials and methods
We conducted a retrospective review of a Williams syndrome patient who underwent heart transplantation at our institution. Case reports do not meet the definition of research under our institutional protocol and do not require Institutional Review Board approval.
Case report
An 11-year-old female with a history of Williams syndrome, left renal hypoplasia, cleft mitral valve, and mild left ventricular dilation presented with cough and fatigue. She was in acute decompensated heart failure with severe mitral regurgitation and severe left ventricular dilation and dysfunction. She had no prior history of supravalvular aortic stenosis, coronary stenosis, or pulmonary stenosis. Workup revealed parainfluenza 3 infection, suggesting viral myocarditis. Her condition worsened; she was intubated and started on inotropes. Cardiac catheterisation demonstrated normal cardiac index and pulmonary vascular resistance. Coronary angiography revealed normal anatomy without stenoses. The aorta appeared diffusely hypoplastic (ascending aorta diameter 14 mm, Z-score −4.88; descending thoracic aorta diameter 10 mm, Z-score, −6.34).
She was unable to be weaned from inotropes and underwent cardiac transplantation 2 months after admission. The donor aorta was larger than the thickened native aorta; the native aorta was spatulated anteriorly to address the size discrepancy. The total ischaemic time was 240 minutes. Intraoperative echocardiogram demonstrated normal left ventricular function and mildly decreased right ventricle function.
The postoperative course was complicated by acute cardiac tamponade secondary to bleeding at the cardioplegia cannulation site in the donor aorta and peripheral blood pressure readings > 200 mmHg. She required intravenous nicardipine, esmolol, and nitroprusside for 2 days, followed by 10 days of intravenous nicardipine. She was transitioned to oral amlodipine and losartan and discharged home 1 month postoperatively on these agents. She remains well 7 years post-transplant, with a recent catheterisation demonstrating no signs of rejection or graft vasculopathy. She remains on losartan and doxazosin with an average blood pressure of 127/88.
Discussion
This case demonstrates long-term survival following cardiac transplantation in a patient with Williams syndrome. Reported experiences with cardiac transplantation in this population are limited, with follow-up durations of 18 months and 3 months in previous cases. Reference Baez Hernandez, Kirk and Davies4,Reference González-López, Pérez-Caballero-Martínez and Granados-Ruiz5 Life expectancy in Williams syndrome is variable, with some individuals living into their 80s. Reference Kozel, Barak and Kim6 Many patients are at risk for hypertension, arrythmias, and heart failure due to arterial stenosis and supravalvular aortic stenosis. Reference Kozel, Barak and Kim6–8 Cardiovascular disease severity tends to have the most profound impact on survival; however, reports of transplantation are limited.
The acute postoperative haemorrhage highlights an important consideration. The relatively non-compliant native aorta dampens impulse transmission throughout the arterial tree, leading to hypertension and increased impulse pressure in the more compliant donor aorta. This underscores the need for aggressive blood pressure control post-transplantation in patients with Williams syndrome. The patient has required long-term antihypertensive management with losartan and doxazosin, with an average blood pressure of 127/88 since her transplant. Successful early optimisation facilitated long-term survival and excellent graft function.
The rarity of cardiac transplantation in this population may reflect either a low incidence of severe heart failure or reduced heart transplant listing given the comorbidity burden. No prior studies assess allograft and patient longevity following cardiac transplantation in Williams syndrome, leaving limited data on unique considerations. This report suggests that medium- to long-term survival is achievable and highlights the importance of acute and chronic blood pressure management.
Acknowledgements
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Financial support
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Competing interests
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