Adjunctive Sildenafil for the Treatment of Pulmonary Hypertension After Mitral Valve Replacement

Severe mitral stenosis or regurgitation can result in increased pulmonary vascular resistance resulting in severe pulmonary hypertension. After surgical correction, the mitral pulmonary pressures usually decrease but, in some cases, residual pulmonary hypertension might persist. In this setting, treatments with continuous inhalation of prostacyclin and nitric oxide have been shown to be effective in treating residual pulmonary hypertension after mitral valve surgery.1, 2 Sildenafil is a selective inhibitor of type 5 phosphodiesterase and is available in oral form. Sildenafil attenuates hypoxia-induced pulmonary hypertension in humans and mice and offers a novel approach to the treatment of this condition.3 The efficacy and safety of sildenafil in the treatment of symptomatic pulmonary arterial hypertension has been established.4 There are anecdotal reports on using sildenafil after cardiac surgery to treat residual pulmonary hypertension. We describe a patient whose pulmonary hypertension was treated effectively with mitral valve replacement in combination with oral sildenafil. A 33-year-old Caucasian woman presented with progressive worsening of shortness of breath, rapidly decreasing activity level, and abdominal and lower extremity swelling. Her medical history was significant for hypothyroidism, obesity, and a recent cholecystectomy with difficult extubation. At the time of presentation, she was moderately hypotensive. On examination, the patient's jugular venous pressure was elevated (15 cmH2O); lung examination revealed bibasilar crackles in up to one third of the lung fields. Heart examination revealed a displaced perioperative myocardial injury, a holosystolic murmur in the 5th intercostal space that radiated to the axillary line, and an accentuated second sound. The abdominal examination revealed hepatomegaly and ascites and peripheral edema (+3+4) bilaterally. The patient was admitted to the critical care unit with a diagnosis of mitral regurgitation and fluid overload. Right- and left-sided heart catheterization was performed. The right-sided heart pressures were: right atrial pressure 20 mm Hg, right ventricular systolic pressure 130 mm Hg, pulmonary artery systolic pressure 120 mm Hg, pulmonary diastolic pressure 40 mm Hg, pulmonary artery pressure mean 66 mm Hg, pulmonary capillary wedge pressure 35 mm Hg mean, and a v wave of 50 mm Hg. The transpulmonary gradient was 31 mm Hg, cardiac output was 6 L/min, and pulmonary vascular resistance was 6 Wood units. In addition, she was evaluated with a 2-dimensional Doppler echocardiogram, which demonstrated moderate-to-severe mitral stenosis (mean transvalvular gradient of 12 mm Hg and calculated valve area of 1.2 cm2), with severe mitral regurgitation, moderate tricuspid regurgitation, a mildly dilated right ventricle with moderately depressed function, and biatrial enlargement. Left ventricular structure and systolic function were preserved. She was treated with IV diuretics (torsemide 5 mg/h), nesiritide 0.01 μg/kg/min, and inhaled nitric oxide; after 48 hours of treatment, the pulmonary systolic pressure decreased to 60 mm Hg and pulmonary vascular resistance decreased to 2 Wood units. She subsequently underwent mitral valve replacement with a 31-mm mechanical prosthesis. Her postoperative course was uneventful. She was discharged on sildenafil 20 mg 3 times a day, enalapril 5 mg daily, furosemide 40 mg daily, and warfarin sodium 5 mg daily. At a follow-up clinic visit after 6 weeks of surgery, she reported marked symptomatic improvement. A follow-up 2-dimensional Doppler echocardiogram demonstrated a normal left ventricular size and function, mildly depressed right ventricular function, and an estimated pulmonary artery systolic pressure of 55 mm Hg. She continued on medical therapy including sildenafil 20 mg 3 times a day. A follow-up right-sided heart catheterization 3 months later showed pulmonary artery systolic pressure of 40 mm Hg and a pulmonary vascular resistance of 2 Wood units. The present case illustrates a favorable effect of adjunctive oral sildenafil in a patient with pulmonary hypertension that persisted after successful mitral valve replacement. Patients with mitral valve disease develop pulmonary hypertension. In some cases, pathologic changes in the pulmonary arteriolar bed, such as intimal fibrosis and excessive thickening of the media of small muscular pulmonary arteries, could explain the development of significant pulmonary hypertension unresponsive only to surgical correction of the mitral valve.5, 6 The efficacy and safety of sildenafil in the treatment of symptomatic idiopathic pulmonary arterial hypertension has been established.4 Moreover, Alaeddini and colleagues7 demonstrated that sildenafil lowers pressures and pulmonary vascular resistance in patients with symptomatic heart failure. Singh and coworkers8 showed that sildenafil significantly improved the symptomatic status, exercise capacity, New York Heart Association class, and hemodynamic parameters of patients with severe pulmonary arterial hypertension either idiopathic or secondary to Eisenmenger syndrome and, therefore, can be safely used as primary or adjunctive treatment.8 Although mitral valve surgery improves pulmonary vascular resistance in the majority of cases, there are few patients in whom pulmonary pressures remain elevated.5, 6 Thus, the symptomatic and objective improvement in our patient suggests that sildenafil may have a role in the treatment of persistent pulmonary hypertension after mitral valve replacement.