Heart Transplantation in a 36-Year-Old Experiencing Terminal Heart Failure Caused by Systemic Sclerosis (2012)

A 34-year-old man was hospitalized with signs of heart failure New York Heart Association class III and arrhythmias (first-degree atrioventricular block and ventricular extrasystoles) in our clinic. Three years before, diagnosis of systemic sclerosis (scleroderma) had been established on the basis of typical skin manifestation and elevated titers of antinuclear antibodies. The patient involuntarily lost weight of 10 kg within 6 months (body mass index, 20.0 kg/m2). Under medical therapy comprising methotrexate or mycophenolate, systemic sclerosis and heart failure had deteriorated. Cardiopulmonary exercise testing showed a decreased V˙O2peak of 12.8 mL/min per kg and rising levels of brain natriuretic peptide/pro–brain natriuretic peptide. Transthoracic echocardiography demonstrated a globally reduced ejection fraction, massively dilated right ventricle (RV) and right atrium (RA), and signs of restrictive filling and hypertrophy (12- to 13-mm wall diameter). Doppler measurement revealed only an oscillating flow (Fig. 1A) over the tricuspid valve as a sign of severe tricuspid insufficiency and reduced myocardial contractility. Myocardial biopsy was performed, which revealed global inflammation and fibrosis (1). After exclusion of coronary heart disease by coronary angiography, magnetic resonance imaging showed hypokinesia of RV anterior wall and dilated RV and RA. In addition, RV function was decreased to an ejection fraction of 32%, and contrast enhancement in the RV matched the diagnosis of endocardial fibrosis (Fig. 1B). Left ventricular ejection fraction was moderately reduced (ejection fraction, 42%).FIGURE 1: A, Ultrasonographic image of the tricuspid valve without coaptation (right) and flow profile with pulse-wave Doppler over the tricuspid valve (left). B, Magnetic resonance image of gadolinium enhancement demonstrates endocardial fibrosis (right atrium [RA], right ventricle [RV], left atrium [LA], and left ventricle [LV]). C, Biventricular massive subendocardial fibrosis (left half) depicted in an Elastica von Gieson stain (collagen fibers [red]; cardiac muscle [yellow/brown]; Elastica von Gieson; magnification ×100).Despite optimal medical treatment, symptoms of heart failure increased more rapidly. Thus, we prepared the patient for listing for heart transplantation. We ruled out the manifestation of scleroderma in other organ systems by computed tomographic scan of the lung and abdomen, gastroscopy including biopsy, colonoscopy with biopsy, and esophageal scintigraphy. Finally, the catheterization of the right side of the heart showed a cardiac index of 2.1 L/min per m2 with increased pressure especially in the RA (RV, 23/9/11 mm Hg; RA, 23/14/18 mm Hg; pulmonary artery pressure, 23/13/16 mm Hg; pulmonary capillary wedge pressure, 13/17/12 mm Hg) but no pulmonary hypertension. Because of the rapid progress of right-sided heart failure and increasing nonsustained ventricular tachyarrhythmia, the patient fulfilled high-urgency criteria for heart transplantation. After intensified medical therapy including intravenous application of catecholamines and diuretics, he could be stabilized until successful heart transplantation. Pathology of the explanted heart confirmed biventricular massive subendocardial fibrosis and minor lipomatosis in line with the underlying diagnosis of systemic sclerosis (Fig. 1C). The patient recovered quickly and without complications from transplantation. Two weeks after the surgery, he was dismissed to the follow-up treatment. One year after transplantation, he could live his life without any signs of heart failure. He was able to walk 4 to 5 km without dyspnea and walk up three to four floors. He gained 10 kg of weight and showed no gastrointestinal problems. Currently, the progress of skin manifestation seems to be well controlled. Systemic sclerosis is a connective tissue disease that affects primarily the skin, leading to hardened and thickened lesions. Other organ manifestations include the gastrointestinal tract (hypomotility of the esophagus and incompetent lower esophageal sphincter in approximately 90%), pulmonary fibrosis (more than 70%), or renal damage in more than 60%. Autopsies demonstrated that up to 70% of patients experiencing systemic sclerosis showed cardiac involvement (2). The typical histologic finding is cardiac fibrosis that mainly may be caused by primary abnormal collagen deposition or a secondary consequence of pulmonary hypertension. Symptoms range from consecutive heart failure (e.g., pulmonary hypertension, edema) to arrhythmias such as ventricular tachycardia or progressive atrioventricular block (3), leading to a 2-year survival rate of less than 40% (4). Treatment options comprise application of cortisone, immunosuppression by azathioprine or cyclophospamide, and surgical therapy. Mortality rate of patients experiencing scleroderma is more than fivefold elevated, resulting in a 5-year mortality of more than 10%. Main causes of death are pulmonary complications. Whereas lung transplantation has been reported in several cases after systemic sclerosis (5), heart transplantation in an adult patient has not yet been described in the literature to the best of our knowledge (3, 6, 7). This may be because of frequent affection of other organs, which finally does not make heart transplantation a promising venture. In contrast, heart transplantation has been described in other diseases leading to cardiac fibrosis such as amyloidosis or sarcoidosis (8, 9). To sum up, we report a case of cardiac manifestation of systemic sclerosis. Because signs of right-sided heart failure and ventricular arrhythmias were the leading signs and symptoms, in this patient, heart transplantation helped to treat this otherwise lethal manifestation of the systemic disease. There is substantiated hope that immunosuppressive treatment required after heart transplantation will help to control symptoms of scleroderma in this patient. Eimo Martens 1 Philipp Lange1 Tilmann Pohl2 Thomas Nickel1 Gerd Juchem3 Ingo Kaczmarek3,4 Daniel Theisen5 Karl Sotlar6 Gerhard Steinbeck1 Stefan Kääb1,7 Hans D. Theiss1