The physical examination showed a patient in reduced overall condition with low arterial blood pressure (90/60 mm Hg), elevated jugular venous pulse, peripheral oedema, a diffuse pain in the abdomen during palpation, especially in the right epigastrium, and a systolic murmur with punctum maximum over the mitral valve area. Blood sample analysis displayed an elevated glutamic oxaloacetic transaminase (GOT) of 33 U/l, a γ-glutamyl transferase (GGT) of 194 U/l, and an alkaline phosphatase (ALP) of 227 U/l. Bilirubin was 1.12 mg/dl and lactate dehydrogenase (LDH) 299 U/l. Creatinine was also slightly elevated, at 1.3 mg/dl. In the serum electrophoresis beta2-globulins were increased to 15.3% (normal range 7.8–13.1%).
The electrocardiogram (ECG) showed sinus rhythm with a heart rate of 69 beats/min, and a low voltage of QRS complexes in all strains (). Except for supraventricular extrasystoles, no episodes of arrhythmia were detected during telemetric observation. Echocardiography revealed left and right concentric ventricular hypertrophy with speckling of the myocardium (), normal end-diastolic (40 mm) and end-systolic (32 mm) left ventricular diameters, impaired left and right ventricular systolic function with a left ventricular ejection fraction (LVEF) of 47%, dilation of the left and right atrium, and mild mitral and tricuspid regurgitation. E/A ratio was inversed, indicating restrictive filling of the left ventricle.
Figure 1 (a) Echocardiographic images showing the concentric hypertrophy of the left and right ventricle and the typical speckling of myocardium in patients with amyloidosis (*). The ECG showed low voltage of QRS complexes in contrast to the cardiac hypertrophy (more ...)
Ultrasound examination of the abdomen showed an enlarged liver with dilated liver veins and ascites. Due to the abdominal pain an endoscopic inspection of the upper and lower gastrointestinal tract was performed, which revealed antrum gastritis and unspecific diffuse inflammation of the colon mucosa. Cardiac catheterisation was performed, including coronary angiography and assessment of haemodynamics, and several myocardial biopsies were taken: cardiac output was 2.9 l/min and cardiac index 1.7 l/min/m2
. The left ventricular pressure curve demonstrated a restrictive filling pattern. Coronary artery disease could be excluded. The myocardial biopsies revealed the presence of amyloid by Congo red staining (). Further immunohistochemical analysis showed ATTR-amyloidosis, using validated antibodies against the major amyloid classes such as AA, ALλ, ALκ, Aβ2
M, ATTR, AFibAα and AApoAI (antibodies form www.amYmed.de
) as shown in . DNA sequencing revealed a point mutation in exon 2, codon 23, of the transthyretin gene leading to a single amino acid substitution of serine by asparagine (). Whole body scintigraphy using TC99m-DPD5
showed the typical image of end stage hereditary amyloidosis caused by ATTR () with predominant tracer retention in the myocardium. A weak retention of TC99m-DPD was observed in bones, bowel, lungs and skin, while liver and stomach showed almost no tracer uptake. The absence of the tracer in the liver, which produces TTR, demonstrates that the tracer does not bind to native TTR but to the TTR derived amyloid.
Figure 2 Diagnosis of amyloid on formalin fixed tissue sections.7 Weak counterstaining with acid hemalum. a–c: Diagnosis of amyloid in an endomyocardial biopsy. (a) Amyloid is weakly stained with Congo red and appears light pinkish red as shown in bright (more ...)