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A 52 year old male with recurrent abdominal pain

The clinical case of the Month: June 2009

Myocardial Disease

Case Presentation:

A 52 year old male with a previous history of hypertension and hypercholesterolaemia, presented to the emergency department of his local hospital with abdominal pain. He had undergone right and left carpal tunnel surgery five and three years previously. He had no family history of cardiac disease or sudden cardiac death. His mother had died from tuberculosis in her fifties and his father was 72 and asymptomatic. He had attended hospital several times during the previous 6 months always complaining of abdominal pain associated with nausea and sweating after meals. He was diagnosed with uncomplicated biliary colic but declined immediate surgical intervention.
Six months later, he represented after a collapse. His electrocardiogram demonstrated complete atrio-ventricular block. An urgent echocardiogram revealed “mild hypertrophy with normal ejection fraction”. A pacemaker was implanted and the patient was discharged on enalapril and simvastatin. Four months after pacemaker insertion he presented with shortness of breath and was still complaining of abdominal pain, asthenia and abdominal distension.

On physical examination his blood pressure was 95/65 mmHg and the jugular vein pressure was slightly raised with hepatic congestion and mild bilateral ankle oedema. The ECG and chest x-ray are presented in Figure 1. The patient was admitted for further investigations. An echocardiogram showed concentric left ventricular hypertrophy (15 mm), granular “sparkling” myocardium, mildly depressed left ventricular ejection fraction (50%) and biatrial enlargement (figure 2).

Figure 1a + b. ECG and Chest X-Ray Figure 1a + b. ECG and Chest X-Ray

What is your diagnosis?

Which further investigations would you perform?

Diagnosis, case resolution and treatment

There were several clues that should have prompted consideration of the diagnosis of cardiac amyloidosis. Specifically: the history of bilateral carpal tunnel surgery; abdominal pain; mild cardiac hypertrophy; and AV block. The echocardiographic findings described in the second echocardiogram performed are typical of cardiac amyloidosis.
An endomyocardial biopsy was performed to confirm the clinical suspicion. This demonstrated amorphous acelluar material that separated myocytes (Figure 1) and displayed apple-green birefringence under polarized light after Congo Red stainning.

Figure 1

Figure 1. Cardiac biopsy showing amorphous material (amyloid) between myocytes

Although serum/urine electrophorexis and immunofixation were normal and bone marrow biopsy did not show any dyscrasia, the patient was considered to have primary amyloidosis. He was discharged and followed at the outpatient clinic.

Two years later and after several admissions due to heart failure, the patient was transferred to our institution to consider heart transplantation. At our centre his echocardiogram now showed severely depressed left ventricular function (20%), his 6 minutes walking test was 310 metres, NT-proBNP was 4212 pg/ml and right catheterisation parameters showed a low cardiac index with pulmonary artery systolic hypertension. Renal function was normal and there was no major involvement of other organs/systems by the disease.
In order to determine the type of amyloidosis, another endomyocardial biopsy was performed. Immunohistochemistry was positive for TTR amyloid and genetic analysis of the TTR gene was performed. A mutation leading to the substitution of Glutamic acid by Lysine in position 89 was found. This mutation has been previously described in a Japanese family which had amyloidotic polyneuropathy.

 TTR familial amyloidosis is an autosomal dominant disorder with high penetrance due to the production of amyloid from a mutant transthyretin (TTR) protein. The onset occurs most commonly after the age of 40 and depending on the type of mutation, peripheral neuropathy or cardiomyopathy may predominate. Some patients may have autonomic neuropathy with diffuse visceral pains. Renal involvement is usually uncommon. This entity is endemic in some regions of Portugal, Sweden and Japan reaching a prevalence of 1:600. More than 100 different mutations have been described so far with the Val122Ile mutation being found in approximately 4% of the black population in the United States. As transthyretin is almost exclusively produced by the liver, liver transplantation removes the source of amylogenic protein. When advanced cardiac amyloidosis is present combined heart and liver transplantation is the only alternative for these patients.

After an electroneurographic study, which showed mild to moderate polyneuropathy, the patient was considered suitable for heart and subsequent liver transplantation.
Heart transplantation was successfully performed (Figure 2) and during the following year he returned to NYHA functional class I. Endomyocardial biopsies performed to monitor cardiac rejection did not show TTR deposits. One year after heart transplant, liver transplantation was performed and the patient’s liver was used for an alternative recipient (domino transplant). Unfortunately, the patient developed hepatic artery thrombosis and had to be retransplanted urgently 1 month later. Almost 4 years after his heart transplant, the patient is well.

Figure 2. Explanted Heart

Figure 2. Explanted Heart


Cardiac amyloidosis is a difficult diagnosis which should be always suspected in patients with suggestive extracardiac signs and symptoms. It is crucial to determine the type of amyloid to offer correct treatment. Treatment of cardiac amyloidosis is very complex and collaboration between physicians of different specialities is essential to achieve good results.


1. Nakamura M, Hamidi Asl K, Benson MD. A novel variant of transthyretin (Glu89Lys) associated with familial amyloidotic polyneuropathy. Amyloid 2000;7:46-50.
2. Selvanayagam JB, Hawkins PN, Paul B, Myerson SG, Neubauer S. Evaluation and management of the cardiac amyloidosis. J Am Coll Cardiol. 2007;50:2101-10.
3. Gomez-Bueno M, Segovia J., Garcia-Pavia P, Barcelo JM, Krisnk I, Sanchez-Turrion V, et al. Cardiac amyloidosis: the importance of multidisciplinary management. Rev Esp Cardiol 2009;62:698-702.

Notes to editor

Presented by Dr. Pablo Garcia-Pavia and Dr. P. M. Elliott, Cardiomyopathy Unit, Heart Transplant Program, Puerta de Hierro University Hospital, Madrid, Spain and Inherited Cardiovascular Disease Unit, Department of Cardiology, The Heart Hospital, University College of London, London, UK.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.