Characterization of untyped cardiac amyloidosis by mass spectrometry in a patient with Gly6Ser transthyretin polymorphism in fatal cardiogenic shock




A 55-year-old Portuguese man with no significant family history was treated for 10 years for progressive hypertrophic restrictive cardiomyopathy. A cardiac magnetic resonance imaging scan performed 3 months before his referral showed left ventricular (LV) hypertrophy without infiltrative cardiopathy. The patient was referred to our hospital for cardiogenic shock. Echocardiography showed LV hypertrophy ( Fig. 1 A ) with restrictive pattern of transmitral flow ( Fig. 1 B), an LV ejection fraction of 45% and altered LV global strain (–7.2%, Fig. 1 C). Despite optimized cardiological treatment, the patient deteriorated. To gain diagnostic insights and to help with a decision regarding ventricular assist device treatment, a cardiac biopsy was performed, showing amyloid deposition with strong transthyretin (TTR) immunostaining ( Fig. 2 A ) and negative kappa and lambda light chain immunostaining. Neurological examination was normal except for bilateral carpal tunnel syndrome. Extensive diagnostic workup – including repeated immunofixation of serum and urine, serum-free light chain and total body computed tomography scan – remained negative, except for the finding of a heterozygous Gly6Ser variant in the TTR gene, previously known as a neutral polymorphism. To elucidate the precursor protein of this documented cardiac amyloidosis (i.e. Gly6Ser TTR versus AL protein), a mass spectrometry analysis was performed on an LV fragment of the biopsy ( Fig. 2 B). Results confirmed that light chain was the major component of the amyloid deposit ( Fig. 2 C). Unfortunately, the patient died shortly afterwards, despite biventricular assist device implantation.


Jul 12, 2017 | Posted by in CARDIOLOGY | Comments Off on Characterization of untyped cardiac amyloidosis by mass spectrometry in a patient with Gly6Ser transthyretin polymorphism in fatal cardiogenic shock

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