Amyloid

Clinical overview Nuklearmedicinskt vårmöte 18/5-17 Björn Pilebro, MD

Functional Transthyretin amyloidosis Systemic amyloidoses affecting the • AL amyloidosis – Hematologic disease • Renal failure • • Familial transthyretin amyloidosis (mATTR) – Autosomal dominant disease caused by >100 mutations in the TTR gene • Heart failure • Polyneuropathy • Wild type transthyretin amyloidosis (wtATTR) – Mainly a disease of older men (age >60) • Heart failure • Carpal tunnel syndrome, spinal stenosis Classification of the Cardiomyopathies

Elliot et al European Heart Journal (2008) 29, 270–276 Hypertrophic

• Thickening of the heart muscle

• In we se a thickening of all heart tissue, including atrial walls and often valves

• Other causes of hypertrophy: – Hypertension, Aortic stenosis, Other hypertrophic cardiomyopathy Restrictive

• Diastolic dysfunction – Impaired filling of the ventricles.

• In amyloid cardiomyopathy biventricular restrictiveness.

• Other causes of diastolic dysfunction: – Hypertension, Diabetes? Other storage diseases, Cardiac Sarcoidosis Ärftlig transthyretinamyloidos -Inte bara en angelägenhet för Norrlänningen TTR V30M frequency (%) in two areas of Västerbotten: Lycksele and Skellefteå

Piteå

2.14 1.95

Olsson M, et al. Amyloid 2013. Cardiomyopathy and polyneuropathy -the swedish spectrum

Mainly neuropathy Mainly cardiomyopathy

V30M –type A fibrills Ala 45Gly V30M –type B fibrills Val 30Leu Val122Ile His88Arg Tyr60Ala Glu57Arg Glu54Leu Ala97Ser

Ala45Asp Ala45Ser Leu55Gln

Tyr 69His Gly53Glu Suhr et al. Amyloid 2017 Amyloid fibrill types in the swedish V30M-population • Early onset • Late onset – Under 50 – After 50 – Mainly polyneuropathy – Mixed phenotype – Liver-tx significantly – Cardiac involvement reduces disease progresses after liver-tx progression – Fragmented amyloid – Full length amyloid fibrills, fibrills, type A-fibrills type B-fibrills

Same mutation!! Same Families!!! ??????? Ihse et J Pathol. 2008 Oct;216(2):253-61 Gustavsson et al. Transplantation. 2012 May 27;93(10):1017-23 Wild Type ATTR amyloidosis (Senile Systemic Amyloidosis) • Not very systemic… – Cardiomyopathy, Spinal stenosis, Carpal tunnel syndrome. • Caused by wild type transthyretin (no mutation) • Mainly older men (above 60 years of age) • Cardiac involvement almost identical to hereditary ATTR-cardiomyopathy. Westermark. Scand J 1979

Why should we diagnose Amyloid cardiomyopathy? • There is treatment • Conventional heart failure treatment does not work • The patients are at high risk for potentially lethal arrythmias Why dont we diagnose Amyloid Cardiomyopathy? • Diagnosis – Rare disease – Many, more common, differential diagnosis (Hypertensive heart disease, Sarcomeric hypertrophic cardiomyopathy) • Treatment – No guidelines – No RCTs Diagnosis

HCM Amyloidosis T1 mapping + LGE

Bulluck, H., Maestrini, V., Rosmini, S., Abdel-Gadir, A., Treibel, T. A., Castelletti, S., … Moon, J. C. (2015). Myocardial T1 mapping. Circulation Journal : Official Journal of the Japanese Circulation Society, 79(3), 487–94. https://doi.org/10.1253/circj.CJ-15-0054 Man 80 år Man 76 år ATTR amyloidos HCM-diagnos QRS voltage = QRS voltage = 19 mm 50 mm

IVS = 20 mm IVS = 20 mm Diagnosis?

• proven amyloidosis – Heart not required – Non cardiac biopsy is diagnostic in 30-75 % of patients with • Left ventricular septal thickness >12 mm

Fine NM et al Am J Cardiol. 2014 May 15;113(10):1723-7