Cardiac Amyloid Load Regression Seen on CMR in Patient with Hereditary Transthyretin Amyloidosis

A middle-aged woman with a 15-year history of hereditary transthyretin amyloidosis (hATTR) had a reduction in cardiac amyloid load, as assessed on cardiac magnetic resonance (CMR) imaging, according to a case report published in a letter to the editors of Clinical Research in Cardiology.

A 58-year old woman presented for cardiac follow-up at an outpatient cardiomyopathy clinic. The patient received genetic confirmation of her hATTR diagnosis (ie, presence of a rare mutation, Gly47Ala, in the TTR gene) at age 43 years. There are limited data on the natural history and disease course of cardiac amyloidosis in patients with this mutation. This was the first case report of an apparent regression of cardiac amyloid load in a patient with hATTR cardiomyopathy.

In June 2019, the patient was seen for follow-up of recurrent paroxysmal atrial fibrillation. She had a history of arterial hypertension and chronic kidney disease and was diagnosed with slowly progressive polyneuropathy 8 years before. The patient had been treated for her polyneuropathy with tafamidis for 5 cumulative years (surrounding an interruption with a trial of inotersen). After an initial failure, a second liver transplantation was successful in early 2018. At presentation, the patient was receiving a posttransplant immunosuppressive regimen and received bisoprolol 2.5 mg twice daily, torsemide 10 mg daily, and edoxaban 30 mg once daily.

Transthoracic echocardiography (TTE) performed in 2013 and 2014 (while receiving tafamidis) showed concentric left ventricular (LV) hypertrophy with a maximum septal wall thickness of 15 mm and diastolic dysfunction. These TTE findings were confirmed with CMR in 2014. A nonischemic pattern of widespread circumferential late gadolinium enhancement across both ventricles and within both atrial walls was also visible on CMR. Although LV hypertrophy was noted with a 15-mm maximal thickness, there was no LV dilation, and systolic function was normal, with an LV ejection fraction (EF) of 63%.

The clinical examination was mostly unremarkable, with no signs of pulmonary or systemic congestion. Laboratory results indicated increased natriuretic peptide (1.849 pg/mL) and slightly elevated high-sensitivity troponin T (80 ng/L), as well as stable elevated creatinine (1.3 mg/dL). Repeat TTE was similar to earlier findings, with unchanged concentric LV hypertrophy and preserved LV systolic function, with an LV-EF of 55%.

At a follow-up CMR conducted in 2019, LV septal hypertrophy was still visible, with a maximum thickness of 14 mm, mild right ventricular (RV) hypertrophy (5 mm maximum thickness) was detected, and systolic function was preserved in both ventricles (LV-EF, 63%; RV-EF, 62%). There was a mild reduction in absolute (151-110 g) and indexed (78-63 g/m²) LV mass, and a constant LV end-diastolic volume (55-63 ml/m²) on the CMR conducted in 2019 vs 2014. A great reduction in the extent of late gadolinium enhancement was detected in the LV lateral wall, the atrial walls, and the septal subendocardium.

“These CMR-based findings suggested an unexpected and quite impressive improvement regarding the extent of cardiac amyloid deposits,” noted the authors. “It is difficult to differentiate to which extent this [regression] is due to one of the anti-amyloid therapies that were implemented in this case. Obviously, the mild cardiac clinical course as well as the noted cardiac phenotype ‘regression’ are unlikely to be only a reflection of the natural history of the disease.”

Reference

Florian A, Bietenbeck M, Chatzantonis G, Hüsing-Kabar A, Schmidt H, Yilmaz A. Regression of cardiac amyloid load documented by cardiovascular magnetic resonance in a patient with hereditary amyloidosis [published online February 11, 2020]. Clin Res Cardiol. doi:10.1007/s00392-020-01611-2