Three cases have been described of the spontaneous reversal of cardiac transthyretin amyloidosis (ATTR-CM), a form of hereditary transthyretin-mediated (hATTR) amyloidosis, due to the presence of antibodies to human ATTR amyloid.

The case reports, published in The New England Journal of Medicine, noted that no such antibodies were found in 350 additional patients with ATTR-CM.

“Here, we report clinical, exploratory, and potentially mechanistic findings in three male patients who were 68, 82, and 76 years of age and who had ATTR-CM-associated heart failure that resolved spontaneously, with reversion to near-normal cardiac structure and function,” the authors wrote. “We investigated the possibility that the three patients had had an antiamyloid immune response, and we identified high-titer circulating polyclonal IgG antibodies to human ATTR amyloid in each of the patients.”

The researchers used technetium-99m-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy and magnetic resonance imaging (MRI) to evaluate the patients. They all had the characteristic hypertrophic phenotype, and scintigraphy revealed Perugini grade 2 uptake.

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None of the patients had received any treatment or recent vaccinations, and none had experienced any infection or myocarditis. At follow-up, they reported symptom resolution, and their recovery was confirmed by improvement in or normalization of echocardiography findings, cardiopulmonary exercise tests, and serum biomarker levels.

Serial MRI scans showed near-complete resolution of myocardial extracellular volume and cardiac remodeling to a near normal function and structure.

The 3 patients all presented polyclonal IgG antibodies to human ATTR amyloid, which bound to ATTR amyloid deposits in mice, humans, and to synthetic ATTR amyloid. The authors searched the case records of 1663 patients with ATTR-CM at a single center in London, finding no other patients with a spontaneous recovery nor any other patient with these antibodies.

Although the cause and significance of the anti-ATTR antibodies remains to be determined, the authors expect that their presence signals the potential for reversibility of ATTR-CM in patients in the future.


Fontana M, Gilbertson J, Verona G. Antibody-associated reversal of ATTR amyloidosis–related cardiomyopathy. N Engl J Med. Published online June 8, 2023. doi:10.1056/NEJMc2304584