Cardiac sympathetic denervation in wild-type transthyretin amyloidosis

Abstract

Background Tissue accumulation of misfolded transthyretin (TTR) may occur because of TTR gene mutations (variant amyloid TTR amyloidosis, ATTRv), or as an age-related phenomenon (wild-type ATTR, ATTRwt). Cardiac sympathetic denervation has been reported in ATTRv, but has never been investigated in ATTRwt. Methods Fifteen consecutive patients with ATTRwt cardiomyopathy (81% men, median age 82 years, no one with prior myocardial infarction) underwent Cadmium Zinc Telluride tomographic imaging for amyloid burden (99mTc-hydroxymethylene diphosphonate – 99mTc-HMDP), innervation (123I-metaiodobenzylguanidine – 123I-MIBG), and perfusion (99mTc-tetrofosmin). Results Median summed 99mTc-HMDP score was 60 (58–62), denoting a severe and diffuse amyloid burden. Planar 123I-MIBG examination showed decreased early and late H/M ratios (late H/M ratio: 1.5 [1.3–1.6], range 1.2–1.9, reference value ≥2.0). Summed 123I-MIBG score was 12 (6–22), with the most prominent denervation in the infero-septal, inferior, and infero-lateral regions; summed rest score was 7 (5–11), with lowest degrees of myocardial perfusion in the inferior and infero-septal regions. The correlation between amyloid burden (as relative 99mTc-HMDP uptake) and innervation (as relative 123I-MIBG uptake) did not achieve statistical significance at both segmental (p = .252) and regional level (p = .251). Nevertheless, denervation tended to worsen in parallel with the amyloid burden, and 123I-MIBG scores increased with 99mTc-HMDP scores. Segments and regions with prominent hypoperfusion also showed a higher degree of denervation (r = 0.500 and 0.591, respectively; both p < .001). Conclusions Patients with ATTRwt cardiomyopathy display cardiac sympathetic denervation, particularly in the inferior and septal myocardial wall. Myocardial hypoperfusion has a similar regional pattern, while the amyloid burden is more extensive.