Extracardiac Biopsy Sensitivity in Transthyretin Amyloidosis Cardiomyopathy Patients With Positive ^{99 m}Tc-Labeled Pyrophosphate Scintigraphy Findings

Abstract

Background:The accurate sensitivity of amyloid deposition in extracardiac tissue (subcutaneous tissue and gastrointestinal tract) has not been evaluated in transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients. This study aimed to evaluate the sensitivity of amyloid deposition in obtained endomyocardial and extracardiac biopsies. Methods and Results:This study retrospectively evaluated 175 consecutive ATTR-CM patients (wild-type [ATTRwt]: 134, hereditary [ATTRv]: 41) who had positive findings on 99 m Tc-labeled pyrophosphate ( 99 m Tc-PYP) scintigraphy and underwent tissue biopsy of at least one organ (subcutaneous tissue, gastrointestinal tract, and endomyocardium). Amyloid deposition was observed in the subcutaneous tissue of 57/150 patients (38%), gastrointestinal tract of 80/131 patients (61%), and endomyocardium of 108/109 patients (99%). Compared to patients with ATTRv, ATTRwt had significantly lower sensitivity in subcutaneous tissue (73% vs. 25%, P<0.01) and tended to be lower in the gastrointestinal tract (74% vs. 57%, P=0.08) biopsies. Among 124 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsies, amyloid was detected in at least 1 specimen in 91 (73%) patients. The sensitivity of the combination of extracardiac biopsies was 66% and 94% in ATTRwt-CM and ATTRv-CM, respectively. Multivariate analysis reveals that ATTRv was the only significant predictor of amyloid deposition in the subcutaneous tissue.Conclusions: Subcutaneous tissue and gastrointestinal tract biopsy sensitivity are inadequate, especially in patients with ATTRwt; however, the combination of these extracardiac biopsies contributes to increased sensitivity in patients with positive 99 m Tc-PYP scintigraphy findings.

A Gluteus Medius Muscle Biopsy to Confirm Amyloid Transthyretin Deposition in Wild-type Transthyretin Cardiac Amyloidosis: A Report of Two Cases

“…In addition, no significant complications, such as intramuscular hematoma, have been reported despite >70% of patients receiving anticoagulants or antiplatelet agents. These results make this biopsy useful as an extracardiac screening biopsy in ATTRwt-CA ( 17 , 18 ).…”

“…Extracardiac biopsies, which are blindly obtained from the subcutaneous abdominal fat or the gastrointestinal tract with no imaging data suggesting the presence of ATTR deposition, are sometimes performed in patients with ATTRwt-CA. The rate of ATTR deposition is not particularly high ( 17 , 18 ). Biopsy techniques that yield sufficient sample sizes of tissue with high ATTR deposition increase the ATTR detection rates; however, biopsy-induced complications, particularly organ damage and hemorrhagic complications, must be avoided.…”

“…When ATTR deposition needs to be confirmed in patients with suspected ATTRwt-CA, we propose proceeding with biopsies in the following order: in patients with a subcutaneous abdominal fat 99m Tc-PYP uptake, particularly those showing mottled or diffuse uptake patterns, as in Case 1, a subcutaneous abdominal fat fine-needle aspiration biopsy, which is a safe and quick bedside procedure, may be selected as the first screening biopsy method ( 3 ); for patients with no 99m Tc-PYP uptake in the subcutaneous abdominal fat, as shown in Case 2, or negative subcutaneous abdominal fat fine-needle aspiration biopsy results, endomyocardial or other extracardiac biopsies should be selected by the mutual decision of patients and medical staff. Regarding extracardiac biopsies, a 99m Tc-PYP imaging-based CT-guided core needle biopsy of the skeletal trunk muscle with a radiotracer uptake can be selected as the preferred method because of its higher sensitivity for detecting ATTR deposits than other biopsy methods ( 17 , 18 ) and low incidence of complications ( 5 ). Future studies should develop an algorithm for choosing a biopsy approach to histologically confirm ATTR deposition in patients with suspected ATTRwt-CA.…”

Case Report: Transthyretin Glu54Leu—a rare mutation with predominant cardiac phenotype

“…p.Glu74Leu is a rare variant, reported in ATTRv patients from Sweden, Belgium, the UK, and Japan (15)(16)(17)(18). The only family with a thorough clinical description so far is a Swedish family.…”

Prevalence and Treatment of Arrhythmias in Patients With Transthyretin and Light-Chain Cardiac Amyloidosis

“… 5 – 7 Cardiac amyloidosis has also recently received much attention in Japan 8 , 9 due to development of new therapeutic agents, including tafamidis, patisiran, and daratumumab, 10 – 12 and advances in cardiac imaging, including nuclear cardiac scintigraphy. 13 , 14 …”