Clinical characteristics and natural history of wild-type transthyretin amyloid cardiomyopathy in Japan

Abstract

Aims: The focus on wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is increasing because of novel treatment options. There is currently no report on a large number of Japanese patients with ATTRwt-CM. The study aimed to examine the characteristics and prognosis of ATTRwt-CM in Japan.

Methods and results: Consecutive patients (78.5 ± 6.4 years old at diagnosis) with ATTRwt-CM diagnosed at Kumamoto University Hospital between December 2002 and December 2019 were retrospectively reviewed. Data, including demographic characteristics, co-morbidities, clinical manifestations at diagnosis, laboratory results, electrocardiographic and echocardiographic data, imaging and pathological findings, and treatment were obtained. Of 129 patients included in this study, 110 patients (85%) were male. The median period from initial symptom onset to diagnosis was 15.5 (2-75) months. Heart failure was the most common clinical manifestation leading to diagnosis (61%) and initial manifestations (49%). Of 106 patients, carpal tunnel syndrome was observed in 57 patients (54%), and the median period from initial symptom onset to diagnosis was 96 (48-120) months. Histopathological confirmation of transthyretin amyloid was achieved in 94 patients (73%), including 66 (51%) and 28 cases (22%) with endomyocardial and extracardiac biopsies. During the observation period (median 15.0 [inter-quartile range, 5.4-33.2] months after diagnosis), 34 patients (26%) died. Of these, 27 patients (79%) had cardiovascular deaths (heart failure, 25; sudden death, two). The median survival duration was 58.9 months and the 5 years' survival rate was 48%. According to a multivariate Cox hazard analysis, age [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.23, P = 0.002] and low serum sodium levels (HR, 0.89; 95% CI, 0.79-0.996; P = 0.04) contributed to all-cause mortality, and low serum sodium levels contributed to hospitalization for heart failure (HR, 0.86; 95% CI, 0.77-0.96; P = 0.005).

Conclusions: Clinical characteristics and prognosis of ATTRwt-CM patients in Japan were examined. Carpal tunnel syndrome can be considered an indication for diagnosis of ATTRwt-CM. Age and low serum sodium level were significant predictive factors of all survival outcomes. The clinical features of ATTRwt-CM should be recognized to provide appropriate treatment.

Keywords: Cardiac amyloidosis; Cardiomyopathy; Heart failure; Prognosis; Transthyretin.

FIGURE 1

Fraction of manifestations leading to the diagnosis of wild‐type transthyretin amyloid (ATTR) cardiomyopathy.

FIGURE 2

Annual number of wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM) diagnosis and method of diagnosis. The pie chart illustrates fraction of method of diagnosis. Group 1, presence of transthyretin (TTR) deposition in the myocardium; Group 2, presence of TTR deposition in extracardiac tissue with positive finding of ^99mTc‐labelled pyrophosphate scintigraphy; Group 3, positive finding of ^99mTc‐labelled pyrophosphate scintigraphy without confirmation of pathological TTR deposition.

FIGURE 3

Fraction of initial manifestation related to transthyretin amyloid (ATTR) before diagnosis.

FIGURE 4

(A) Kaplan–Meier curve of all‐cause survival; table showing number at risk and survival rate by year. Median survival period was 58.9 months. (B) Kaplan–Meier curve of readmission for heart failure; table showing number at risk and event‐free ratio by year. Median event‐free period was 43.7 months.

FIGURE 5

Kaplan–Meier curve representing association between ages and all survival rate. Patients were classified into three groups based on age at diagnosis (low group, age < 70 years; mid group, age 75–80 years; high group, age > 80 years).