Prevalence of transthyretin amyloidosis among heart failure patients with preserved ejection fraction in Japan

Abstract

Aims Heart failure with preserved ejection fraction (HFpEF), which is caused by wide various conditions, has become a major public health problem. Transthyretin amyloid cardiomyopathy (ATTR‐CM), which is thought to be an underdiagnosed disease, can cause HFpEF. Non‐invasive diagnosis using 99mTechnetium (Tc)‐pyrophosphate (PYP) scintigraphy enables accurate diagnosis of ATTR‐CM. The aim of this study was to clarify the prevalence and characteristics of ATTR‐CM among Japanese patients with HFpEF. Methods and results This study was a multicentre, prospective, observational study conducted in Japan. We enrolled 373 patients with HFpEF [left ventricular (LV) ejection fraction ≥50%] aged ≥65 years who were admitted to the department of cardiology from September 2018 to January 2022. A 99mTc‐PYP scintigraphy scan was performed during admission in all eligible patients. Cardiac 99mTc‐PYP retention was graded according to a previously reported visual scale ranging from 0 to 3 points. The scan was considered positive when it revealed moderate‐to‐severe 99mTc‐PYP uptake (Grade 2–3) in both ventricles. Patients were divided into ATTR‐CM and non‐ATTR‐CM patients according to positive (Grade 2–3) or negative (Grade 0–1) 99mTc‐PYP scintigraphy, respectively. Medical history, blood tests, electrocardiogram, echocardiography, and magnetic resonance imaging in the two groups of patients were compared. Among the 373 patients with HFpEF, 53 patients (14.2%; 95% confidence interval: 10.7–17.7) showed positive uptake on 99mTc‐PYP scintigraphy. An endomyocardial biopsy was performed in 32 patients and confirmed amyloidosis in all cases. There were no significant differences between the two groups in age, severity of heart failure as assessed by the New York Heart Association (NYHA) functional classification, renal function values, left ventricular ejection fraction, and tricuspid regurgitant pressure gradient (ATTR‐CM, n = 53 vs. non‐ATTR‐CM, n = 320). Patients in the ATTR‐CM group had a higher N‐terminal pro‐brain natriuretic peptide level [2314 (1081–3398) vs. 900 (415–1828), P < 0.001], higher sensitive troponin T level (0.074 ± 0.049 vs. 0.035 ± 0.038, P < 0.001), and higher mean LV maximal wall thickness [12.5 (11–14) vs. 10.5 (9.5–11.5), P < 0.001]. Conclusions ATTR‐CM is an underdiagnosed disease with a significant prevalence in Japanese patients with HFpEF. This study showed that results of examinations for ATTR‐CM patients appear to be worse than those for non‐ATTR‐CM patients, but clinical severities of heart failure as assessed by the NYHA functional classification are similar in ATTR‐CM and non‐ATTR‐CM patients, and the clinical overlap between ATTR‐CM and non‐ATTR‐CM is high.

Transthyretin amyloidosis prevalence and characteristics in Korean patients with heart failure with preserved or mildly reduced ejection fractions

“…In a recently published Japanese multi-centre registry, 14.2% of patients with HFpEF who underwent bone scintigraphy regardless of LV wall thickness were diagnosed with ATTR-CM. [34] Meanwhile, in data from China, the prevalence of ATTR-CM in patients with HFpEF or HFmrEF with an LV wall thickness > 12 mm was approximately 5.3%, which was signi cantly lower than that reported among Western populations. [35] Among Asian populations, only one multinational study identi ed the common genetic variation and phenotypic characteristics of hereditary TTR amyloidosis in a Southeast Asian cohort.…”

Transthyretin cardiac amyloidosis in Saudi Arabia and the Middle East: insights, projected prevalence and practical applications

“…Moreover, ATTR-CA can mimic other forms of hypertrophic and restrictive cardiomyopathy (3). Studies published over the past decade, mainly in western countries, indicate that ATTR-CA is more common than previously believed and that it is significantly underdiagnosed (4)(5)(6)(7)(8). The emergence of novel disease-modifying therapies has led to a global effort to improve the diagnosis and management of ATTR-CA (9).…”

Molecular Research on Amyloidosis

“…Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis in patients who do not have a monoclonal gammopathy [ 13 ]. Recent studies found that by using this method, the prevalence of cardiac ATTR amyloidosis in patients with heart failure with a preserved ejection fraction is 13–18% [ 14 , 15 , 16 ].…”