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

Abstract

The diagnosis and awareness of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in heart failure with left ventricular ejection fraction (LVEF) > 40% remains under-recognized. This study aimed to investigate the prevalence and characteristics of ATTR-CM in patients with heart failure with LVEF > 40%. Patients with LVEF > 40% and maximal left ventricular wall thickness (MWT) > 10 mm who underwent bone scintigraphy were retrospectively investigated. Patients with a definite cause of heart failure were excluded. ATTR-CM was diagnosed when grade 2 or 3 myocardial uptake was observed on scintigraphy. Among 97 patients (male, 62.5%; median age, 69 years), 13 (13.4%) were diagnosed with ATTR-CM (wild type, 69.2%; hereditary type, 30.8%). Age or biomarker levels did not differ significantly; however, all patients with ATTR-CM were male. The ATTR-CM group had a significantly higher prevalence of polyneuropathy or carpal tunnel syndrome than the non-ATTR-CM group, accompanied by a longer PR interval, thicker MWT, larger left atrial volume index, and higher E/e'. Accordingly, ATTR was present in a substantial number, particularly among men. Clinicians should suspect ATTR when a male patient exhibits neurologic symptoms, diastolic dysfunction, and a long PR interval.

Fig. 1

Flow chart of the study population. CMP cardiomyopathy, DCMP dilated cardiomyopathy, HCMP hypertrophic cardiomyopathy, HF heart failure, LVEF left ventricular ejection fraction, MELAS Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, MM multiple myeloma, MWT maximal LV wall thickness, POEMS polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes, TTE transthoracic echocardiography.

Fig. 2

The representative case of ATTR-CM patient. A 67-year-old male patient was diagnosed with ATTR-CM. (A) PR interval was prolonged to 280 ms on electrocardiography. (B) Grade 3 uptake in the left ventricular myocardium was showed in bone scintigraphy. (C) Transthoracic echocardiography showed advanced diastolic dysfunction with left and right ventricular myocardial wall thickening.

Fig. 3

The distribution of MWT, LVMI, PR interval, and E/e′ in ATTR-CM and non-ATTR-CM. In analysis for PR interval, values from 9 patients in the ATTR-CM group and 64 patients in the non-ATTR-CM group were used in the analysis, excluding patients with no values; in analysis for MWT, LVMI, E/e′, values from all patients were used in the analysis. MWT maximal wall thickness, LVMI left ventricular mass index.