Exploration of electrocardiographic and echocardiographic findings to screen transthyretin amyloid cardiomyopathy in patients with mild left ventricular hypertrophy
Authors: Saito M , Nakao Y , Inoue K , Higaki R , Yokomoto Y , Ogimoto A , Suzuki M , Kawakami H , Hiasa G , Okayama H , Ikeda S , Yamaguchi O 
Published: October 2021

Abstract

Background
The transthyretin amyloid cardiomyopathy (ATTR-CM), a common condition in the elderly, is a life-threatening disease; however, it is treatable. The early accurate diagnosis is, therefore, an important key to improve the patient's outcomes. Electrocardiography and echocardiography are instant diagnostic tools with red flags for the screening of the ATTR-CM. In fact, ATTR-CM often mimics left ventricular hypertrophy (LVH), and the differential diagnosis is difficult to establish. Thus, the characteristics of cardiac amyloidosis may be obscured in ATTR-CM patients with mild LVH, possibly making the disease difficult to diagnose. Therefore, in this study, the effect of LVH on the occurrence of electrocardiographic and echocardiographic parameters for ATTR-CM was investigated, and their incremental value over the age for the screening of ATTR-CM in the patients with mild LVH was recorded.

Methods
This study retrospectively studied 319 consecutive nonischemic LVH patients with a sinus rhythm who underwent detailed diagnostic tests. The light chain-associated amyloidosis was an exclusion criterion. The mean left ventricular wall thickness (MWT) &lt;12 mm was defined as mild LVH, while MWT ≥12 mm was defined as moderate to severe LVH. The ATTR-CM was diagnosed with biopsy or 99 mTc-PYP scintigraphy. The elderly were defined as people aged ≥65 years in males and ≥70 years in females, according to the literature. Each electrocardiographic and echocardiographic parameter was binarized with an external cut-off point to increase the external validity, being the incremental benefit of each parameter over age for identifying ATTR-CM assessed using a receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC).

Results
Fourteen patients (8%) among the 170 patients with mild LVH had ATTR-CM, while 27 patients (18%) among the 149 patients with moderate to severe LVH had ATTR-CM. The patients with mild LVH had fewer electrocardiographic and echocardiographic parameters, showing a significant difference between ATTR-CM and non-ATTR-CM patients than those with moderate to severe LVH (Table 1). Among several binarized parameters, the voltage-to-mass ratio, E/A ratio, the global longitudinal strain, and also the relative apical sparing pattern demonstrated additive value for identifying the ATTR-CM over aging (Table 2). In addition, the discriminative ability of the propensity score calculated from these four variables and age was considered excellent for the screening of ATTR-CM (AUC = 0.98).

Conclusion
The patients with mild LVH appear to have fewer electrocardiographic and echocardiographic specific findings of the ATTR-CM compared to patients with moderate to severe LVH. However, several red flags may be useful for screening ATTR-CM even in patients with a mild LVH.

Funding Acknowledgement
Type of funding sources: None. Table 1Table 2