His108Arg Transthyretin Amyloidosis-Shedding Light on a Distinctively Malignant Variant

Area of Science:

• Cardiology
• Genetics
• Rare Diseases

Background:

• Variant transthyretin amyloidosis cardiomyopathy (ATTRv-CM) is a rare cardiac condition with diverse genetic mutations.
• The His108Arg transthyretin gene mutation is the most common variant in Austria, yet its clinical profile remains understudied.

Purpose of the Study:

• To characterize the clinical phenotype, cardiac involvement, and outcomes of patients with the His108Arg variant.
• To investigate disease progression, treatment response, and imaging findings in this specific ATTRv-CM population.

Main Methods:

• Prospective enrollment from a cardiac amyloidosis registry.
• Comprehensive baseline assessments including echocardiography, cardiac MRI, biomarkers, and clinical evaluation.
• Longitudinal follow-up recording arrhythmias, heart failure hospitalizations, and response to therapies.

Main Results:

• Twenty His108Arg variant carriers identified; 12 with cardiac involvement, 8 asymptomatic.
• Median age at diagnosis 62.3 years; heterogeneous presentations observed.
• High rates of arrhythmias, reduced ejection fraction, elevated biomarkers, and varied responses to therapy.

Conclusions:

• This study provides a comprehensive analysis of the His108Arg variant in ATTR-CM.
• The His108Arg variant exhibits significant clinical heterogeneity and impacts cardiac function and outcomes.
• Findings underscore the need for individualized management and close monitoring in affected patients.