Unmasking hereditary transthyretin amyloidosis in Mexico: lessons from active field screening in a high-prevalence region. First interim analysis
E Chuquiure-Valenzuela, C M Eroza-Osorio, G Martinez-Gonzalez, A Mendoza-Cortez, K Bautista-Hernandez, F Bejarano-Vergara, R Garduno-Correa, F Gonzalez-Mayo, E Silva-Mauricio, M Chuquiure-Gil, R Lozano-Corral, V Flores-Gutierrez, A Perez-Falcon, M Tapia-SansoresAbstract
Background
Cardiac amyloidosis is an underdiagnosed cause of heart failure and restrictive cardiomyopathy, particularly in hereditary transthyretin (hATTR) forms. Early identification of at-risk individuals, especially asymptomatic relatives in high-prevalence regions, remains a significant clinical challenge. Comprehensive characterization of subclinical manifestations supported by genetic screening is essential to optimize early detection strategies.
Purpose
To identify and characterize the epidemiological, clinical, electrocardiographic, and genetic profiles of individuals at high risk for hereditary amyloidosis within a defined geographic population.
Methods
We conducted a prospective, observational, exploratory study using active field screening in a region of Mexico with a high reported burden of amyloidosis. We evaluated high-risk adults and first- and second-degree relatives without overt clinical manifestations. Assessment included medical history, physical examination, baseline laboratories, ECG, echocardiography, EQ-5D quality of life survey, mNIS+7 score, pedigree analysis, and targeted genetic testing for cardiomyopathy-associated genes. We present the first interim analysis of this cohort.
Results
The interim analysis included 33 individuals. Nine participants (27.3%) carried genetic variants associated with hATTR, while 24 (72.7%) were non-carriers. The mean overall age was 52.5 years (range 21–79). Among carriers, the mean age was 50.5 ± 17.7 years for men and 37.6 ± 6.8 years for women; 66% were male. Regarding clinical findings in carriers: 44% exhibited peripheral neuropathy, 22% renal involvement, 22% hepatic damage, and 55% gastrointestinal symptoms. One patient presented with severe neurological deterioration and cardiogenic shock, while another remained entirely asymptomatic. Cardiovascular manifestations included dyspnea (n=5), paroxysmal nocturnal dyspnea (n=1), and NYHA Functional Class II–IV (n=4). Physical signs included lower limb edema (n=2), ascites (n=2), and anasarca (n=1). The predominant TTR genetic variant identified was p.Val142Ile.
Conclusions
In this interim analysis, approximately one-quarter of individuals in a high-risk population carried hATTR-associated variants, underscoring the necessity of systematic genetic evaluation for relatives in endemic regions. We identified subclinical cardiovascular and systemic involvement in supposedly "asymptomatic" individuals. These findings highlight the importance of active screening and close monitoring with biomarkers and imaging to identify the "tipping point" toward restrictive cardiomyopathy, enabling timely therapeutic intervention before advanced heart failure develops.