Shifting paradigms in amyloidosis: transition to non-invasive diagnostics and cardiovascular characterization. A 17-year real-world experience

Background

Systemic amyloidosis is a complex infiltrative disorder characterized by the extracellular deposition of misfolded protein fibrils, leading to progressive organ dysfunction. Cardiac amyloidosis (CA) has emerged as a frequent, though historically underdiagnosed, driver of heart failure.

Objective

The study aims to evaluate demographic trends, the multisystemic comorbidity burden, and the evolution of diagnostic pathways, emphasizing the cardiovascular manifestations and functional impairment of this population.

Methods

We conducted a retrospective, longitudinal cohort study including confirmed diagnosis of amyloidosis managed between January 2008 and December 2025. Data extraction focused on clinical phenotyping, extracardiac involvement (renal, gastrointestinal, neurological, and hepatic). Diagnostic modalities were categorized to track the transition from invasive histopathology to non-invasive multimodality imaging and genetic analyses

Results

A total of 89 patients were analyzed 56.3% male; 43.7% female, with a mean BMI of 25.8 kg/m². The cohort exhibited a remarkably high burden of comorbidities, highlighting the systemic nature of the disease. Renal insufficiency was the most prevalent comorbidity at 53.2%, with nearly half of the total cohort 45% requiring renal replacement therapy. Anemia was present in 60.6% of cases. Cardiovascular risk factors included hypertension 45%, dyslipidemia 19.5%, and diabetes 18%, while 11% had a history of myocardial infarction. Extracardiac involvement was significant, with gastrointestinal 15.5%, neurological 11.6%, and hepatic 9.1% manifestations. 44.1% of patients required biopsy confirmation, with the kidney being the primary site of histological yield.

From a cardiovascular perspective, 46.8% of patients presented with overt heart failure symptoms, and 28.6% were in NYHA III-IV. Electrocardiographic: Low QRS voltage was highly prevalent at 80.5%, while atrial fibrillation was documented in 23.4% and bundle branch blocks in 16.8%. Only one patient exhibited a pseudoinfarction pattern. Biomarkers: NT-proBNP was significantly elevated >2,000pg/mL in 80.5% of the cohort. Serum troponin values showed a wide range, from 3.2 to 2,213 pg/mL. Echocardiographic findings revealed that 54.4% of patients maintained a preserved LVEF, contrasting with 14.3% who presented with an LVEF<40%. Structural remodeling was characterized by significant ventricular wall hypertrophy and longitudinal strain pattern was identified. Nuclear scintigraphy: Perugini grade 3 myocardial uptake was the most observed.

Conclusions

This 17-year institutional experience provides a unique perspective on the shifting diagnostic paradigm of amyloidosis in Mexico. Our findings document a high-risk population characterized by advanced renal and cardiac involvement. The data reflect a clear transition from a reliance on invasive histopathology predominantly renal to the integration of non-invasive cardiovascular imaging.