JACC Case Rep. 2026 Jul 17:109237. doi: 10.1016/j.jaccas.2026.109237. Online ahead of print.
ABSTRACT
BACKGROUND: Val142Ile hereditary transthyretin amyloidosis (hATTR) is an underrecognized cause of heart failure with preserved ejection fraction (HFpEF) in older individuals of African ancestry.
CASE SUMMARY: An 83-year-old woman with persistent atrial fibrillation, chronic obstructive pulmonary disease, and HFpEF presented with progressive exertional dyspnea. Transthoracic echocardiography demonstrated preserved ejection fraction with increased ventricular wall thickness, biatrial enlargement, and pulmonary hypertension. Technetium-99 m pyrophosphate imaging showed grade 3 myocardial uptake, and monoclonal protein studies were negative. Genetic testing confirmed the TTR c.424G > A (p.Val142Ile) variant. Tafamidis was initiated, but worsening symptoms, declining transthyretin (prealbumin), and rising natriuretic peptides suggested disease progression. Therapy was escalated to the RNA-silencing agent vutrisiran, resulting in clinical stabilization and biomarker improvement.
DISCUSSION: This case highlights nonbiopsy diagnosis of hATTR cardiomyopathy and escalation to gene-silencing therapy when progression occurs despite stabilizer therapy.
TAKE-HOME MESSAGES: Val142Ile hATTR should be considered in patients with HFpEF, atrial arrhythmias, and increased ventricular wall thickness. Progression despite tafamidis warrants reassessment and consideration of gene-silencing therapy.
PMID:42470418 | DOI:10.1016/j.jaccas.2026.109237