Key result
Escalation to the RNA-silencing agent vutrisiran resulted in clinical stabilization and biomarker improvement in an 83-year-old woman with hATTR cardiomyopathy progressing on tafamidis.
Why the study?
Val142Ile hereditary transthyretin amyloidosis is an underrecognized cause of HFpEF in older individuals of African ancestry.
Does vutrisiran improve clinical status and biomarkers in a patient with Val142Ile hATTR cardiomyopathy progressing on tafamidis?
Case Report (n=1)
Does vutrisiran improve clinical status and biomarkers in a patient with Val142Ile hATTR cardiomyopathy progressing on tafamidis?
Escalation to gene-silencing therapy like vutrisiran may be effective for hATTR cardiomyopathy patients who progress despite stabilizer therapy with tafamidis.
Prompts hATTR screening in older African-ancestry HFpEF with wall thickening; leaves open validation of routine genetic testing.
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.
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Almanzar et al. (2026) conducted a case report in Val142Ile hereditary transthyretin amyloidosis (hATTR) cardiomyopathy (n=1). Vutrisiran was evaluated on Clinical stabilization and biomarker improvement. Escalation to the RNA-silencing agent vutrisiran resulted in clinical stabilization and biomarker improvement in an 83-year-old woman with hATTR cardiomyopathy progressing on tafamidis.
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