Don't raise your white flag facing a sea of red ones: when cardiac amyloidosis mimics hypertrophic cardiomyopathy

Background: Cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) present significant diagnostic challenges due to their phenotypic overlap, with both conditions commonly manifesting as increased ventricular wall thickness and diastolic dysfunction. Accurate differentiation is critical as prognostic implications and therapeutic strategies differ significantly. Case report: We describe the case of a 65-year-old male initially diagnosed with non-obstructive HCM, presenting with syncope and exercise-induced non-sustained ventricular tachycardia (NSVT). Despite a confounding clinical presentation mimicking classical sarcomeric HCM, a systematic diagnostic evaluation revealed key "red flag" features including low-voltage ECG findings, pseudonecrosis, and a history of bilateral carpal tunnel surgery, raising suspicion of infiltrative cardiomyopathy. Further investigations, including cardiac magnetic resonance imaging, demonstrated diffuse subendocardial late gadolinium enhancement and elevated T1/T2 mapping values, strongly suggestive of CA. Technetium-99m scintigraphy confirmed transthyretin amyloidosis (ATTR), and genetic testing excluded pathogenic variants associated with sarcomeric HCM and hereditary ATTR. Targeted therapy with tafamidis and a mineralocorticoid receptor antagonist was initiated, while the initial indication for implantable cardioverter-defibrillator implantation was reconsidered based on the updated diagnosis and current guidelines. At 18-month follow-up, the patient remains clinically stable, with preserved functional capacity, normal NT-proBNP levels, and no adverse events. Conclusion: This case underscores the importance of a systematic diagnostic approach in differentiating CA from HCM, particularly in the presence of characteristic clinical and imaging findings. Early recognition and treatment of CA with disease-modifying therapies can alter its trajectory, highlighting the need for increased clinical suspicion and integration of advanced diagnostic modalities in similar cases.