Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative heart disease driven by protein instability. Normally a tetramer, transthyretin can dissociate into monomers that misfold, aggregate, and deposit as amyloid fibrils within the myocardial extracellular matrix as reported in the Journal of Cardiothoracic and Vascular Anesthesia.  These deposits thicken and stiffen the heart, impairing diastolic and eventually systolic function, and culminating in heart failure. Beyond mechanical burden, chronic exposure to circulating, cytotoxic amyloid precursors further injures myocardium, compounding structural and functional decline.

Once viewed as rare, ATTR-CM is now recognized as the most common form of cardiac amyloidosis and occurs in two principal forms. Variant ATTR-CM stems from an inherited transthyretin gene alteration that introduces an amino acid substitution, destabilizing the protein and predisposing it to tetramer dissociation and monomer misfolding. Wild-type ATTR-CM arises from a normal gene and manifests primarily in older adults.

A deepening understanding of the molecular cascade—from tetramer destabilization to fibril deposition—has catalyzed a therapeutic revolution. Three drug classes target distinct checkpoints in disease biology:

• Transthyretin stabilizers that preserve the tetrameric structure and reduce dissociation into misfolding-prone monomers.
• Gene silencers that diminish hepatic transthyretin production, lowering the circulating pool of amyloidogenic precursors.
• Agents aimed at degrading established amyloid fibrils, including monoclonal antibodies that seek to clear deposits from the myocardium.

Clinical trials have demonstrated efficacy for transthyretin stabilizers and gene silencers, supporting meaningful benefits on disease progression. Early experience with monoclonal antibodies suggests the potential to degrade fibrils and reverse structural and functional cardiac consequences. Collectively, these advances are transforming ATTR-CM from a debilitating, uniformly fatal disorder into a more manageable chronic illness, with the promise of extended survival and preserved quality of life.

The evolving therapeutic landscape also carries implications for perioperative and anesthetic care. As patients live longer and with improved function, anesthesiologists must account for dynamic changes in cardiac stiffness, preload dependence, and conduction characteristics, as well as potential interactions between disease-modifying therapies and hemodynamic management. Awareness of ongoing pharmacotherapy—whether stabilizing, silencing, or fibril-targeting—may influence monitoring strategies and perioperative risk assessment.