In ATTR, mutations cause TTR tetramers to dissociate into misfolded monomers that aggregate into fibrils. What is the resulting effect on the heart?

• A. Reduced myocardial contractility
• B. Stiffened ventricular walls leading to impaired filling
• C. Increased heart rate
• D. Improved diastolic filling

Answer: (B)

The key idea is that transthyretin amyloid deposits in the heart stiffen the ventricular walls, making them noncompliant. This increased stiffness impairs filling during diastole, producing diastolic dysfunction and a restrictive cardiomyopathy pattern. Because the main problem is the heart’s ability to fill, not its ability to pump, systolic contractility is often preserved early on, so reduced contractility isn’t the central issue. The result is a heart with stiff chambers that struggle to fill properly, matching the option describing stiffened ventricles with impaired filling. Increased heart rate or improved diastolic filling aren’t characteristic of this process, further supporting the correct choice.