Microvascular dysfunction in patients with transthyretin cardiac amyloidosis evaluated by 13N-ammonia positron emission tomography-computed tomography: is it an early marker of the disease?

PURPOSE: To evaluate coronary microvascular function using 13N-ammonia positron emission tomography/ computed tomography in individuals with pathogenic transthyretin (TTR) gene mutations, with and without cardiac involvement. This study is the first to assess coronary flow reserve (CFR) in this population before overt cardiac amyloidosis (CA) is detectable by conventional imaging.

METHODS

We evaluated microvascular impairment by measuring CFR in 20 patients with and 20 patients without cardiac involvement due to TTR amyloidosis (ATTR), all presumed to be free from epicardial coronary artery disease and carrying TTR gene mutations.

RESULTS

The study revealed a significantly reduced mean global CFR in the cardiac involvement group (1.849 ± 0.379 vs. 2.952 ± 0.7, P < 0.001). Global CFR inversely correlated with age, functional class, troponin, and B-type natriuretic peptide while positively correlating with the 6-minute walk test distance, mean blood pressure, and global longitudinal strain. Receiver operating characteristic curve analysis identified an optimal cutoff value of global CFR < 2.58, yielding a sensitivity of 100% and a specificity of 75% for detecting cardiac involvement.

CONCLUSION

In patients with ATTR CA, coronary microvascular dysfunction emerges as a clinically relevant marker of cardiac involvement, even in the absence of structural abnormalities or obstructive coronary disease.

CLINICAL SIGNIFICANCE: CFR assessment may aid in diagnostic suspicion, risk stratification, and understanding of angina symptoms in this population.