First of all, HFpEF represents a complex and heterogeneous phenotypic set, including patients with several different comorbidities (such as diabetes, atrial fibrillation, chronic kidney disease) and with different clinical characteristics, such as those subjects with wild-type transthyretin (TTR) amyloidosis (Mohammed et al., 2014; Russo et al., 2020) who often remain underdiagnosed or misdiagnosed, being inappropriately enrolled in clinical trials and showing an unsatisfactory response to neurohormonal inhibitors (Maurer et al., 2018). This evidence concerns the gene TTR and atrial fibrillation.