The epidemiology of cardiac amyloidosis (CA), traditionally considered a rare and incurable disease, has changed drastically over the last ten years, particularly due to the advances in diagnostic methods and therapeutic options in the field of transthyretin CA (ATTR-CA). On the one hand, the possibility of employing cardiac scintigraphy with bone tracers to diagnose ATTR-CA without a biopsy has unveiled the real prevalence of the disease; on the other, the emergence of effective treatments, such as tafamidis, has rendered an early and accurate diagnosis critical. Interestingly, the following subgroups of patients have been found to have a higher prevalence of CA: elderly subjects > 75 years, patients with cardiac hypertrophy hospitalized for heart failure with preserved ejection fraction, subjects operated on for bilateral carpal tunnel syndrome, patients with cardiac hypertrophy not explained by concomitant factors and individuals with aortic valve stenosis. Many studies investigating the prevalence of CA in these particular populations have contributed to rewriting the epidemiology of the disease, increasing the awareness of the medical community for a previously underappreciated condition. In this review, we summarized the latest evidence on the epidemiology of CA according to the different clinical settings typically associated with the disease.

Survivors after a myocardial infarction (MI), especially those with diabetes mellitus (DM), remain at high risk of further events. Identifying and treating factors that may influence survival may open new therapeutic strategies. We assessed the impact on prognosis of DM and hypovitaminosis D (hypovitD), alone or combined. In this prospective, observational study, 1081 patients were enrolled surviving an MI and divided into four groups according to their diabetic and VitD status. The primary end-point was composite of all-cause mortality, angina/MI and heart failure (HF). Secondary outcomes were mortality, HF and angina/MI. During a follow-up of 26.1 months (IQR 6.6–64.5), 391 subjects experienced the primary end-point. Patients with DM or hypovitD had similar rate of the composite end-point. Patients with only hypovitD or DM did not differ regarding components of composite end-point (angina p = 0.97, HF p = 0.29, mortality p = 0.62). DM and VitD deficiency had similarly adjusted risks for primary end-point (HR 1.3, 95%CI 1.05–1.61; HR 1.3, 95% CI 1.04–1.64). The adjusted HR for primary composite end-point for patients with hypovitD and DM was 1.69 (95%CI 1.25–2.29, p = 0.001) in comparison to patients with neither hypoD nor DM. In conclusion, DM and hypovitD, individually and synergistically, are associated with a worse outcome after MI.

Radionuclide bone scintigraphy is the cornerstone of an imaging-based algorithm for accurate non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). In patients with heart failure and suggestive echocardiographic and/or cardiac magnetic resonance imaging findings, the positive predictive value of Perugini grade 2 or 3 myocardial uptake on a radionuclide bone scan approaches 100% for the diagnosis of ATTR-CA as long as there is no biochemical evidence of a clonal dyscrasia. The technetium-labelled tracers that are currently validated for non-invasive diagnosis of ATTR-CA include pyrophosphate (^99mTc-PYP); hydroxymethylene diphosphonate (^99mTc-HMDP); and 3,3-diphosphono-1,2-propanodicarboxylate (^99mTc-DPD). Although nuclear scintigraphy has transformed the contemporary diagnostic approach to ATTR-CA, a number of grey areas remains, including the mechanism for binding tracers to the infiltrated heart, differences in the kinetics and distribution of these radiotracers, differences in protocols of image acquisition worldwide, the clinical significance of extra-cardiac uptake, and the use of this technique for prognostic stratification, monitoring disease progression and assessing the response to disease-modifying treatments. This review will deal with the most relevant unmet needs and clinical questions concerning scintigraphy with bone tracers in ATTR-CA, providing expert opinions on possible future developments in the clinical application of these radiotracers in order to offer practical information for the interpretation of nuclear images by physicians involved in the care of patients with this ATTR-CA.

This review will deal with the most relevant unmet needs and clinical questions concerning scintigraphy with bone tracers in ATTR-CA, providing expert opinions on possible future developments in the clinical application of these radiotracers, in order to offer practical information for interpretation of nuclear images to physicians involved in the care of patients with this ATTR-CA.