Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the AC‐TIVE study, an Italian nationwide survey

Abstract

Aim To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions. Methods and results This is an Italian prospective multicentre study, involving a clinical and instrumental work‐up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non‐dilated left ventricles with preserved ejection fraction). The study was registered at http://clinicaltrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%–35%). Transthyretin‐related AC (ATTR‐AC) was diagnosed in 51 and light chain‐related AC (AL‐AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%. Conclusion In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy.

Re-Definition of the Epidemiology of Cardiac Amyloidosis

“…Specific clinical settings have been recognized as strongly associated with CA but further studies are needed to better characterize these populations, mainly to stratify patient risk and evaluate which patients are ideal candidates for the newly available disease-modifying therapies. Acknowledgments: We would like to thank all the nuclear medicine doctors, hematologists, neurologists, pathologists and nephrologists of the participating centres for providing their essential [8,[13][14][15][16]20,27,28,33,[36][37][38][39]41,42,[46][47][48][49][50][51][54][55][56].…”

“… Prevalence of CA in different screening studies [ 8 , 13 , 14 , 15 , 16 , 20 , 27 , 28 , 33 , 36 , 37 , 38 , 39 , 41 , 42 , 46 , 47 , 48 , 49 , 50 , 51 , 54 , 55 , 56 ]. …”

“…ATTR-CA diagnosis increased with age from 12% at <70 years to 33% in patients ≥ 80 years. Compared to non-CA patients, CA patients were more frequently referred for echocardiography for heart failure (HF) and unexplained left ventricular hypertrophy (LVH) [ 7 , 8 ]. Based on these results, it appears important to change our approach to patients undergoing an echocardiogram, in order to systematically search for CA red flags, regardless of the exam indication; in this way, the echocardiography laboratory will become essential for obtaining an early diagnosis.…”

“…Figure 1. Prevalence of CA in different screening studies[8,[13][14][15][16]20,27,28,33,[36][37][38][39]41,42,[46][47][48][49][50][51][54][55][56].…”

Restrictive Atrial Dysfunction in Cardiac Amyloidosis: Differences between Immunoglobulin Light Chain and Transthyretin Cardiac Amyloidosis Patients

“…However, a reduction in the left ventricular deposition and function loss was not seen, underlining the importance of an early diagnosis. Already, the addition of global left ventricular strain by the use of speckle tracking offers incremental diagnostic value; in particular, the distinct pattern of ‘apical sparing’ is suggestive of amyloid deposition [ 37 ]. Since atrial amyloidosis is characterized by a significant loss of atrial function, atrial reservoir function measurement might further increment the diagnostic value of echocardiography, especially in early stages where ventricular deposition is not yet very advanced.…”