Red flags for the diagnosis of cardiac amyloidosis: simple suggestions to raise suspicion and achieve earlier diagnosis

Abstract

Cardiac amyloidosis is an infiltrative disease characterized by extracellular deposition of insoluble amyloid fibrils in the heart leading to organ dysfunction. Despite recent diagnostic advances, the diagnosis of cardiac amyloidosis is often delayed or even missed. Furthermore, a long diagnostic delay is associated with adverse outcomes, with the early diagnosed patients showing the longest survival. In this narrative review we aimed to summarize the ‘red flags’ that may facilitate the correct diagnosis. The red flags may be classified as clinical, biohumoral, electrocardiographic, echocardiographic, and cardiac magnetic resonance features and should promptly raise the suspicion of cardiac amyloidosis in order to start a correct diagnostic pathway and targeted treatment strategies that may improve patients’ outcomes.

Establishment of a Comprehensive Cardiac Amyloidosis Center in a Community Hospital Setting

“…Other indicators include hypertension that eventually goes away or needs down-titration of antihypertensives and an inability to tolerate beta-blockers or ACE inhibitors/angiotensin receptor blockers. Early clues or red flags to ATTR-CA may include bilateral carpal tunnel syndrome, lumbar spinal stenosis, previous orthopedic procedures, and spontaneous biceps tendon rupture [ 23 , 24 ].…”

Temporal implementation of a regional referral pathway in transthyretin cardiac amyloidosis: Emilia-Romagna experience

“…HF with preserved ejection fraction (HFpEF), a discordance between QRS voltages at the ECG and left ventricle wall thickness at the echocardiogram and/or troponin elevation], which are termed 'red flags'. 3,[5][6][7][8][9] Despite ATTR-CA remaining a complex disease to diagnose, remarkable advances in cardiac imaging in the last two decades have increased ATTR-CA diagnosis. 2 In the past, endomyocardial biopsy was required to achieve a definitive diagnosis of ATTR-CA.…”

“…proteinuria, macroglossia, skin bruises, carpal tunnel syndrome (CTS)] and/or cardiac alteration [e.g. HF with preserved ejection fraction (HFpEF), a discordance between QRS voltages at the ECG and left ventricle wall thickness at the echocardiogram and/or troponin elevation], which are termed ‘red flags’ 3,5–9 . Despite ATTR-CA remaining a complex disease to diagnose, remarkable advances in cardiac imaging in the last two decades have increased ATTR-CA diagnosis 2 .…”

Cardiovascular imaging updates and future perspectives

“…Echocardiography may have a pivotal role in the screening process of cardiac amyloidosis. The main ‘red flags’ are increased left ventricle (LV) wall thickness, usually with a symmetric distribution, ‘apical sparing’ pattern on myocardial deformation imaging assessment, right ventricular (RV) thickening, reduced LV cavity size, bi-atrial dilatation, atrioventricular valve thickening, increased interatrial septum thickness, and pericardial and pleural effusion 2,3 . Transthyretin amyloid (ATTR) mutation is correlated with augmented atrial stiffness, and all three components of atrial function (reservoir, conduit and contraction) are significantly impaired 4,5 .…”

“…The main 'red flags' are increased left ventricle (LV) wall thickness, usually with a symmetric distribution, 'apical sparing' pattern on myocardial deformation imaging assessment, right ventricular (RV) thickening, reduced LV cavity size, bi-atrial dilatation, atrioventricular valve thickening, increased interatrial septum thickness, and pericardial and pleural effusion. 2,3 Transthyretin amyloid (ATTR) mutation is correlated with augmented atrial stiffness, and all three components of atrial function (reservoir, conduit and contraction) are significantly impaired. 4,5 Variables reflecting concentric hypertrophy, increased LV filling pressure, right ventricular dysfunction [relative wall thickness >0.52, E/e 0 > 10, tricuspid annular plane systolic excursion (TAPSE) <19 mm and longitudinal strain <14%] confirm the presence of amyloid light chain amyloidosis-related cardiomyopathy in 50% of patients.…”