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Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by extracellular deposition of amyloid fibrils, mainly derived from transthyretin, either wild-type or hereditary variants, or immunoglobulin light chains misfolding. It is characterized by an increased left ventricular (LV) mass and diastolic dysfunction, which can lead to heart failure with preserved ejection fraction and/or conduction disturbances. The diagnosis is based on invasive pathology demonstration of amyloid deposits, or non-invasive criteria using advanced cardiovascular imaging techniques. Nevertheless, 12-lead electrocardiogram (ECG) remains of crucial importance in the assessment of patients with CA, since they can manifest peculiar features such as low QRS voltages, in discordance with the LV hypertrophy, but also pseudo-infarction patterns, sinus node dysfunction, atrioventricular blocks, premature supraventricular and ventricular beats, which support the presence of a myocardial disease. Great awareness of these common ECG characteristics of CA is needed to increase diagnostic performance and improve patient's outcome. In the present review, we discuss the current role of the ECG in the diagnosis and management of CA, focusing on the most common ECG abnormalities and rhythm disorders., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt-CA diagnosis, and their potential association with survival., Methods and Results: This was a retrospective study of patients diagnosed with ATTRwt-CA at 17 Italian referral centres for CA. Patients were categorized into different 'pathways' according to the medical reason that triggered the diagnosis of ATTRwt-CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all-cause mortality as endpoint. Overall, 1281 ATTRwt-CA patients were included in the study. The diagnostic pathway leading to ATTRwt-CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III-IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III-IV and some comorbidities but not the HF pathway were independently associated with worse survival., Conclusions: Half of contemporary ATTRwt-CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an underappreciated cause of heart failure that results from misfolded TTR (prealbumin) protein. Diflunisal is an approved non-steroidal anti-inflammatory drug that stabilizes TTR, with limited data available regarding effects on cardiac structure and function., Methods and Results: ATTR-CM patients (n=81, 41% treated with 250 mg twice-daily diflunisal by clinical practice) were retrospectively identified with baseline and follow-up (median interval 1 year) serum biomarker and echocardiographic data compared, including global longitudinal strain (GLS). Chi-squared and Wilcoxon tests assessed differences between subjects, divided by treatment group, and univariable and multivariable linear regression was performed. At baseline, patients treated with diflunisal were younger (68 vs 77 years, P = .0001), with lower B-type natriuretic peptide (BNP; 249 vs 545 pg/mL, P = .009) and serum creatinine (1.1 vs 1.2 mg/dL, P = .04), but similar TTR concentration (P = .31), cardiac troponin I (P = .06), and GLS (P = .67). At follow-up, diflunisal untreated versus treated patients showed differences in TTR concentration (19 vs 33 mg/dL, P = .01) and favorable differences in left atrial volume index (+4.6 vs -1.4 mL/m 2 , P = .002) and cardiac troponin I (+0.03 vs -0.01 ng/mL, P = .01) for the entire cohort. Among the subset with wild-type ATTR (n=53), diflunisal treatment was associated with differences in GLS (+1.2% untreated vs +0.1% treated, P = .03). Changes in wall thickness (P = .2), left ventricular ejection fraction (P = .71), and BNP (P = .42) were similar between groups., Conclusions: In ATTR-CM, diflunisal treatment resulted in measurable differences in some parameters of cardiac structure and function after only 1 year of administration. Further longer-term analysis is warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Systemic amyloidoses are rare and proteiform diseases, caused by extracellular accumulation of insoluble misfolded fibrillar proteins. Prognosis is dictated by cardiac involvement, which is especially frequent in light chain (AL) and in transthyretin variants (ATTR, both mutated, (ATTRm), and wild-type, (ATTRwt)). Recently, ATTRwt has emerged as a potentially relevant cause of a heart failure with preserved ejection fraction (HFpEF). Cardiac amyloidosis is an archetypal example of restrictive cardiomyopathy, with signs and symptoms of global heart failure and diastolic dysfunction. Independent of the aetiology, cardiac amyloidosis is associated with left ventricular concentric "hypertrophy" (i.e. increased wall thickness), preserved (or mildly depressed) ejection fraction, reduced midwall fractional shortening and global longitudinal function, as well as evident diastolic dysfunction, up to an overly restrictive pattern of the left ventricular filling. Cardiac biomarkers such as troponins and natriuretic peptides are very robust and widely accepted diagnostic as well as prognostic tools. Owing to its dismal prognosis, accurate and early diagnosis is mandatory and potentially life-saving. Although pathogenesis is still not completely understood, direct cardiomyocyte toxicity of the amyloidogenic precursor proteins and/or oligomer aggregates adds on tissue architecture disruption caused by amyloid deposition. The clarification of mechanisms of cardiac damage is offering new potential therapeutic targets, and several treatment options with a relevant impact on prognosis are now available.

Background and Purpose: To evaluate the prevalence and the prognostic implications of conduction delays in a large cohort of cardiac AL patients., Methods: Echo Doppler and 12-lead ECG were collected in 344 consecutive patients in whom diagnosis of AL amyloidosis was concluded between 2008 and 2010. Patients were subdivided according to the presence (n = 240) or absence (n = 104) of cardiac involvement., Results: When compared with patients without myocardial involvement, cardiac AL was associated with prolonged PQ, QRS, QT and QTc intervals (P < 0.05), and with higher prevalence of intraventricular blocks (27.5% vs. 16.5%, P < 0.05), that was associated with higher wall thickness, worse diastolic and regional systolic function, higher NT-proBNP values (all P < 0.05), and higher mortality (P = 0.0001; median follow-up: 402 days)., Conclusion: Intraventricular conduction delays have a negative prognostic impact in patients with cardiac AL amyloidosis. Their presence should not be overlooked in the diagnostic workup, prompting a more accurate cardiological support., (©2013, Wiley Periodicals, Inc.)

Background: In cardiac AL amyloidosis, myocardial infiltration is typically associated with "low QRS voltages" at the 12-lead electrocardiogram (ECG). Although considered as one of the hallmarks of the disease, its reported prevalence varies from 45% to 70%, mainly because of nonhomogeneous definitions., Methods: To identify the "low QRS voltage" parameter having the best diagnostic value in identifying cardiac amyloidosis, and to assess its possible prognostic role, ECG and echocardiographic data were collected at diagnosis in 337 consecutive never-treated AL patients (233 with, 104 without cardiac involvement). Prognosis was assessed after a median follow-up of 14.5 months., Results: "Low QRS voltage" prevalence varied from 84.12% when using Sokolow-Lyon index ≤15 mm to 27.04% with the definition of low total voltages (QRS amplitude ≤5 mm in each peripheral and ≤10 mm in each precordial lead), the widely used definition of low peripheral voltages (≤5 mm in each peripheral lead) being able to identify 66.52% cardiac AL patients. The presence of "low peripheral voltages" was associated with a more severe cardiac involvement, and was able to differentiate Mayo stage II patients' survival (i.e., AL patients with intermediate prognosis). According to receiver operator characteristic (ROC) curve analysis, sensitivity and specificity were 58.72% and 80.00%, for a peripheral QRS amplitude ≤24.5 mm (the sum of QRS in all the 6 peripheral leads), and 76.26% and 65.00% for a Sokolow-Lyon index ≤11 mm., Conclusions: In cardiac AL amyloidosis the prevalence of low QRS voltages is highly dependent on the method used for defining this ECG alteration., (©2013, Wiley Periodicals, Inc.)