Baseline ECG Features and Arrhythmic Profile in Transthyretin Versus Light Chain Cardiac Amyloidosis
2020; Lippincott Williams & Wilkins; Volume: 13; Issue: 3 Linguagem: Inglês
10.1161/circheartfailure.119.006619
ISSN1941-3297
AutoresFrancesco Cappelli, Elisa Vignini, Raffaele Martone, Stefano Perlini, Roberta Mussinelli, Anna Sabena, Sofia Morini, Martina Gabriele, Giulia Taborchi, Simone Bartolini, A Lossi, Giulia Nardi, Niccolò Marchionni, Carlo Di Mario, Iacopo Olivotto, Federico Perfetto,
Tópico(s)Sarcoidosis and Beryllium Toxicity Research
ResumoHomeCirculation: Heart FailureVol. 13, No. 3Baseline ECG Features and Arrhythmic Profile in Transthyretin Versus Light Chain Cardiac Amyloidosis Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBBaseline ECG Features and Arrhythmic Profile in Transthyretin Versus Light Chain Cardiac Amyloidosis Francesco Cappelli, MD, Elisa Vignini, MD, Raffaele Martone, MD, Stefano Perlini, MD, PhD, Roberta Mussinelli, MD, Anna Sabena, MD, Sofia Morini, MD, Martina Gabriele, MD, Giulia Taborchi, MD, Simone Bartolini, MD, Angelica Lossi, MD, Giulia Nardi, MD, Niccolò Marchionni, MD, PhD, Carlo Di Mario, MD, PhD, Iacopo Olivotto, MD and Federico Perfetto, MD, PhD Francesco CappelliFrancesco Cappelli Tuscan Regional Amyloidosis Center, Careggi University Hospital, Florence, Italy (F.C., E.V., R. Martone, S.M., G.T., S.B., F.P.). , Elisa VigniniElisa Vignini Correspondence to: Elisa Vignini, MD, Tuscan Regional Amyloidosis Center, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy. Email E-mail Address: [email protected] Tuscan Regional Amyloidosis Center, Careggi University Hospital, Florence, Italy (F.C., E.V., R. Martone, S.M., G.T., S.B., F.P.). , Raffaele MartoneRaffaele Martone Tuscan Regional Amyloidosis Center, Careggi University Hospital, Florence, Italy (F.C., E.V., R. Martone, S.M., G.T., S.B., F.P.). , Stefano PerliniStefano Perlini Emergency Department, Amyloid Research and Treatment Center, IRCCS Policlinico San Matteo Foundation, University of Pavia, Italy (S.P., R. Mussinelli, A.S.). , Roberta MussinelliRoberta Mussinelli Emergency Department, Amyloid Research and Treatment Center, IRCCS Policlinico San Matteo Foundation, University of Pavia, Italy (S.P., R. Mussinelli, A.S.). , Anna SabenaAnna Sabena Emergency Department, Amyloid Research and Treatment Center, IRCCS Policlinico San Matteo Foundation, University of Pavia, Italy (S.P., R. Mussinelli, A.S.). , Sofia MoriniSofia Morini Tuscan Regional Amyloidosis Center, Careggi University Hospital, Florence, Italy (F.C., E.V., R. Martone, S.M., G.T., S.B., F.P.). , Martina GabrieleMartina Gabriele Division of General Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy (M.G., A.L., G.N., N.M.). , Giulia TaborchiGiulia Taborchi Tuscan Regional Amyloidosis Center, Careggi University Hospital, Florence, Italy (F.C., E.V., R. Martone, S.M., G.T., S.B., F.P.). , Simone BartoliniSimone Bartolini Tuscan Regional Amyloidosis Center, Careggi University Hospital, Florence, Italy (F.C., E.V., R. Martone, S.M., G.T., S.B., F.P.). , Angelica LossiAngelica Lossi Division of General Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy (M.G., A.L., G.N., N.M.). , Giulia NardiGiulia Nardi Division of General Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy (M.G., A.L., G.N., N.M.). , Niccolò MarchionniNiccolò Marchionni Division of General Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy (M.G., A.L., G.N., N.M.). , Carlo Di MarioCarlo Di Mario Division of Interventional Structural Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy (C.D.M.). , Iacopo OlivottoIacopo Olivotto Cardiomyopathy Unit, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy (I.O.). and Federico PerfettoFederico Perfetto Tuscan Regional Amyloidosis Center, Careggi University Hospital, Florence, Italy (F.C., E.V., R. Martone, S.M., G.T., S.B., F.P.). Originally published13 Mar 2020https://doi.org/10.1161/CIRCHEARTFAILURE.119.006619Circulation: Heart Failure. 2020;13:e006619The ECG is a remarkable tool for the diagnosis of cardiac amyloidosis (CA), but systematic comparisons of ECG abnormalities between light chain (AL) and transthyretin (ATTR) CA are lacking. In this retrospective study, we aimed to compare the prevalence of electrophysiological abnormalities in 3 groups of patients with AL, wild-type ATTR (wtATTR), and variant ATTR (vATTR) CA, seen at 2 referral centers in Italy. Consecutive patients with an established diagnosis of ATTR or AL amyloidosis and objective evidence of cardiac involvement were included. The study was authorized by local Ethics Committee; due to its retrospective nature, informed consent was waived for patients who had died or were lost to follow-up. Diagnosis of AL amyloidosis was confirmed by biopsy of abdominal fat pad or of an involved organ with amyloid deposits characterized as AL type by immunohistochemistry, optic/immunoelectron microscopy, or proteomics. Cardiac involvement in AL was established according to current guidelines.1 Diagnosis of ATTR-CA was made when diastolic interventricular septum thickness was >12 mm on echocardiography without other causes of left ventricular hypertrophy, in the presence of documented TTR amyloid deposits in at least one involved organ or according to noninvasive algorithm.2 All patients diagnosed with ATTR-CA underwent genetic testing. DNA was extracted from peripheral blood samples and exons 2, 3, and 4 of TTR gene were amplified by polymerase chain reaction. Polymerase chain reaction products were purified and sequenced on 3730 DNA Analysers. Data obtained from the Seqscape Analysis Software V2.7 (Applied Biosystems) were aligned with the wild-type TTR gene sequence to identify variants in the gene sequence. A standard 12-lead ECG recording (filter range, 0.05–50 Hz, 25 mm/s, 10 mm/mV) was part of standard evaluation at the time of CA diagnosis. Low voltage was defined as a QRS amplitude ≤0.5 mV in all limb leads or ≤1 mV in all precordial leads. A pseudoinfarction pattern was defined as pathological Q waves (1/4 R amplitude) or QS waves on 2 consecutive leads in the absence of previous ischemic heart disease, left bundle branch block, or LV wall motion abnormalities. AV conduction defect, defined as first, second, and third AV block, intraventricular conduction defect defined as left bundle branch block, right bundle branch block, incomplete right bundle branch block, or left anterior hemiblock were also recorded. All patients underwent a comprehensive echocardiographic evaluation.3 Data were expressed as mean±SD or median (interquartile range) for continuous variables, as appropriate, and as frequencies (percentages) for categorical variables. Pairwise comparisons were made with 1-way ANOVA and Kruskal-Wallis test for continuous variables, and with Pearson χ2 test for categorical variables. Analyses were performed with SPSS 20 IBM Package, with values <0.05 considered statistically significant.We included 244 patients (106 AL and 138 ATTR) seen between January 2000 and May 2019, with a baseline ECG available for analysis obtained within 1 month from diagnosis. In the ATTR group, 108 patients were wild type while 30 carried a TTR mutation (vATTR: 16 Ile68Leu, 10 Val122Ile and 4 private mutations). At the time of diagnosis, prevalence of atrial fibrillation (AF) was 40% in wtATTR and 20% in vATTR, that is, 6-fold and 4-fold greater than AL, respectively (Table). wtATTR showed the highest prevalence of AV block grade I or greater, while vATTR more often showed intraventricular delay. Conversely, low voltage pattern was more common in AL. A pseudonecrosis pattern had similar prevalence among groups.Table. Clinical, Laboratory, Echocardiographic, and Electrocardiographic CharacteristicsAL (n=106)wtATTR (n=108)vATTR (n=30)AL vs wtATTRAL vs vATTRwtATTR vs vATTRPValuePValuePValueDemographics Age, y62.5±10.378.4±6.471.1±11.2<0.001<0.001<0.001 BSA, m21.77±0.191.86±0.171.80±0.140.0010.5120.087 Heart rate, bpm80±1473±1173±14<0.0010.0110.865 SBP, mm Hg127±23124±17121±190.2520.1900.417 DBP, mm Hg76±1272±970±110.0090.0230.332Biomarkers eGFR, mL/min per 1.73 m269±3265±1867±300.4270.8540.734 NT-proBNP, pg/mL2249 (5241–1153)3566 (4924–1245)3393 (5009–1516)0.9530.7900.852 TnI, ng/mL0.05 (0.16–0.02)0.07 (0.10–0.05)0.11 (0.17–0.05)0.2550.1890.176Imaging findings LVEDD, mm42.9±5.046.2±7.944.0±5.4<0.0010.0660.575 LVESD, mm27.3±5.332.3±8.130.6±8.60.0020.3120.158 IVS, mm14.5±2.417.8±2.617.4±2.8<0.001<0.0010.476 LVPW, mm13.7±2.316.1±2.416.9±3.2<0.001<0.0010.149 LA area, cm221.8±8.727.1±5.727.2±7.0<0.0010.0110.937 LVEDV ind., mL/m233±1552±1644±12<0.0010.0010.015 LVESV ind., mL/m214.5±7.925.2±11.421.1±8.9<0.001<0.0010.084 LVEF (%)57.9±8.753.7±9.952.5±9.90.0010.0050.569 LV mass ind., g/m2153±49186±47184±47<0.0010.0030.780 E/e'12.6±7.216.2±5.917.6±5.4<0.0010.0020.295 TAPSE, mm17.0±4.817.9±4.516.3±5.00.1580.5170.127ECG findings Atrial fibrillation6/106 (6%)43/108 (40%)6/30 (20%)<0.0010.0250.053 AV block grade I or greater13/100 (13%)27/65 (41%)6/23 (26%)<0.0010.1200.316Intraventricular delay24/106 (23%)38/100 (38%)14/26 (54%)0.0220.0030.181Low voltage52/106 (49%)31/101 (31%)7/26 (27%)0.0070.0490.813Pseudonecrosis41/106 (39%)33/98 (34%)6/26 (23%)0.4700.1730.350Pacemaker/defibrillator1/106 (1%)16/108 (15%)9/30 (30%)<0.001<0.0010.065Data are expressed as mean±SD, median (interquartile range) or n (%). AL indicates abnormalities between light chain; BSA, body surface area; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; ind., index for body surface area; IVS, interventricular septum; LA, left atrium; LV, left ventricular; LVEDD, left ventricular end-diastolic diameter; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; LVESV, left ventricular end-systolic volume; LVPW, left ventricular posterior wall; NT-proBNP, N-terminal pro–B-type natriuretic peptide; SBP, systolic blood pressure; TAPSE, tricuspid annular plane systolic excursion; TnI, troponin I; vATTR, variant transthyretin; and wtATTR, wild-type transthyretin.Device implantation before first diagnosis, due to slow AF (n=12), extreme bradycardia/advanced AV block (n=9), primary (n=2), and secondary (n=1) prevention of ventricular arrhythmias or ablate and pace (n=1), was almost exclusively seen in ATTR, compared with only 1/106 AL patient (due to advanced AV block). Among ATTR patients, vATTR showed the highest prevalence of device implantation before diagnosis (30%).Our main finding is that the electrophysiological profile of CA varies markedly based on its etiology. Over one-third of our wtATTR patients presented with AF compared with 20% of vATTR and only 6% of those with AL-CA. AF with slow ventricular response, AV block, and intraventricular delay were also more common among ATTR patients, leading to a significant prevalence of device implantation before diagnosis. Conversely, AL subjects more often presented in sinus rhythm and displayed the typical low voltage pattern at diagnosis.A plausible interpretation is that ATTR-CA behaves as a progressive cardiomyopathy4 characterized by slow amyloid deposition within the atria, the ventricles, and the conduction system, while AL rather resembles an acute myocarditis with early symptoms onset and rapid disease progression to end-stage heart failure, despite lesser degrees of infiltration, due to the toxic effects of AL chains.4,5 Symptom onset and clinical identification of ATTR subjects occur late in the course of the disease (especially for wtATTR), accounting for the higher prevalence of AF at presentation. Overall, these findings suggest the presence of different electrophysiological tales in CA, reflecting substantial diversity in the pathophysiology and clinical course of different etiologies. These findings have potential relevance for arrhythmic surveillance and management strategies in CA.DisclosuresNone.Footnotes*Drs Cappelli and Vignini contributed equally to this work.Data Availability: Data available on request from the authors.For Disclosures, see page 3.Correspondence to: Elisa Vignini, MD, Tuscan Regional Amyloidosis Center, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy. Email [email protected]comReferences1. Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, Merlini G, Moreau P, Ronco P, Sanchorawala Vet al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th international symposium on amyloid and amyloidosis, Tours, France, 18-22 April 2004.Am J Hematol. 2005; 79:319–328. doi: 10.1002/ajh.20381CrossrefMedlineGoogle Scholar2. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan Met al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis.Circulation. 2016; 133:2404–2412. doi: 10.1161/CIRCULATIONAHA.116.021612LinkGoogle Scholar3. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova Tet al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.Eur Heart J Cardiovasc Imaging. 2015; 16:233–270. doi: 10.1093/ehjci/jev014CrossrefMedlineGoogle Scholar4. Rapezzi C, Merlini G, Quarta CC, Riva L, Longhi S, Leone O, Salvi F, Ciliberti P, Pastorelli F, Biagini Eet al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types.Circulation. 2009; 120:1203–1212. doi: 10.1161/CIRCULATIONAHA.108.843334LinkGoogle Scholar5. Longhi S, Quarta CC, Milandri A, Lorenzini M, Gagliardi C, Manuzzi L, Bacchi-Reggiani ML, Leone O, Ferlini A, Russo Aet al. Atrial fibrillation in amyloidotic cardiomyopathy: prevalence, incidence, risk factors and prognostic role.Amyloid. 2015; 22:147–155. doi: 10.3109/13506129.2015.1028616CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Bay K, Gustafsson F, Maiborg M, Bagger‐Bahnsen A, Strand A, Pilgaard T and Poulsen S (2022) Suspicion, screening, and diagnosis of wild‐type transthyretin amyloid cardiomyopathy: a systematic literature review, ESC Heart Failure, 10.1002/ehf2.13884, 9:3, (1524-1541), Online publication date: 1-Jun-2022. Galante N, Ciprandi B, Franceschetti L, Leone B, Riva S and Gentilomo A (2022) A case of medical liability involving an unexpected systemic amyloidosis, Legal Medicine, 10.1016/j.legalmed.2022.102049, 56, (102049), Online publication date: 1-May-2022. Tini G, Cappelli F, Biagini E, Musumeci B, Merlo M, Crotti L, Cameli M, Di Bella G, Cipriani A, Marzo F, Guerra F, Forleo C, Gagliardi C, Zampieri M, Carigi S, Vianello P, Mandoli G, Ciliberti G, Lichelli L, Mariani D, Porcari A, Russo D, Licordari R, Ponziani A, Porto I, Perfetto F, Autore C, Rapezzi C, Sinagra G and Canepa M (2021) Current patterns of beta‐blocker prescription in cardiac amyloidosis: an Italian nationwide survey, ESC Heart Failure, 10.1002/ehf2.13411, 8:4, (3369-3374), Online publication date: 1-Aug-2021. Dumont C and Liprandi M (2021)(2021)(2021)(2021) Ventricular Arrythmias in Cardiac Amyloidosis: It is Possible to Prevent Sudden Death?, ABC: Heart Failure & Cardiomyopathy, 10.36660/abchf.20210035, 1:2, (103-111), Online publication date: 10-Dec-2021., Online publication date: 10-Dec-2021., ., . Cappelli F, Perfetto F, Martone R and Di Mario C (2021) Cardiac Amyloidosis in Patients Undergoing TAVR: Why We Need to Think About It, Cardiovascular Revascularization Medicine, 10.1016/j.carrev.2020.06.005, 22, (109-114), Online publication date: 1-Jan-2021. Khanna S, Lo P, Cho K and Subbiah R (2020) Ventricular Arrhythmias in Cardiac Amyloidosis: A Review of Current Literature, Clinical Medicine Insights: Cardiology, 10.1177/1179546820963055, 14, (117954682096305), Online publication date: 1-Jan-2020. Ng P, Lim Y, Evangelista L, Wong R, Chai P, Sia C, Loi H, Yeo T and Lin W (2022) Utility and pitfalls of the electrocardiogram in the evaluation of cardiac amyloidosis, Annals of Noninvasive Electrocardiology, 10.1111/anec.12967 Eötvös C, Lazar R, Zehan I, Lévay-Hail E, Pastiu G, Pop M, Bojan A, Pop S and Blendea D (2021) Cardiac Amyloidosis with Discordant QRS Voltage between Frontal and Precordial Leads, Medicina, 10.3390/medicina57070660, 57:7, (660) March 2020Vol 13, Issue 3 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.119.006619PMID: 32164434 Originally publishedMarch 13, 2020 KeywordsimmunohistochemistryamyloidosisproteomicsalgorithmPDF download Advertisement SubjectsOmics
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