Electrical Dyssynchrony in Cardiac Amyloidosis: Prevalence, Predictors, Clinical Correlates, and Outcomes


      • Electrical dyssynchrony occurs in 20% of patients with cardiac amyloidosis and is more common in elderly white patients with transthyretin amyloidosis and coronary artery disease.
      • QRS prolongation is not determined by the degree of left ventricular wall thickness.
      • Electrical dyssynchrony is associated with a higher New York Heart Association class, higher risk for permanent pacemaker implant and higher risk for all-cause mortality.



      Conduction-system involvement in cardiac amyloidosis (CA) is common. The prevalence, clinical correlates and impact on outcome related to ventricular electrical dyssynchrony in CA remain insufficiently elucidated.


      Data from a prospectively maintained registry of patients with CA diagnosed in the Cleveland Clinic’s amyloidosis clinic was used to determine the frequency of electrical dyssynchrony (defined as a QRS > 130 msec). The relation with the clinical profile and clinical outcome was assessed. To determine the impact of hypertrophy on QRS prolongation, a QRS-matched cohort without CA was used for comparison of cardiac magnetic resonance imaging.


      A total of 1140 patients with CA (39% AL, 61% TTR) were evaluated, of whom 230 (20%) had electrical dyssynchrony. The type of conduction block was predominantly a right bundle branch block (BBB, 48%) followed by left BBB (35%) and intraventricular conduction delay (17%). Presence of transthyretin amyloidosis (ATTR-CA), older age, male gender, white race, and coronary artery disease were independently (P< 0.05 for all) associated with electrical dyssynchrony, and patients were more commonly prescribed a mineralocorticoid receptor antagonist. In ATTR-CA, specifically, every increase in ATTR-CA disease stage was associated with a 1.55-fold (1.23--1.95; P< 0.001) increased odds for electrical dyssynchrony. In a subset of patients with CA who underwent cardiac magnetic resonance imaging (n = 41), left ventricular mass index was unrelated to the QRS duration (r = 0.187; P = 0.283) in CA, in contrast to a non-CA QRS-matched cohort (r = 0.397; P< 0.001). Patients with electrical dyssynchrony were more symptomatic at initial presentation, as illustrated by a higher New York Heart Association class (P= 0.041). During a median follow-up of 462 days (IQR:138--996 days), a higher proportion of patients with electrical dyssynchrony died from all-cause death (P= 0.037) or developed a permanent pacing indication (3% vs 10.4%; P< 0.001) during follow-up.


      Electrical dyssynchrony is common in CA, especially in ATTR-CA, and is associated with worse functional status and clinical outcome. Given the high rate of permanent pacing indications at follow-up, additional studies are necessary to determine the best monitoring and pacing strategies in CA.

      Graphical abstract

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Cardiac Failure
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Falk RH
        • Alexander KM
        • Liao R
        • Dorbala S.AL
        (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy.
        J Am Coll Cardiol. 2016; 68: 1323-1341
        • Gillmore JD
        • Maurer MS
        • Falk RH
        • et al.
        Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis.
        Circulation. 2016; 133: 2404-2412
        • Maurer MS
        • Schwartz JH
        • Gundapaneni B
        • et al.
        Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy.
        N Engl J Med. 2018; 379: 1007-1016
        • Kastritis E
        • Palladini G
        • Minnema MC
        • et al.
        Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.
        N Engl J Med. 2021; 385: 46-58
        • Orini M
        • Graham AJ
        • Martinez-Naharro A
        • et al.
        Noninvasive mapping of the electrophysiological substrate in cardiac amyloidosis and its relationship to structural abnormalities.
        J Am Heart Assoc. 2019; 8e012097
        • Ridolfi RL
        • Bulkley BH
        • Hutchins GM.
        The conduction system in cardiac amyloidosis: clinical and pathologic features of 23 patients.
        Am J Med. 1977; 62: 677-686
        • von EE
        • Altman DG
        • Egger M
        • Pocock SJ
        • Gotzsche PC
        • Vandenbroucke JP.
        The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
        Lancet. 2007; 370: 1453-1457
        • Kumar S
        • Dispenzieri A
        • Lacy MQ
        • et al.
        Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements.
        J Clin Oncol. 2012; 30: 989-995
        • Gillmore JD
        • Damy T
        • Fontana M
        • et al.
        A new staging system for cardiac transthyretin amyloidosis.
        Eur Heart J. 2018; 39: 2799-2806
        • Buja LM
        • Khoi NB
        • Roberts WC.
        Clinically significant cardiac amyloidosis: clinicopathologic findings in 15 patients.
        Am J Cardiol. 1970; 26: 394-405
        • Strauss DG
        • Selvester RH
        • Wagner GS.
        Defining left bundle branch block in the era of cardiac resynchronization therapy.
        Am J Cardiol. 2011; 107: 927-934
        • Waller BF
        • Gering LE
        • Branyas NA
        • Slack JD.
        Anatomy, histology, and pathology of the cardiac conduction system: part VI.
        Clin Cardiol. 1993; 16: 623-628
        • Donnellan E
        • Wazni OM
        • Hanna M
        • Kanj M
        • Saliba WI
        • Jaber WA.
        Cardiac resynchronization therapy for transthyretin cardiac amyloidosis.
        J Am Heart Assoc. 2020; 9e017335
        • Donnellan E
        • Wazni OM
        • Hanna M
        • et al.
        Atrial fibrillation in transthyretin cardiac amyloidosis: predictors, prevalence, and efficacy of rhythm control strategies.
        JACC Clin Electrophysiol. 2020; 6: 1118-1127
        • Donnellan E
        • Wazni OM
        • Saliba WI
        • et al.
        Prevalence, incidence, and impact on mortality of conduction system disease in transthyretin cardiac amyloidosis.
        Am J Cardiol. 2020; 128: 140-146
        • Volpi A
        • Cavalli A
        • Maggioni AP
        • Matturri L
        • Rossi L.
        Cardiac amyloidosis involving the conduction system and the aortocoronary neuroreceptors: clinicopathologic correlates.
        Chest. 1986; 90: 619-621
        • Hartnett J
        • Jaber W
        • Maurer M
        • et al.
        Electrophysiological manifestations of cardiac amyloidosis.
        JACC Cardio Oncol. 2021; 3: 506-515
        • Tang AS
        • Wells GA
        • Talajic M
        • et al.
        Cardiac-resynchronization therapy for mild-to-moderate heart failure.
        N Engl J Med. 2010; 363: 2385-2395
        • Bristow MR
        • Saxon LA
        • Boehmer J
        • et al.
        Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure.
        N Engl J Med. 2004; 350: 2140-2150
        • Jastrzebski M
        • Moskal P
        • Huybrechts W
        • et al.
        Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT): results from an international LBBAP collaborative study group.
        Heart Rhythm. 2021; 19: 13-21