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A troubled marriage: When electrical and mechanical dyssynchrony don’t go along

  • Marat Fudim
  • Salvador Borges-Neto
Editorial
  • 196 Downloads

The following editorial refers to the article published by Sillanmäki et al. titled “Relationships between electrical and mechanical dyssynchrony in patients with left bundle branch block and healthy controls” in the XX edition of the Journal of Nuclear Cardiology.

Mechanical contraction of the heart muscle is initiated by electrical activation of myocytes. Left ventricular mechanical dyssynchrony (LVMD) refers to a difference in the timing of mechanical contraction or relaxation between different segments of the left ventricle (LV). It is important to acknowledge that mechanical dyssynchrony does not equal electrical dyssynchrony which is defined by an asynchronous electrical activation of the LV leading to a prolonged QRS duration (> 120 ms) on the ECG, and is usually the result of a left bundle branch block (LBBB). Although electrical and mechanical dyssynchrony often coincide, electrical and mechanical dyssynchrony are commonly not present at the same time in a given patient.1,2

Cardiac resynchronization therapy (CRT) was developed with the goal to treat mechanical dyssynchrony with the hope it will improve cardiac performance and improve outcomes.3-5 Right at the get-go the simple assumption was made that electrical dyssynchrony and mechanical dyssynchrony track well with each other, and since it is so much easier to measure and quantify electrical dyssynchrony (presence of absence of a LBBB and QRS width), the electrical dyssynchrony on ECG became the designated target of CRT. Currently, presence of electrical dyssynchrony is among the inclusion criteria for CRT in heart failure (HF) patients. Other criteria include left ventricular ejection fraction (LVEF) ≤ 35% and New York Heart Association class II-IV despite optimal medical therapy. Under those criteria, biventricular pacing has been shown to reduce all-cause mortality.6 Nonetheless, among patients who meet the criteria, around 30% to 40% fail to show an improvement in clinical symptoms and cardiac function,7 suggesting the need for a more efficient selection of CRT candidates to improve patient outcomes and decrease costs. Today we know that diseased hearts with electrical dyssynchrony do not equally respond to CRT. The two key determinants of treatment response that emerged are QRS width and presence of LBBB. Meta-analysis of three randomized trials suggests that a wide QRS duration > 150 ms, regardless of QRS morphology, is most important for CRT response.8 Further, the majority of clinical trials that studied CRT have found that it is mostly efficacious in patients with LBBB.9-11 More recent work now suggests that LBBB in itself may represent a previously unrecognized cause of LV dysfunction and may impair left ventricular recovery.12

In the present analysis the authors set out to investigate the LBBB and its relationship with mechanical dyssynchrony using myocardial perfusion imaging (MPI) and vector electrocardiography (VECG, another surrogate of mechanical myocyte activation, derived form an ECG analysis). In a retrospective analysis the authors selected 45 patients with LBBB and 24 controls out of a cohort of 994 patients. The authors found a large degree of electromechanical dissociation (~ 40% of cases). Electromechanical dissociation refers to the fact that patients with LBBB (electrical dyssynchrony) can have no evidence of mechanical dyssynchrony on myocardial perfusion imaging. Several ECG/VECG parameters correlated significantly with mechanical dyssynchrony when the whole population was studied. In a multivariate analysis, independent predictors of mechanical dyssynchrony were QRS duration and end diastolic volume (a marker of ventricular dilation/dysfunction). The most significant contribution of this publication is the confirmation of the “etiological diversity of the LBBB.” In other words, not all LBBB are alike and only a slim majority is accompanied by mechanical dyssynchrony. Whether these findings can be extrapolated to other types of electrical dyssynchrony such as right bundle branch blocks or nonspecific intraventricular conduction delays needs to be determined. It is though worth mentioning that QRS width and end diastolic volume predicted up to 55% of the variation in mechanical dyssynchrony (phase bandwidth).

This study raises several important questions. Do LBBBs with mechanical dyssynchrony have worse outcomes than LBBBs without mechanical dyssynchrony? Does targeting LBBB with mechanical dyssynchrony in patients undergoing CRT going to make a difference?

LVMD was found to have significant prognostic implications in a variety of patient groups. In an earlier study on HF patients with LVEF ≤ 45% and no history of myocardial infarction (MI), those with LVMD as measured by tissue Doppler echocardiography had significantly higher risks of cardiac events irrespective of QRS width and LVEF.13 Furthermore, in a large cohort of patients with CAD, a recent study demonstrated that measured LVMD had a stronger relationship with all-cause death and cardiovascular death independent of electrical dyssynchrony.14,15

Several studies suggested that the lack of response to CRT in some patients meeting traditional criteria may be due to the absence of LVMD.16,17 Using speckle-tracking strain imaging to assess mechanical dyssynchrony, Hara and colleagues noted that presence of LVMD improves CRT response with more favorable long-term outcomes especially in non-LBBB patients.18 Moreover, earlier studies assessing LVMD by tissue Doppler echocardiography proposed that reversal of ventricular remodeling by CRT is mainly attributable to an improved mechanical synchrony.19,20 Finally, in some patients with HF and no electrical dyssynchrony (i.e., QRS < 120 ms), LVMD might still be present and those patients may benefit from CRT.21 The evidence suggests that the benefit of CRT is driven by the presence of LVMD, yet in the clinical setting electrical dyssynchrony (aka. QRS width/presence of LBBB) is used as the primary and only target.1

The above cited evidence was recently challenged by large randomized trials which found that no echocardiographic parameter of LVMD can predict CRT response accurately.22,23 Importantly, those two trials assessed LVMD by tissue Doppler echocardiography limited by reproducibility and standardization in methodology. More recently nuclear imaging techniques were developed to allow for a more accurate measurement of LVMD, eliminating the inter- and intra-observer variability that plagued echocardiography-based techniques.24 Assessment of LVMD by MPI has indeed shown to aid in selecting CRT candidates.25,26 Using cut-off values of 72.5° for histogram bandwidth (HBW) and 19.6° for phase standard deviation (SD), Boogers and colleagues found 83% sensitivity and 81% specificity for prediction of CRT response.27 Using cut-off values for MPI dyssynchrony parameters could further aid clinical decision making regarding CRT implantation.28 Recently, new cut-off values for the four dyssynchrony parameters obtained by MPI in CRT candidates were determined, and they could possibly be used as part of an algorithm that includes other variables (clinical information, LVEF, etc.) to help come up with a decision about CRT implantation.28,29 Unfortunately, to date we lack prospective randomized trials to show the value of such MPI dyssynchrony parameters on clinical decision making for CRT patient selection and CRT lead positioning. Thus future work will be tremendously important to clarify the significance of MPI-derived dyssynchrony in patients with and without electrical dyssynchrony and whether it is of value in guiding treatment pathways.

Notes

Disclosure

MF is supported by an American Heart Association Grant (17MCPRP33460225) and a NIH T32 Grant (5T32HL007101). Further he is on the advisory board for GE Healthcare. SB received research Grant support from GE Healthcare.

References

  1. 1.
    Yu CM, Lin H, Zhang Q, Sanderson JE. High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration. Heart 2003;89:54-60.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Yu CM, Yang H, Lau CP, Wang Q, Wang S, Lam L, et al. Regional left ventricle mechanical asynchrony in patients with heart disease and normal QRS duration: Implication for biventricular pacing therapy. Pacing Clin Electrophysiol 2003;26:562-70.CrossRefPubMedGoogle Scholar
  3. 3.
    Leclercq C, Kass DA. Retiming the failing heart: Principles and current clinical status of cardiac resynchronization. J Am Coll Cardiol 2002;39:194-201.CrossRefPubMedGoogle Scholar
  4. 4.
    Auricchio A, Abraham WT. Cardiac resynchronization therapy: Current state of the art: Cost versus benefit. Circulation. 2004;109:300-7.CrossRefPubMedGoogle Scholar
  5. 5.
    Leclercq C, Hare JM. Ventricular resynchronization: Current state of the art. Circulation 2004;109:296-9.CrossRefPubMedGoogle Scholar
  6. 6.
    Woods B, Hawkins N, Mealing S, Sutton A, Abraham WT, Beshai JF, et al. Individual patient data network meta-analysis of mortality effects of implantable cardiac devices. Heart 2015;101:1800-6.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bertini M, Höke U, van Bommel RJ, Ng AC, Shanks M, Nucifora G, et al. Impact of clinical and echocardiographic response to cardiac resynchronization therapy on long-term survival. Eur Heart J Cardiovasc Imaging 2013;14:774-81.CrossRefPubMedGoogle Scholar
  8. 8.
    Linde C, Abraham WT, Gold MR, Daubert JC, Tang ASL, Young JB, et al. Predictors of short-term clinical response to cardiac resynchronization therapy. Eur J Heart Fail 2017;19:1056-63.CrossRefPubMedGoogle Scholar
  9. 9.
    Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 2010;363:2385-95.CrossRefPubMedGoogle Scholar
  10. 10.
    Zareba W, Klein H, Cygankiewicz I, Hall WJ, McNitt S, Brown M, et al. Effectiveness of cardiac resynchronization therapy by QRS morphology in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT). Circulation 2011;123:1061-72.CrossRefPubMedGoogle Scholar
  11. 11.
    Bilchick KC, Kamath S, DiMarco JP, Stukenborg GJ. Bundle-branch block morphology and other predictors of outcome after cardiac resynchronization therapy in Medicare patients. Circulation 2010;122:2022-30.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Sze E, Samad Z, Dunning A, Campbell KB, Loring Z, Atwater BD, et al. Impaired recovery of left ventricular function in patients with cardiomyopathy and left bundle branch block. J Am Coll Cardiol 2018;71:306-17.CrossRefPubMedGoogle Scholar
  13. 13.
    Bader H, Garrigue S, Lafitte S, Reuter S, Jaïs P, Haïssaguerre M, et al. Intra-left ventricular electromechanical asynchrony. A new independent predictor of severe cardiac events in heart failure patients. J Am Coll Cardiol 2004;43:248-56.CrossRefPubMedGoogle Scholar
  14. 14.
    Hess PL, Shaw LK, Fudim M, Iskandrian AE, Borges-Neto S. The prognostic value of mechanical left ventricular dyssynchrony defined by phase analysis from gated single-photon emission computed tomography myocardial perfusion imaging among patients with coronary heart disease. J Nucl Cardiol. 2016.Google Scholar
  15. 15.
    Hess PL, Shaw LK, Vemulapalli S, Pagnanelli R, O’Connor CM, Borges-Neto S. An alternative method to examine the predictive value of mechanical dyssynchrony. J Nucl Cardiol 2015;22:686-9.CrossRefPubMedGoogle Scholar
  16. 16.
    Emkanjoo Z, Esmaeilzadeh M, Mohammad Hadi N, Alizadeh A, Tayyebi M, Sadr-Ameli MA. Frequency of inter- and intraventricular dyssynchrony in patients with heart failure according to QRS width. Europace 2007;9:1171-6.CrossRefPubMedGoogle Scholar
  17. 17.
    Perry R, De Pasquale CG, Chew DP, Aylward PE, Joseph MX. QRS duration alone misses cardiac dyssynchrony in a substantial proportion of patients with chronic heart failure. J Am Soc Echocardiogr 2006;19:1257-63.CrossRefPubMedGoogle Scholar
  18. 18.
    Hara H, Oyenuga OA, Tanaka H, Adelstein EC, Onishi T, McNamara DM, et al. The relationship of QRS morphology and mechanical dyssynchrony to long-term outcome following cardiac resynchronization therapy. Eur Heart J 2012;33:2680-91.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Yu CM, Chau E, Sanderson JE, Fan K, Tang MO, Fung WH, et al. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105:438-45.CrossRefPubMedGoogle Scholar
  20. 20.
    Stellbrink C, Breithardt OA, Franke A, Sack S, Bakker P, Auricchio A, et al. Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances. J Am Coll Cardiol 2001;38:1957-65.CrossRefPubMedGoogle Scholar
  21. 21.
    Bleeker GB, Schalij MJ, Molhoek SG, Verwey HF, Holman ER, Boersma E, et al. Relationship between QRS duration and left ventricular dyssynchrony in patients with end-stage heart failure. J Cardiovasc Electrophysiol 2004;15:544-9.CrossRefPubMedGoogle Scholar
  22. 22.
    Chung ES, Leon AR, Tavazzi L, Sun JP, Nihoyannopoulos P, Merlino J, et al. Results of the predictors of response to CRT (PROSPECT) trial. Circulation 2008;117:2608-16.CrossRefPubMedGoogle Scholar
  23. 23.
    Ruschitzka F, Abraham WT, Singh JP, Bax JJ, Borer JS, Brugada J, et al. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N Engl J Med 2013;369:1395-405.CrossRefPubMedGoogle Scholar
  24. 24.
    Boogers MJ, Chen J, Veltman CE, van Bommel RJ, Mooyaart EA, Al Younis I, et al. Left ventricular diastolic dyssynchrony assessed with phase analysis of gated myocardial perfusion SPECT: A comparison with tissue Doppler imaging. Eur J Nucl Med Mol Imaging 2011;38:2031-9.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Henneman MM, Chen J, Dibbets-Schneider P, Stokkel MP, Bleeker GB, Ypenburg C, et al. Can LV dyssynchrony as assessed with phase analysis on gated myocardial perfusion SPECT predict response to CRT? J Nucl Med 2007;48:1104-11.CrossRefPubMedGoogle Scholar
  26. 26.
    Azizian N, Rastgou F, Ghaedian T, Golabchi A, Bahadorian B, Khanlarzadeh V, et al. LV dyssynchrony assessed with phase analysis on gated myocardial perfusion SPECT can predict response to crt in patients with end-Stage heart failure. Res Cardiovasc Med 2014;3:e20720.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Boogers MM, Van Kriekinge SD, Henneman MM, Ypenburg C, Van Bommel RJ, Boersma E, et al. Quantitative gated SPECT-derived phase analysis on gated myocardial perfusion SPECT detects left ventricular dyssynchrony and predicts response to cardiac resynchronization therapy. J Nucl Med 2009;50:718-25.CrossRefPubMedGoogle Scholar
  28. 28.
    Borges-Neto S, Samad Z. In search of the perfect indicators of left ventricular mechanical dyssynchrony. J Nucl Cardiol 2015;22:1259-61.CrossRefPubMedGoogle Scholar
  29. 29.
    Romero-Farina G, Aguadé-Bruix S, Candell-Riera J, Pizzi MN, García-Dorado D. Cut-off values of myocardial perfusion gated-SPECT phase analysis parameters of normal subjects, and conduction and mechanical cardiac diseases. J Nucl Cardiol 2015;22:1247-58.CrossRefPubMedGoogle Scholar

Copyright information

© American Society of Nuclear Cardiology 2018

Authors and Affiliations

  1. 1.Duke Department of Medicine and Division of CardiologyDurhamUSA
  2. 2.Duke Clinical Research InstituteDurhamUSA
  3. 3.Duke Department of Radiology and Division of Nuclear MedicineDurhamUSA

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