Association of ECG parameters with late gadolinium enhancement and outcome in patients with clinical suspicion of acute or subacute myocarditis referred for CMR imaging

Kady Fischer, Maximilian Marggraf, Anselm W Stark, Kyoichi Kaneko, Ayaz Aghayev, Dominik P Guensch, Adrian T Huber, Michael Steigner, Ron Blankstein, Tobias Reichlin, Stephan Windecker, Raymond Y Kwong, Christoph Gräni, Kady Fischer, Maximilian Marggraf, Anselm W Stark, Kyoichi Kaneko, Ayaz Aghayev, Dominik P Guensch, Adrian T Huber, Michael Steigner, Ron Blankstein, Tobias Reichlin, Stephan Windecker, Raymond Y Kwong, Christoph Gräni

Abstract

Background: Risk stratification of myocarditis is challenging due to variable clinical presentations. Cardiovascular magnetic resonance (CMR) is the primary non-invasive imaging modality to investigate myocarditis while electrocardiograms (ECG) are routinely included in the clinical work-up. The association of ECG parameters with CMR tissue characterisation and their prognostic value were investigated in patients with clinically suspected myocarditis.

Methods and results: Consecutive patients with suspected myocarditis who underwent CMR and ECG were analysed. Major adverse cardiovascular event (MACE) included all-cause death, hospitalisation for heart failure, heart transplantation, documented sustained ventricular arrhythmia, or recurrent myocarditis. A total of 587 patients were followed for a median of 3.9 years. A wide QRS-T angle, low voltage and fragmented QRS were significantly associated with late gadolinium enhancement. Further, a wide QRS-T angle, low voltage and prolonged QTc duration were associated with MACE in the univariable analysis. In a multivariable model, late gadolinium enhancement (HR: 1.90, 95%CI: 1.17-3.10; p = 0.010) and the ECG parameters of a low QRS voltage (HR: 1.86, 95%CI: 1.01-3.42; p = 0.046) and QRS-T-angle (HR: 1.01, 95%CI: 1.00-1.01; p = 0.029) remained independently associated with outcome. The cumulative incidence of MACE was incrementally higher when findings of both CMR and ECG were abnormal (p<0.001).

Conclusion: In patients with clinically suspected myocarditis, abnormal ECG parameters are associated with abnormal tissue characteristics detected by CMR. Further, ECG and CMR findings have independent prognostic implications for morbidity and mortality. Integrating both exams into clinical decision-making may play a role in risk stratification in this heterogeneous patient population.

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Gräni receives funding support from the Novartis Foundation for Medical-Biological Research, Bangerter-Rhyner Foundation, Swiss Sports Medicine Society (SGSM) and Kreislauf Kardiologie Foundation. Dr. Kwong receives research support from NIH awards 1UH2 TR000901, 1RO1DK083424-01, and 1U01HL117006, Alnylam Pharmaceuticals, and the Society for the Cardiovascular Magnetic Resonance. The authors declare that they have no other conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Patient enrolment.
Fig 1. Patient enrolment.
A total of 744 patients were referred to cardiovascular magnetic resonance for suspected myocarditis with 587 patients included in the final analysis.
Fig 2. Relationship between ECG and CMR…
Fig 2. Relationship between ECG and CMR parameters and their association with MACE.
Brown connecting lines indicate significant associations (p

Fig 3. Cumulative incidence of MACE.

Kaplan…

Fig 3. Cumulative incidence of MACE.

Kaplan Meier curve of cumulative incidence, based on the…

Fig 3. Cumulative incidence of MACE.
Kaplan Meier curve of cumulative incidence, based on the presence of late gadolinium enhancement (LGE) and an abnormal electrocardiogram (ECG) marker of either fragmented QRS, wide QRS-T angle, prolonged QTc duration or low QRS voltage.

Fig 4. Patient with sustained ventricular tachycardia.

Fig 4. Patient with sustained ventricular tachycardia.

This is a case of a 62 year…

Fig 4. Patient with sustained ventricular tachycardia.
This is a case of a 62 year old male who experienced sustained ventricular tachycardia 4 months following the CMR exam, followed by death after 3.0 years. LGE Images (A-C) show a midwall distribution and linear pattern in the long-axis view (A), of which the extent of LGE was 11.0% highlighted yellow in the short-axis view (B). A bullseye plot representing the full left ventricle, shows the relative enhancement (yellow and black) afflicted all ventricular walls. The ECV map (D) demonstrated a similar pattern with a global ECV of 39.8% (red), while some oedema in the lateral wall (blue) was detected in the T2w images (E). At the CMR exam, left ventricular ejection fraction was 40%. A wide QRS-T angle was detected in the ECG. ECV: Extracellular Volume, fQRS: Fragmented QRS, LGE: Late Gadolinium Enhancement, T2w: T2 Weighted.
Fig 3. Cumulative incidence of MACE.
Fig 3. Cumulative incidence of MACE.
Kaplan Meier curve of cumulative incidence, based on the presence of late gadolinium enhancement (LGE) and an abnormal electrocardiogram (ECG) marker of either fragmented QRS, wide QRS-T angle, prolonged QTc duration or low QRS voltage.
Fig 4. Patient with sustained ventricular tachycardia.
Fig 4. Patient with sustained ventricular tachycardia.
This is a case of a 62 year old male who experienced sustained ventricular tachycardia 4 months following the CMR exam, followed by death after 3.0 years. LGE Images (A-C) show a midwall distribution and linear pattern in the long-axis view (A), of which the extent of LGE was 11.0% highlighted yellow in the short-axis view (B). A bullseye plot representing the full left ventricle, shows the relative enhancement (yellow and black) afflicted all ventricular walls. The ECV map (D) demonstrated a similar pattern with a global ECV of 39.8% (red), while some oedema in the lateral wall (blue) was detected in the T2w images (E). At the CMR exam, left ventricular ejection fraction was 40%. A wide QRS-T angle was detected in the ECG. ECV: Extracellular Volume, fQRS: Fragmented QRS, LGE: Late Gadolinium Enhancement, T2w: T2 Weighted.

References

    1. Fabre A, Sheppard MN. Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death. Heart Br Card Soc. 2006. March;92(3):316–20.
    1. Kawai C. From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future. Circulation. 1999. March 2;99(8):1091–100. 10.1161/01.cir.99.8.1091
    1. Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT, et al. Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009. April 28;53(17):1475–87. 10.1016/j.jacc.2009.02.007
    1. Mahrholdt H, Goedecke C, Wagner A, Meinhardt G, Athanasiadis A, Vogelsberg H, et al. Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology. Circulation. 2004. March 16;109(10):1250–8. 10.1161/01.CIR.0000118493.13323.81
    1. Morgera T, Di Lenarda A, Dreas L, Pinamonti B, Humar F, Bussani R, et al. Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes. Am Heart J. 1992. August;124(2):455–67. 10.1016/0002-8703(92)90613-z
    1. Porela P, Kytö V, Nikus K, Eskola M, Airaksinen KEJ. PR depression is useful in the differential diagnosis of myopericarditis and ST elevation myocardial infarction. Ann Noninvasive Electrocardiol Off J Int Soc Holter Noninvasive Electrocardiol Inc. 2012. April;17(2):141–5.
    1. Das Mithilesh K., Khan Bilal, Jacob Sony, Kumar Awaneesh, Mahenthiran Jo. Significance of a Fragmented QRS Complex Versus a Q Wave in Patients With Coronary Artery Disease. Circulation. 2006. May 30;113(21):2495–501. 10.1161/CIRCULATIONAHA.105.595892
    1. Konno T, Hayashi K, Fujino N, Oka R, Nomura A, Nagata Y, et al. Electrocardiographic QRS Fragmentation as a Marker for Myocardial Fibrosis in Hypertrophic Cardiomyopathy. J Cardiovasc Electrophysiol. 2015. October;26(10):1081–7. 10.1111/jce.12742
    1. Gräni C, Eichhorn C, Bière L, Murthy VL, Agarwal V, Kaneko K, et al. Prognostic Value of Cardiac Magnetic Resonance Tissue Characterization in Risk Stratifying Patients With Suspected Myocarditis. J Am Coll Cardiol. 2017. October 17;70(16):1964–76. 10.1016/j.jacc.2017.08.050
    1. Gräni C, Bière L, Eichhorn C, Kaneko K, Agarwal V, Aghayev A, et al. Incremental value of extracellular volume assessment by cardiovascular magnetic resonance imaging in risk stratifying patients with suspected myocarditis. Int J Cardiovasc Imaging. 2019. June;35(6):1067–78. 10.1007/s10554-019-01552-6
    1. Caforio ALP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013. September 1;34(33):2636–48. 10.1093/eurheartj/eht210
    1. Bozkurt Biykem, Colvin Monica, Cook Jennifer, Cooper Leslie T., Deswal Anita, Fonarow Gregg C., et al. Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association. Circulation. 2016. December 6;134(23):e579–646. 10.1161/CIR.0000000000000455
    1. Madias JE. Transient attenuation of the amplitude of the QRS complexes in the diagnosis of Takotsubo syndrome. Eur Heart J Acute Cardiovasc Care. 2014. March;3(1):28–36. 10.1177/2048872613504311
    1. Jain R, Singh R, Yamini S, Das MK. Fragmented ECG as a risk marker in cardiovascular diseases. Curr Cardiol Rev. 2014. August;10(3):277–86. 10.2174/1573403X10666140514103451
    1. Straus SMJM, Kors JA, De Bruin ML, van der Hooft CS, Hofman A, Heeringa J, et al. Prolonged QTc Interval and Risk of Sudden Cardiac Death in a Population of Older Adults. J Am Coll Cardiol. 2006. January 17;47(2):362–7. 10.1016/j.jacc.2005.08.067
    1. De Lazzari M, Zorzi A, Baritussio A, Siciliano M, Migliore F, Susana A, et al. Relationship between T-wave inversion and transmural myocardial edema as evidenced by cardiac magnetic resonance in patients with clinically suspected acute myocarditis: clinical and prognostic implications. J Electrocardiol. 2016. July 1;49(4):587–95. 10.1016/j.jelectrocard.2016.04.002
    1. Thygesen Kristian, Alpert Joseph S., Jaffe Allan S., Simoons Maarten L., Chaitman Bernard R., White Harvey D. Third Universal Definition of Myocardial Infarction. Circulation. 2012. October 16;126(16):2020–35. 10.1161/CIR.0b013e31826e1058
    1. Kawel-Boehm N, Maceira A, Valsangiacomo-Buechel ER, Vogel-Claussen J, Turkbey EB, Williams R, et al. Normal values for cardiovascular magnetic resonance in adults and children. J Cardiovasc Magn Reson Off J Soc Cardiovasc Magn Reson. 2015. April 18;17:29.
    1. Gräni C, Eichhorn C, Bière L, Kaneko K, Murthy VL, Agarwal V, et al. Comparison of myocardial fibrosis quantification methods by cardiovascular magnetic resonance imaging for risk stratification of patients with suspected myocarditis. J Cardiovasc Magn Reson. 2019. February 28;21(1):14 10.1186/s12968-019-0520-0
    1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016. 14;37(27):2129–200. 10.1093/eurheartj/ehw128
    1. Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, et al. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol. 2018. December 10;72(24):3158–76. 10.1016/j.jacc.2018.09.072
    1. Fronza M, Raineri C, Valentini A, Bassi EM, Scelsi L, Buscemi ML, et al. Relationship between electrocardiographic findings and Cardiac Magnetic Resonance phenotypes in patients with Hypertrophic Cardiomyopathy. IJC Heart Vasc. 2016. June 1;11:7–11.
    1. Maanja Maren, Wieslander Björn, Schlegel Todd T., Bacharova Ljuba, Abu Daya Hussein, Fridman Yaron, et al. Diffuse Myocardial Fibrosis Reduces Electrocardiographic Voltage Measures of Left Ventricular Hypertrophy Independent of Left Ventricular Mass. J Am Heart Assoc. 6(1):e003795 10.1161/JAHA.116.003795
    1. Deluigi CC, Ong P, Hill S, Wagner A, Kispert E, Klingel K, et al. ECG findings in comparison to cardiovascular MR imaging in viral myocarditis. Int J Cardiol. 2013. April 30;165(1):100–6. 10.1016/j.ijcard.2011.07.090
    1. Di Bella G, Florian A, Oreto L, Napolitano C, Todaro MC, Donato R, et al. Electrocardiographic findings and myocardial damage in acute myocarditis detected by cardiac magnetic resonance. Clin Res Cardiol. 2012. August 1;101(8):617–24. 10.1007/s00392-012-0433-5
    1. Chen S, Hoss S, Zeniou V, Shauer A, Admon D, Zwas DR, et al. Electrocardiographic Predictors of Morbidity and Mortality in Patients With Acute Myocarditis: The Importance of QRS-T Angle. J Card Fail. 2018;24(1):3–8. 10.1016/j.cardfail.2017.11.001
    1. Ukena C, Mahfoud F, Kindermann I, Kandolf R, Kindermann M, Böhm M. Prognostic electrocardiographic parameters in patients with suspected myocarditis. Eur J Heart Fail. 2011;13(4):398–405. 10.1093/eurjhf/hfq229
    1. Hung Y, Lin W-H, Lin C-S, Cheng S-M, Tsai T-N, Yang S-P, et al. The Prognostic Role of QTc Interval in Acute Myocarditis. Acta Cardiol Sin. 2016. March;32(2):223–30. 10.6515/ACS20150226A
    1. Laukkanen JA, Di Angelantonio E, Khan H, Kurl S, Ronkainen K, Rautaharju P. T-wave inversion, QRS duration, and QRS/T angle as electrocardiographic predictors of the risk for sudden cardiac death. Am J Cardiol. 2014. April 1;113(7):1178–83. 10.1016/j.amjcard.2013.12.026
    1. Schumm J, Greulich S, Wagner A, Grün S, Ong P, Bentz K, et al. Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis. J Cardiovasc Magn Reson Off J Soc Cardiovasc Magn Reson. 2014. January 26;16:14.
    1. Aquaro GD, Perfetti M, Camastra G, Monti L, Dellegrottaglie S, Moro C, et al. Cardiac MR With Late Gadolinium Enhancement in Acute Myocarditis With Preserved Systolic Function: ITAMY Study. J Am Coll Cardiol. 2017. October 17;70(16):1977–87. 10.1016/j.jacc.2017.08.044
    1. Grün S, Schumm J, Greulich S, Wagner A, Schneider S, Bruder O, et al. Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis: Predictors of Mortality and Incomplete Recovery. J Am Coll Cardiol. 2012. May 1;59(18):1604–15. 10.1016/j.jacc.2012.01.007
    1. Imazio M, Trinchero R. Myopericarditis: Etiology, management, and prognosis. Int J Cardiol. 2008. June 23;127(1):17–26. 10.1016/j.ijcard.2007.10.053
    1. von Knobelsdorff-Brenkenhoff F, Schüler J, Dogangüzel S, Dieringer MA, Rudolph A, Greiser A, et al. Detection and Monitoring of Acute Myocarditis Applying Quantitative Cardiovascular Magnetic Resonance. Circ Cardiovasc Imaging. 2017. February;10(2).
    1. Kotanidis CP, Bazmpani M-A, Haidich A-B, Karvounis C, Antoniades C, Karamitsos TD. Diagnostic Accuracy of Cardiovascular Magnetic Resonance in Acute Myocarditis: A Systematic Review and Meta-Analysis. JACC Cardiovasc Imaging. 2018. November 1;11(11):1583–90. 10.1016/j.jcmg.2017.12.008

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다