Skip to main content

Advertisement

SpringerLink
Log in

Myocardial fibrosis and ventricular ectopy in patients with non-ischemic systolic heart failure: results from the DANISH trial

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Patients with non-ischemic systolic heart failure (HF) have increased risk of sudden cardiovascular death (SCD). The initiation and substrate for ventricular arrhythmias remains poorly understood. Our purpose was to describe the relationship between cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) and Holter recorded ventricular arrhythmic activity. Patients from the DANISH trial underwent a Holter-recording and a CMR-scan. The presence of non-sustained ventricular tachycardia (NSVT) and premature ventricular contractions (PVC) were examined in relation to presence and amount of LGE. Outcome measures were all-cause mortality and SCD. Overall, 180 patients were included. LGE was present in 86 (47%). NSVT occurred in 72 (40%), not different according to LGE status (p = 0.65). The amount of LGE was not correlated to the occurrence of NSVT (p = 0.40). The occurrence of couplet PVCs (p = 0.997), frequent PVCs (p = 0.12), PVCs in bigemini (p = 0.29), in trigemini (p = 0.26), or in quadrimini (p = 0.35) did not differ according to LGE status. LGE was significantly associated with risk of all-cause mortality (HR 2.14; 95% CI 1.05–4.37, p = 0.04). NSVT did not increase risk of all-cause mortality in either patients with LGE (HR 1.00; 95% CI 0.46–2.16, p = 0.996) or without LGE (HR 1.37; 95% CI 0.46–4.08, p = 0.57). There was no interaction between LGE and NSVT for the risk of all-cause mortality (p = 0.62). In patients with non-ischemic systolic HF there was no relationship between the presence of LGE and NSVT or any other Holter recorded ventricular tachyarrhythmia. LGE was associated with increased risk of mortality, independent of the presence of NSVT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ørn S, Dickstein K (2002) How do heart failure patients die? Eur Heart J Suppl 4:D59–D65

    Article  Google Scholar 

  2. Neilan TG, Coelho-Filho OR, Danik SB, Shah RV, Dodson JA, Verdini DJ, Tokuda M, Daly CA, Tedrow UB, Stevenson WG, Jerosch-Herold M, Ghoshhajra BB, Kwong RY (2013) CMR quantification of myocardial scar provides additive prognostic information in nonischemic cardiomyopathy. JACC Cardiovasc Imaging 6:944–954

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gulati A, Jabbour A, Ismail TF, Guha K, Khwaja J, Raza S, Morarji K, Brown TDH, Ismail NA, Dweck MR, Di Pietro E, Roughton M, Wage R, Daryani Y, O’Hanlon R, Sheppard MN, Alpendurada F, Lyon AR, Cook SA, Cowie MR, Assomull RG, Pennell DJ, Prasad SK (2013) Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA 309:896–908

    Article  CAS  PubMed  Google Scholar 

  4. Wu KC, Weiss RG, Thiemann DR, Kitagawa K, Schmidt A, Dalal D, Lai S, Bluemke DA, Gerstenblith G, Marbán E, Tomaselli GF, Lima JAC (2008) Late gadolinium enhancement by cardiovascular magnetic resonance heralds an adverse prognosis in nonischemic cardiomyopathy. J Am Coll Cardiol 51:2414–2421

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ruberman W, Weinblatt E, Goldberg JD, Frank CW, Shapiro S (1977) Ventricular premature beats and mortality after myocardial infarction. N Engl J Med 297:750–757

    Article  CAS  PubMed  Google Scholar 

  6. Ruberman W, Weinblatt E, Goldberg JD, Frank CW, Chaudhary BS, Shapiro S (1981) Ventricular premature complexes and sudden death after myocardial infarction. Circulation 64:297–305

    Article  CAS  PubMed  Google Scholar 

  7. Doval HC, Nul DR, Grancelli HO, Varini SD, Soifer S, Corrado G, Dubner S, Scapin O, Perrone SV (1996) Nonsustained ventricular tachycardia in severe heart failure. Independent marker of increased mortality due to sudden death. GESICA-GEMA Investigators. Circulation 94:3198–3203

    Article  CAS  PubMed  Google Scholar 

  8. Boas R, Thune JJ, Pehrson S, Køber L, Nielsen JC, Videbæk L, Haarbo J, Korup E, Bruun NE, Brandes A, Eiskjær H, Thøgersen AM, Philbert BT, Svendsen JH, Dixen U (2020) Prevalence and prognostic association of ventricular arrhythmia in non-ischaemic heart failure patients: results from the DANISH trial. Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol 23:587–595

    Google Scholar 

  9. Elming MB, Hammer-Hansen S, Voges I, Nyktari E, Raja AA, Svendsen JH, Pehrson S, Signorovitch J, Køber L, Prasad SK, Thune JJ (2020) Myocardial fibrosis and the effect of primary prophylactic defibrillator implantation in patients with non-ischemic systolic heart failure-DANISH-MRI. Am Heart J 221:165–176

    Article  PubMed  Google Scholar 

  10. Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbæk L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjær H, Brandes A, Thøgersen AM, Gustafsson F, Egstrup K, Videbæk R, Hassager C, Svendsen JH, Høfsten DE, Torp-Pedersen C, Pehrson S, DANISH Investigators (2016) Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med 375:1221–1230

    Article  PubMed  Google Scholar 

  11. Thune JJ, Pehrson S, Nielsen JC, Haarbo J, Videbæk L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjær H, Brandes A, Thøgersen AM, Egstrup K, Hastrup-Svendsen J, Høfsten DE, Torp-Pedersen C, Køber L (2016) Rationale, design, and baseline characteristics of the DANish randomized, controlled, multicenter study to assess the efficacy of Implantable cardioverter defibrillators in patients with non-ischemic systolic heart failure on mortality (DANISH). Am Heart J 179:136–141

    Article  PubMed  Google Scholar 

  12. Amado LC, Gerber BL, Gupta SN, Rettmann DW, Szarf G, Schock R, Nasir K, Kraitchman DL, Lima JAC (2004) Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model. J Am Coll Cardiol 44:2383–2389

    Article  PubMed  Google Scholar 

  13. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, González-Juanatey JR, Harjola V-P, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P (2016) 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 37:2129–2200

    Article  PubMed  Google Scholar 

  14. Karamitsos TD, Francis JM, Myerson S, Selvanayagam JB, Neubauer S (2009) The role of cardiovascular magnetic resonance imaging in heart failure. J Am Coll Cardiol 54:1407–1424

    Article  PubMed  Google Scholar 

  15. de Boer RA, De Keulenaer G, Bauersachs J, Brutsaert D, Cleland JG, Diez J, Du X-J, Ford P, Heinzel FR, Lipson KE, McDonagh T, Lopez-Andres N, Lunde IG, Lyon AR, Pollesello P, Prasad SK, Tocchetti CG, Mayr M, Sluijter JPG, Thum T, Tschöpe C, Zannad F, Zimmermann W-H, Ruschitzka F, Filippatos G, Lindsey ML, Maack C, Heymans S (2019) Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology. Eur J Heart Fail 21(3):272–285

    Article  PubMed  Google Scholar 

  16. Mikami Y, Jolly U, Heydari B, Peng M, Almehmadi F, Zahrani M, Bokhari M, Stirrat J, Lydell CP, Howarth AG, Yee R, White JA (2017) Right ventricular ejection fraction is incremental to left ventricular ejection fraction for the prediction of future arrhythmic events in patients with systolic dysfunction. Circ Arrhythm Electrophysiol. https://doi.org/10.1161/CIRCEP.116.004067

    Article  PubMed  Google Scholar 

  17. Gulati A, Ismail TF, Jabbour A, Alpendurada F, Guha K, Ismail NA, Raza S, Khwaja J, Brown TDH, Morarji K, Liodakis E, Roughton M, Wage R, Pakrashi TC, Sharma R, Carpenter J-P, Cook SA, Cowie MR, Assomull RG, Pennell DJ, Prasad SK (2013) The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy clinical perspective. Circulation 128:1623–1633

    Article  PubMed  Google Scholar 

  18. Elming MB, Hammer-Hansen S, Voges I, Nyktari E, Raja AA, Svendsen JH, Pehrson S, Signorovitch J, Køber LV, Prasad SK, Thune JJ (2019) Right ventricular dysfunction and the effect of defibrillator implantation in patients with nonischemic systolic heart failure. Circ Arrhythm Electrophysiol 12:e007022

    Article  PubMed  Google Scholar 

  19. Romano S, Judd RM, Kim RJ, Kim HW, Klem I, Heitner JF, Shah DJ, Jue J, White BE, Indorkar R, Shenoy C, Farzaneh-Far A (2018) Feature-tracking global longitudinal strain predicts death in a multicenter population of patients with ischemic and nonischemic dilated cardiomyopathy incremental to ejection fraction and late gadolinium enhancement. JACC Cardiovasc Imaging. 11:1419–1429

  20. Kawakubo M, Yamasaki Y, Toyomura D, Yamamura K, Sakamoto I, Moriyama T, Yabuuchi H, Ishigami K (2021) Unchanged right ventricular strain in repaired tetralogy of Fallot after pulmonary valve replacement with radial long-axis cine magnetic resonance images. Sci Rep 11:18879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Acosta J, Fernández-Armenta J, Borràs R, Anguera I, Bisbal F, Martí-Almor J, Tolosana JM, Penela D, Andreu D, Soto-Iglesias D, Evertz R, Matiello M, Alonso C, Villuendas R, de Caralt TM, Perea RJ, Ortiz JT, Bosch X, Serra L, Planes X, Greiser A, Ekinci O, Lasalvia L, Mont L, Berruezo A (2018) Scar characterization to predict life-threatening arrhythmic events and sudden cardiac death in patients with cardiac resynchronization therapy. JACC Cardiovasc Imaging 11:561–572

    Article  PubMed  Google Scholar 

  22. Schmidt A, Azevedo CF, Cheng A, Gupta SN, Bluemke DA, Foo TK, Gerstenblith G, Weiss RG, Marbán E, Tomaselli GF, Lima JAC, Wu KC (2007) Infarct tissue heterogeneity by magnetic resonance imaging identifies enhanced cardiac arrhythmia susceptibility in patients with left ventricular dysfunction. Circulation 115:2006–2014

    Article  PubMed  PubMed Central  Google Scholar 

  23. Heidary S, Patel H, Chung J, Yokota H, Gupta SN, Bennett MV, Katikireddy C, Nguyen P, Pauly JM, Terashima M, McConnell MV, Yang PC (2010) Quantitative tissue characterization of infarct core and border zone in patients with ischemic cardiomyopathy by magnetic resonance is associated with future cardiovascular events. J Am Coll Cardiol 55:2762–2768

    Article  PubMed  Google Scholar 

  24. Roes SD, Borleffs CJW, van der Geest RJ, Westenberg JJM, Marsan NA, Kaandorp TAM, Reiber JHC, Zeppenfeld K, Lamb HJ, de Roos A, Schalij MJ, Bax JJ (2009) Infarct tissue heterogeneity assessed with contrast-enhanced MRI predicts spontaneous ventricular arrhythmia in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillator. Circ Cardiovasc Imaging 2:183–190

    Article  PubMed  Google Scholar 

  25. Goldberger JJ, Subačius H, Patel T, Cunnane R, Kadish AH (2014) Sudden cardiac death risk stratification in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol 63:1879–1889

    Article  PubMed  Google Scholar 

  26. Berkowitsch A, Zareba W, Neumann T, Erdogan A, Nitt SM, Moss AJ, Pitschner HF (2004) Risk stratification using heart rate turbulence and ventricular arrhythmia in MADIT II: usefulness and limitations of a 10-minute holter recording. Ann Noninvasive Electrocardiol 9:270–279

    Article  PubMed  PubMed Central  Google Scholar 

  27. Podrid PJ, Fogel RI, Fuchs TT (1992) Ventricular arrhythmia in congestive heart failure. Am J Cardiol 69:82G-95G (discussion 95G–96G)

    Article  CAS  PubMed  Google Scholar 

  28. Teerlink JR, Jalaluddin M, Anderson S, Kukin ML, Eichhorn EJ, Francis G, Packer M, Massie BM (2000) Ambulatory ventricular arrhythmias in patients with heart failure do not specifically predict an increased risk of sudden death. PROMISE (Prospective Randomized Milrinone Survival Evaluation) Investigators. Circulation 101:40–46

    Article  CAS  PubMed  Google Scholar 

  29. Pogwizd SM (1995) Nonreentrant mechanisms underlying spontaneous ventricular arrhythmias in a model of nonischemic heart failure in rabbits. Circulation 92:1034–1048

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The work was sponsored by The Danish Heart Foundation (Hjerteforeningen) and the Lundbeck Foundation (Lundbeckfonden). The contrast used for the CMR scans (Gadovist) was sponsored by Bayer. The DANISH trial was supported by grants from Medtronic and St. Jude Medical.

Author information

Authors and Affiliations

  1. Department of Cardiology, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 3, 9841, 2100, Copenhagen, Denmark

    Marie Bayer Elming, Sophia Hammer-Hansen, Jesper Hastrup Svendsen, Steen Pehrson, Berit T. Philbert & Lars Køber

  2. Department of Cardiology, Zealand University Hospital Roskilde, Roskilde, Denmark

    Marie Bayer Elming

  3. Department of Cardiology, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark

    Rune Boas & Ulrik Dixen

  4. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Rune Boas, Jesper Hastrup Svendsen, Steen Pehrson, Ulrik Dixen, Lars Køber & Jens Jakob Thune

  5. Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Sophia Hammer-Hansen

  6. Department of Congenital Heart Disease and Paediatric Cardiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Inga Voges

  7. Department of Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK

    Inga Voges, Eva Nyktari & Sanjay K. Prasad

  8. BIOLATRIKI HealthGROUP, CMR Unit, Athina, Greece

    Eva Nyktari

  9. Department of Cardiology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark

    Jens Jakob Thune

Authors
  1. Marie Bayer Elming
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rune Boas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sophia Hammer-Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Inga Voges
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eva Nyktari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jesper Hastrup Svendsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Steen Pehrson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ulrik Dixen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Berit T. Philbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sanjay K. Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lars Køber
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jens Jakob Thune
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marie Bayer Elming.

Ethics declarations

Conflict of interest

Dr. JH. Svendsen reports grants, personal fees and other from Medtronic. Dr. SK. Prasad reports honoraria for talks from Bayer Schering. Remaining authors have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 58 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elming, M.B., Boas, R., Hammer-Hansen, S. et al. Myocardial fibrosis and ventricular ectopy in patients with non-ischemic systolic heart failure: results from the DANISH trial. Int J Cardiovasc Imaging 38, 2437–2445 (2022). https://doi.org/10.1007/s10554-022-02653-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-022-02653-5

Keywords

Search

Navigation