The effectiveness of cardiac resynchronization therapy in patients with chronic heart failure of various origin depending on the structural myocardial injury in cardiac magnetic resonance imaging

Aim. To assess the effect of the size and pattern of myocardial structural injury, determined by magnetic resonance imaging (MRI), on response to cardiac resynchronization therapy (CRT) in patients with ischemic and non-ischemic heart failure (HF).

Material and methods. Forty seven patients with ischemic and non-ischemic HF (age 62,3±8,9 years (mean±SD), 44,6% females and 55,4% males), left ventricle (LV) ejection fraction <35%, QRS complex >130 ms, and sinus rhythm were included in the study. Late-gadolinium enhancement-cardiovascular magnetic resonance (LGE-CMR) was undertaken to evaluate myocardial scar prior to CRT devices implantation. All CMR analysis was performed on CVI42 software. According to signal intensity, fibrosis zone and “grey zone” were defined for quantitative analysis (proportion and mass) of injury. Scar zone included fibrosis zone and “grey zone”. Scar location was assessed using a 16-segmentLV model. Response was defined as a reduction inLV end systolic volume of >15% at 6 months follow-up and HF functional class amelioration.

Results. In nonresponse group there was significantly higher proportion and mass of total scar (median 4% [2,5; 19] vs 24% [7; 44], p=0,012,6 g [3,5; 32,5] vs41 g [8; 86], p=0,013)), fibrosis zone (median 0% [0; 3,5] vs 8% [0; 19], p=0,01,0 g [0; 6] vs14 g [0; 34], p=0,014) and “grey zone” (4% [2,5; 15] vs 15% [7; 23], p=0,018,6 g [3,5; 27,5] vs23 g [8; 39], p=0,25). Response proportion in non-ischemic HF patients was higher than in ischemic HF patients (78,5% vs 28,5%, p<0,01). Response to CRT was less in patients with posterolateral scar, more specifically in segments 4,5,6,11,12,15,16 (p<0,05). CRT response in ischemic HF did not depend on size of myocardial structural injury, but depend on scar localization. Lateral scar was associated with poor response. In non-ischemic HF, proportion and mass of fibrosis zone was less in responder group (median 0% [0; 1] vs 8,5% [0; 11], p<0,05,0 g [0; 1] vs14,5 g [0; 22], p<0,05.

Conclusion. Response to CRT is significantly higher in non-ischemic than in ischemic HF patients. Nonresponse to CRT is associated with posterolateral scar, regardless of the HF origin. In patients with non-ischemic HF, size of fibrosis zone is lower in the responder group. In patients with ischemic HF, size ofLV structural injury does not affect the CRT efficiency, but lateral scar is associated with CRT nonresponse.

1. Linde C, Leclercq C, Rex S, et al. Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. J. Am. Coll. of Cardiol. 2002;40:111-8. doi:10.1016/s0735-1097(02)01932-0.

2. Chung ES, Leon AR, Tavazzi L, et al. Results of the Predictors of Response to CRT (PROSPECT) trial. Circulation. 2008;117(20):2608-16. doi:10.1161/circulationaha.107.743120.

3. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2016;37(27):2129-2200. doi:10.1093/eurheartj/ehw128.

4. Zareba W, Klein H, Cygankiewicz I, et al. for the MADIT-CRT Investigators. 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. doi:10.1161/circulationaha.110.960898.

5. Mewton N, Liu CY, Croisille P, et al. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol. 2011;57:891-903. doi:10.1016/j.jacc.2010.11.013.

6. Mironova NA, Yeghiazaryan LH, Aparina OP, et al. Relations between structural changes in the myocardium and rhythm disturbance in patients with chronic myocardial infarction. Russian Electronic Journal of Radiology. 2017;7(3):53-68. (In Russ.) doi:10.21569/2222-7415-2017-7-3-53-68.

7. Zhambeev AA, Gasparyan AZh, Stukalova OV, Shlevkov NB. Value of contrast-enhanced MRI for risk-stratification of sudden cardiac death in different patients with structural heart disease. Russian Electronic Journal of Radiology. 2017;7(4):130-9. (In Russ.) doi:10.21569/2222-74152017-7-4-130-139.

8. Dill T. Contraindications to magnetic resonance imaging. Heart. 2008;94(7):943-8. doi:10.1136/hrt.2007.125039.

9. Kramer CM, Barkhausen J, Flamm SD, et al. Society for Cardiovascular Magnetic Resonance Board of Trustees Task Force on Standardized Protocols. Standardized cardiovascular magnetic resonance (CMR) protocols 2013 update. J Cardiovasc Magn Reson. 2013;15:91. doi:10.1186/1532-429X-15-91.

10. Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart. Circulation. 2002;105(4):539-42. doi:10.1161/hc0402.102975.

11. Wikstrom G, Blomstrom-Lundqvist C, Andren B, et al. The effects of aetiology on outcome in patients treated with cardiac resynchronization therapy in the CARE-HF trial. Eur Heart J. 2009;30:782-8. doi:10.1093/eurheartj/ehn577.

12. Kwon DH, Halley CM, Carrigan TP, et al. Extent of left ventricular scar predicts outcomes in ischemic cardiomyopathy patients with significantly reduced systolic function: a delayed hyperenhancement cardiac magnetic resonance study. J Am Coll Cardiol Cardiovasc Imaging. 2009;2:34-44. doi:10.1016/j.jcmg.2008.09.010.

13. Chalil S, Foley PWX, Muyhaldeen SA, et al. Late gadolinium enhancement cardiovascular magnetic resonance as a predictor of response to cardiac resynchronization therapy in patients with ischaemic cardiomyopathy. Europace. 2007;9:1031-7. doi:10.1093/europace/eum133.

14. White JA, Yee R, Yuan X, et al. Delayed enhancement magnetic resonance imaging predicts response to cardiac resynchronization therapy in patients with intraventricular dyssynchrony. J Am Coll Cardiol. 2006;48:1953-60. doi:10.1016/j.jacc.2006.07.046.

15. Ypenburg C, Roes SD, Bleeker GB, et al. Effect of total scar burden on contrast-enhanced magnetic resonance imaging on response to cardiac resynchronization therapy. Am J Cardiol. 2007;99(5):657-60. doi:10.1016/j.amjcard.2006.09.115.

16. Chalil S, Stegemann B, Muhyaldeen S, et al. Effect of posterolateral left ventricular scar on mortality and morbidity following cardiac resynchronization therapy. Pacing Clin Electrophysiol. 2007;10:1201-7. doi:10.1111/j.1540-8159.2007.00841.

17. Bleeker GB. Effect of posterolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronization therapy. Circulation. 2006;113:969-76. doi:10.1161/circulationaha.105.543678.

18. Chen Z, Sohal M, Sammut E, et al. Focal but not diffuse myocardial fibrosis burden quantification using cardiac magnetic resonance imaging predicts left ventricular reverse modeling following cardiac resynchronization therapy. J Cardiovasc Electrophysiol. 2016;27(2):203-9. doi:10.1111/jce.12855.

19. Leong DP, Chakrabarty A, Shipp N, et al. Effects of myocardial fibrosis and ventricular dyssynchrony on response to therapy in new-presentation idiopathic dilated cardiomyopathy: insights from cardiovascular magnetic resonance and echocardiography. Eur Heart J. 2012;33(5):640-8. doi:10.1093/eurheartj/ehr391.