Risk factors for the development of adverse cardiovascular events in patients with a combination of non-compaction and dilated cardiomyopathy

The objective is to identify factors associated with adverse cardiovascular events in a cohort of patients with a combination of non-compaction (NCCM) and dilated cardiomyopathy (DCM) in order to reveal high-risk patients.
Materials and methods. 104 patients with a combination of NCCM and DCM aged 31 to 52 years (median age 41 years; 81 men; 23 women) were examined, who, in addition to traditional clinical research methods, underwent cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement. The endpoints of the study included progression of chronic heart failure (CHF) to functional class (FC) III NYHA requiring hospitalization, ventricular tachyarrhythmias and thromboembolic events.
Results. During the 24-month follow-up period (from 7 to 183) adverse cardiovascular events were registered in 84 (80.7%) patients, of which progression of CHF to FC III NYHA – in 47 (45.2%). Univariate analysis showed that the following characteristics were independent risk factors for the progression of CHF: symptoms of CHF II FC at the initial examination (HR 15.4; 95% CI 1.9-125.3, p = 0.0002), male gender (HR 4.6; 95% CI 1.3-16.1, p = 0.01), LVEF < 40% (HR 1.3; 95% CI 1.1-1.4, p = 0.0004), an increase in left ventricular end-diastolic volume index (LV EDVI) (HR 1.02; 95% CI 1.01-1.04, p = 0.0262), an increase in left ventricular end-systolic volume index (LV ESVI) (HR 1.04; 95% CI 1.01-1.06, p = 0.0080), right ventricular fractional area change (RV FAC) (HR 0.9; 95% CI 0.8-1.0, p = 0.0478) according to transthoracic echocardiogram (TTE) data, a decrease in global longitudinal strain (GLS) level ≤ 11% (HR 4.7; 95% CI 1.2-17.4, p = 0.0207) according to 2D Strain and percentage of myocardial fibrosis according to CMR imaging with late gadolinium enhancement (HR 0.94; 95% CI 0.9-1.0, p = 0.0329).
26 (25.0%) patients developed ventricular tachyarrhythmias, associated with the following risk factors: premature ventricular contractions (PVCs) > 500 bpm (HR 45; 95% CI 7.5-751.2, p = 0.0005), a decrease in the GLS level ≤ 11% (HR 5.3; 95% CI 1.03-27.4, p = 0.0282) according to 2D Strain data.
11 (10.6%) developed embolic events, the predictors of which were: atrial fibrillation/flutter (HR 24; 95% CI 3.0-188.2, p = 0.0037), left atrium volume index (LAVI) (HR 32.2; 95% CI 1.2-956, p = 0.0352) and LVEF < 40% according to CMR (HR 1.33; 95% CI 1.03-1.7, p = 0.0269).
Conclusion. Factors associated with the risk of adverse events are the pre- sence at the initial examination of symptoms of FC II CH by NYHA, male gender, LVEF ≤ 40%, an increase in LAVI ≥ 57 ml/m2, a decrease in GLS ≤ 11%, the presence of myocardial fibrosis according to CMR imaging with late gadolinium enhancement, PVCs > 500 bpm according to 24-hour ECG monitoring, which can be used to identify patients at high risk of adverse cardiovascular events.

1. Arbustini E., Weidemann F., Hall J. Left ventricular noncompaction: a distinct cardiomyopathy or a trait shared by different cardiac diseases? J Am Coll Cardiol, 2014, vol. 64, pp. 1840-1850. DOI: 10.1016/j.jacc.2014.08.030.

2. Maron B.J., Towbin J.A., Thiene G., Antzelevitch C., Corrado D., Arnett D., Moss A.J., Seidman C.E., Young J.B. Contemporary Definitions and Classification of the Cardiomyopathies: An American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation, 2006, vol. 113(14), pp. 1807-1816. DOI: 10.1161/CIRCULATIONAHA. 106.174287.

3. Elliott P., Andersson B., Arbustini E., Bilinska Z., Cecchi F., Charron P., Dubourg O., Kühl U., Maisch B., McKenna W.J., Monserrat L., Pankuweit S., Rapezzi C., Seferovic P., Tavazzi L., Keren A. Classification of the cardiomyopathies: a position statement from the european society of cardiology working group on myocardial and pericardial diseases. Eur Heart J, 2007, vol. 29(2), pp. 270-276. DOI: 10.1093/eurheartj/ehm342.

4. Arbustini E., Favalli V., Narula N., Serio A., Grasso M. Left Ventricular Noncompaction: A Distinct Genetic Cardiomyopathy? J Am Coll Cardiol, 2016, vol. 68(9), pp. 949-966. DOI: 10.1016/j.jacc.2016.05.096.

5. van Waning J.I., Caliskan K., Michels M., Schinkel A.F.L., Hirsch A., Dalinghaus M., Hoedemaekers Y.M., Wessels M.W., IJpma A.S., Hofstra R.M.W., van Slegtenhorst M.A., Majoor-Krakauer D. Cardiac Phenotypes, Genetics, and Risks in Familial Noncompaction Cardiomyopathy. J Am Coll Cardiol, 2019, vol. 73(13), pp. 1601-1611. DOI: 10.1016/j.jacc.2018.12.085.

6. Aras D., Tufekcioglu O., Ergun K., Ozeke O., Yildiz A., Topaloglu S., Deveci B., Sahin O., Kisacik H.L., Korkmaz S. Clinical features of isolated ventricular noncompaction in adults long-term clinical course, echocardiographic properties, and predictors of left ventricular failure. J Card Fail, 2006, vol. 12(9), pp. 726-733. DOI: 10.1016/j.cardfail.2006.08.002.

7. Hänselmann A., Veltmann C., Bauersachs J., Berliner D. Dilated cardiomyopathies and non-compaction cardiomyopathy. Herz, 2020, vol. 45(3), pp. 212-220. DOI: 10.1007/s00059-020-04903-5.

8. Amzulescu M.S., Rousseau M.F., Ahn S.A., Boileau L., de Meester de Ravenstein C., Vancraeynest D., Pasquet A., Vanoverschelde J.L., Pouleur A.C., Gerber B.L. Prognostic Impact of Hypertrabeculation and Noncompaction Phenotype in Dilated Cardiomyopathy: A CMR Study. JACC Cardiovasc Imaging, 2015, vol. 8(8), pp. 934-946. DOI: 10.1016/j.jcmg.2015.04.015.

9. Sedaghat-Hamedani F., Haas J., Zhu F., Geier C., Kayvanpour E., Liss M., Lai A., Frese K., Pribe-Wolferts R., Amr A., Li D.T., Samani O.S., Carstensen A., Bordalo D.M., Müller M., Fischer C., Shao J., Wang J., Nie M., Yuan L., Haßfeld S., Schwartz C., Zhou M., Zhou Z., Shu Y., Wang M., Huang K., Zeng Q., Cheng L., Fehlmann T., Ehlermann P., Keller A., Dieterich C., Streckfuß-Bömeke K., Liao Y., Gotthardt M., Katus H.A., Meder B. Clinical genetics and outcome of left ventricular non-compaction cardiomyopathy. Eur Heart J, 2017, vol. 38(46), pp. 3449-3460. DOI: 10.1093/eurheartj/ehx545.

10. Ivanov A., Dabiesingh D.S., Bhumireddy G.P., Mohamed A., Asfour A., Briggs W.M., Ho J., Khan S.A., Grossman A., Klem I., Sacchi T.J., Heitner J.F. Prevalence and Prognostic Significance of Left Ventricular Noncompaction in Patients Referred for Cardiac Magnetic Resonance Imaging. Circ Cardiovasc Imaging, 2017, vol. 10(9), pp. e006174. DOI: 10.1161/CIRCIMAGING.117.006174.

11. Zemrak F., Ahlman M.A., Captur G., Mohiddin S.A., Kawel-Boehm N., Prince M.R., Moon J.C., Hundley W.G., Lima J.A., Bluemke D.A., Petersen S.E. The relationship of left ventricular trabeculation to ventricular function and structure over a 9.5-year follow-up: the MESA study. J Am Coll Cardiol, 2014, vol. 64(19), pp. 1971-1980. DOI: 10.1016/j.jacc.2014.08.035.

12. Andreini D., Pontone G., Bogaert J., Roghi A., Barison A., Schwitter J., Mushtaq S., Vovas G., Sormani P., Aquaro G.D., Monney P., Segurini C., Guglielmo M., Conte E., Fusini L., Dello Russo A., Lombardi M., Gripari P., Baggiano A., Fiorentini C., Lombardi F., Bartorelli A.L., Pepi M., Masci P.G. Long-Term Prognostic Value of Cardiac Magnetic Resonance in Left Ventricle Noncompaction: A Prospective Multicenter Study. J Am Coll Cardiol, 2016, vol. 68(20), pp. 2166-2181. DOI: 10.1016/j.jacc.2016.08.053.

13. Grigoratos C., Barison A., Ivanov A., Andreini D., Amzulescu M.S., Mazurkiewicz L., De Luca A., Grzybowski J., Masci P.G., Marczak M., Heitner J.F., Schwitter J., Gerber B.L., Emdin M., Aquaro G.D. Meta-Analysis of the Prognostic Role of Late Gadolinium Enhancement and Global Systolic Impairment in Left Ventricular Noncompaction. JACC Cardiovasc Imaging, 2019, vol. 12(11 Pt 1), pp. 2141-2151. DOI: 10.1016/j.jcmg.2018.12.029.

14. Jenni R., Oechslin E., Schneider J., Attenhofer Jost C., Kaufmann P.A. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart (British Cardiac Society), 2001, vol. 86(6), pp. 666-671. PMID: 11711464.

15. Petersen S.E., Selvanayagam J.B., Wiesmann F., Robson M.D., Francis J.M., Anderson R.H., Watkins H., Neubauer S. Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging. J Am Col Cardiol, 2005, vol. 46(1), pp. 101-105. DOI: 10.1016/j.jacc.2005.03.045.

16. Jacquier A., Thuny F., Jop B., Giorgi R., Cohen F., Gaubert J.Y., Vidal V., Bartoli J.M., Habib G., Moulin G. Measurement of trabeculated left ventricular mass using cardiac magnetic resonance imaging in the diagnosis of left ventricular non-compaction. Eur Heart J, 2010, vol. 31(9), pp. 1098-1104. DOI: 10.1093/eurheartj/ehp595.

17. Lang R.M., Bierig M., Devereux R.B., Flachskampf F.A., Foster E., Pellikka P.A., Picard M.H., Roman M.J., Seward J., Shanewise J., Solomon S., Spencer K.T., St John Sutton M., Stewart W. American Society of Echocardiography’s Nomenclature and Standards Committee; Task Force on Chamber Quantification; American College of Cardiology Echocardiography Committee; American Heart Association; European Association of Echocardiography, European Society of Cardiology. Recommendations for chamber quantification. Eur J Echocardiogr, 2006, vol. 7(2), pp. 79-108. DOI: 10.1016/j.euje.2005.12.014.

18. McDonagh T.A., Metra M., Adamo M., Gardner R.S., Baumbach A., Böhm M., Burri H., Butler J., Čelutkienė J., Chioncel O., Cleland J.G.F., Coats A.J.S., Crespo-Leiro M.G., Farmakis D., Gilard M., Heymans S., Hoes A.W., Jaarsma T., Jankowska E.A., Lainscak M., Lam C.S.P., Lyon A.R., McMurray J.J.V., Mebazaa A., Mindham R., Muneretto C., Francesco Piepoli M., Price S., Rosano G.M.C., Ruschitzka F., Kathrine Skibelund A. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J, 2021, vol. 42(36), pp. 3599-3726. DOI: 10.1093/eurheartj/ehab368.

19. Lausen B., Hothorn T., Bretz F., Schumacher M. Assessment of Optimal Selected Prognostic Factors. Biometrical Journal, 2004, vol. 46(3), pp. 364-374. DOI: 10.1002/bimj.200310030.

20. Kalbfleisch J.D., Prentice R.L. The statistical analysis of failure time data. John Wiley & Sons, 2011. DOI: 10.1002/9781118032985.

21. Aung N., DOImo S., Ricci F., Sanghvi M.M., Pedrosa C., Woodbridge S.P., Al-Balah A., Zemrak F., Khanji M.Y., Munroe P.B., Naci H., Petersen S.E. Prognostic Significance of Left Ventricular Noncompaction: Systematic Review and Meta-Analysis of Observational Studies. Circ Cardiovasc Imaging, 2020, vol. 13(1), pp. e009712. DOI: 10.1161/CIRCIMAGING.119.009712.

22. Di Marco A., Anguera I., Schmitt M., Klem I., Neilan T.G., White J.A., Sramko M., Masci P.G., Barison A., Mckenna P., Mordi I., Haugaa K.H., Leyva F., Rodriguez Capitán J., Satoh H., Nabeta T., Dallaglio P.D., Campbell N.G., Sabaté X., Cequier Á. Late gadolinium enhancement and the risk for ventricular arrhythmias or sudden death in dilated cardiomyopathy. JACC Heart Fail, 2017, vol. 5(1), pp. 28-38. DOI: 10.1016/j.jchf.2016.09.017.

23. Halliday B.P., Gulati A., Ali A., Guha K., Newsome S., Arzanauskaite M., Vassiliou V.S., Lota A., Izgi C., Tayal U., Khalique Z., Stirrat C., Auger D., Pareek N., Ismail T.F., Rosen S.D., Vazir A., Alpendurada F., Gregson J., Frenneaux M.P., Cowie M.R., Cleland J.G.F., Cook S.A., Pennell D.J., Prasad S.K. Association between midwall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction. Circulation, 2017, vol. 135(22), pp. 2106-2115. DOI: 10.1161/CIRCULATIONAHA.116.026910.

24. Arunamata A., Stringer J., Balasubramanian S., Tacy T.A., Silverman N.H., Punn R. Cardiac Segmental Strain Analysis in Pediatric Left Ventricular Noncompaction Cardiomyopathy. J Am Soc Echocardiogr, 2019, vol. 32(6), pp. 763-773.e1. DOI: 10.1016/j.echo.2019.01.014.

25. Huttin O., Venner C., Frikha Z., Voilliot D., Marie P.Y., Aliot E., Sadoul N., Juillière Y., Brembilla-Perrot B., Selton-Suty C. Myocardial deformation pattern in left ventricular non-compaction: Comparison with dilated cardiomyopathy. Int J Cardiol Heart Vasc, 2014, vol. 5, pp. 9-14. DOI: 10.1016/j.ijcha.2014.11.001.