AN INDIVIDUALIZED RISK ASSESSMENT OF SUDDEN CARDIAC DEATH IN DILATION CARDIOMYOPATHY PATIENTS

Search for effective methods of risk stratification in patients with higher risk of lifethreatening ventricular tachyarrhythmias (VTA) and sudden cardiac death is important task for applied healthcare and a priority scientific field.

Aim. To invent a mathematic model and algorithm of individualized risk assessment for sudden cardiac death (SCD) in dilation cardiomyopathy patients (DCMP).

Material and methods. Totally, 165 patients included, with verified DCMP (mean age 49,2±11,5 y; 135/81,8% males; NYHA class 2,67±0,45; LV ejection fraction 26,7±10,1%; follow-up 46,7±12,5 months). With an original software “Intecard 7”, with the data of 7-minute ECG-12 registration, we evaluated markers of electrical instability of myocardium — microvoltage alternans of T-waves (mATW), turbulence of cardiac rhythm (TCR), intervals QT and JT dispersion, acceleration and deceleration of cardiac rhythm. As primary endpoints for multifactorial Cox-analysis we used sustained ventricular tachicardia (VT) or ventricular fibrillation, shocks of implanted devices and documented SCD. We analyzed clinical, electrocardiographic, echocardiographic data and results of molecular-genetic study of lamin A/C gene (LMNA).

Results. As result of multifactor regression analysis we found 2 cumulative independent predictors (HR 5,23; 95% CI 1,45-16,9; р=0,013) of life-threatening VTA events in DCMP patients: paroxysms of non-sustained VT (≥5 ventricular complexes with HR ≥150 bpm) and changes in LMNA gene (missense mutations and polymorhpism of 10 exon of rs4641). With binary logit-regression analysis of independent risk factors (VES, sVT, mATW, TCR, JTd and GLS LV) we built-up a model of binary regression (F=31,2; χ2=143,2; p=0,0000) and developed an algorithm of SCD risk evaluation that make it to classify with high prediction power up to 93,9%, cases of DCMP (OR 470; sensitivity 80,8%, specificity 99,1%).

Conclusion. The invented algorithm of SCD risk is non-ivasive, individualized, easily applicable and interpretable technology that makes it to stratify patients with higher risk of life-threatening VTA with standard clinical and instrumental methods of investigation (ECG, EchoCG, Holter ECG). Implementation of the oroginal riskstratification model makes it to optimize tactics of DCMP patients treatment and strategy of selection of potential candidates for cardioverter-defibrillator implanting for primary SCD prevention.

1. Hayashi M, Shimizu W, Albert CM. The spectrum of epidemiology underlying sudden cardiac death. Circ Res. 2015; 116: 1887-906. doi: 10.1161/CIRCRESAHA.116.304521

2. Schliamser JE, Kadish AH, Subacius H, et al. Significance of follow-up left ventricular ejection fraction measurements in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial. Heart Rhythm. 2013; 10: 838-46. doi: 10.1016/j.hrthm.2013.02.017.

3. Zecchin M, Merlo M, Pivetta A, et al. How can optimization of medical treatment avoid unnecessary implantable cardioverter-defibrillator implantations in patients with idiopathic dilated cardiomyopathy presenting with “SCD-HeFT criteria?” Am J Cardiol. 2012; 109: 729-35. doi: 10.1016/j.amjcard.2011.10.033.

4. Kuruvilla S, Adenaw N, Katwal AB, et al. Late Gadolinium Enhancement on CMR Predicts Adverse Cardiovascular Outcomes in Non-ischemic Cardiomyopathy: A Systematic Review and Meta-analysis. Circ Cardiovasc Imaging. 2014; 7(2): 250-8. doi:10.1161/CIRCIMAGING.113.001144.

5. Kusumoto FM, Calkins H, Boehmer J, et al. HRS/ACC/AHA expert consensus statement on the use of implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials. Circulation. 2014; 130: 94-125. doi:10.1016/j.jacc.2014.04.008

6. Bloomfield DM, Steinman RC, Namerow PB, et al. Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy. A solution to the multicenter automatic defibrillator implantation trial (MADIT) II conundrum. Circulation. 2004; 110: 1885-9. DOI: 10.1161/01.CIR.0000143160.14610.53

7. van Berlo JH, de Voogt WG, van der Kooi AJ, et al. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death? J Mol Med. 2005; 83: 79-83. DOI: 10.1007/s00109-004-0589-1

8. Pasotti M, Klersy C, Pilotto A, et al. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol. 2008; 52: 1250-60. doi: 10.1016/j.jacc.2008.06.044.

9. Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika. 1994; 81: 515-26. DOI: 10.1093/biomet/81.3.515.

10. Grimm W, Christ M, Maisch B. Long runs of non-sustained ventricular tachycardia on 24- hour ambulatory electrocardiogram predict major arrhythmic events in patients with idiopathic dilated cardiomyopathy. Pacing Clin Electrophysiol. 2005; 28 (suppl 1): S207-S210. DOI: 10.1111/j.1540-8159.2005.00035.

11. Grimm W, Christ M, Bach J, et al. Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study. Circulation. 2003; 108: 2883-91. DOI: 10.1161/01.CIR.0000100721.52503.85

12. van Rijsingen IA, Arbustini E, Elliott PM, et al. Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study. J Am Coll Cardiol. 2012; 59: 493-500. doi: 10.1016/j.jacc.2011.08.078.