2015


To access this material please log in or register

Register Authorize
2015/№6

The algorithm of diagnosis and treatment for patients with dilated cardiomyopathy

Vaykhanskaya T. G.1, Kurushko T. V.1, Sivitskaya L. N.2, Danilenko N. G.2, Shestakova L. G.1, Frolov A. V.1
1 – State Institution Republican Science and Practice Center “Cardiology”, R. Luxemburg 110, Minsk 220036, Republic of Belarus
2 – State Science Institution, “Institute of Genetics and Cytology of Belarus National Academy of Sciences”, Akademicheskaya 27, Minsk 220072, Republic of Belarus

Keywords: dilated cardiomyopathy, microvolt T-wave alteration, heart rate turbulence, lamin A/C gene, sudden cardiac death, cardiac resynchronization therapy, cardioverter-defibrillator

DOI: 10.18087/rhfj.2015.6.2165

Background. The major causes of death from dilated cardiomyopathy (DCMP) are sudden cardiac death (SCD) and decompensated congestive HF. Cardiac resynchronization therapy (CRT) using biventricular stimulation allows increasing survival of patients with systolic dysfunction and HF. An important issue of CRT is the lack of effect in 30–37 % of patients. This article present results of a multifactorial regression analysis for risk markers of SCD and predictors of response to CRT in patients with DCMP. Aim. To develop an algorithm for diagnosis and treatment and for selection of an optimal electrophysiological therapy in patients with familial and idiopathic DCMP based on the use of 4th generation digital electrocardiography and molecular genetic analysis of the lamin gene. Materials and methods. The study included 207 patients with DCMP (males, 81.2 %; 48.9±11.4; NYHA FC, 3.01±0.29; LV EF, 28.6±9.12 %). A comprehensive examination, including EchoCG, Holter ECG monitoring (HM); 7‑min ECG recording using the Intecard-7 analysis of heart rate turbulence (HRT) and microvolt T-wave alternations, was performed for all patients. According to the developed algorithm for detection of DCMP a virological screening (PCR method) was used for 143 patients who noticed a connection of first HF symptoms with a past viral infection; a genetic study (SSCP and sequencing) of the lamin A / C gene (LMNA) was performed in 116 patients (18 probands with familial DCMP and 98 idiopathic cases with primary manifestation of heart rhythm and conductance disorders). Results. The regression analysis included all analyzed parameters (ECG / HM, EchoCG, virus positivity, and changes in the lamin gene). The multifactorial analysis showed that the index of left ventricular systolic dysfunction (LV EF ≤21 %), a positive mTWA test (mTWA ≥35.4 mcV), nucleotide replacements rs4641С / Т in exon 10 of the LMNA gene, and abnormal HRT (TO ≥1.31 %) were independent predictors of SCD. A combination of these factors was used for risk stratification, and a group of potential candidates for CVD implantation was identified. OR and ROC analyses identified an independent predictor for a positive response to CRT, duration of the RS interval in the chest lead V1 with a threshold value of RS ≥127 ms (OR, 3.94; 95 % CI, 1.65–9.23; p<0.001), as an additional criterion supplementing standard indications for CRT to enhance the method effectiveness. Conclusion. Based on the obtained data and evaluating the identified risk predictors for SCD and the ECG marker for CRT effectiveness, an algorithm was developed for selection of an optimum electrophysiological treatment (CVD implantation, CRT-P, or CRT-D) of patients with DCMP.
  1. Watkins H, Ashrafian H, Fedwood C. Inherited cardiomyopathies. New Engl J Med. 2011 Apr 28;364 (17):1643–56.
  2. Landolina M, Perego GB, Lunati M, Curnis A, Guenzati G, Vicentini A et al. Remote monitoring reduces healthcare use and improves quality of care in heart failure patients with implantable defibrillators: the evolution of management strategies of heart failure patients with implantable defibrillators (EVOLVO) study. Circulation. 2012 Jun 19;125924):2985–92.
  3. Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B et al. Combined cardiac resynchronization and implan­table cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA. 2003 May 28;289 (20):2685–94.
  4. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004 May 20;350 (21):2140–50.
  5. Saxon LA, Olshansky B, Volosin K, Steinberg JS, Lee BK, Tomassoni G et al. Influence of left ventricular lead location on outcomes in the COMPANION study. J Cardiovasc Electrophysiol. 2009 Jul;20 (7):764–8.
  6. Thebault C, Donal E, Meunier C, Gervais R, Gerritse B, Gold MR et al. Sites of left and right ventricular lead implantation and response to cardiac resynchronization therapy observations from the REVERSE trial. Eur Heart J. 2012 Nov;33 (21):2662–71.
  7. Singh JP, Klein HU, Huang DT, Reek S, Kuniss M, Quesada A et al. Left ventricular lead position and clinical outcome in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) trial. Circulation. 2011 Mar 22;123 (11):1159–66.
  8. Khan FZ, Virdee MS, Palmer CR, Pugh PJ, O’Halloran D, Elsik M et al. Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial. J Am Coll Cardiol. 2012 Apr 24;59 (17):1509–18.
  9. Abraham WT, Leon AR, St John Sutton MG, Keteyian SJ, Fieberg AM, Chinchoy E, Haas G. Randomized controlled trial comparing simultaneous versus optimized sequential interventricular stimulation during cardiac resynchronization therapy. Am Heart J. 2012 Nov;164 (5):735–41.
  10. Boriani G, Muller CP, Seidl KH, Grove R, Vogt J, Danschel W et al. Randomized comparison of simultaneous biventricular stimulation versus optimized interventricular delay in cardiac resynchronization therapy. The Resynchronization for the HemodYnamic Treatment for Heart Failure Management II implantable cardioverter defibrillator (RHYTHM II ICD) study. Am Heart J. 2006 May;151 (5):1050–8.
  11. Bradley DJ, Bradley EA, Baughman KL, Berger RD, Calkins H, Goodman SN et al. Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials. JAMA. 2003 Feb 12;289 (6):730–40.
  12. Boriani G, Gardini B, Diemberger I, Bacchi Reggiani ML, Biffi M, Martignani C et al. Meta-analysis of randomized controlled trials evaluating left ventricular vs. biventricular pacing in heart failure: effect on all-cause mortality and hospitalizations. Eur J Heart Fail. 2012 Jun;14 (6):652–60.
  13. Higgins SL, Hummel JD, Niazi IK, Giudici MC, Worley SJ, Saxon LA et al. Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias. J Am Coll Cardiol. 2003 Oct 15;42 (8):1454–9.
  14. McAlister FA, Ezekowitz JA, Wiebe N, Rowe B, Spooner C, Crumley E et al. Systematic review: cardiac resynchronization in patients with symptomatic heart failure. Ann Intern Med. 2004 Sep 7;141 (5):381–90.
  15. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352 (15):1539–49.
  16. Gervais R, Leclercq C, Shankar A, Jacobs S, Eiskjaer H, Johannessen A et al. Surface electrocardiogram to predict outcome in candidates for cardiac resynchronization therapy: a sub-analysis of the CARE-HF trial. Eur J Heart Fail. 2009 Jul;11 (7):699–705.
  17. Arbustini E, Narula N, Dec GW, Reddy KS, Greenberg B, Kushwaha S et al. The MOGE (S) classification for a phenotype-genotype nomenclature of cardiomyopathy: endorsed by the World Heart Federation. J Am Coll Cardiol. 2013 Dec 3;62 (22):2046–72.
  18. Charron P, Arad M, Arbustini E, Basso C, Bilinska Z, Elliott P et al. Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2010 Nov;31 (22):2715–26.
  19. Hershberger RE, Morales A, Siegfried JD. Clinical and genetic issues in dilated cardiomyopathy: a review for genetics professio­nals. Genet Med. 2010 Nov;12 (11):655–67.
  20. Van Tintelen JP, Pieper PG, Van Spaendonck-Zwarts KY, Van Den Berg MP. Pregnancy, cardiomyopathies, and genetics. Cardiovasc Res. 2014 Mar 15;101 (4):571–8.
  21. Hershberger RE, Siegfried JD. Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol. 2011 Apr 19:57 (16):1641–9.
  22. Van Rijsingen IA, Arbustini E, Elliott PM, Mogensen J, Hermans-van Ast JF, van der Kooi AJ et al. Risk factors for malignant ventricular arrhythmias in lamin A / C mutation carriers a European cohort study. J Am Coll Cardiol. 2012 Jan 31;59 (5):493–500.
  23. Meune C, Van Berlo JH, Anselme F, Bonne G, Pinto YM, Duboc D. Primary prevention of sudden death in patients with la­min A / C gene mutations. N Engl J Med. 2006 Jan 12;354 (2):209–10.
  24. Mestroni L, Maisch B, McKenna W, Schwartz K, Charron P, Rocco C et al. Guidelines for the study of familial dilated cardiomyopathies. Eur Heart J. 1999 Jan;20 (2):93–102.
  25. Goodwin JF, Oakley CM. The cardiomyopathies. Br Heart J. 1972;34:545–52.
  26. Verrier R, Klingenheben T, Malik M, El-Sherif N, Exner DV, Hohnloser SH et al. Microvolt T-wave alternans: physiological basis, methods of measurement, and clinical utility – Consensus Guidelines by International Society for Holter Monitoring and Noninvasive Electrocardiology. J Am Coll Cardiol. 2011 Sep 20;58 (3):1309–24.
  27. Bauer A, Malik M, Schmidt G, Barthel P, Bonnemeier H, Guzik P et al. Heart rate turbulence: standards of measurement, physiologicalinterpretation, and clinical use: International Society for Holter and Noninvasive Electrophysiology Consensus. J Am Coll Cardiol. 2008 Oct 21;52 (17):1353–65.
  28. Brignole М, Auricchio А, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. The Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Eur Heart J. 2013 Aug;34 (29):2281–329.
  29. Вайханская Т. Г., Курушко Т. В., Cидоренко И. В., Коптюх Т. М., Гуль Л. М., Mельникова О. П. и др. Электрокардиографические предикторы ответа на ресинхронизирующую терапию сердечной недостаточности у пациентов с дилатационной кардиомиопатией. Кардиология. 2013;53 (3):48–54.
Vaykhanskaya T. G., Kurushko T. V., Sivitskaya L. N., Danilenko N. G., Shestakova L. G., Frolov A. V. The algorithm of diagnosis and treatment for patients with dilated cardiomyopathy. Russian Heart Failure Journal. 2015;16 (6):344–359

To access this material please log in or register

Register Authorize
Ru En