NEUROTROPIC MYOCARDIAL SCINTIGRAPHY IN THE EVALUATION OF SUDDEN CARDIAC DEATH PROGNOSIS IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

Objective. To explore the features of cardiac sympathetic activity impairments using neurotropic scintigraphy and singlephoton emission tomography (SPECT) in patients with hypertrophic cardiomyopathy (HCM), including the context of the risk of sudden cardiac death (SCD).

Material and methods. 36 patients with HCM, II–IV NYHA CHF grade, underwent cardiac neurotropic scintigraphy and SPECT with 123I-MIBG. 30 patients also underwent cardiac perfusion SPECT with 99mTc-MIBI, standard quantitative parameters of global and local left ventricular sympathetic activity and perfusion impairments were obtained. After 5 years of follow-up, the analysis of the dependence of the frequency of SCD in patients with HCM on the values of the above parameters was performed.

Results. All parameters of perfusion and neurotropic myocardial SPECT were significantly different in patients with HCM compared with the control group (p<0.001). According to perfusion SPECT data, significant transient ischemia of the myocardium (SDS>4) in the main group was detected in 32% of cases, while it had a diffuse character and had no connection with certain coronary artery regions. The volume of regional innervation defects (SMSe) in HCM patients significantly exceeded the total volume of perfusion defects (SSS, p<0.001). SMSe and SSS parameters had a direct correlation (r=0.52, p=0.002). SMSe was higher in patients with HCM with arrhythmias (p=0.046), and lower in patients with HCM with manifestations of angina and cardialgia (p=0.04). Based on the results of a five-year follow-up, SCD occurred in 8 patients with HCM. SMSe was a predictor of SCD (AUC=0.76, p=0.01), its value >14 predicted the occurrence of SCD with sensitivity of 87.5% and specificity of 57.1%. The risk of five-year mortality from SCD was significantly higher when SMSe >14 (p=0.024).

Conclusion. Neurotropic SPECT in patients with HCM is able to identify a group of patients at high risk of sudden cardiac death.

1. Wigle E.D., Rakowski H., Kimball B.P., Williams W.G. Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation. 1995; 92 (7): 1680–92.

2. Semsarian C., Ingles J., Maron M.S., Maron B.J. New perspectives on the prevalence of hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 2015; 65 (12): 1249–54.

3. Maron B.J., Olivotto I., Spirito P., Casey S.A., Bellone P., Gohman T.E. et al. Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large non-referral-based patient population. Circulation. 2000; 102 (8): 858–64.

4. Maron B.J., Epstein S.E., RobertsW. C. Hypertrophic cardiomyopathy and transmural myocardial infarction without significant atherosclerosis of the extramural coronary arteries. Am. J. Cardiol. 1979; 43 (6): 1086–102.

5. Pedrinelli R., Spessot M., Chiriatti G., Gistri R., Salvadori P., Catapano G. et al. Evidence for a systemic defect of resistance-sized arterioles in hypertrophic cardiomyopathy. Coron. Artery Dis. 1993; 4 (1): 67–72.

6. Roberts R. Molecular genetics. Therapy or terror? Circulation. 1994; 89 (1): 499–502.

7. Watkins H., McKenna W.J., Thierfelder L., Suk H.J., Anan R., O'Donoghue A. et al. Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N. Engl. J. Med. 1995; 332 (16): 1058–64.

8. Shaver J.A., Salerni R., Curtiss E.I., Follansbee W.P. Clinical presentation and noninvasive evaluation of the patient with hypertrophic cardiomyopathy. Cardiovasc. Clin. 1988; 19 (1): 149–92.

9. Mohri M., Takeshita A. Coronary microvascular disease in humans. Jpn Heart J. 1999; 40 (2): 97–108.

10. Ho C.Y., Sweitzer N.K., McDonough B., Maron B.J., Casey S.A., Seidman J.G. et al. Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation. 2002; 105 (25): 2992–7.

11. Goodwin J.F. Cardiomyopathies and specific heart muscle diseases. Definitions, terminology, classifications and new and old approaches. Postgrad. Med. J. 1992; 68 (Suppl. 1): S3–6.

12. Spirito P., Seidman C.E., McKennaW. J., Maron B.J. The management of hypertrophic cardiomyopathy. N. Engl. J. Med. 1997; 336 (11): 775–85.

13. Rapacciuolo A., Esposito G., Caron K., Mao L., Thomas S.A., Rockman H.A. Important role of endogenous norepinephrine and epinephrine in the development of in vivo pressure- overload cardiac hypertrophy. J. Am. Coll. Cardiol. 2001; 38 (3): 876–82.

14. Rockman H.A., Koch W.J., Lefkowitz R.J. Seven-transmembranespanning receptors and heart function. Nature. 2002; 415 (6868): 206–12.

15. Швалев В.Н., Реутов В.П., Рогоза А.Н., Сергиенко В.Б., Аншелес А.А., Ковалев В.П. Развитие современных представлений о нейрогенной природе кардиологических заболеваний. Тихоокеанский медицинский журнал. 2014; 1: 10–4. [Shvalev V.N., Reutov V.P., Rogoza A.N., Sergienko V.B., Ansheles A.A., Kovalev V.P. Development of modern ideas about the neurogenic nature of cardiac diseases. Tikhookeanskiy Meditsinskiy Zhurnal (Pacific Medical Journal, Russian journal). 2014; 1: 10–4 (in Russ.).]

16. Лишманов Ю.Б., Завадовский К.В., Ефимова И.Ю., Кривоногов Н.Г., Веснина Ж.В., Сазонова С.И. и др. Возможности ядерной медицины в диагностике сердечно-сосудистых заболеваний. Сибирский медицинский журнал. 2015; 30 (2): 21–9. [Lishmanov Yu.B., Zavadovskiy K.V., Efimova I.Yu., Krivonogov N.G., Vesnina Zh.V., Sazonova S.I. et al. The possibilities of nuclear medicine in the diagnosis of cardiovascular diseases. Sibirskiy Meditsinskiy Zhurnal (Siberian Medical Journal, Russian journal). 2015; 30 (2): 21–9 (in Russ.).]

17. Лишманов Ю.Б., Саушкина Ю.В., Минин С.М., Ефимова И.Ю., Кистенева И.В., Попов С.В. Сцинтиграфическая оценка состояния симпатической иннервации сердца и миокардиальной перфузии у пациентов с фибрилляцией предсердий. Российский кардиологический журнал. 2014; 12: 13–8. [Lishmanov Yu.B., Saushkina Yu.V., Minin S.M., Efimova I.Yu., Kisteneva I.V., Popov S.V. Scintigraphic evaluation of cardiac sympathetic innervation and myocardial perfusion in patients with atrial fibrillation. Rossiyskiy Kardiologicheskiy Zhurnal (Russian Cardiology Journal). 2014; 12: 13–8 (in Russ.).]

18. Wichter T., Schafers M., Rhodes C.G., Borggrefe M., Lerch H., Lammertsma A.A. et al. Abnormalities of cardiac sympathetic innervation in arrhythmogenic right ventricular cardiomyopathy: quantitative assessment of presynaptic norepinephrine reuptake and postsynaptic beta-adrenergic receptor density with positron emission tomography. Circulation. 2000; 101 (13): 1552–8.

19. Somsen G.A., Verberne H.J., Fleury E., Righetti A. Normal values and within-subject variability of cardiac I-123 MIBG scintigraphy in healthy individuals: implications for clinical studies. J. Nucl. Cardiol. 2004; 11 (2): 126–33.

20. Knollmann D., Knebel I., Koch K.C., Gebhard M., Krohn T., Buell U., Schaefer W.M. Comparison of SSS and SRS calculated from normal databases provided by QPS and 4D- MSPECT manufacturers and from identical institutional normals. Eur. J. Nucl. Med. Mol. Imag. 2008; 35 (2): 311–8.

21. Holly T.A., Abbott B.G., Al-Mallah M., Calnon D.A., Cohen M.C., DiFilippo F.P. et al. Single photonemission computed tomography. J. Nucl. Cardiol. 2010; 17 (5): 941–73.

22. Hachamovitch R., Hayes S.W., Friedman J.D., Cohen I., Berman D.S. A prognostic score for prediction of cardiac mortality risk after adenosine stress myocardial perfusion scintigraphy. J. Am. Coll. Cardiol. 2005; 45 (5): 722–9.

23. Hachamovitch R., Hayes S.W., Friedman J.D., Cohen I., Berman D.S. Stress myocardial perfusion singlephoton emission computed tomography is clinically effective and cost effective in risk stratification of patients with a high likelihood of coronary artery disease (CAD) but no known CAD. J. Am. Coll. Cardiol. 2004; 43 (2): 200–8.

24. Сергиенко В.Б., Самойленко Л.Е. Радионуклидная оценка состояния симпатической иннервации миокарда. Кардиологический вестник. 2006; 2: 43–51. [Sergienko V.B., Samoylenko L.E. Radionuclide evaluation of sympathetic innervation of the myocardium. Kardiologicheskiy Vestnik (Cardiological Bulletin, Russian journal). 2006; 2: 43–51 (in Russ.).]

25. Imamura Y., Ando H., Mitsuoka W., Egashira S., Masaki H., Ashihara T., Fukuyama T. Iodine-123 metaiodobenzylguanidine images reflect intense myocardial adrenergic nervous activity in congestive heart failure independent of underlying cause. J. Am. Coll. Cardiol. 1995; 26 (7): 1594–9.

26. Gimelli A., Liga R., Genovesi D., Giorgetti A., Kusch A., Marzullo P. Association between left ventricular regional sympathetic denervation and mechanical dyssynchrony in phase analysis: a cardiac CZT study. Eur. J. Nucl. Med. Mol. Imag. 2014; 41 (5): 946–55.

27. Лишманов Ю.Б., Ефимова И.Ю., Чернов В.И., Веснина Ж.В., Кривоногов Н.Г., Макарова Е.В. и др. Сцинтиграфия как инструмент диагностики, прогнозирования и мониторинга лечения болезней сердца. Сибирский медицинский журнал. 2007; 22 (3): 74–7. [Lishmanov Yu.B., Efimova I.Yu., Chernov V.I., Vesnina Zh.V., Krivonogov N.G., Makarova E.V. et al. Scintigraphy as a tool for diagnosing, predicting and monitoring the treatment of heart diseases. Sibirskiy Meditsinskiy Zhurnal (Siberian Medical Journal, Russian journal). 2007; 22 (3): 74–7 (in Russ.).]

28. Аншелес А.А., Сергиенко В.Б. Современные возможности радионуклидной диагностики при артериальной гипертензии. Системные гипертензии. 2016; 13 (1): 22– 8. [Ansheles A.A., Sergienko V.B. Modern possibilities of nuclear imaging diagnostics in arterial hypertension. Sistemnye Gipertenzii (Systemic Hypertension, Russian journal). 2016; 13 (1): 22–8 (in Russ.).]

29. Аншелес А.А., Шульгин Д.Н., Соломяный В.В., Сергиенко В.Б. Сопоставление результатов нагрузочных проб, данных однофотонной эмиссионной компьютерной томографии миокарда и коронарографии у больных ишемической болезнью сердца. Кардиологический вестник. 2012; VII (2): 10–6. [Ansheles A.A., Shul’- gin D.N., Solomyanyy V.V., Sergienko V.B. Comparison of the results of stress tests, single-photon emission computer tomography of myocardium and coronarography in patients with ischemic heart disease. Kardiologicheskiy Vestnik (Cardiological Bulletin, Russian journal). 2012; VII (2): 10–6 (in Russ.).]

30. Zipes D.P. Influence of myocardial ischemia and infarction on autonomic innervation of heart. Circulation. 1990; 82 (4): 1095–105.

31. Bax J.J., Kraft O., Buxton A.E., Fjeld J.G., Parizek P., Agostini D. et al. 123 I-mIBG scintigraphy to predict inducibility of ventricular arrhythmias on cardiac electrophysiology testing: a prospective multicenter pilot study. Circ. Cardiovasc. Imag. 2008; 1 (2): 131–40.

32. Maron B.J. Hypertrophic cardiomyopathy: a systematic review. JAMA. 2002; 287 (10): 1308–20.

33. Pace L., Betocchi S., Losi M.A., Della Morte A.M., Ciampi Q., Nugnez R. et al. Sympathetic nervous function in patients with hypertrophic cardiomyopathy assessed by [123I]-MIBG: relationship with left ventricular perfusion and function. Q. J. Nucl. Med. Mol. Imag. 2004; 48 (1): 20–5.

34. Casset-Senon D., Philippe L., Cosnay P., Lopez-Moutault J., Turot- Bracq V., Fauchier J.P., Pottier J.M. Isotopic study of myocardial perfusion and innervation in 28 patients with primary hypertrophic cardiomyopathy: relation to ventricular arrhythmia. Arch. Mal. Coeur. Vaiss. 1994; 87 (4): 475–83.