Intramyocardial transplantation of autologous bone marrow mononuclear cells (BMMC) is believed to be a promising method for the treatment of patients with chronic ischemic heart disease. The aim of this study was to evaluate long-term results of intramyocardial bone marrow cell transplantation in patients with severe ischemic heart failure. One hundred nine patients with chronic myocardial infarction and end-stage chronic heart failure were randomized into two groups: 55 patients received intramyocardial BMMC injection and 54 received optimal medical therapy. The NOGA system (Biosense-Webster) was used to administer 41 +/- 16 x 106 BMMC into the border zone of myocardial infarction. None of the patients developed periprocedural complications following BMMC injections. The injections led to improvement of CCS class (3.1 +/- 0.4 to 1.6 +/- 0.6 after 6 months and 1.6 +/- 0.4 after 12 months; p = 0.001) and NYHA functional class (3.3 +/- 0.2 to 2.3 +/- 0.2 after 6 months and 2.5 +/- 0.1 after 12 months; p = 0.006). Left ventricular ejection fraction increased significantly in the BMMC group (27.8 +/- 3.4% vs 32.3 +/- 4.1%; p = 0.04) while it tended to decrease in the control group (26.8 +/- 3.8% to 25.2 +/- 4.1%; p = 0.61). Summed rest score improved in the BMMC group after 12 months (30.2 +/- 5.6 to 27.8 +/- 5.1; p = 0.032). The improvement of stress score was more noticeable (34.5 +/- 5.4 to 28.1 +/- 5.2; p = 0.016). Neither stress nor rest score changed in patients numbers on medical therapy. In BMMC group 6 (10.9%) patients died at 12-month follow-up compared with 21 (38.9%) in control group (log-rank test, p = 0.0007). Intramyocardial bone marrow cell transplantation to patients with ischemic heart failure is safe and improved survival, clinical symptoms, and has beneficial effect on LV function.

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Резюме Цель исследования. Изучить диагностически значимые для стабильных и нестабильных атеросклеротических бляшек (АСБ) разных типов показатели активности матриксных металлопротеиназ-ММП-3, ММП-7, ММП-9 в гомогенатах и тканевую экспрессию ММП-2, ММП-9 и коллагена 4-го типа. Материалы и методы. В исследование включены 54 мужчины с коронарным атеросклерозом без острого коронарного синдрома, у которых в ходе операции коронарного шунтирования проведена эндартерэктомия из коронарной артерии. В полученных образцах методом иммуноферментного анализа определяли уровни ММП-3, ММП-7 и ММП-9; выявляли тканевую экспрессию ММП-2, ММП-9 и коллагена 4-го типа. Результаты. В нестабильных АСБ повышена активность ММП-7 и ММП-9, отмечаются значительное увеличение тканевой экспрессии ММП-2 и ММП-9, снижение экспрессии коллагена 4-го типа. Из 3 типов нестабильных АСБ наибольшая тканевая экспрессия ММП-9 выявлена в АСБ липидного типа в сравнении с дистрофически-некротическим и воспалительно-эрозивным, а экспрессия коллагена 4-го типа преобладала в дистрофически-некротических АСБ. Заключение. Проведенное исследование определяет тканевую экспрессию коллагена как маркер стабильности фиброзной покрышки, а наличие металлопротеиназ в некротическом детрите, структурах внеклеточного матрикса и клеточных элементах может характеризовать АСБ как нестабильную либо находящуюся в переходном структурном состоянии. Иммуногистохимический метод позволяет выявить структурные элементы, характеризующие нестабильность в АСБ различных типов.

Most studies have confirmed the beneficial effects of autologous bone marrow mononuclear cell (BMMC) transplantation on angina, myocardial perfusion, regional wall motion, and LV ejection fraction (LVEF). Cardiac resynchronization therapy (CRT) has also shown a beneficial effect in patients with heart failure (HF) and electrical/mechanical dyssynchrony. However, the relative contribution of BMMC and CRT in patients with ischemic HF and electromechanical dyssynchrony has never been investigated. The aim of this study was to evaluate the benefit of combining BMMC transplantation with CRT in patients with severe ischemic HF, left bundle branch block (LBBB), and mechanical dyssynchrony. Patients with ischemic HF, LVEF < 35%, LBBB, and mechanical dyssynchrony underwent intramyocardial transplantation of BMMC and CRTD system implantation. This randomized, single-blind, crossover study compared clinical and echocardiographic parameters during two follow-up periods: 6 months of active CRT (BMMC + CRTact) and 6 months of inactive CRT (BMMC + CRTinact). Physical performance was assessed by means of a 6-min walking test. Myocardial perfusion was evaluated by SPECT. Quality of Life (QoL) was assessed through the Minnesota Living with HF Questionnaire (MLwHFQ). Twenty-six patients (64 ± 7 years) were enrolled in the study. The distance covered by the patients during the 6-min walking test significantly increased in the BMMC + CRTinact phase (BMMC therapy only) in comparison with the baseline (269 ± 68 vs 206 ± 51; p = 0.007) and in the BMMC + CRTact phase (BMMC therapy + CRT) in comparison with the BMMC + CRTinact (378 ± 59 vs 269 ± 68; p < 0.001). The summed rest and stress score (SPECT) decreased significantly in the BMMC + CRTact and BMMC + CRTinact phases in comparison with the baseline (p ≤ 0.03). Both phases showed equivalent myocardial perfusion in the segments into which BMMC had been injected. QoL score was significantly lower in the BMMC + CRTinact phase than at the baseline (44.1 ± 14 vs 64.8 ± 19; p < 0.001), and in the BMMC + CRTact phase than in the BMMC + CRTinact phase (26.4 ± 12 vs 44.1 ± 14; p = 0.004). BMMC and CRT seem to act independently on myocardial perfusion and electromechanical dyssynchrony, respectively. Combining these two complementary therapies can significantly improve LV performance in patients with severe HF and electromechanical dyssynchrony.