经心内膜注射骨髓源 CD133 细胞对难治性心绞痛患者左心室灌注和功能的影响：随机、双盲、安慰剂对照的 REGENT-VSEL 试验的最终结果。
Effects of Transendocardial Delivery of Bone Marrow-Derived CD133 Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial.
机构信息
From the Third Division of Cardiology (W.W., T.J., A.M.-W., Z.P., W.R., A.B., W.W., J.C., B.O., W.C., W.W., S.D., G.S., T.P., A.O., M.T.), Department of Hematology and Bone Marrow Transplantation (M.M., M.D.-M.), and Division of Diagnostic Imaging (K.G.), Medical University of Silesia, Katowice, Poland; Department of Nuclear Medicine Hospital John Paul II, Kraków, Poland (M.K.); 2nd Department of Cardiology and Cardiovascular Interventions (Ł.R., W.Z.) and Department of Angiology (Ł.P.), University Hospital, Krakow, Poland; Krakow Cardiovascular Research Institute, Kraków, Poland (Ł.P., W.Z.); and Department of Vascular Surgery, Medical University of Silesia, Katowice, Poland (W.K.).
出版信息
Circ Res. 2017 Feb 17;120(4):670-680. doi: 10.1161/CIRCRESAHA.116.309009. Epub 2016 Nov 30.
RATIONALE
New therapies for refractory angina are needed.
OBJECTIVE
Assessment of transendocardial delivery of bone marrow CD133 cells in patients with refractory angina.
METHODS AND RESULTS
Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II-IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], =0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], =0.32; absolute changes of summed difference score: -1.38 [5.2] versus -0.73 [1.9], =0.65; and total perfusion deficit: -1.33 [3.3] versus -2.19 [6.6], =0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: -4.3 [11.3] versus 7.4 [11.8], =0.02; end-diastolic volume: -9.1 [14.9] versus 7.4 [15.8], =0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; =0.68), 4 (50% versus 33.3%; =0.63), 6 (70% versus 50.0%; =0.42), and 12 months (55.6% versus 81.8%; =0.33) and use of nitrates after 12 months.
CONCLUSION
Transendocardial CD133 cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.
背景
需要新的治疗难治性心绞痛的方法。
目的
评估经心内膜骨髓 CD133 细胞移植治疗难治性心绞痛患者的效果。
方法和结果
这项随机、双盲、安慰剂对照试验共纳入 31 例加拿大心血管学会 II-IV 级复发性心绞痛患者，这些患者在接受最佳药物治疗后仍存在心绞痛，且单光子发射计算机断层扫描（SPECT）显示至少 1 个心肌节段存在可诱导缺血。这些患者接受了骨髓活检，并被随机分配至细胞组（n=16）或安慰剂组（n=15）。主要终点是 SPECT 检测的心肌缺血的绝对变化。次要终点是磁共振成像（MRI）检测的左心室功能和容量以及心绞痛严重程度。4 个月后，两组间可诱导缺血的程度无显著差异（总和差异评分均值[±SD]：2.60[2.6] 与 3.63[3.6]，=0.52；总灌注缺损：3.60[3.6] 与 5.01[4.3]，=0.32；总和差异评分的绝对变化：-1.38[5.2] 与-0.73[1.9]，=0.65；总灌注缺损：-1.33[3.3] 与-2.19[6.6]，=0.65）。细胞组的左心室容量显著减少（收缩末期容积：-4.3[11.3] 与 7.4[11.8]，=0.02；舒张末期容积：-9.1[14.9] 与 7.4[15.8]，=0.02），左心室射血分数无显著变化。治疗 1、4、6 和 12 个月后，分别有 41.7%（n=7）、50%（n=8）、70%（n=11）和 55.6%（n=9）的患者加拿大心血管学会心绞痛分级至少改善 1 级，差异均无统计学意义（=0.68、=0.63、=0.42 和=0.33）；治疗 12 个月后，分别有 58.3%（n=9）、33.3%（n=5）、50.0%（n=8）和 81.8%（n=13）的患者需要使用硝酸酯类药物，差异也均无统计学意义（=0.68、=0.63、=0.42 和=0.33）。细胞治疗安全。由于研究样本量小，本研究无法明确验证该疗法的疗效，但结果显示该疗法与安慰剂相比，并未显著减少心肌缺血和心绞痛。
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