Goland Sorel, Weinstein Jean Marc, Zalik Adi, Kuperstein Rafael, Zilberman Liaz, Shimoni Sara, Arad Michael, Ben Gal Tuvia, George Jacob
From the Heart Institute, Kaplan Medical Center, Rehovot, Israel (S.G., A.Z., L.Z., S.S., J.G.); Heart Insitute, Sheba Medical Center, Ramat Gan, Israel (R.K., M.A.); Heart Insitute, Soroka Medical Center, Beersheba, Israel (J.M.W.); and Heart Insitute, Rabin Medical Center, Petah Tikva, Israel (T.B.G.).
Circ Heart Fail. 2016 Nov;9(11). doi: 10.1161/CIRCHEARTFAILURE.116.003349.
Recent studies suggest that angiogenic imbalance during pregnancy may lead to acute peripartum cardiomyopathy (PPCM). We propose that angiogenic imbalance and residual cardiac dysfunction may exist even after recovery from PPCM.
Twenty-nine women at least 12 months after presentation with PPCM, who exhibited recovery of left ventricular (LV) ejection fraction (≥50%), were included in the study (mean age 35±6 years, LV ejection fraction 61.0±3.9%). The number of circulating endothelial progenitor cells (EPCs) and plasma levels of proangiogenic vascular endothelial growth factor and of soluble vascular endothelial growth factor receptor Flt1 (sFlt1) were measured. All patients underwent comprehensive cardiac function assessment, including tissue Doppler imaging and 2-dimensional (2D) strain echocardiography. All measurements were compared with healthy controls. Patients with a history of PPCM have significantly higher sFlt1 concentrations (median [25th-75th percentile]; 149.57, [63.14-177.89] versus 20.29, [15.00-53.89] pg/mL, P<0.001) and significantly decreased vascular endothelial growth factor/sFlt1 ratio (P=0.012) compared with controls, with a trend toward lower concentration of circulating CD34/KDR levels. In addition, patients with PPCM had lower early velocities E' septal (9.9±2.1 versus 11.0±1.5 cm/s, P=0.02), with a significantly lower systolic velocity S' septal (7.6±1.2 versus 8.5±1.2 cm/s, P=0.003) by tissue Doppler imaging. Significantly lower LV global longitudinal (-19.1±3.3 versus -22.7±2.2%, P<0.001) and apical circumferential 2D strain (-16.6±4.9 versus -21.2±7.9, P=0.02) were present in patients with PPCM compared with controls.
Higher concentration of sFlt1 with concomitant decreased circulating endothelial progenitor cell levels along with inappropriate attenuated vascular endothelial growth factor levels may imply an angiogenic imbalance that exists even after recovery and may thus predispose to PPCM. In addition, tissue Doppler imaging and 2D strain were able to identify residual myocardial injury in post-PPCM women with apparent recovery of LV systolic function. Both angiogenic imbalance and residual myocardial injury may play an important role in the recurrence of LV dysfunction during subsequent pregnancies.
近期研究表明，孕期血管生成失衡可能导致急性围产期心肌病（PPCM）。我们提出，即使在PPCM恢复后，血管生成失衡和残余心脏功能障碍可能依然存在。
本研究纳入了29例PPCM发病至少12个月后左心室（LV）射血分数恢复（≥50%）的女性患者（平均年龄35±6岁，LV射血分数61.0±3.9%）。测量循环内皮祖细胞（EPCs）数量以及促血管生成的血管内皮生长因子和可溶性血管内皮生长因子受体Flt1（sFlt1）的血浆水平。所有患者均接受了包括组织多普勒成像和二维（2D）应变超声心动图在内的全面心功能评估。所有测量结果均与健康对照进行比较。与对照组相比，有PPCM病史的患者sFlt1浓度显著更高（中位数[第25 - 75百分位数]；149.57，[63.14 - 177.89]对20.29，[15.00 - 53.89] pg/mL，P<0.001），血管内皮生长因子/sFlt1比值显著降低（P = 0.012），循环CD34/KDR水平有降低趋势。此外，通过组织多普勒成像，PPCM患者的室间隔E'早期速度较低（9.9±2.1对11.0±1.5 cm/s，P = 0.02），室间隔收缩期速度S'显著更低（7.6±1.2对8.5±1.2 cm/s，P = 0.003）。与对照组相比，PPCM患者的LV整体纵向应变（-19.1±3.3对-22.7±2.2%，P<0.001）和心尖圆周2D应变（-16.6±4.9对-21.2±7.9，P = 0.02）显著更低。
sFlt1浓度升高，同时循环内皮祖细胞水平降低以及血管内皮生长因子水平不适当衰减，可能意味着即使在恢复后仍存在血管生成失衡，这可能是PPCM的易感因素。此外，组织多普勒成像和2D应变能够识别LV收缩功能明显恢复的PPCM后女性患者的残余心肌损伤。血管生成失衡和残余心肌损伤在随后妊娠期间LV功能障碍复发中可能都起重要作用。
