title: Angiogenic Imbalance and Residual Myocardial Injury in Recovered Peripartum Cardiomyopathy Patients.
abstract: 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.
authors.affiliation: 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.). sorelgoland@yahoo.com.
authors.forename: Sorel
authors.initials: S
authors.lastname: Goland
authors.affiliation: 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.).
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Weinstein
authors.affiliation: 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.).
authors.forename: Adi
authors.initials: A
authors.lastname: Zalik
authors.affiliation: 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.).
authors.forename: Rafael
authors.initials: R
authors.lastname: Kuperstein
authors.affiliation: 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.).
authors.forename: Liaz
authors.initials: L
authors.lastname: Zilberman
authors.affiliation: 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.).
authors.forename: Sara
authors.initials: S
authors.lastname: Shimoni
authors.affiliation: 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.).
authors.forename: Michael
authors.initials: M
authors.lastname: Arad
authors.affiliation: 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.).
authors.forename: Tuvia
authors.initials: T
authors.lastname: Ben Gal
authors.affiliation: 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.).
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D009202:Cardiomyopathies / Q000097:blood / Q000000981:diagnostic imaging*; D016022:Case-Control Studies; D004452:Echocardiography; D015150:Echocardiography, Doppler; D025401:Echocardiography, Stress; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D018919:Neovascularization, Physiologic; D058725:Peripartum Period; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood / Q000000981:diagnostic imaging*; D011644:Puerperal Disorders / Q000097:blood / Q000000981:diagnostic imaging*; D020127:Recovery of Function; D013318:Stroke Volume; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000000981:diagnostic imaging*; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; C000588866:KDR protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: cardiomyopathycirculating endothelial progenitor cells; echocardiography; pregnancyvascular endothelial growth factorsVEGF receptor, FLT