Background-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. Methods and Results-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) Conclusions-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. (Circ Heart Fail. 2016;9:e003349.

Introduction Takotsubo cardiomyopathy (TCM) is characterized by transient left ventricle dysfunction. Hypothesis A residual cardiac and endothelial dysfunction is present in patients who recovered from TCM. Methods In this single‐center prospective study, patients with prior TCM were included and followed for 6.4 ± 1.6 years. All underwent comprehensive cardiac function assessment, including tissue Doppler imaging (TDI) and 2‐dimensional strain (2DS) echocardiography at their first visit. The number of circulating endothelial progenitor cells and levels of proangiogenic vascular endothelial growth factor (VEGF) and its receptor (VEGF‐R) were measured. All measurements were compared with healthy controls. Results Forty‐two women (age 58. ±8.6 years, LVEF 58.1 ± 6.1%) comprised the TCM group. Patients post‐TCM had significantly lower early velocities E′ (6 (5.0–8.0) vs. 9 (7.0–11.0) cm/s, p = .001) by TDI and higher E/E′ ratio (p = .002), lower LV global average longitudinal strain (LGS) (−18.9 ± 3.5% vs. −21.7 ± 2.3%, p = .002) and RV LGS (−20.1 ± 3.9% vs. −23.4 ± 2.8%, p = .003) were evident. There was a trend toward a higher VEGF‐R (p = .09) along with decreased VEGF/VEGF‐R ratio representing inadequate VEGF production. In‐hospital mortality was not reported and only two non‐cardiac deaths occurred at long‐term follow‐up. Conclusions Altered TDI and 2DS indices suggest residual biventricular myocardial injury in post‐TCM patients with the apparent LV function recovery. Inappropriate production of VEGF and VEGF‐R were observed, suggesting a possible underlying endothelial dysfunction in these patients.