Circulating Regulatory B-Lymphocytes in Patients with Acute Myocardial Infarction: A Pilot Study.

Background: Inflammation plays on important role in plaque instability and acute coronary syndromes. The anti-inflammatory effects of B-regulatory lymphocytes (B-regs) in atherosclerosis was tested mainly in animal models with inconclusive results. Herein, we studied for the first time, levels of circulating B-regs in patients with acute myocardial infarction (MI). Methods: We examined circulating levels of B-regs by flow cytometry in 29 patients with recent ST-segment elevation MI and 18 patients with stable angina pectoris (SAP) and coronary artery disease. We re-assessed B-reg levels on average 4 months later. Results: The mean level of CD20+ cells was similar in patients with MI and patients with SAP (p = 0.60). The levels of CD24hiCD38hi cells among CD20+ cells were 5.7 ± 4% and 11.6 ± 6% in patients with MI and SAP, respectively, (p < 0.001). The level of CD24hiCD38hi B-regs remained related to acute MI after correcting for age, gender, and risk factors. Circulating levels of CD24hiCD38hi B-regs in patients with MI did not change significantly at follow-up in a small patient groups (p = 0.408). Conclusions: Circulating B-regs are reduced in patients with MI compared to patients with SAP. This finding may shed further light on the inflammatory pathophysiologic factors related to plaque rupture.

Residual alterations of cardiac and endothelial function in patients who recovered from Takotsubo cardiomyopathy.

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.

Angiogenic Imbalance and Residual Myocardial Injury in Recovered Peripartum Cardiomyopathy Patients.

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) 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. 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.