Pre-existing endothelial cell activation predicts vasoplegia after mitral valve surgery†

OBJECTIVES: Post-cardiac surgery vasoplegia is a common complication of cardiac surgery, characterized by profound loss of systemic vascular resistance. This results in severe hypotension, high cardiac output and metabolic acidosis reflecting inadequate tissue perfusion. The pathophysiological mechanisms underlying this syndrome remain unknown. We hypothesized that this vasoplegia reflects endothelial dysfunction, either as pre-existing condition or as a consequence of the surgical procedure. METHODS: To examine these mechanisms, six established and distinct markers of endothelial cell activation were measured pre- and perioperatively in patients undergoing mitral valve surgery. Arterial (radial artery) and myocardial venous blood samples (coronary sinus) were collected simultaneously over the reperfused heart at various time points during the first hour after reperfusion. Additional samples were collected at baseline (brachial vein) and 1 day post-reperfusion (radial artery). Post-cardiac surgery vasoplegia was defined as a mean arterial blood pressure of <60 mmHg, with a cardiac index of ≥2.2 l/min/m(2) treated with continuous intravenous administration of norepinephrine. RESULTS: No myocardial release of endothelial cell activation markers was observed upon reperfusion in patients with vasoplegia (n = 15; mean age 71 years, 73% male). In contrast, in patients without vasoplegia (n = 24; mean age 64 years, 54% male), reperfusion was characterized by a myocardial release of three endothelial cell activation markers. Myocardial von Willebrand Factor propeptide, osteoprotegerin and interleukin-8 were increased 107% (P < 0.001), 106% (P = 0.02) and 116% (P = 0.009), respectively, compared with arterial levels upon reperfusion. Similar systemic levels of all markers were found upon reperfusion in both groups, except for 120% increased soluble P-selectin (sP-selectin) levels in vasoplegia patients (P = 0.03). Remarkably, postoperative vasoplegia was identified with baseline von Willebrand Factor propeptide levels with a cut-off value of 11.9 nM as well as with baseline sP-selectin levels with a cut-off value of 64.4 ng/ml. CONCLUSIONS: Pre-existing endothelial cell activation, reflected by higher baseline von Willebrand Factor propeptide and sP-selectin levels, is a predisposing factor for post-cardiac surgery vasoplegia. The pre-existing endothelial cell activation may have resulted in desensibilization of endothelium in patients who develop vasoplegic syndrome, resulting in no myocardial release of endothelial cell activation markers upon reperfusion

Galectin-3 and left ventricular reverse remodelling after surgical mitral valve repair

<p>Mitral valve repair in patients with functional mitral regurgitation (FMR) has been associated with beneficial left ventricular (LV) reverse remodelling. Recently, galectin-3 emerged as a marker of myocardial inflammation and fibrosis which may influence LV remodelling after surgery. The aim of the current study was to evaluate the association between pre-operative galectin-3 levels and LV reverse remodelling in heart failure patients with significant FMR who underwent mitral valve repair.</p><p>In total, 42 heart failure patients (66 10 years, 69 male) were evaluated. Plasma galectin-3 levels were assessed pre-operatively. Two-dimensional echocardiographic parameters were measured at baseline, and at 6 and 12 months after surgery. LV reverse remodelling was defined as a decrease in LV end-systolic volume 15 at 6 months follow-up. In total, 57 of the patients showed LV reverse remodelling. Patients with LV reverse remodelling showed significantly lower pre-operative galectin-3 levels (17.5 5.6 vs. 23.7 9.9 ng/mL, P 0.009) compared with patients without LV reverse remodelling. In addition, patients with galectin-3 18.2 ng/mL had a six-fold higher probability of showing LV reverse remodelling after surgery as compared with patients with levels 18.2 ng/mL (odds ratio 6.58, 95 confidence interval 1.3233.33, P 0.02).</p><p>High pre-operative plasma galectin-3 is independently associated with the absence of LV reverse remodelling after mitral valve repair. Galectin-3 may be useful to identify heart failure patients who will need additional treatment to obtain beneficial LV reverse remodelling.</p>