Guy Vandenplas

Secretory Products From Epicardial Adipose Tissue of Patients With Type 2 Diabetes Mellitus Induce Cardiomyocyte Dysfunction

Background— Secreted factors from epicardial adipose tissue (EAT) have been implicated in the development of cardiomyocyte dysfunction. This study aimed to assess whether alterations in the secretory profile of EAT in patients with type 2 diabetes mellitus (DM2) affect contractile function and insulin action in cardiomyocytes. Methods and Results— Contractile function and insulin action were analyzed in primary adult rat cardiomyocytes incubated with conditioned media (CM) generated from explants of EAT biopsies obtained from patients without and with DM2. CM from subcutaneous and pericardial adipose tissue biopsies from the same patients served as the control. Cardiomyocytes treated with CM (EAT) from DM2 patients showed reductions in sarcomere shortening, cytosolic Ca2+ fluxes, expression of sarcoplasmic endoplasmic reticulum ATPase 2a, and decreased insulin-mediated Akt-Ser473-phosphorylation as compared with CM from the other groups. Profiling of the CM showed that activin A, angiopoietin-2, and CD14 selectively accumulated in CM-EAT-DM2 versus CM-EAT in patients without DM2 and CM from the other fat depots. Accordingly, EAT biopsies from DM2 patients were characterized by clusters of CD14-positive monocytes. Furthermore, SMAD2-phosphorylation, a downstream target of activin A signaling, was elevated in cardiomyocytes treated with CM (EAT) from DM2 patients, and the detrimental effects of CM (EAT) from DM2 patients were partially abolished in cardiomyocytes pretreated with a neutralizing antibody against activin A. Finally, both recombinant activin A and angiopoietin-2 reduced cardiomyocyte contractile function, but only activin A reduced the expression of sarcoplasmic endoplasmic reticulum ATPase 2a. Conclusions— Collectively, our data implicate DM2-related alterations in the secretory profile of EAT in the pathogenesis of diabetes mellitus–related heart disease.

Relation between mixed venous oxygen saturation and cerebral oxygen saturation measured by absolute and relative near-infrared spectroscopy during off-pump coronary artery bypass grafting

BACKGROUND We hypothesized that previously reported contradictory results regarding the equivalence of mixed venous (Smv(O(2))) and cerebral (rS(c)O(2)) oxygen saturation might be related to time delay issues and to measurement technology. In order to explore these two factors, we designed a prospective clinical study comparing with relative (INVOS(®)) and absolute (Foresight(®)) rS(c)O(2) measurements. METHODS Forty-two consenting patients undergoing elective off-pump coronary artery bypass grafting were included. Two INVOS and two Foresight sensors continuously registered rS(c)O(2). Smv(O(2)) was measured continuously via a pulmonary artery catheter. Data were assessed by within- and between-group comparisons and correlation analysis. RESULTS A similar time delay of 19 (4) and 18 (4) s was found for compared with rS(c)O(2) measurements by Foresight and INVOS, respectively, during haemodynamic changes. After adjusting for this time delay, the correlation between Smv(O(2)) and rS(c)O(2) increased from r=0.25 to 0.75 (P<0.001) for Foresight, and from r=0.28 to 0.73 (P<0.001) for INVOS. Comparison of Foresight and INVOS revealed significant differences in absolute rS(c)O(2) values (range 58-89% for Foresight and 28-95% for INVOS). Changes in rS(c)O(2) in response to acute haemodynamic alterations were significantly more pronounced with INVOS compared with Foresight (P<0.001). CONCLUSIONS Considering the important time delay with Smv(O(2)), rS(c)O(2) seems to reflect more appropriately acute haemodynamic alterations. This might suggest its use as a valid alternative to invasive monitoring of tissue oxygen saturation. Relative and absolute rS(c)O(2) measurements demonstrated significant differences in measured rS(c)O(2) values and in the magnitude of rS(c)O(2) changes during haemodynamic alterations.

Endogenous oestradiol and cardiovascular disease in healthy men: a systematic review and meta-analysis of prospective studies

Context The literature provides no clear answer as to whether total oestradiol (E2) concentrations increase the risk of incident cardiovascular disease (CVD) in healthy men. Objective The authors conducted a systematic review and meta-analysis to estimate the predictive value of E2 for CVD, and to identify study features explaining conflicting results. Data sources Articles were identified by a Medline and Embase search and citation tracking. Study selection Eligible articles were prospective population-based cohorts and nested case-control studies on E2 and incident cardiovascular disease (CVD), including myocardial infarction, stroke or death from coronary heart disease. Data-extraction Independent researchers re-expressed associations of E2 and incident CVD in a uniform manner to be used in meta-regression analyses for identification of study features explaining conflicting results, and to estimate the predictive value of E2 for CVD. Results and conclusions 14 studies out of 128 electronically identified articles were eligible. Data to be used for meta-analysis could be calculated in seven cases, and in the remaining seven cases, data of three more became available by contacting those authors. Overall, a non-significant association was found with an estimated summary RR of 0.98 for a change of >75th versus <25th percentile in E2 (95% CI 0.74 to 1.31). Mean body mass index (BMI) of the study population (βs −0.8, p<0.004), and quality of E2 assay (βs −0.6, p<0.08) may have modified the relationship between E2 and incident CVD. The present systematic review does not provide evidence for a pronounced harmful or beneficial effect of E2 on risk for incident CVD in healthy men. If present, an effect of E2 on risk for CVD might be modulated by BMI.

Short-term systolic and diastolic ventricular performance after surgical ventricular restoration for dilated ischemic cardiomyopathy.

OBJECTIVE Based on the adverse relationship between left ventricular (LV) remodeling and clinical outcome in ischemic cardiomyopathy, surgical ventricular restoration (SVR) is proposed as a valuable adjunct procedure. This study reports on the short-term clinical and hemodynamical performance of SVR. METHODS Using end-systolic LV volume as indication for SVR, 78 patients with ischemic cardiomyopathy are divided in two groups: group 1 comprised 55 patients treated by coronary revascularization and mitral annuloplasty, group 2 comprised 23 patients undergoing additional SVR. Hemodynamic investigation included echocardiographic assessment of systolic and diastolic function. Clinical follow-up focused on survival and functional status with exercise performance. RESULTS Both surgical approaches resulted in improvement of NYHA class (2.9-1.6 in group 1; 3.3-1.5 in group 2, p<0.001), achieving similar exercise performance (peak VO2 13.7 vs 15.4 ml/kgmin in groups 1 and 2, p=0.25) and plasma BNP values (group 1: 1350 pg/ml and group 2: 767 pg/ml, p=0.23). SVR provided additional benefit as patients basically had a worse NYHA class (2.9 in group 1 vs 3.3 in group 2, p=0.03). Within mean follow-up of 20 months, survival rate was 84% in group 1 and 74% in group 2 (p=0.11), including operative mortality of 7% and 13% (p=0.42). Through effective volume reduction (LVEDVI 41%; LVESVI 49%) systolic function improved immediately after SVR (LVEF 27-39% in group 2, p<0.05). Worsening of diastolic function was specifically observed after SVR within the first year (E/A-ratio 1.38-1.74 cm/s, p=0.02). Recurrent mitral regurgitation (p=0.004) and secondary remodeling (p=0.01) were major determinants of decreasing LV compliance. Clinical outcome in terms of cardiac events and survival was compromised by restrictive diastolic function (p=0.02) and increased LV volumes (p=0.04). CONCLUSION SVR in addition to coronary revascularization and restrictive mitral annuloplasty results in significant clinical improvement in selected patients with advanced ischemic heart disease and severely dilated ventricles. SVR entails immediate improvement of systolic function, which remains sustained during short-term follow-up. Serial assessment of diastolic function is mandatory as LV compliance seems more sensitive to early changes induced by recurrence of mitral regurgitation and secondary ventricular dilation. Moreover, worsening of diastolic dysfunction should be timely recognized because of its adverse clinical impact.

Reappraisal of a single-centre policy on the contemporary surgical management of active infective endocarditis

OBJECTIVES We studied a contemporary cohort of adult patients treated surgically for infective endocarditis (IE) in order to evaluate the surgical approach and predictors of outcomes, in relation to the intercurrent adaptation of the 2006 ACC/AHA guidelines. METHODS One hundred and eighty-six consecutive patients operated on for active IE from August 1999 to September 2012 were reviewed retrospectively. Clinical presentation, surgical management and outcomes in the two study periods before and after January 2007 were compared (Period 1: n = 95 and Period 2: n = 91). RESULTS The mean (SD) follow-up was 4.3 (3.8) years and was 99.5% complete. Patients in Period 2 had more frequently associated coronary artery disease (31 vs 18%, P = 0.06), while the microbiology revealed more Staphylococcus species (43 vs 26%, P = 0.02), predominantly Staphylococcus aureus (31 vs 19%; P = 0.07), and less culture-negative cases (7 vs 17%; P = 0.05). The median delay between diagnosis and surgery was 7 days in Period 2 compared with 14 days in Period 1 (P = 0.001). Surgery in Period 2 included more root replacements for aortic valve endocarditis (11 vs 2%; P = 0.02) and mitral valve repairs (18 vs 5%; P = 0.01), while the use of homografts for aortic valve endocarditis was almost abandoned (1 vs 15%; P = 0.001). Hospital mortality was 13% and did not change significantly over both periods (P = 0.66). The independent predictors of hospital mortality were age (P = 0.03), female gender (P = 0.02), previous cardiac surgery (P = 0.02), preoperative serum creatinine level >2 mg/dl (P = 0.05), S. aureus infection (P = 0.02), emergent or salvage operation (P = 0.001) and concomitant coronary artery bypass grafting (P = 0.03). The 1-, 3-, 5- and 10-year survival were 84, 72, 64 and 57%, respectively. Late survival was negatively influenced by S. aureus endocarditis (P < 0.001) and peripheral vascular disease (P = 0.03), whereas associated coronary artery disease (P = 0.07) had a strong impact. CONCLUSIONS Adaptation of the 2006 ACC/AHA guidelines in the contemporary management of IE led to a shorter interval between diagnosis and surgery. Despite a more extensive and earlier operative approach, IE caused by S. aureus still remains a major determinant of early and late outcomes.

Active or passive bio-coating: does it matters in extracorporeal circulation?

Background: Two types of surface coating for cardiopulmonary bypass (CPB) are used: bioactive (heparin, nitric oxide) and biopassive (albumin, polyethyleneoxide (PEO), phosphorylcholine). When haemocompatible coatings are combined with the separation of pleuro-pericardial aspiration, attenuation of both the coagulation and complement cascades, as well as better platelet preservation, has been demonstrated. This study wants to investigate if the combination of a bioactive with a biopassive coating (unfractionated heparin embedded in a phosphorylcholine matrix) combines the beneficial effects of both approaches. Materials and methods: Thirty patients undergoing elective CABG were prospectively randomized into two groups of 15 patients. The sole exclusion criterion was an ejection fraction of less than 40%. In the control group (PC), the whole CPB circuit was coated with phosphorylcholine (PC). In the study group (XPC), unfractionated heparin was embedded in the PC matrix of the oxygenator and arterial line filter. Results: No differences were found for haemolytic index, thrombin-anti-thrombin complex (TAT), IL-6, IL-10 and blood loss. PF4 plasma concentration increased from 27.6±22.0 IU/mL to 165.7±43.9 IU/mL (p<0.001) at 15 minutes of CPB in the PC and from 16.0±9.7 IU/mL to 150.9 ± 61.3 IU/mL (p<0.001) in the XPC group. Terminal complement complex (TCC) increased over time in both groups until the end of CPB (Figure 2A). Within each group, TCC generation was statistically significantly higher after the release of the aortic cross-clamp (p<0.001) and at the end of CPB (p<0.001). Total TCC generation was statistically significantly higher in the XPC group compared to the PC group (p=0.026). The difference was statistically significant after the release of the aortic cross-clamp (p=0.005) and at the end of CPB (p=0.001). Conclusions: Based on our results, there is no additional benefit in combining phosphorylcholine with unfractionated heparin in elective patients undergoing coronary artery bypass grafting (CABG). Massive haemodilution leads to enhanced complement activation.

Ultrasound-guided thoracotomy for implantation of an epicardial left ventricular lead after left pneumonectomy

Surgical placement of a left ventricular epicardial pacing lead is a valuable alternative to the standard approach of endovascular placement of a pacing lead in the coronary sinus for cardiac resynchronization therapy. Despite higher perioperative morbidity, surgically placed leads perform well with lower revision and dislocation rates. Moreover, surgery is the only option when an endovascular approach proves to be unsuccessful. We report a successful implantation of an epicardial left ventricular lead through an ultrasound-guided lateral left mini-thoracotomy in a patient with a severely disturbed thoracic anatomy due to left pneumonectomy.

A giant post-dissection aneurysm of the ascending aorta in an octogenarian

Aneurysm formation is a well-known complication of untreated long-standing dissection of the aorta. Despite numerous advances in cardiac surgery, intrinsic diseases of the ascending aorta and aortic arch requiring surgical therapy, remain a technical challenge. However, surgery is the only option for effective treatment of ascending aorta aneurysm but carries an increased risk of severe morbidity and mortality, particularly in the elderly. We report on the successful repair of a giant ascending aorta aneurysm due to chronic dissection in an elderly woman with dyspnoea as main symptom.