Nicolas Bonnet

Biventricular repair approach in ducto-dependent neonates with hypoplastic but morphologically normal left ventricle

OBJECTIVES Increased afterload and multilevel LV obstruction is constant. We assumed that restoration of normal loading conditions by relief of LV obstructions promotes its growth, provided that part of the cardiac output was preoperatively supported by the LV, whatever the echocardiographic indexes. BACKGROUND Whether to perform uni- or biventricular repair in ducto dependent neonates with hypoplastic but morphologically normal LV (hypoplastic left heart syndrome classes II & III) remains unanswered. Echocardiographic criteria have been proposed for surgical decision. METHODS Twenty ducto dependent neonates presented with this anomaly. All had aortic coarctation associated to multilevel LV obstruction. Preoperative echocardiographic assessment showed: mean EDLW of 12.4 +/- 3.03 ml/m2 and mean Rhodes score of -1.73 +/-0.8. Surgery consisted in relief of LV outflow tract obstruction by coarctation repair in all associated to aortic commissurotomy in one and ASD closure in 2. RESULTS There were 3 early and 2 late deaths. Failure of biventricular repair and LV growth was obvious in patients with severe anatomic mitral stenosis. The other demonstrated growth of the left heart. At hospital discharge the EDLVV was 19.4+/-3.12 ml/m2 (p = 0.0001) and the Rhodes score was -0.38+/-1.01 (p = 0.0003). Actuarial survival and freedom from reoperation rates at 5 years were 72.5% and 46%, respectively. CONCLUSIONS Biventricular repair can be proposed to ducto dependent neonates with hypoplastic but morphologically normal LV provided that all anatomical causes of LV obstruction can be relieved. Secondary growth of the left heart then occurs; however, the reoperation rate is high.

Downregulation of the calcium current in human right atrial myocytes from patients in sinus rhythm but with a high risk of atrial fibrillation

AIMS A decrease in L-type calcium current (ICaL) is an important mechanism favouring atrial fibrillation (AF). Here, we aimed to identify pathogenic factors associated with ICaL downregulation. METHODS AND RESULTS Atrial myocytes were isolated from right atrial appendages obtained from 86 adult patients in sinus rhythm with coronary artery disease, aortic valve disease, or mitral valve disease (MVD). Current was recorded in isolated myocytes using the whole-cell patch-clamp technique. The ICaL recorded in the 172 myocytes studied showed a marked variability of peak density ranging from 0.1 to 9.0 pA/pF. The ICaL peak density did not correlate with membrane capacitance or changes in current biophysical properties. The ICaL peak density was homogeneous for a given sample. Small ICaL values were recorded in patients with MVD or with a low left ventricular ejection fraction (<45%). Small ICaL values were more sensitive to the beta-adrenergic agonist, isoproterenol (1 microM), and to the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (10 microM). CONCLUSION In human atrial myocytes, the variability of ICaL is related to the clinical history of the donors. The downregulation of ICaL is already observed in patients in sinus rhythm with a high risk of AF and is associated with the greatest response to beta-adrenergic agonist.

Left Ventricular Alterations in a Model of Fetal Left Ventricular Overload

Congenital aortic coarctation is well tolerated by the fetus because the foramen ovale and ductus arteriosus equalize intracardiac and great arteries pressures and shunts. The pathologic consequences only emerge after birth with closure of the foramen ovale and ductus arteriosus. There is, however, no documentation of myocardial effects in utero of the left ventricular (LV) pressure overload induced by aortic banding. We investigated whether prenatal aortic banding could be detrimental at the structural and/or functional level. The goal of the present study was to investigate the cardiac effects of LV pressure overload in a fetal lamb model. Nine fetal lambs underwent preductal banding of the aortic arch in utero at midgestation (CoA group), whereas their twins underwent sham surgery. All fetuses were studied between 27 and 37 d after surgery for LV pressure, anatomic and histologic anomalies, and steady state sarcoendoplasmic reticulum calcium ATPase (SERCA 2a) mRNA and protein levels and pump activity. Surgery resulted in severe aortic coarctation in all the animals in the CoA group and was associated with a 65% increase in the LV weight to body weight ratio relative to the sham-operated group (p < 0.001). Hemodynamic and histologic studies showed an evolutionary pattern depending on duration of the experimental coarctation with a shift occurring at 30 d of coarctation. The initial response of cardiomyocytes to ventricular overload was hypertrophy of the myocytes, followed by myocyte hyperplasia. Compared with sham, there was an apparent decrease in the percentage of binucleated cells in the CoA group after 30 d of coarctation. The earliest response to LV pressure overload appears to occur at the molecular level. Indeed, sarcoendoplasmic reticulum calcium ATPase (SERCA 2a) mRNA levels fell significantly to only 28.6% of the sham group value (p = 0.023), independently of the duration of coarctation. In the fetal lamb, the pressure overload-induced hypertrophy resulting from progressive aortic coarctation leads to hemodynamic and lesional abnormalities and slows ontogenic maturation.

Silvio’s Party

Italy is going through a new crisis in its party system comparable in many respects to the one that brought down the First Republic at the beginning of the 1990s. On 12 November 2011, against the background of a global economic and financial crisis that hit the southern countries in the euro zone particularly severely with Italy according to the experts threatened with bankruptcy in the same way as Greece and Portugal, Silvio Berlusconi, under pressure from Brussels and the financial markets, was forced to tender his resignation as Italy’s Prime minister. A few days later, the President of the Republic, Giorgio Napolitano, appointed Professor Mario Monti who quickly put together a government of political and financial experts. The Monti administration immediately imposed a raft of austerity measures that, after only a few months, had the effect of restoring Italy’s credibility in the international financial markets. At the end of 2012, after some hesitation, emboldened by his initial success, Monti announced that he would lead a centrist coalition in snap parliamentary elections held on 24 and 25 February 2013. However, the strong medicine Italians had been forced to swallow to restore the health of the state’s finances seriously undermined the popularity of the man who had entered office as ‘Super Mario’, and the ‘Con Monti per l’Italia’ list, far from carrying off the anticipated victory suffered a drop in support that was seen as an outright rejection.1