Mitral regurgitation in dilated cardiomyopathy: value of both regional left ventricular contractility and dyssynchrony

Aims: Mitral regurgitation (MR) is common and independently predictsmortality in patients with left ventricular (LV) systolic dysfunction.Its management remains challenging because of the complexityand variety of potential mechanisms implicated. We sought todetermine which LV functional characteristics are the most importantdeterminants of the severity of the MR associated with dilatedcardiomyopathies. Methods and results: We performed echocardiographic studies in 87 consecutive patientswith dilated cardiomyopathy. The degree of MR was quantifiedaccording to guidelines. LV, left atrial and mitral annulusdimensions, mitral valve tenting, estimated filling pressures,regional myocardial contractility, and dyssynchrony (using regionalstrain () analysis) were recorded too. Determinants of significantMR was thus assessed using multivariate models. Mitral regurgitantvolume correlated with mitral annulus diameter (P < 0.001),mitral valve tenting height (P < 0.001), LV volumes (P =0.004), LV ejection fraction, mid-lateral wall peak of (P =0.01), and its delay (P < 0.001). That inter-relation betweenthe mitral annulus, the ventricle shape, contractility, anddyssynchrony was founded in the multivariate analysis. As amatter of fact, the model predicting the best the MR volume(R = 0.78) included: mitral annulus diameter, dyssynchrony,tenting heigh and contractility of the LV mid-lateral wall (measuredby ). Conclusion: The MR of the dilated cardiomyopathy is multifactorial. Ourdata suggest that analysing only LV geometry and mitral orificeis insufficient to correctly describe functional MR determinant.LV contractility and dyssynchrony are essential too.     

The truncated prelamin A in Hutchinson-Gilford progeria syndrome alters segregation of A-type and B-type lamin homopolymers

Hutchinson-Gilford progeria syndrome (HGPS) is a dominant autosomal premature aging syndrome caused by the expression of a truncated prelamin A designated progerin (Pgn). A-type and B-type lamins are intermediate filament proteins that polymerize to form the nuclear lamina network apposed to the inner nuclear membrane of vertebrate somatic cells. It is not known if in vivo both type of lamins assemble independently or co-assemble. The blebbing and disorganization of the nuclear envelope and adjacent heterochromatin in cells from patients with HGPS is a hallmark of the disease, and the ex vivo reversal of this phenotype is considered important for the development of therapeutic strategies. Here, we investigated the alterations in the lamina structure that may underlie the disorganization caused in nuclei by Pgn expression. We studied the polymerization of enhanced green fluorescent protein- and red fluorescent protein-tagged wild-type and mutated lamins in the nuclear envelope of living cells by measuring fluorescence resonance energy transfer (FRET) that occurs between the two fluorophores when tagged lamins interact. Using time domain fluorescence lifetime imaging microscopy that allows a quantitative analysis of FRET signals, we show that wild-type lamins A and B1 polymerize in distinct homopolymers that further interact in the lamina. In contrast, expressed Pgn co-assembles with lamin B1 and lamin A to form a mixed heteropolymer in which A-type and B-type lamin segregation is lost. We propose that such structural lamina alterations may be part of the primary mechanisms leading to HGPS, possibly by impairing functions specific for each lamin type such as nuclear membrane biogenesis, signal transduction, nuclear compartmentalization and gene regulation.     

Endoscopic-ultrasound-guided endoscopic transmural drainage of pancreatic pseudocysts and abscesses

Objective. Surgery is the traditional treatment for symptomatic pancreatic pseudocysts and abscesses, but morbidity and mortality are still too high. Minimally invasive approaches have been encouraged. The aim of this study was to evaluate the results of the endoscopic-ultrasound-guided (EUS) endoscopic transmural drainage of these pancreatic collections. Material and methods. In this retrospective review of consecutive cases from a single referral centre, cystogastrostomy and cystoduodenostomy were created with an interventional linear echoendoscope under endosonographic and fluoroscopic control by the endoscopic insertion of straight or double pigtail stents. Results. Fifty-one symptomatic patients (33 men; mean age 58 years) were submitted to 62 procedures from January 2003 to December 2005. EUS-guided drainage was successful in 48 (94%) patients. Only three patients needed surgery. There were two procedure-related complications managed clinically. During a mean follow-up of 39 weeks, recurrence due to migration or obstruction of the stent was 17.7%. All these cases were submitted to a new session of endoscopic drainage. There was no mortality. Complications were more frequent in patients with a recent episode of acute pancreatitis (38.5% versus 10%; p=0.083). The endoscopic approach was not more hazardous for abscesses in regard to complications rate (19% versus 16.6%; p>0.05). In abscesses, a nasocystic drain did not decrease the complications rate (27% versus 13%; p=0.619), but the placement of 2 stents did decrease this rate (18% versus 20%; p>0.05), although increased it in pseudocysts (40% versus 13%; p=0.185). Conclusions. Endoscopic transmural drainage is a minimally invasive, effective and safe approach in the management of pancreatic pseudocysts and abscesses.     

Relationship between sleep and acid gastro-oesophageal reflux in neonates

The aim of the present study was to investigate the impact of gastro‐oesophageal acid reflux on sleep in neonates and, reciprocally, the influence of wakefulness (W) and sleep stages on the characteristics of the reflux (including the retrograde bolus migration of oesophageal acid contents). The pH and multichannel intraluminal impedance were measured during nocturnal polysomnography in 25 infants hospitalised for suspicion of gastro‐oesophageal reflux. Two groups were constituted according to whether or not the infants displayed gastro‐oesophageal reflux (i.e. a reflux group and a control group). There were no differences between the reflux and control groups in terms of sleep duration, sleep structure and sleep state change frequency. Vigilance states significantly influenced the gastro‐oesophageal reflux pattern: the occurrence of gastro‐oesophageal reflux episodes was greater during W (59 ± 32%) and active sleep (AS; 35 ± 30%) than during quiet sleep (QS; 6 ± 11%), whereas the mean duration of gastro‐oesophageal reflux episodes was higher in QS than in W and AS. The percentage of retrograde bolus migrations of distal oesophageal acid content was significantly higher in AS (62 ± 26%) than in W (42 ± 26%) and QS (4.5 ± 9%). In neonates, gastro‐oesophageal reflux occurred more frequently during W, whereas the physiological changes associated with sleep state increase the physiopathological impact of the gastro‐oesophageal reflux. The duration of oesophagus–acid contact was greater during sleep; AS facilitated the retrograde migration of oesophageal acid content, and QS was characterised by the risk of prolonged acid mucosal contact.