A-kinase anchoring protein Lbc coordinates a p38 activating signaling complex controlling compensatory cardiac hypertrophy

In response to stress, the heart undergoes a remodeling process associated with cardiac hypertrophy that eventually leads to heart failure. A-kinase anchoring proteins (AKAPs) have been shown to coordinate numerous prohypertrophic signaling pathways in cultured cardiomyocytes. However, it remains to be established whether AKAP-based signaling complexes control cardiac hypertrophy and remodeling in vivo. In the current study, we show that AKAP-Lbc assembles a signaling complex composed of the kinases PKN, MLTK, MKK3, and p38α that mediates the activation of p38 in cardiomyocytes in response to stress signals. To address the role of this complex in cardiac remodeling, we generated transgenic mice displaying cardiomyocyte-specific overexpression of a molecular inhibitor of the interaction between AKAP-Lbc and the p38-activating module. Our results indicate that disruption of the AKAP-Lbc/p38 signaling complex inhibits compensatory cardiomyocyte hypertrophy in response to aortic banding-induced pressure overload and promotes early cardiac dysfunction associated with increased myocardial apoptosis, stress gene activation, and ventricular dilation. Attenuation of hypertrophy results from a reduced protein synthesis capacity, as indicated by decreased phosphorylation of 4E-binding protein 1 and ribosomal protein S6. These results indicate that AKAP-Lbc enhances p38-mediated hypertrophic signaling in the heart in response to abrupt increases in the afterload.

Transcatheter aortic valve implantation: predictors of procedural success--the Siegburg-Bern experience

The purpose of the present analysis was to identify predictors of procedural success of percutaneous transcatheter aortic valve implantation (TAVI).

Standardized definitions and clinical endpoints in carotid artery and supra-aortic trunk revascularization trials

Endovascular therapy has emerged as a promising alternative to open surgery for stroke prevention in patients with obstructive disease of the supra-aortic arteries. Although most previous studies have used similar safety and efficacy endpoints, differences in definitions, timing of assessments, and standards of reporting have hampered direct comparisons across various trials.

Computed tomographic coronary angiography in patients with surgically treated type A aortic dissection: preliminary results

Acute type A aortic dissection is a serious emergency with a mortality rate of up to 40% within the first 24 h when left untreated. Surgical therapy needs to be initiated promptly. Due to this urgent situation, preoperative evaluation of the coronary arteries is not routinely performed in these patients. The aim of this study was to evaluate the accuracy of 64-slice computed tomography angiography (CTA) for postoperative coronary artery assessment in these patients. Ten consecutive patients with two or more cardiovascular risk factors were prospectively enrolled. Patients had type A aortic dissection treated surgically with a supracoronary graft of the ascending aorta. Performance of CTA to exclude significant stenosis (>50% lumen narrowing) and/or coronary artery dissection was compared with quantitative coronary angiography. A total of 147 segments were evaluated. Three segments (2%) were excluded from analysis. CTA correctly assessed one of three significant stenoses in three patients and correctly excluded coronary artery disease (CAD) in six of ten patients. One patient was rated false positive. Overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT for identifying coronary artery disease by segment was 98%, 33%, 99%, 50%, and 99%, respectively (P<0.05). By patient, it was 70%, 33%, 86%, 50%, and 75%, respectively. No coronary artery dissection was found. Noninvasive CTA may be a viable alternative to conventional angiography for postoperative coronary artery evaluation in patients with surgically treated type A aortic dissection and cardiovascular risk factors. An NPV of 99% should allow for reliable exclusion of CAD. Further studies with higher patient numbers are warranted.

Ventricular prosthesis embolization during transapical aortic valve implantation: the role of transesophageal echocardiography in diagnosis and management

The authors present the case of an 81-year-old patient with severe aortic stenosis who experienced left ventricular embolization of an aortic bioprosthesis during transapical aortic valve implantation. The authors discuss reasons for prosthesis embolization and reinforce the attention to technical details and the widespread use of multimodality imaging techniques. In this context, transesophageal echocardiography appears indispensable in the detection and management of procedure-related complications.

Incidence and predictors of atrioventricular conduction impairment after transcatheter aortic valve implantation

Atrioventricular (AV) conduction impairment is well described after surgical aortic valve replacement, but little is known in patients undergoing transcatheter aortic valve implantation (TAVI). We assessed AV conduction and need for a permanent pacemaker in patients undergoing TAVI with the Medtronic CoreValve Revalving System (MCRS) or the Edwards Sapien Valve (ESV). Sixty-seven patients without pre-existing permanent pacemaker were included in the study. Forty-one patients (61%) and 26 patients (39%) underwent successful TAVI with the MCRS and ESV, respectively. Complete AV block occurred in 15 patients (22%), second-degree AV block in 4 (6%), and new left bundle branch block in 15 (22%), respectively. A permanent pacemaker was implanted in 23 patients (34%). Overall PR interval and QRS width increased significantly after the procedure (p <0.001 for the 2 comparisons). Implantation of the MCRS compared to the ESV resulted in a trend toward a higher rate of new left bundle branch block and complete AV block (29% vs 12%, p = 0.09 for the 2 comparisons). During follow-up, complete AV block resolved in 64% of patients. In multivariable regression analysis pre-existing right bundle branch block was the only independent predictor of complete AV block after TAVI (relative risk 7.3, 95% confidence interval 2.4 to 22.2). In conclusion, TAVI is associated with impairment of AV conduction in a considerable portion of patients, patients with pre-existing right bundle branch block are at increased risk of complete AV block, and complete AV block resolves over time in most patients.

Percutaneous aortic valve replacement: valvuloplasty studies in vitro

Valvuloplasty of the aortic valve is currently used in selected patients for severe calcified aortic valve disease, but clinical effectiveness is low and complication rate remains high. In this study, the total particle load after valvuloplasty and the embolization risk of calcific debris into the coronary arteries was analyzed in an in vitro model.

Aortic arch morphometry in living humans

Anatomical features of the aortic arch such as its steepness, the take-off angles and the distances between its supra-aortic branches can influence the feasibility and difficulty of interventional and/or surgical maneuvers. These anatomical characteristics were assessed by means of 3D multiplanar reconstruction of thoracic angio-computed tomography scans of 92 living patients (79 males, 13 females, mean age 69.4 ± 9.9 years) carried out for various indications (gross pathology of the thoracic aorta excluded). There was a significant variation of all measured parameters between the subjects - a standard aortic arch (i.e. with all measured parameters within 2 SD) does not seem to exist. There were no significant differences between genders but some of the parameters correlated significantly to age.

Early hemodynamic and neurohormonal response after transcatheter aortic valve implantation

The conventional surgical aortic bioprostheses used for treatment of aortic stenosis (AS) are inherently stenotic in nature. The more favorable mechanical profile of the Medtronic CoreValve bioprosthesis may translate into a better hemodynamic and neurohormonal response.

Prevention of rupture of abdominal aortic aneurysm

Two thirds of patients with an abdominal aortic aneurysm (AAA) have relevant coronary artery disease (CAD). AAAs are prevalent in up to 16% of smokers with CAD. General screening of AAA is controversial. Aim was to assess the potential of finding AAA prior to rupture among patients with known CAD. Main endpoint was whether AAA could have been found during follow-up by sonography or at other time of cardiovascular evaluation.