We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA) and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocalization of wild-type and mutant rod proteins in SMC, in conjunction with differences in their coimmunoprecipitation capacities, strongly suggest a dominant-negative effect. Human MYH11 gene mutations provide the first example of a direct change in a specific SMC protein leading to an inherited arterial disease.
This prospective registry reflects the real-life experience of transcatheter aortic valve implantation in high-risk elderly patients in France. The early results are satisfactory in terms of feasibility, short-term haemodynamic and functional improvement, and safety. Longer term follow-up will be further assessed.
A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine.
Losartan was able to decrease blood pressure in patients with MFS but not to limit aortic dilatation during a 3-year period in patients >10 years old. β-Blocker therapy alone should therefore remain the standard first line therapy in these patients.
Objective: To assess the mechanisms through which an enlarged aortic root may facilitate right to left shunting through a patent foramen ovale. Patients: 19 patients with the platypnoea-orthodeoxia syndrome (POS) were compared with 30 control patients without platypnoea. Interventions: Multiplane transoesophageal echocardiography. Main outcome measures: The aortic root diameter, atrial septal dimension behind the aortic root, and amplitude of the phasic oscillation of the septum were measured. Four groups of patients were compared: 12 platypnoeic patients with a dilated aortic root (POS-D), 7 platypnoeic patients with a normal aortic root (POS-N), 15 control patients with a dilated aortic root (CONT-D), and 15 control patients with a normal aortic root (CONT-N). Results: In POS-D and CONT-D patients, the apparent atrial septal dimension was 16.3 (2.7) mm and 17.4 (5.9) mm respectively, compared with 24.4 (5.2) mm in POS-N patients and 25 (4) mm in CONT-N (p , 0.005). Furthermore, the amplitude of septal oscillation was 14.7 (2.5) mm in the POS-D group versus 5.8 (2.4) mm in CONT-N (p , 0.001) compared with 23.3 (3) mm in seven patients with an atrial septal aneurysm (p ,0.001). Conclusion: Patients with an enlarged aorta have an apparently smaller dimension and increased mobility of the atrial septum. These findings appear to result from compression by the aortic root and decreased septal tautness. Consequently, a ''spinnaker effect'' with the inferior vena caval flow may take place, opening the foramen ovale and leading to sustained right to left shunting.A patent foramen ovale (PFO) is a defect in the atrial septum that results from incomplete fusion of the septum primum to the septum secundum. The persistence of a PFO into adulthood may lead to several complications, including paradoxical embolism of thrombus, air or tumoural material, and refractory hypoxaemia.Normally, even if a potential channel between the atria remains, the higher left atrial pressure keeps the flap-like valve of the foramen ovale opposed to the septum secundum. Most cases of sustained right to left shunting through a PFO are seen in situations where right atrial pressure exceeds that of the left, forcing open the potentially patent foramen ovale.However, right to left shunting can be less often observed in the absence of any demonstrable pressure gradient between right and left atria. Right to left shunting despite normal right atrial pressure has been reported after right pneumonectomy 1 2 or in association with venous embryonic remnants. 3 4 In these situations, an altered relation between the caval veins and the atrial septum presumably accounts for flow related rather than pressure related shunting.A few cases of aneurysm of the ascending aorta associated with right to left shunting across a PFO have been reported, 5-10 but evidence for a non-fortuitous association is still lacking. Therefore, we conducted a study to further analyse factors facilitating right to left shunting in patients with PFO, with particular attention paid to t...
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