Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice.

Laminopathies are a group of disorders caused by mutations in the LMNA gene that encodes the nuclear lamina proteins, lamin A and lamin C; their pathophysiological basis is unknown. We report that lamin A/C-deficient (Lmna(-/-)) mice develop rapidly progressive dilated cardiomyopathy (DCM) characterized by left ventricular (LV) dilation and reduced systolic contraction. Isolated Lmna(-/-) myocytes show reduced shortening with normal baseline and peak amplitude of Ca(2+) transients. Lmna(-/-) LV myocyte nuclei have marked alterations of shape and size with central displacement and fragmentation of heterochromatin; these changes are present but less severe in left atrial nuclei. Electron microscopy of Lmna(-/-) cardiomyocytes shows disorganization and detachment of desmin filaments from the nuclear surface with progressive disruption of the cytoskeletal desmin network. Alterations in nuclear architecture are associated with defective nuclear function evidenced by decreased SREBP1 import, reduced PPARgamma expression, and a lack of hypertrophic gene activation. These findings suggest a model in which the primary pathophysiological mechanism in Lmna(-/-) mice is defective force transmission resulting from disruption of lamin interactions with the muscle-specific desmin network and loss of cytoskeletal tension. Despite severe DCM, defects in nuclear function prevent Lmna(-/-) cardiomyocytes from developing compensatory hypertrophy and accelerate disease progression.

A Potential Echocardiographic Classification for Constrictive Pericarditis Based on Analysis of Abnormal Septal Motion.

BACKGROUND: Constrictive pericarditis is an uncommon condition that could be easily confused with congestive heart failure. In symptomatic patients, septal "wobble" on echocardiography may be an important sign of constrictive physiology. This study was planned to investigate the effects of constriction on septal motion as identified by echocardiography. METHODS: In this retrospective observational study, nine consecutive patients with constriction underwent careful echocardiographic analysis of the interventricular septum (IVS) with slow motion 2-dimensional echocardiography and inspiratory manoeuvres. Six patients who had undergone cardiac magnetic resonance imaging underwent similar analysis. Findings were correlated with haemodynamic data in five patients who had undergone cardiac catheterisation studies. RESULTS: In mild cases of constriction a single wobble of the IVS was seen during normal respiration. In more moderate cases a double motion of the septum (termed "double wobble") was seen where the septum bowed initially into the left ventricle (LV) cavity in diastole then relaxed to the middle only to deviate again into the LV cavity late in diastole after atrial contraction. In severe cases, the septum bowed into the LV cavity for the full duration of diastole (pan-diastolic motion). We describe how inspiration also helped to characterize the severity of constriction especially in mild to moderate cases. CONCLUSION: Echocardiography appears a simple tool to help diagnose constriction and grade its severity. Larger studies are needed to confirm whether the type of wobble motions helps to grade the severity of constrictive pericarditis.

Post-transcoronary ethanol septal ablation (TESA) infective endocarditis complicated by a ventricular septal defect.

A 52-year-old man was referred to the cardiology outpatient service with exertional angina and shortness of breath due to hypertrophic obstructive cardiomyopathy. He underwent transcoronary ethanol septal ablation (TESA) with successful procedural outcome. The patient returned to hospital with a 3-week history of intermittent fever and a positive blood culture showing Staphylococcus aureus, sensitive to flucloxacillin. Transoesophageal echocardiography on admission demonstrated vegetation on interventricular septum and a repeated scan 10 days later demonstrated Doppler flow across the interventricular septum, confirming the presence of a small ventricular septal defect. This patient was successfully managed with 6 weeks of intravenous antibiotics and remained well at 1-year follow-up.

Coagulase-negative Staphylococcus endocarditis: Staphylococcus lugdunensis.

Staphylococcus lugdunensis is an infrequent cause of native valve endocarditis. A case of triple-valve involvement of Staphylococcus lugdunensis with intracardiac fistula formation in a 47-year-old woman was managed successfully with surgery. The importance of early diagnosis and prompt referral for surgical treatment is highlighted.