Increased myocardial GRP94 amounts during sustained atrial fibrillation: a protective response?

BACKGROUND: Structural and phenotypic changes of cardiomyocytes characterize atrial fibrillation. We investigated whether changes in the glucose-regulated protein GRP94, which is essential for cell viability, occur in the presence of chronic atrial fibrillation. METHODS AND RESULTS: Samples of fibrillating atrial myocardium obtained from both goat and human hearts were analyzed for GRP94 expression by an immunologic approach. In goats, atrial fibrillation was induced and maintained for 2, 4, 8, and 16 weeks. After 16 weeks of atrial fibrillation, cardioversion was applied and followed by 8 weeks of sinus rhythm. GRP94 levels doubled in goat atrial myocytes after 4 to 16 weeks of fibrillation with respect to normal atria and returned to control levels in atrial myocardium of cardioverted goats. Immunohistochemical analyses confirm that GRP94 increase occurred within cardiomyocytes. Significantly, increased levels of GRP94 were also observed in samples from human fibrillating atria. In the absence of signs of myocyte irreversible damage, the GRP94 increase in fibrillating atria is comparable to GRP94 levels observed in perinatal goat myocardium. However, calreticulin, another endoplasmic reticulum protein highly expressed in perinatal hearts, does not increase in fibrillating atria, whereas inducible HSP70, a cytoplasm stress protein that is expressed in perinatal goat hearts at levels comparable to those observed in the adult heart, shows a significant increase in chronic fibrillating atria. CONCLUSIONS: Our data demonstrate a large, reversible increase in GRP94 in fibrillating atrial myocytes, which may be related to the appearance of a protective phenotype.

Repair of aortico-left ventricular tunnel originating from the left aortic sinus.

We report on a case of an 11-year-old asymptomatic child with aortico-left ventricular tunnel arising from the left aortic sinus. Preoperative transesophageal echocardiography showed a dilated aortic root with mild aortic valve incompetence and demonstrated the course of the tunnel, which originated from the left coronary sinus entering the outlet portion of the left ventricular outflow tract. Patch closure of the aortic end of the tunnel eliminated left ventricular volume overload with immediate marked reduction of cardiomegaly. At 10-month follow-up the child is asymptomatic and receiving no oral medications. Control two-dimensional Doppler echocardiography shows trivial central aortic valve incompetence.

Mechanics of cryopreserved aortic and pulmonary homografts.

BACKGROUND AND AIM OF THE STUDY: The surgical placement of pulmonary valve grafts into the aortic position (the Ross procedure) has been performed for three decades. Cryopreserved pulmonary valves have had mixed clinical results, however. The objectives of this study were to compare the mechanics of cryopreserved human aortic and pulmonary valve cusps and roots to determine if the pulmonary root can withstand the greater pressures of the aortic position. METHODS: Six aortic and six pulmonary valve roots were obtained from the Oxford Valve Bank. They were harvested during cardiac transplantation from hearts explanted for dilated cardiomyopathy (mean patient age 68 years). The whole roots were initially stored frozen at -186 degrees C, then shipped packed on dry ice. After complete thawing, the roots were pressurized whole; test strips were then cut from the valve cusps, roots and sinuses and tested for stress/strain, stress relaxation, and ultimate failure strength. RESULTS: The pulmonary roots were more distensible (30% versus 20% strain to lock-up) and less compliant when loaded to aortic pressures. The pulmonary valve cusp and root tissue also showed greater extensibility and greater stiffness (lower compliance) when subjected to the same loads. CONCLUSION: We conclude that mechanical differences between aortic and pulmonary valve tissues are minimal. The pulmonary root should withstand the forces imposed on it when placed in the aortic position. However, if implanted whole, the pulmonary root will distend about 30% more than the aortic root when subjected to aortic pressures. These geometric changes may affect valve function in the long term and should be appreciated when implanting a pulmonary valve graft.

Repair of complete common atrioventricular canal defects in patients younger than four months of age.

BACKGROUND: The purpose of this study was to evaluate the impact of age at repair and atrioventricular (AV) valve anatomy on preoperative and postoperative AV valve incompetence (AVVR) was done to test the hypothesis that early repair (less than 4 months of life) can be safely accomplished and not only control heart failure but also improve surgical results on AV valve reconstruction. METHODS AND RESULTS: One hundred patients, median age 6.1 months, underwent repair of the complete common AV canal defect (CAVC) between 1981 and 1996. Surgery was performed in 37 patients (37%) less than 4 months of age (Group 1) and in 63 patients (63%) more than 4 months of age (Group 2). Surgical correction included double patch septal reconstruction in all. Trifoliate reconstruction of the left AV valve was selected in 93 patients (93%). Parametric time-related predicted survival was 92.9% at 14 years in Group 1 (70% confidence limits, 87.6% to 96.1%) and 75.9% at 15.4 years in Group 2 (70% confidence limits, 70.08% to 81.02%) (P=.038). Multivariate analysis in hazard function domain shows early repair as a negative risk factor for death (P=.038). Ordinal logistic regression equation indicates a higher probability of preoperative AVVR with older age at operation (P=.019). Regression analysis demonstrates good correlation between annular size and age at repair (r=.87, P < .01) and between annular size and AVVR (r=0.68, P < .01). Parametric time-related predicted freedom from reoperation was 82.7% at 15.4 years (70% confidence limits, 76.9% to 88.5%). Multivariate analysis in hazard function domain demonstrated Down's syndrome as a negative risk factor for reoperation (P=.05), whereas annular dilation increased the risk of this event (P=.027). CONCLUSIONS: Early correction of CAVCs is safe and beneficial not only in controlling chronic heart failure, but also in preventing annular dilation secondary to large QP/QS, as a potential mechanism of preoperative AVVR. Annular dilation is an incremental risk factor for reoperation. Early correction according to the double patch technique and trifoliate approach to the left AV valve reconstruction allows respect of valvar and subvalvar apparatus architecture, with a low incidence of postoperative AVVR, excellent survival rate, and low reoperative rate for residual AVVR.

Unexpected mechanical bileaflet valve thrombosis in mitral position: what is better to do, re-replacement or thrombolysis.

BACKGROUND AND AIMS: The longevity of the mechanical heart valve prosthesis is an advantage when compared with its biological counterpart, although the former carries a risk of thrombosis depending on valve design, materials and host-related interface; therefore, a patient with a mechanical valve prosthesis, particularly in mitral position, is at risk for systemic thromboembolism even when properly anticoagulated. PATIENTS AND METHODS: We report a case of a 60-year-old woman who underwent a mitral valve replacement with a St. Jude Medical (SJM) standard bileaflet mechanical heart valve. RESULTS: On the twelfth post-operative day a primary thrombosis with blockage of the anterior valve leaflet occurred. CONCLUSIONS: Aware of the risk of recurrent thromboembolism in this special clinical framework and possible cerebral bleeding in case of thrombolysis, we replaced the prosthesis with a new biologic porcine valve, the SJM Biocor.