Pregnancy outcomes in women with a mitral valve prosthesis: A systematic review and meta-analysis.

Objectives: To evaluate the ongoing debate concerning the choice of valve prosthesis for women requiring mitral valve replacement (MVR) and who wish to conceive. Bioprostheses are associated with risk of early structural valve deterioration. Mechanical prostheses require lifelong anticoagulation and carry maternal and fetal risks. Also, the optimal anticoagulation regimen during pregnancy after MVR remains unclear. Methods: A systematic review and meta-analysis was conducted of studies reporting on pregnancy after MVR. Valve- and anticoagulation-related maternal and fetal risks during pregnancy and 30 days' postpartum were analyzed. Results: Fifteen studies reporting 722 pregnancies were included. In total, 87.2% of pregnant women had a mechanical prosthesis and 12.5% a bioprosthesis. Maternal mortality risk was 1.33% (95% confidence interval [CI], 0.69-2.56), any hemorrhage risk 6.90% (95% CI, 3.70-12.88). Valve thrombosis risk was 4.71% (95% CI, 3.06-7.26) in patients with mechanical prostheses. 3.23% (95% CI, 1.34-7.75) of the patients with bioprostheses experienced early structural valve deterioration. Of these, the mortality was 40%. Pregnancy loss risk was 29.29% (95% CI, 19.74-43.47) with mechanical prostheses versus 13.50% (95% CI, 4.31-42.30) for bioprostheses. Switching to heparin during the first trimester demonstrated a bleeding risk of 7.78% (95% CI, 3.71-16.31) versus 4.08% (95% CI, 1.17-14.28) for women on oral anticoagulants throughout pregnancy and a valve thrombosis risk of 6.99% (95% CI, 2.08-23.51) versus 2.89% (95% CI, 1.40-5.94). Administration of anticoagulant dosages greater than 5 mg resulted in a risk of fetal adverse events of 74.24% (95% CI, 56.11-98.23) versus 8.85% (95% CI, 2.70-28.99) in ≤5 mg. Conclusions: A bioprosthesis seems the best option for women of childbearing age who are interested in future pregnancy after MVR. If mechanical valve replacement is preferred, the favorable anticoagulation regimen is continuous low-dose oral anticoagulants. Shared decision-making remains priority when choosing a prosthetic valve for young women.

Altered abundances of human immunoglobulin M and immunoglobulin G subclasses in Alzheimer's disease frontal cortex.

The immune system has been described to play a role in the development of Alzheimer's disease (AD), but the distribution of immunoglobulins and their subclasses in brain tissue has not been explored. In this study, examination of pathologically diagnosed frontal cortex gray matter revealed significantly higher levels of IgM and IgG in late-stage AD (Braak and Braak stages V and VI) compared to age-matched controls. While levels of IgG2 and IgG4 constant region fragments were higher in late-stage AD, concentration of native-state IgG4 with free Fc regions was increased in AD III and VI. RNA analysis did not support parenchymal B-cell production of IgG4 in AD III and V, indicating possible peripheral or meningeal B-cell involvement. Changes in the profile of IgM, IgG and IgG subclasses in AD frontal cortex may provide insight into understanding disease pathogenesis and progression.

COSMC mutations reduce T-synthase activity in advanced Alzheimer's disease.

INTRODUCTION: Mutations in brain tissues that cumulate with age may contribute to Alzheimer's disease (AD). Abnormal glycoprotein and Tn antigen expression have been demonstrated in AD. We identified C1GALT1C1/COSMC mutations in AD and age-matched normals without AD. The COSMC coding mutations resulted in a significant reduction in T-synthase activity in advanced AD cases. METHODS: Identification of COSMC mutations, Real-Time Quantitative Reverse Transcription PCR (Q-RT-PCR), western blotting, and T-synthase activity assays. RESULTS: COSMC mutations were detected in the promotor, coding region and 3'UTR in AD and normals. COSMC coding mutations demonstrated a correlation with AD progression. T-synthase levels were significantly elevated in advanced AD compared to AD III (P = 0.03) and normals (P = 0.002). T-synthase activity in advanced AD {Braak and Braak (B&B) stages V and VI} with COSMC coding mutations was 3-fold lower than advanced AD without mutations, and 1.3-fold lower than normal (P = 0.001) and AD B&B stage III (P = 0.01) with coding mutations. DISCUSSION: COSMC coding mutations significantly diminished T-synthase activity in advanced AD, potentially causing defective galactosylation.

A new approach to determine the results of minimally invasive pulmonary vein isolation using a continuous loop monitor: preliminary results.

OBJECTIVES: Surgical ablation is a well-known treatment for atrial fibrillation (AF); however, little is known about the absolute success rate. The aim of this study is to compare the absolute pre- and postoperative incidence of AF after minimally invasive surgical ablation for paroxysmal AF. METHODS: Twenty consecutive patients (mean age 55 ± 8; 55% male) received a continuous loop monitor (CLM) 4 weeks prior to a minimally invasive pulmonary vein isolation (MIPVI). The mean preoperative AF burden was compared with the mean AF burden during follow-up. Follow-up was achieved for a period of 12 months. RESULTS: Seventeen patients underwent an MIPVI successfully. Two patients did not reach the threshold for surgery. In 1 patient, surgery was discontinued because of a perioperative bleeding due to adhesions after a previous percutaneous AF ablation. Mean AF burden preoperatively was 66%. After 12 months, there was an absolute reduction in AF burden of 65% (95% CI 42-88, P < 0.001) and 12 of 15 patients in follow-up (80%) were free of AF without antiarrhythmic drugs (AADs). CONCLUSIONS: The use of a CLM in the follow-up of surgical ablation is a very accurate way to confirm absolute surgical results. Furthermore, with the use of a CLM, preoperative evaluation can be done more accurately, and the surgical procedure can be adjusted to the patients' needs.

Pulmonary artery remodeling in transposition of the great arteries: relevance for neoaortic root dilatation.

OBJECTIVE: Transposition of the great arteries is currently treated by performing the arterial switch operation. Dilatation of the neoaortic root is a late complication with unknown cause. Samples of patients with untreated transposition of the great arteries and patients with normally related great arteries were compared to investigate a possible role for vascular remodeling in the dilatation process. METHODS: Aortic and pulmonary artery vessel wall and sinus samples were taken from 20 untreated human heart specimens with transposition of the great arteries and 9 age-matched, normal, postmortem human heart specimens, divided into 2 groups according to age. Routine histology and immunohistochemical staining for smooth muscle cell differentiation markers alpha-smooth muscle actin, SM22, and calponin were performed. RESULTS: This study revealed structural differences between the normal aorta and pulmonary artery in the early group, which became more pronounced in the late group. In the early stage in transposition of the great arteries, no marked differences were seen between the aorta and pulmonary artery. With increasing age, however, there was a pronounced down-regulation of all smooth muscle cell markers in the pulmonary artery. CONCLUSIONS: There is a structural difference between the normal neonatal aorta and pulmonary artery. The great arteries in transposition of the great arteries differ from each other and from normal vessels, indicating a structural vascular difference in transposition of the great arteries. In the pulmonary artery and sinus of untreated transposition of the great arteries, there is a dedifferentiation of smooth muscle cells with increasing age that we could not correlate to altered flow. This structural abnormality might provide an explanation for the neoaortic root dilatation that has been reported as a late complication of the arterial switch operation.

Neo-coarctation after the arterial switch operation.

Neo-coarctation following arterial switch operation (ASO) for transposition of the great arteries (TGA) is a complication that is not regularly described, but may occur. We describe five patients who developed a neo-coarctation after operation. They were diagnosed with TGA, either with or without ventricular septal defect without signs or symptoms of a coarctation. Except for one patient, all patients were reoperated for a neo-coarctation within one year after the ASO. Several explanations are discussed as a possible cause for this phenomenon.

Thirty-year experience with the arterial switch operation.

BACKGROUND: We evaluated the results of the arterial switch operation (ASO) being performed at our institution for more than 30 years and identified risk factors for mortality and reoperation. METHODS: Clinical outcome of 332 consecutive patients with transposition of the great arteries undergoing ASO was retrospectively analyzed, using surgical reports, medical charts, and latest follow-up echocardiography. Statistical analysis was performed using the Kaplan-Meier method and univariable and multivariable binary logistic and Cox regression analyses. RESULTS: In-hospital mortality was 11.4%. At 15 years, estimated overall survival was 85.2%, and estimated freedom from reoperation was 74.0%. Cross-clamp time (p=0.001) and absence of the Lecompte maneuver (p=0.001) were identified as independent risk factors for in-hospital mortality, whereas coronary problems during surgery (p=0.009) and postoperative pacemaker implantation (p<0.001) were independent risk factors for late mortality. Independent risk factors for reoperation were higher age at the time of the ASO (p=0.002), presence of arch abnormalities (p<0.001), coronary problems during surgery (p=0.005), and duration of ventilation (p<0.001). At latest echocardiography, moderate or severe neoaortic regurgitation was present in 3.4% of the patients. CONCLUSIONS: Overall, 30 years of experience with the ASO shows good survival and event-free survival rates. Coronary transfer problems during surgery were found to be an important risk factor for late mortality and reoperation. However, coronary anatomy other than 1LCx-2R and an intramural course of the left coronary artery or left anterior descending artery were not risk factors for mortality or reoperation. Neoaortic regurgitation does not seem to form a major problem.

Long-term follow-up of arterial switch operation with an emphasis on function and dimensions of left ventricle and aorta.

OBJECTIVE: To analyze size and function of aortic root and left ventricle as well as quality of life in patients 20 years after arterial switch procedure. METHODS: Thirty-nine patients who underwent arterial switch operation between 1977 and 1989 were examined. Perioperative and follow-up data were analyzed. Evaluation included clinical assessment, ECG, echocardiography and quality of life questionnaire. RESULTS: Patients had simple transposition (24), transposition with ventricle septal defect (7), Taussig-Bing anomaly (4) or transposition with ventricle septal defect and aortic arch obstruction (4). Mean age at evaluation was 19.9+/-2.6 years. Seven patients required reintervention for pulmonary stenosis (4), coarctation (2) and subaortic stenosis, followed by valve replacement 10 years later (1). Arrhythmia occurred in four patients. Patients were in New York Heart Association functional class I (38) or II (1). Quality of life scores were comparable to normal controls except for the lower score in the domains of vitality, aggressive and depressive mood. Diameters of aortic annulus, sinus of Valsalva and sinotubular junction were 26.5+/-4.1, 36.5+/-5.6 and 29.2+/-6.6mm respectively. Sixty-five percent of sinus of Valsalva and 38% of sinotubular junction indexed to body surface area fall outside the 95% confidence interval. Aortic regurgitation was absent in 72%, mild in 13% and moderate in 15%. No patient had severe regurgitation. Patients without regurgitation had smaller diameters of annulus (p=0.005) and sinus of Valsalva (p=0.01). Left ventricular end-diastolic and end-systolic diameters were 51+/-7mm and 34+/-6mm respectively. Fractional shortening was 34+/-5%; no regional wall motion abnormalities were observed. CONCLUSIONS: Clinical outcome is good 20 years after arterial switch operation and aortic valve function remains preserved in most patients. However, aortic root dilatation is present in two thirds of patients emphasizing the need for careful follow-up.

The outflow tract in transposition of the great arteries: an anatomic and morphologic study.

BACKGROUND: Neoaortic root dilatation is observed after the arterial switch operation for transposition of the great arteries. Although structural differences in the vessel wall of these patients may be of influence, we hypothesize that a histomorphologic difference in composition and embedding of the fibrous annulus in transposition of the great arteries may play a role in neoaortic root dilatation. METHODS: Two normal human hearts and two unoperated human hearts with transposition of the great arteries, 1 day postnatal, were studied. Histologic sections stained for collagen, myocardium, and elastin were prepared, and three-dimensional reconstructions of the outflow tracts were made to enable comparison of the morphologic structures between the normal hearts and those with transposition of the great arteries. RESULTS: The amount of collagen in the arterial roots was diminished in hearts with transposition of the great arteries compared with the normal hearts. In addition, the anchorage and embedding of both arterial roots in the myocardium was less extensive in transposition of the great arteries. The changed position of the arteries in the malformed hearts results in less support for the roots from the surrounding atrioventricular myocardium. CONCLUSIONS: The combination of the observed histomorphologic differences in amount of collagen and myocardial support may be an explanation for the neoaortic root dilatation observed after the arterial switch operation. The developmental background of the observed deficient fibrous annulus formation may originate from an epicardial problem.