Technical possibilities and limitations of mechanical circulatory support

Ventricular assist devices (VAD) to support the left (LVAD), the right (RVAD) or both ventricles (BVAD) have emerged as one standard of care for advanced heart failure patients. Initially used to bridge patients to transplantation (BTT) they are now more frequently implanted as permanent support (destination therapy, DT). Bridge to recovery (BTR) is a valid option for only a small number of patients. Although there are different devices available, patient selection, preoperative and intraoperative management, and the timing of VAD implantation are the elements critical to successful circulatory support.     

放宽心脏移植供、受者年龄的可行性研究

目的 探讨临床上放宽心脏移植供、受者年龄的可行性。方法 回顾分析９８９例心脏移植的临床资料,比较供、受者的年龄对术后受者存活率的影响。结果 供者年龄（大于５５岁和小于５５岁比较）对术后受者存活率的影响不显著（Ｐ＝０．９９）,受者年龄（大于６０岁和小于６０岁比较）对术后其存活率的影响也不显著（Ｐ＝０．１０）;另外,供心冷缺血时间也可适当延长。结论 在严格掌握指征的前提下,可适当放宽心脏移植供、受者的     

Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients

Background:

In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methylator phenotype (CIMP) status are indicators of patient outcome, but the molecular events that give rise to these outcomes remain largely unknown. Wnt5a is a critical regulator of non-canonical Wnt activity and promoter hypermethylation of this gene has emerging prognostic roles in CRC; however the frequency and prognostic significance of this epigenetic event have not been explored in the context of colorectal tumour subtype. Consequently, we investigated the frequency and prognostic significance of Wnt5a methylation in a large cohort of MSI-stratified CRCs.

Methods:

Methylation was quantified in a large cohort of 1232 colorectal carcinomas from two clinically distinct populations from Canada. Associations were examined between methylation status and clinicopathlogical features, including tumour MSI status, BRAF V600E mutation, and patient survival.

Results:

In Ontario, Wnt5a methylation was strongly associated with MSI tumours after adjustment for age, sex, and tumour location (odds ratio (OR)=4.2, 95% confidence interval (CI)=2.4–7.4, P<10⁻⁶) and with BRAF V600E mutation, a marker of CIMP (OR=12.3, 95% CI=6.9–21.7, P<10⁻¹⁷), but was not associated with patient survival. Concordant results were obtained in Newfoundland.

Conclusion:

Methylation of Wnt5a is associated with distinct tumour subtypes, strengthening the evidence of an epigenetic-mediated Wnt bias in CRC.     

Giant aneurysm of the right coronary artery and fistula to the coronary sinus

We describe the case of a 67-year-old man with a rare combination of a giant coronary artery aneurysm with a fistula draining into the coronary sinus. The patient presented with a sensation of retrosternal pressure. He was examined by coronary angiography, which revealed a large aneurysm of the right coronary artery (RCA) with a fistula. This fistula originated from the distal RCA shortly beyond the crux and drained into the coronary sinus. The aneurysm was in the proximal portion of the RCA, measuring 4 cm in diameter and 7 cm in length. Surgical repair by closure of the fistula under direct vision, suture closure and plication of the aneurysm, and coronary artery bypass was performed. Postoperative echocardiography and computed tomography confirmed closure of the fistula. The patient remains symptom-free at 4 months after surgery.     

The ‘beating-heart butterfly technique’ for repair of basal post-infarction ventricle septum defect

Ischaemic ventricular septal defect is a serious complication of acute myocardial infarction with poor outcome. We present the ‘beating-heart butterfly’ technique to close the ventricular septal defect with a double-layered pericardial patch sewn to the intact septum under beating-heart cardiopulmonary bypass in 4 highest-risk patients. This technique combined with a liberal postoperative mechanical circulatory support and open-chest treatment allowed excellent results with 12 months of survival in all patients.     

Permanent mechanical circulatory support in patients of advanced age.

OBJECTIVE: This study details our initial results of long-term left ventricular assist device (LVAD) support in patients suffering from catecholamine-dependent end-stage heart failure or cardiogenic shock with age above 65 years or age above 60 and contraindications to cardiac transplantation. METHODS: Between September 2000 and July 2002, 27 patients received implantation of left ventricular assist devices (Micromed DeBakey (n=15), Berlin Heart Excor (n=6), Arrow Lion Heart (n=4) and Novacor N100 (n=2)). The mean age of this group was 66.2+/-4.1 (60-77) years. The patients presented with the following features by the time of LVAD implantation: failure of weaning from inotropic support (78%), either profound cardiogenic shock (37%) or instable hemodynamic status (22%), high-dose inotropic (52%) or intraaortic balloon pump support (11%), dialysis (15%), artificial ventilation (15%), and at least one previous cardiac procedure (44%). RESULTS: The cumulative survival rate for the whole group was 63% at 30 days, 30% at 180 days, and 22% at 2 years. The presence of preoperative cardiogenic shock was associated with a higher perioperative mortality rate. Late complications (n=7) included replacement of two thrombosed DeBakey LVADs and five late deaths secondary to thrombembolism/intracranial hemorrhage (DeBakey LVAD, n=3) or septicemia (n=2). As of May 15, 2003, six patients remain on LVAD support for an average of 653 (339-953) days, three patients now for more than 2 years. Ten patients were discharged home to spend 73% of their life span on out-of-hospital long-term LVAD support. CONCLUSION: This study reports the first single-center experience of permanent LVAD support in patients of advanced age. For this initial experience, many patients with critical circulatory status and previous cardiac operations were included and a high postoperative mortality rate was encountered among them. Older age and associated multimorbidity are the key determinants rendering the conditions of LVAD therapy for this patient cohort to be different from the bridge-to-transplant experience. The LVADs employed in this study showed different capabilities with regard to long-term support. Our experience shows that permanent mechanical circulatory support does have the potential to evolve as a treatment option in selected elderly patients with end-stage heart failure.     

Heparan sulfate chains with antimitogenic properties arise from mesangial cell-surface proteoglycans.

Heparan sulfate (HS) chains accumulate in both the medium and the cell layer of mesangial cell cultures. When given in fresh medium to quiescent cultures at naturally occurring concentrations, they suppress entry into the cell cycle and progression to DNA synthesis. We have attempted to identify the proteoglycan (PG) source of the antimitogenic HS chains from mesangial cell layers (HS(c)) and medium (HS(c)). When cells were labeled for 16 hours with [35S]sulfate, 25% of the label was found in intracellular HS chains and 5% in extracellular HSPGs. Cell-surface HSPGs accounted for the remaining 70% of the label associated with cell-layer HS and were released by either trypsin or 2% Triton X-100. About 20% of this cell-surface fraction was released by treatment with phosphatidylinositol-specific phospholipase C (PI-PLC), and probably represents glypican-like PG; glypican mRNA was present in the cells. The remainder of this fraction could be incorporated into liposomes, indicating the presence of hydrophobic transmembrane regions suggestive of syndecans. Upon purification and deglycosylation, an antiserum to rat liver HSPGs that reacts primarily with syndecan-2 showed a strong signal corresponding to this protein and three weaker bands that may represent additional syndecans. mRNAs for syndecan-1, -2, and -4 were present in the cultures. Syndecan-1 and -2 mRNAs were increased 30 minutes after stimulation of quiescent rat mesangial cells (RMCs) with serum. Heparin, HS(c), and HS(m) all prevented this increase. Syndecan-4 mRNA was not affected by serum, heparin, or HS. In pulse-chase experiments, the amount of 35S appearing in the cellular protein-free HS fraction was accounted for almost entirely by cell-surface PGs, as matrix-associated label was a minor contribution at the end of the pulse-labeling. The appearance of [35S]HS in cell extracts was unaffected by phospholipase C treatment, indicating that turnover of the newly labeled syndecan fraction is the source of the antimitogenic HS chains.