Long-term outcome of heart transplantation performed after ventricular assist device compared with standard heart transplantation.

BACKGROUND: Data on the long-term outcome of heart transplantation in patients with a ventricular assist device (VAD) are scarce. AIM: To evaluate long-term outcome after heart transplantation in patients with a VAD compared with no mechanical circulatory support. METHODS: Consecutive all-comers who underwent heart transplantation were included at a single high-volume centre from January 2005 until December 2012, with 5 years of follow-up. Clinical and biological characteristics, operative results, outcomes and survival were recorded. Regression analyses were performed to determine predictors of 1-year and 5-year mortality. RESULTS: Fifty-two patients with bridge to transplantation by VAD (VAD group) and 289 patients transplanted without a VAD (standard group) were enrolled. The mean age was 46±11 years in the VAD group compared with 51±13 years in the standard group (P=0.01); 17% of the VAD group and 25% of the standard group were women (P=0.21). Ischaemic time was longer in the VAD group (207±54 vs 169±60minutes; P<0.01). There was no difference in primary graft failure (33% vs 25%; P=0.22) or 1-year mortality (17% vs 28%; P=0.12). In the multivariable analysis, preoperative VAD was an independent protective factor for 1-year mortality (odds ratio 0.40, 95% confidence interval 0.17-0.97; P=0.04). Independent risk factors for 1-year mortality were recipient age>60 years, recipient creatinine, body surface area mismatch and ischaemic time. The VAD and standard groups had similar long-term survival, with 5-year mortality rates of 35% and 40%, respectively (P=0.72). CONCLUSIONS: Bridge to transplantation by VAD was associated with a reduction in 1-year mortality, leading critically ill patients to similar long-term survival compared with patients who underwent standard heart transplantation. This alternative strategy may benefit carefully selected patients.

Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria.

The abundance of epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), the most frequent cardiac arrhythmia. However, both the origin and the factors involved in EAT expansion are unknown. Here, we found that adult human atrial epicardial cells were highly adipogenic through an epithelial-mesenchymal transition both in vitro and in vivo. In a genetic lineage tracing the WT1CreERT2+/-RosatdT+/- mouse model subjected to a high-fat diet, adipocytes of atrial EAT derived from a subset of epicardial progenitors. Atrial myocardium secretome induces the adipogenic differentiation of adult mesenchymal epicardium-derived cells by modulating the balance between mesenchymal Wingless-type Mouse Mammary Tumor Virus integration site family, member 10B (Wnt10b)/ß-catenin and adipogenic ERK/MAPK signaling pathways. The adipogenic property of the atrial secretome was enhanced in AF patients. The atrial natriuretic peptide secreted by atrial myocytes is a major adipogenic factor operating at a low concentration by binding to its natriuretic peptide receptor A (NPRA) receptor and, in turn, by activating a cGMP-dependent pathway. Hence, our data indicate cross-talk between EAT expansion and mechanical function of the atrial myocardium.

Atrial fibrillation is associated with the fibrotic remodelling of adipose tissue in the subepicardium of human and sheep atria.

AIMS: Accumulation of atrial adipose tissue is associated with atrial fibrillation (AF). However, the underlying mechanisms remain poorly understood. We examined the relationship between the characteristics of fatty infiltrates of the atrial myocardium and the history of AF. METHODS AND RESULTS: Atrial samples, collected in 92 patients during cardiac surgery and in a sheep model of persistent AF, were subjected to a detailed histological analysis. In sections of human right atrial samples, subepicardial fatty infiltrations were commonly observed in the majority of patients. A clear difference in the appearance and fibrotic content of these fatty infiltrations was observed. Fibro-fatty infiltrates predominated in patients with permanent AF (no AF: 37 ± 24% vs. paroxysmal AF: 50 ± 21% vs. permanent AF: 64 ± 23%, P < 0.001). An inverse correlation between fibrotic remodelling and the amount of subepicardial adipose tissue suggested the progressive fibrosis of fatty infiltrates with permanent AF. This hypothesis was tested in a sheep model of AF. In AF sheep, an increased accumulation of peri-atrial fat depot was observed on cardiac magnetic resonance imaging and dense fibro-fatty infiltrations predominated in the left atria of AF sheep. Cellular inflammation, mainly consisting of functional cytotoxic T lymphocytes, was observed together with adipocyte cell death in human atria. CONCLUSION: Atrial fibrillation is associated with the fibrosis of subepicardial fatty infiltrates, a process in which cytotoxic lymphocytes might be involved. This remodelling of the atrial subepicardium could contribute to structural remodelling forming a substrate for AF.

Can magnetic targeting of magnetically labeled circulating cells optimize intramyocardial cell retention?

Therapeutic intracavitary stem cell infusion currently suffers from poor myocardial homing. We examined whether cardiac cell retention could be enhanced by magnetic targeting of endothelial progenitor cells (EPCs) loaded with iron oxide nanoparticles. EPCs were magnetically labeled with citrate-coated iron oxide nanoparticles. Cell proliferation, migration, and CXCR4 chemokine receptor expression were assessed in different labeling conditions and no adverse effects of the magnetic label were observed. The magnetophoretic mobility of labeled EPCs was determined in vitro, with the same magnet as that subsequently used in vivo. Coronary artery occlusion was induced for 30 min in 36 rats (31 survivors), followed by 20 min of reperfusion. The rats were randomized to receive, during brief aortic cross-clamping, direct intraventricular injection of culture medium (n = 7) or magnetically labeled EPCs (n = 24), with (n = 14) or without (n = 10) subcutaneous insertion of a magnet over the chest cavity (n = 14). The hearts were explanted 24 h later and engrafted cells were visualized by magnetic resonance imaging (MRI) of the heart at 1.5 T. Their abundance in the myocardium was also analyzed semiquantitatively by immunofluorescence, and quantitatively by real-time polymerase chain reaction (RT-PCR).Although differences in cell retention between groups failed to be statistically significant using RT-PCR quantification, due to the variability of the animal model, immunostaining showed that the average number of engrafted EPCs was significantly ten times higher with than without magnetic targeting. There was thus a consistent trend favoring the magnet-treated hearts, thereby suggesting magnetic targeting as a potentially new mean of enhancing myocardial homing of intravascularly delivered stem cells. Magnetic targeting has the potential to enhance myocardial retention of intravascularly delivered endothelial progenitor cells.

Diagnosis and surgical treatment of a Takayasu disease on an abdominal aortic dissection.

BACKGROUND: To report the rare diagnosis and the surgical treatment of a young patient presenting a symptomatic dissection of the abdominal aorta revealing a Takayasu's arteritis (TA). METHODS AND RESULTS: A 24-year-old woman developed a painful chronic dissection of the infrarenal aorta associated with a claudication of both lower extremities. As the patient was still symptomatic despite an optimal medical treatment, a surgical revascularization was proposed. An aortobifemoral bypass was performed allowing the removal of infrarenal aorta and the histologic diagnosis of TA. CONCLUSION: Isolated abdominal aortic dissection is an unusual event in TA, and this is the first surgically treated case. Only few reports of aortic dissection in TA have been published so far which are commented in this article.

The significance of endoleaks in thoracic endovascular aneurysm repair.

BACKGROUND: Endoleak is one of the rare complications that occur after thoracic endovascular aneurysm repair (TEVAR). The aim of this study was to assess the incidence of endoleaks and the predictive factors for their occurrence, as well as their effect on secondary interventions after TEVAR. METHODS: Medical and radiological data of all TEVAR procedures performed between 2004 and 2008 were entered prospectively into our database and reviewed retrospectively. Primary endpoints included were the incidence and the type of endoleak, aneurysmal sac expansion, and secondary interventions. RESULTS: In all, 67 patients (18 women and 49 men; mean age, 67 ± 14 years) were treated consecutively for descending thoracic aortic aneurysms (mean diameter: 69 ± 18 mm) by TEVAR during the observed period, using 83 stent-grafts (11 Cook TX2, 31 Gore TAG, and 41 Medtronic Valiant), with a median follow-up of 27 months (range: 2-64). In 13 of 67 patients, 14 (19.4%) endoleaks were diagnosed, of which 71% (10 of 14) were type I, 29% (4 of 14) were type II, and none were type III. Ten endoleaks (71%) were diagnosed on the first postoperative computed tomographic angiography at 1 month, and the other four (29%) developed later on. Predictive factors for endoleaks on univariate analysis included age (p = 0.04), length of the proximal neck immediately after the left subclavian artery (p = 0.04), the fusiform morphology of the descending thoracic aortic aneurysms (p = 0.04), and the type of stent-graft used (p = 0.02). Eight of the 10 type I endoleaks (80%) were successfully treated by endovascular means, using proximal cuffs (n = 5) or distal extensions (n = 3). None of type II endoleaks were treated by secondary intervention. The six endoleaks treated conservatively were all associated with a significant mean increase of their aneurysmal sac (+3.2 ± 2.6 mm) during follow-up. No secondary conversion to open surgery was performed to treat an endoleak. CONCLUSIONS: On the basis of the study, it seems as if endoleaks are detected in one of the five patients treated with TEVAR during follow-up period, particularly if they are old with a proximal and fusiform aneurysm. Short- and mid-term follow-up suggest that most type I endoleaks can successfully be treated by endovascular techniques and that type II endoleaks treated conservatively require a close radiological monitoring.

Skeletal myoblasts preserve remote matrix architecture and global function when implanted early or late after coronary ligation into infarcted or remote myocardium.

BACKGROUND: The inability of skeletal myoblasts to transdifferentiate into cardiomyocytes suggests that their beneficial effects on cardiac function after a myocardial infarction are mediated by paracrine effects. We evaluated the roles of these factors in the preservation of matrix architecture (in the infarct and remote regions) by varying the timing (postmyocardial infarction) and delivery site of the implanted cells. METHODS AND RESULTS: Skeletal myoblasts (5x10(6)) or control media were injected into the infarct or noninfarcted myocardium at 5 or 30 days after coronary artery ligation in rats. Function was assessed by echocardiography before transplantation and 14 and 30 days thereafter and with a Millar catheter at 30 days after transplantation. Ventricular geometry, remote fibrillar collagen architecture, and changes in the matrix metalloproteinase-TIMP system were evaluated. Myoblast implantation in both sites and at both times preserved matrix architecture (length and width of collagen fibers) in the remote myocardium (in association with some decreases in remote myocardial matrix metalloprotease activity), improved global cardiac function, and attenuated the progressive increase in end diastolic volume (P<0.05 for all measures compared with medium controls). Cells delivered into the infarct region preserved scar thickness; cells delivered into the noninfarcted myocardium preserved wall thickness. CONCLUSIONS: Regardless of whether the cells were injected into the infarct or the noninfarcted myocardium early after an myocardial infarction or later, skeletal myoblasts improved cardiac function by preventing ventricular dilation and preserving matrix architecture in the remote region, likely mediated by paracrine effects.