Distinct Roles of DRP1 in Conventional and Alternative Mitophagy in Obesity Cardiomyopathy.

BACKGROUND: Obesity induces cardiomyopathy characterized by hypertrophy and diastolic dysfunction. Whereas mitophagy mediated through an Atg7 (autophagy related 7)-dependent mechanism serves as an essential mechanism to maintain mitochondrial quality during the initial development of obesity cardiomyopathy, Rab9 (Ras-related protein Rab-9A)-dependent alternative mitophagy takes over the role during the chronic phase. Although it has been postulated that DRP1 (dynamin-related protein 1)-mediated mitochondrial fission and consequent separation of the damaged portions of mitochondria are essential for mitophagy, the involvement of DRP1 in mitophagy remains controversial. We investigated whether endogenous DRP1 is essential in mediating the 2 forms of mitophagy during high-fat diet (HFD)-induced obesity cardiomyopathy and, if so, what the underlying mechanisms are. METHODS: Mice were fed either a normal diet or an HFD (60 kcal %fat). Mitophagy was evaluated using cardiac-specific Mito-Keima mice. The role of DRP1 was evaluated using tamoxifen-inducible cardiac-specific Drp1knockout (Drp1 MCM) mice. RESULTS: Mitophagy was increased after 3 weeks of HFD consumption. The induction of mitophagy by HFD consumption was completely abolished in Drp1 MCM mouse hearts, in which both diastolic and systolic dysfunction were exacerbated. The increase in LC3 (microtubule-associated protein 1 light chain 3)-dependent general autophagy and colocalization between LC3 and mitochondrial proteins was abolished in Drp1 MCM mice. Activation of alternative mitophagy was also completely abolished in Drp1 MCM mice during the chronic phase of HFD consumption. DRP1 was phosphorylated at Ser616, localized at the mitochondria-associated membranes, and associated with Rab9 and Fis1 (fission protein 1) only during the chronic, but not acute, phase of HFD consumption. CONCLUSIONS: DRP1 is an essential factor in mitochondrial quality control during obesity cardiomyopathy that controls multiple forms of mitophagy. Although DRP1 regulates conventional mitophagy through a mitochondria-associated membrane-independent mechanism during the acute phase, it acts as a component of the mitophagy machinery at the mitochondria-associated membranes in alternative mitophagy during the chronic phase of HFD consumption.

Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL.

The Hippo pathway, evolutionarily conserved from flies to mammals, promotes cell death and inhibits cell proliferation to regulate organ size. The core component of this cascade, Mst1 in mammalian cells, is sufficient to promote apoptosis. However, the mechanisms underlying both its activation and its ability to elicit cell death remain largely undefined. We here identify a signaling cassette in cardiac myocytes consisting of K-Ras, the scaffold RASSF1A, and Mst1 that is localized to mitochondria and promotes Mst1 activation in response to oxidative stress. Activated Mst1 phosphorylates Bcl-xL at Ser14, which resides in the BH4 domain, thereby antagonizing Bcl-xL-Bax binding. This, in turn, causes activation of Bax and subsequent mitochondria-mediated apoptotic death. Our findings demonstrate mitochondrial localization of Hippo signaling and identify Bcl-xL as a target that is directly modified to promote apoptosis.

Aortic remodeling of the provisional extension to induce complete attachment technique in DeBakey type IIIb aortic dissection.

BACKGROUND/PURPOSE: Data about volumetric remodeling of the provisional extension to induce complete attachment (PETTICOAT) technique on DeBakey type IIIb aortic dissection in acute and subacute phases were scarce. The proper timing to perform this technique to promote false lumen reduction was also unknown. METHODS: Patients with DeBakey type IIIb aortic dissection who underwent the PETTICOAT technique between December 2005 and March 2017 were reviewed and divided into acute (treatment occurred ≦14 days after symptom onset) and subacute (15-90 days) groups. Remodeling parameters of the true and false lumens were analyzed. Receiver operating characteristic curve was used to deduce the timing of this technique. RESULTS: In the 2-year follow-up, the acute group (N = 20) demonstrated significant true lumen expansion and false lumen regression in the thoracic, abdominal, and total aorta. However, the subacute group (N = 20) only showed significant shrinkage in the false lumen of the thoracic and total aorta. Using PETTICOAT technique within 36 days after the aortic event may result in better total false lumen reduction. CONCLUSION: For DeBakey type IIIb aortic dissection, more prominent true lumen expansion and false lumen reduction were noted when using the PETTICOAT technique in the acute phase. When performed within 36 days after symptoms onset, the PETTICOAT technique may potentiate better total false lumen regression.

Cardiac Dopamine-Secreting Paraganglioma with Involved Skull Base and Retroperitoneum After a History of Pheochromocytoma Post Adrenalectomy.

Cardiac paragangliomas are exceedingly rare. Herein, we describe a patient with a large dopaminesecreting cardiac paraganglioma who had a history of pheochromocytoma after right adrenalectomy. The cardiac surgery was uneventful and without blood pressure fluctuations.The measurement of plasma-free metanephrines or urinary fractionated metanephrines is used as an initial screening test for pheochromocytoma or paraganglioma detection. However, these results must be combined with those of a plasma 3-methoxytyramine test to accurately establish the rare dopaminergic phenotype of pheochromocytomas or paragangliomas, if suspected. F-FDOPA (6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine)-based positron emission tomography (PET) and PET-computed tomography are relatively sensitive and specific; therefore, these techniques are recommended for patients with pheochromocytomas or paragangliomas before operation or during postoperative follow-up.

Hippo Deficiency Leads to Cardiac Dysfunction Accompanied by Cardiomyocyte Dedifferentiation During Pressure Overload.

RATIONALE: The Hippo pathway plays an important role in determining organ size through regulation of cell proliferation and apoptosis. Hippo inactivation and consequent activation of YAP (Yes-associated protein), a transcription cofactor, have been proposed as a strategy to promote myocardial regeneration after myocardial infarction. However, the long-term effects of Hippo deficiency on cardiac function under stress remain unknown. OBJECTIVE: We investigated the long-term effect of Hippo deficiency on cardiac function in the presence of pressure overload (PO). METHODS AND RESULTS: We used mice with cardiac-specific homozygous knockout of WW45 (WW45cKO), in which activation of Mst1 (Mammalian sterile 20-like 1) and Lats2 (large tumor suppressor kinase 2), the upstream kinases of the Hippo pathway, is effectively suppressed because of the absence of the scaffolding protein. We used male mice at 3 to 4 month of age in all animal experiments. We subjected WW45cKO mice to transverse aortic constriction for up to 12 weeks. WW45cKO mice exhibited higher levels of nuclear YAP in cardiomyocytes during PO. Unexpectedly, the progression of cardiac dysfunction induced by PO was exacerbated in WW45cKO mice, despite decreased apoptosis and activated cardiomyocyte cell cycle reentry. WW45cKO mice exhibited cardiomyocyte sarcomere disarray and upregulation of TEAD1 (transcriptional enhancer factor) target genes involved in cardiomyocyte dedifferentiation during PO. Genetic and pharmacological inactivation of the YAP-TEAD1 pathway reduced the PO-induced cardiac dysfunction in WW45cKO mice and attenuated cardiomyocyte dedifferentiation. Furthermore, the YAP-TEAD1 pathway upregulated OSM (oncostatin M) and OSM receptors, which played an essential role in mediating cardiomyocyte dedifferentiation. OSM also upregulated YAP and TEAD1 and promoted cardiomyocyte dedifferentiation, indicating the existence of a positive feedback mechanism consisting of YAP, TEAD1, and OSM. CONCLUSIONS: Although activation of YAP promotes cardiomyocyte regeneration after cardiac injury, it induces cardiomyocyte dedifferentiation and heart failure in the long-term in the presence of PO through activation of the YAP-TEAD1-OSM positive feedback mechanism.

Feasibility and rationale of direct current cardioversion immediately after transcatheter percutaneous edge-to-edge mitral valve repair.

AIMS: Atrial fibrillation (AF) is a frequent comorbidity among patients with severe mitral regurgitation (MR). Direct current (DC) cardioversion is one of the strategies for rhythm control. However, the safety and feasibility of immediate DC cardioversion after MitraClip are not elucidated. METHODS AND RESULTS: In this study, patients with symptomatic severe MR who underwent MitraClip were included. After fixing the MR, synchronized DC cardioversion was attempted for those with AF. A total of consecutive 60 patients, 36 subjects (60%), comorbid with AF. DC cardioversion was performed in 30 patients (mean age of 76.0 ± 9.3 years), and the successful conversion was achieved in 15 patients (50%). There was no any adverse event related to the cardioversion. Subjects with sustained conversion to SR experienced significant improvement in 6MWT (failed: 285 ± 110-308 ± 135 m, P = .278; successful: 269 ± 109 m-328 ± 78, P = .047) and reduction in NT-proBNP level (failed: 4411 ± 7401-3296 ± 4299 ng/mL, P = .217; successful: 4094 ± 2735-2353 ± 2856 ng/mL, P = .026) at 1 month. CONCLUSIONS: Direct current cardioversion seemed to be safe and feasible immediately after the transcatheter edge-to-edge mitral valve repairs. Subjects who maintain SR experienced better functional improvement.

DDAH-2 alleviates contrast medium iopromide-induced acute kidney injury through nitric oxide synthase.

BACKGROUND: Contrast medium-induced acute kidney injury (CI-AKI) is one of the most common causes of hospital-acquired acute renal failure. However, the pathogenesis of CI-AKI remains unclear. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor that is largely metabolised by dimethylarginine dimethylaminohydroxylase (DDAH) in humans. Two isoforms of DDAH exist, namely, DDAH-1 and DDAH-2. In the present study, we examined whether the DDAH-2/ADMA/NOS pathway is involved in the pathogenesis of CI-AKI. METHODS AND RESULTS: Exposure to the contrast medium iopromide led to increase in creatinine and blood urea nitrogen (BUN) levels, accumulation of ADMA, increase in reactive oxygen species (ROS) generation, and an inflammatory response in mice kidney tissue. The injection of adenovirus-harbouring DDAH-2 lowered renal ADMA levels and had a reno-protective effect against contrast-medium injury by decreasing cell apoptosis, ROS, and fibrosis. By contrast, contrast medium-induced renal injury was exacerbated in heterozygous DDAH-2 knockout mice. In the in vitro study, overexpression of DDAH-2 increased the levels of nitrite and intracellular cGMP, while the DDAH-2 knockdown induced the opposite effect. These findings were also observed in the in vivo sample. CONCLUSIONS: Our findings provide the first evidence that the DDAH-2/ADMA/NOS pathway is involved in the pathogenesis of CI-AKI and that the protective effect of DDAH-2 probably arises from the modulation of NOS activity, oxidative stress, and the inflammatory process.

Efficacy of ascending aortic banding technique concomitant with type I hybrid aortic arch repair in high-risk patients.

Banding of the ascending aorta has been introduced as a less complex procedure to optimize the proximal landing zone of the stent graft in hybrid aortic arch surgery. However, data about the long-term results and effects of this technique are still limited. We aimed to study the efficacy of banding of the ascending aorta in hybrid aortic arch repair. The study included 11 high-risk patients with dilated ascending aorta (wider than 38 mm in diameter) undergoing ascending aortic banding for hybrid arch repair. Clinical outcomes, including technical success, endoleaks, perioperative mortality and morbidity, and sequential remodeling of the ascending aorta were investigated. The average diameter of the ascending aorta had been reduced (p = 0.02) from 42.1 mm (range = 39.0-46.4) to 37.2 mm (range = 35.6-38.6) after banding procedure. The technical success rate was 100.0%. No type I endoleak occurred, but 2 cases of distal stent graft-induced new entry required re-interventions. The 5-year survival and freedom from aortic events rates both were 81.8%. The ascending aortic diameter remained stable and no proximal migration of the stent graft was observed during the study period. The 5-year results validated the durability of this therapeutic modality, especially in high-risk patients.

Atypical Antipsychotic Drug Olanzapine Deregulates Hepatic Lipid Metabolism and Aortic Inflammation and Aggravates Atherosclerosis.

BACKGROUND/AIMS: Olanzapine, an atypical antipsychotic drug, has therapeutic effects for schizophrenia. However, clinical reports indicate that patients taking atypical antipsychotic drugs are at high risk of metabolic syndrome with unclear mechanisms. We investigated the effect of olanzapine on atherosclerosis and the mechanisms in apolipoprotein E-null (apoE-/-) mice. METHODS: ApoE-/- mice were used as in vivo models. Western blot analysis was used to evaluate protein expression. Conventional assay kits were applied to assess the levels of cholesterol, triglycerides, free cholesterol, cholesteryl ester, fatty acids, glycerol, and cytokines. RESULTS: Daily treatment with olanzapine (3 mg/kg body weight) for four weeks increased mean arterial blood pressure and the whitening of brown adipose tissue in mice. In addition, olanzapine impaired aortic cholesterol homeostasis and exacerbated hyperlipidemia and aortic inflammation, which accelerated atherosclerosis in mice. Moreover, lipid accumulation in liver, particularly total cholesterol, free cholesterol, fatty acids, and glycerol, was increased with olanzapine treatment in apoE-/- mice by upregulating the expression of de novo lipid synthesis-related proteins and downregulating that of cholesterol clearance- or very low-density lipoprotein secretion-related proteins. CONCLUSION: Olanzapine may exacerbate atherosclerosis by deregulating hepatic lipid metabolism and worsening hyperlipidemia and aortic inflammation.

NF2 Activates Hippo Signaling and Promotes Ischemia/Reperfusion Injury in the Heart.

RATIONALE: NF2 (neurofibromin 2) is an established tumor suppressor that promotes apoptosis and inhibits growth in a variety of cell types, yet its function in cardiomyocytes remains largely unknown. OBJECTIVE: We sought to determine the role of NF2 in cardiomyocyte apoptosis and ischemia/reperfusion (I/R) injury in the heart. METHODS AND RESULTS: We investigated the function of NF2 in isolated cardiomyocytes and mouse myocardium at baseline and in response to oxidative stress. NF2 was activated in cardiomyocytes subjected to H2O2 and in murine hearts subjected to I/R. Increased NF2 expression promoted the activation of Mst1 (mammalian sterile 20-like kinase 1) and the inhibition of Yap (Yes-associated protein), whereas knockdown of NF2 attenuated these responses after oxidative stress. NF2 increased the apoptosis of cardiomyocytes that appeared dependent on Mst1 activity. Mice deficient for NF2 in cardiomyocytes, NF2 cardiomyocyte-specific knockout (CKO), were protected against global I/R ex vivo and showed improved cardiac functional recovery. Moreover, NF2 cardiomyocyte-specific knockout mice were protected against I/R injury in vivo and showed the upregulation of Yap target gene expression. Mechanistically, we observed nuclear association between NF2 and its activator MYPT-1 (myosin phosphatase target subunit 1) in cardiomyocytes, and a subpopulation of stress-induced nuclear Mst1 was diminished in NF2 CKO hearts. Finally, mice deficient for both NF2 and Yap failed to show protection against I/R indicating that Yap is an important target of NF2 in the adult heart. CONCLUSIONS: NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through the activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart.

The Intra-Pericardial Paraganglioma Presenting as Ascites and Hemopericardium with Impending Tamponade.

The intra-pericardial paraganglioma is very rare and most of them present with hypertension or palpitations. Here we reported an extraordinarily rare case of intra-pericardial paraganglioma presenting as faint, pitting edema, abdominal fullness with ascites, and hemopericardium with impending tamponade, which was treated successfully by emergent pericardiocentesis and surgical resection.

Coronary Artery Bypass Surgery versus Percutaneous Coronary Intervention for Left Main Coronary Artery Disease with Chronic Kidney Disease.

Percutaneous coronary intervention (PCI) has emerged as an alternative treatment to coronary artery bypass grafting (CABG) in patients with unprotected left main coronary artery disease (ULMCAD). However, the optimal treatment for ULMCAD concomitant with chronic kidney disease (CKD) was rarely addressed. Herein, we compare the long-term outcomes of these patients treated with CABG or PCI.From January 2004 to December 2010, 185 patients with ULMCAD and CKD undergoing PCI (n = 84) or CABG (n = 101) were matched for the selection criteria. The primary end points included all-cause death, myocardial infarction (MI), stroke, repeat revascularization and major adverse cardiovascular and cerebrovascular event (MACCE).The mean age was 73.4 ± 10.3 years with male (84%) predominance. Baseline characteristics of both groups were similar, except that patients in CABG group were more frequently associated with significant stenosis of right coronary artery and triple vessel disease. Furthermore, most patients belonged to higher surgical risk population (EuroSCORE ≥ 6, PCI group: 80.9%, CABG group: 75.2%). After treatment, the 30-day mortality was 3.5% in PCI and 8.9% in CABG (P = 0.14). During the median follow-up of 3.5 years, the risk of MACCE (67% versus 55%, P = 0.048), MI (15.5% versus 6.9%, P = 0.024), and repeat revascularization (30.9% versus 7.9%, P < 0.001) was significantly higher in the PCI compared with CABG. There were no significant differences in long-term all-cause death, stroke, and impact on renal function.CABG was associated with significantly less long-term risk of MI and repeat revascularization in patients with ULMCAD and CKD.

Drp1-Dependent Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload-Induced Mitochondrial Dysfunction and Heart Failure.

BACKGROUND: Mitochondrial autophagy is an important mediator of mitochondrial quality control in cardiomyocytes. The occurrence of mitochondrial autophagy and its significance during cardiac hypertrophy are not well understood. METHODS AND RESULTS: Mice were subjected to transverse aortic constriction (TAC) and observed at multiple time points up to 30 days. Cardiac hypertrophy developed after 5 days, the ejection fraction was reduced after 14 days, and heart failure was observed 30 days after TAC. General autophagy was upregulated between 1 and 12 hours after TAC but was downregulated below physiological levels 5 days after TAC. Mitochondrial autophagy, evaluated by electron microscopy, mitochondrial content, and Keima with mitochondrial localization signal, was transiently activated at ≈3 to 7 days post-TAC, coinciding with mitochondrial translocation of Drp1. However, it was downregulated thereafter, followed by mitochondrial dysfunction. Haploinsufficiency of Drp1 abolished mitochondrial autophagy and exacerbated the development of both mitochondrial dysfunction and heart failure after TAC. Injection of Tat-Beclin 1, a potent inducer of autophagy, but not control peptide, on day 7 after TAC, partially rescued mitochondrial autophagy and attenuated mitochondrial dysfunction and heart failure induced by overload. Haploinsufficiency of either drp1 or beclin 1 prevented the rescue by Tat-Beclin 1, suggesting that its effect is mediated in part through autophagy, including mitochondrial autophagy. CONCLUSIONS: Mitochondrial autophagy is transiently activated and then downregulated in the mouse heart in response to pressure overload. Downregulation of mitochondrial autophagy plays an important role in mediating the development of mitochondrial dysfunction and heart failure, whereas restoration of mitochondrial autophagy attenuates dysfunction in the heart during pressure overload.

Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in Patients with Diabetic Nephropathy and Left Main Coronary Artery Disease.

BACKGROUND: Patients with diabetic nephropathy and unprotected left main (LM) coronary artery disease suffer from high cardiovascular morbidity and mortality. Although surgical revascularization is currently recommended in this special patient population, the optimal revascularization method for this distinct patient group has remained unclear. METHODS: We collected 99 consecutive patients with unprotected LM disease and diabetic nephropathy, including 46 patients who had undergone percutaneous coronary intervention (PCI), and 53 who had coronary artery bypass grafting (CABG), with a mean age of 72 ± 10; with 80.8% male. Diabetic nephropathy was defined as overt proteinuria (proteinuria > 500 mg/day) and estimated glomerular filtration rate (eGFR) by the modified Modification of Diet in Renal Disease (MDRD) equation of less than 60 mL/min/1.73 m2. The baseline characteristics, angiographic results and long-term clinical outcomes were retrospectively analyzed. RESULTS: The baseline characteristic of all patients were similar except for smokers, low density lipoprotein (LDL) level and extension of coronary artery disease involvement. The median follow-up period was 3.8 years. There were 73 patients (74%) considered as high risk with additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) ≥ 6. During follow-up period, the long term rate of all-cause death (PCI vs. CABG: 45.7% vs. 58.5%, p = 0.20) and all-cause death/myocardial infarction (MI)/stroke (PCI vs. CABG: 52.2% vs. 60.4%, p = 0.41) were comparable between the PCI and CABG group, whereas the repeat revascularization rate was significantly higher in the PCI group (PCI vs. CABG: 32.6% vs. 9.4%, p < 0.01). eGFR remained an independent predictor for all-cause death [hazard ratio: 0.97, 95% confidence interval: 0.96 to 0.99; p = 0.002] in multivariate logistic regression. CONCLUSIONS: In the real-world practice of high-risk patients with unprotected LM disease and diabetic nephropathy, we found that PCI was a comparable alternative to CABG in terms of long-term risks of all-cause death/MI/stroke, with significantly higher repeat revascularization rate. Given the small patient number and retrospective nature, our findings should be validated by larger-scale randomized studies.

Rhodiola Inhibits Atrial Arrhythmogenesis in a Heart Failure Model.

INTRODUCTION: Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation. METHODS: This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined. RESULTS: Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group. CONCLUSIONS: Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling.

Association between Aortic Remodeling and Stent Graft-Induced New Entry in Extensive Residual Type A Dissecting Aortic Aneurysm after Hybrid Arch Repair.

BACKGROUND: This study evaluated sequential aortic morphologic remodeling and influencing factors between distal stent graft-induced new entry (SINE) in chronic residual type A dissecting aortic aneurysm after extensive hybrid arch repair. METHODS: We retrospectively analyzed operative and follow-up data of 30 consecutive patients with chronic residual type A aortic dissection aneurysm treated by hybrid type III arch repair (ascending aortic and arch replacement combined with elephant trunk technique before stent-graft deployment) between November 2006 and October 2011. RESULTS: In 3 years, follow-up of 24 patients with successful 1-stage hybrid arch repair and stent grafting. The ratio of true lumen area increased at pulmonary artery level, but minimal change was seen in the thoracic segment distal to stent graft and abdominal aorta. Late distal SINE occurred in 14 patients (SINE group). Cross-sectional area showed significant differences in distal end of pre-stenting graft oversizing ratio (SINE group 4.32 vs. non-SINE group 2.23, P = 0.021(∗)). The thoracic segment thrombosis rate was 90% in SINE and 57% in non-SINE (P = 0.089) groups. CONCLUSIONS: In homogenous population of chronic residual type A dissection, noticeable false lumen thrombosis with true lumen progressive dilatation was only found at the proximal descending aortic segment extending to the middle of stent grafts in both groups. A smaller size selection of the distal stent graft by area measurement would be accompanied with poor aortic remodeling but might be beneficial for SINE prevention. On the other hand, a larger size selection of the distal stent graft area might be favorable for aortic remodeling but could potentially induce SINE.

Extracorporeal membrane oxygenation use, expenditure, and outcomes in taiwan from 2000 to 2010.

BACKGROUND: No study to date has systematically examined use, expenditure, and outcomes associated with extracorporeal membrane oxygenation (ECMO) use in Taiwan. The aim of this study was to examine ECMO use, expenditure, and outcomes during an 11-year period in Taiwan. METHODS: Claims data were collected from the Taiwan National Health Insurance Research Database for patients who received ≥1 ECMO treatment between January 2000 and December 2010. Measurements included demographics, indications for ECMO use, length of hospital stay, outcome, and expenditure. RESULTS: A total of 3969 patients received ECMO during the study period (median age: 54.6 years). The number of patients receiving ECMO increased from 52 in 2000 to 1045 in 2010. The major indication for ECMO was cardiovascular disease (68.7%), followed by respiratory disease (17.9%). Median length of hospital stay was 13 days in 2000 and 17 days in 2010. Median expenditure (New Taiwan dollars) was $604 317 in 2000 and $673 888 in 2010. Some variables significantly differed by age, sex, hospital setting, calendar year, and indication for ECMO, and were associated with in-hospital and after-discharge mortality. CONCLUSIONS: ECMO use has increased dramatically in Taiwan over the last decade. The high mortality rate of ECMO users suggested that ECMO may be being used in Taiwan for situations in which it provides no added benefit. This situation may be a reflection of the current reimbursement criteria for National Health Insurance in Taiwan. Refinement of the indications for use of ECMO is suggested.

Percutaneous pharmacomechanical thrombectomy offers lower risk of post-thrombotic syndrome than catheter-directed thrombolysis in patients with acute deep vein thrombosis of the lower limb.

BACKGROUND: Despite optimal anticoagulant therapy, patients with proximal deep vein thrombosis (DVT) will often develop post-thrombotic syndrome (PTS). Early thromboreduction can potentially decrease the risk of PTS by restoring venous patency and preserving valvular function. This study was undertaken to compare the efficacy and treatment outcomes of patients with acute proximal DVT of the lower limb who underwent either catheter-directed thrombolysis (CDT) or percutaneous pharmacomechanical thrombectomy (PMT). METHODS: Thirty-nine patients with acute proximal DVT of the lower limb who were diagnosed by Wells' Score, PMT or CDT was chosen depending on the patient. They underwent early thromboreduction, and 3 died postoperatively in less than 12 months, while 2 were removed for not following-up. Thirty-four patients, 16 in PMT and 18 in CDT, were followed up for more than 1 year. Venous Registry Index (VRI) was used to evaluate the postprocedural patency, while PTS was assessed using the Villalta scale. RESULTS: The technical success was 100% in both the groups, without any 30-day mortality. VRI changed from 13.1 ± 4.3 preoperatively to 2.4 ± 1.5 postoperatively in the PMT group, and from 11.8 ± 2.4 to 3.6 ± 2.2 in the CDT group. Thrombolysis rate was 81.5 ± 8.5% and 67.7 ± 21.0% in the PMT and CDT groups, respectively (P = 0.059). There were no differences in complications, thrombus score, and VRI between the 2 groups. Primary patency rate at 1 year was 93.8% in the PMT group and 88.9% in the CDT group (P = 0.648). The Villalta scale was 2.1 ± 3.0 in the PMT group and 5.1 ± 4.1 in the CDT group (P = 0.030). CONCLUSIONS: Both PMT and CDT are effective treatment modalities in patients with acute proximal DVT. Compared with CDT, PMT provides similar treatment success, but with lower risk of PTS at 1-year follow-up.

Nickel ions from a corroded cardiovascular stent induce monocytic cell apoptosis: Proposed impact on vascular remodeling and mechanism.

BACKGROUND/PURPOSE: Monocytes play important roles in inflammatory responses and vascular remodeling after vascular stenting. This research focused on impacts of nickel (Ni) ions released from a corroded cardiovascular stent on cytotoxicity and monocyte activation. METHODS: A human promonocytic (macrophage-like) cell line (U937) was exposed to graduated concentrations of Ni(2+)in vitro. Cells were observed and harvested at indicated times to determine the effects using histological and biochemical methods. RESULTS: Ni caused U937 cell death in dose- and time-dependent manners. In vitro, high concentrations of Ni(2+) (>240 µM) significantly induced cell apoptosis and increased terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-positive cells according to flow cytometric surveillance and triggered apoptotic cell death. Although no significant changes in Bcl-2 or Bax expressions were detected after 24 hours of Ni(2+) treatment, increasing cleavage of caspase-3 and -8 was present. Results showed that cleavage of caspase-8 was inhibited by the presence of the inhibitor, Z-IETD-FMK, and this suggested the presence of Ni(2+)-induced U937 cell death through a death receptor-mediated pathway. Simultaneously, when treated with a high concentration of Ni(2+) ions, expressions of the vascular remodeling factors, matrix metalloproteinases (MMP)-9 and -2, were activated in dose- and time-dependent manners. Secretion of the proliferative factor, monocyte chemoattractant protein (MCP)-1, significantly increased during the first 6 hours of incubation with 480 µM Ni(2+)-treated medium. CONCLUSION: Our results demonstrated that a high concentration of Ni ions causes apoptotic cell death of circulating monocytes. They may also play different roles in vascular remodeling during the corrosion process following implantation of Ni alloy-containing devices.