Outcomes of abdominal false lumen embolization for chronic aortic dissection after prior proximal repair with stent-graft.

BACKGROUND: Persistent false lumen (FL) perfusion with aneurysmal formation is common after thoracic endovascular aortic repair (TEVAR) for typical extended aortic dissection and is associated with poor outcomes. Endovascular FL embolization (FLE) has recently been tried for treatment of postdissection aortic aneurysm (PDAA). However, most reports address thoracic rather than abdominal FLE. In this study, we present the results of abdominal FLE in patients with residual patent abdominal FL following stent-graft repair for aortic dissection. METHODS: Between 2015 and 2019, 24 patients (mean age: 56.7 ± 11.8 years, range: 40-84 years, 18 male) received endovascular abdominal FLE using vascular plugs, coils, or candy plugs as the main surgery (5 patients) or auxiliary procedure (19 patients) after earlier stent-graft repair for aortic dissection (Type A: 9, Type B: 15). The medical records were reviewed and aortic remodeling was examined comparing the preembolization computed tomography (CT) and the most recent CT before reintervention. RESULTS: Technical success was achieved without any intraoperative complications, early morbidity, or mortality. Median follow-up was 34.4 months (range: 12-71). Regarding thoracic FL, 15 patients exhibited complete thrombosis before the procedure and did not change status thereafter except for 1 patient with distal stent-graft-induced new entry. In the other 9 patients, 6 exhibited increased thrombosis. With regard to the abdominal aorta, increased FL thrombosis only occurred in 8 patients with 3 (12.5%) achieving complete thrombosis. The maximal thoracic aortic diameter did not change (1.4 ± 5.6 mm) statistically, but the abdominal diameter increased significantly (4.3 ± 3.7 mm, p < 0.005). CONCLUSION: From our results, abdominal FLE is a safe procedure. However, covering all the re-entry tears is complex and the possibility of complete FL thrombosis is low. The abdominal aortic diameter appears to become enlarged in these patients. Continuous follow-up is necessary after FLE.

TIMP-1 in the prognosis of patients who underwent coronary artery bypass surgery: a 12-year follow-up study.

Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been linked to clinical outcomes in patients with coronary artery disease (CAD). However, the prognostic value of TIMP-1 in patients with CAD who underwent coronary artery bypass grafting (CABG) has not been elucidated. We aimed to investigate the correlations of TIMP-1 with high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the long-term prognosis of consecutive patients who underwent CABG. Methods: A total of 234 patients (age: 70.4 ± 10.5 years, 84.6% men) with CAD who underwent CABG were prospectively enrolled. Preoperative levels of MMPs, TIMP-1, hs-CRP, and NT-proBNP were recorded. Major adverse cardiovascular events (MACE) were defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Results: During a median follow-up of 12.1 years, 120 deaths were recorded. The deceased were older, had more manifest acute coronary syndrome (ACS), a lower left ventricular ejection fraction (LVEF), and an estimated glomerular filtration rate (eGFR), but significantly higher MMP13, TIMP-1, hs-CRP, and NT-proBNP compared with the survivors. After adjusting for age, sex, manifest ACS, eGFR, LVEF, total cholesterol, and triglycerides, TIMP-1 (hazard ratio and 95% confidence intervals per SD: 1.506, 1.183-1.917), hs-CRP (1.349, 1.183-1.561), and NT-ProBNP (1.707, 1.326-2.199) were all independently associated with all-cause mortality. The mediation analysis revealed that the mortality risks of TIMP-1 were partially mediated by NT-proBNP (62.2%) and hs-CRP (25.3%). The associations of TIMP-1 with MACE were partially mediated by NT-proBNP (54.4%) but not hs-CRP. Conclusions: TIMP-1 was an independent predictor of long-term outcomes after CABG, with possible roles in subclinical inflammation and postoperative cardiac remodeling.

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.

Midterm result of custom-made iliac branch device for common iliac aneurysm with and without abdominal aortic aneurysm.

OBJECTIVES: Although commercial iliac branch devices offer a new and valid endovascular approach to treating iliac aneurysm and effectively preserve antegrade flow of the internal iliac artery, their use may not be suited for all types of challenging anatomy, especially isolated common iliac artery aneurysm. Our custom-made iliac bifurcation device has a unique design and excludes both combined and isolated iliac branch aneurysm. This study validated the efficacy and safety of the custom device by comparing clinical outcomes between groups receiving commercial and custom devices. METHODS: Data of consecutive patients receiving iliac bifurcation device implantation for iliac aneurysm with or without concomitant endovascular repair for abdominal aortic aneurysm from January 2010 to May 2019 were reviewed. RESULTS: Iliac bifurcation device implantation with or without concomitant abdominal aortic aneurysm stent grafting was completed in 46 patients (commercial, n = 35; custom, n = 11). No significant differences were observed regarding postoperative complications, occlusion or endoleak. Comparisons of primary (80.8% vs 85.7%, P = 0.88) and secondary (86.5% vs 85.7%, P = 0.85) patency and freedom from reintervention (88.2% vs 100%, P = 0.33), all-cause mortality (78.6% vs 100%, P = 0.25) and aneurysm-related mortality (100% vs 100%, P = 1.00) also indicated no differences at a 5-year surveillance point. Furthermore, the iliac aneurysms of the groups displayed similar shrinkage 1 year after procedures. CONCLUSIONS: For iliac aneurysm, the novel custom-made iliac bifurcation device is an adaptable design not inferior to commercial devices with regard to postoperative complications, bridge occlusion, endoleak and short-term aneurysm remodelling. It provides an alternative for treatment, particularly when certain anatomic challenges are present. CLINICAL TRIAL REGISTRATION: 2018-07-050BC, 2017-01-023ACF.

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.

Yes-Associated Protein (YAP) Facilitates Pressure Overload-Induced Dysfunction in the Diabetic Heart.

Patients with diabetes are more prone to developing heart failure in the presence of high blood pressure than those without diabetes. Yes-associated protein (YAP), a key effector of the Hippo signaling pathway, is persistently activated in diabetic hearts, and YAP plays an essential role in mediating the exacerbation of heart failure in response to pressure overload in the hearts of mice fed a high-fat diet. YAP induced dedifferentiation of cardiomyocytes through activation of transcriptional enhancer factor 1 (TEAD1), a transcription factor. Thus, YAP and TEAD1 are promising therapeutic targets for diabetic patients with high blood pressure to prevent the development of heart failure.

The detrimental effect of asymmetric dimethylarginine on cholesterol efflux of macrophage foam cells: Role of the NOX/ROS signaling.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor and has been proposed to be an independent risk factor for cardiovascular diseases. However, little is known about its role in the regulation of lipid metabolism. In this study, we investigated the effect of ADMA on cholesterol metabolism and its underlying molecular mechanism. METHODS: Oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cells were used as an in vitro model. Apolipoprotein E-deficient (apoE-/-) hyperlipidemic mice were used as an in vivo model. Western blot analysis was used to evaluate protein expression. Luciferase reporter assays were used to assess the activity of promoters and transcription factors. Conventional assay kits were used to measure the levels of ADMA, cholesterol, triglycerides, and cytokines. RESULTS: Treatment with oxLDL decreased the protein expression of dimethylarginine dimethylaminohydrolase-2 (DDAH-2) but not DDAH-1. Incubation with ADMA markedly increased oxLDL-induced lipid accumulation in macrophages. ADMA impaired cholesterol efflux following oxLDL challenge and downregulated the expression of ATP-binding cassette transporter A1 (ABCA1) and ABCG1 by interfering with liver X receptor α (LXRα) expression and activity. Additionally, this inhibitory effect of ADMA on cholesterol metabolism was mediated through the activation of the NADPH oxidase/reactive oxygen species pathway. In vivo experiments revealed that chronic administration of ADMA for 4 weeks exacerbated systemic inflammation, decreased the aortic protein levels of ABCA1 and ABCG1, and impaired the capacity of reverse cholesterol transport, ultimately, leading to the progression of atherosclerosis in apoE-/- mice. CONCLUSION: Our findings suggest that the ADMA/DDAH-2 axis plays a crucial role in regulating cholesterol metabolism in macrophage foam cells and atherosclerotic progression.

Can Elderly Patients with Severe Mitral Regurgitation Benefit from Trans-catheter Mitral Valve Repair?

BACKGROUND AND OBJECTIVES: Age is a traditional risk factor for open-heart surgery. The efficacy and safety of transcatheter edge-to-edge mitral valve repair, using MitraClip (Abbott Vascular), has been demonstrated in patients with severe mitral regurgitation (MR). Since octogenarians or older patients are usually deferred to receive open-heart surgery, the main interest of this study is to elucidate the procedural safety and long-term clinical impact of MitraClip in elderly patients. METHODS: Patients with symptomatic severe MR were evaluated by the heart team. For those with high or prohibitive surgical risks, transcatheter mitral valve repair was performed in hybrid operation room. Transthoracic echocardiography (TTE), blood tests, and six-minute walk test (6MWT) were performed before, 1-month, 6-months, and 1 year after index procedure. RESULTS: A total of 46 consecutive patients receiving MitraClip procedure were enrolled. Nineteen patients (84.2±4.0 years) were over 80-year-old and 27 (73.4±11.1 years) were younger than 80. Compare to baseline, the significant reduction in MR severity was achieved after the procedure and sustained. All the patients benefited from significant improvement in New York Heart Association functional class. The 6-minute walk test (6MWT) increased from 259±114 to 319±92 meters (p=0.03) at 1 year. The overall 1-year survival rate was 80% in the elderly and 88% in those <80 years, p=0.590. Baseline 6MWT was a predictor for all-cause mortality (odds ratio, 0.99; 95% confidence interval, 0.982-0.999; p=0.026) after the MitraClip procedure. CONCLUSIONS: Trans-catheter edge-to-edge mitral valve repairs are safe and have positive clinical impact in subjects with severe MR, even in advanced age.

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.

Aortic remodeling after hybrid provisional extension to induce complete attachment aortic repair of chronic residual type I aortic dissection.

OBJECTIVES: Our objective was to examine the role of the provisional extension to induce complete attachment (PETTICOAT) aortic dissection repair technique with bare metal stents (BMSs) in abdominal remodeling of residual DeBakey type I aortic dissection. METHODS: We retrospectively reviewed the records of patients with chronic aneurysm formation and residual DeBakey type I aortic dissection (ie, original acute aortic dissection DeBakey type I after primary surgical open repair) who underwent arch reoperation with frozen elephant trunk replacement or endovascular debranching with or without an abdominal BMS between December 2006 and December 2016. We analyzed diameters and volumes in 3 dimensions for the true and false lumens of the thoracic and abdominal aorta as well as the thrombosis percentage of the false lumen between the non-BMS (non-PETTICOAT) and BMS (PETTICOAT) groups. RESULTS: Forty-seven patients who had completed at least 1 year of follow-up were included. The non-BMS (without abdominal BMS) and BMS groups had significant differences in abdominal true lumen diameter and volumetric change at the first postoperative examination and at the examination 1 year after surgery (26.8 mL, median [19.4-34.1 mL, interquartile range (IQR)]) in non-BMS vs 42.5 mL, median [31.1-57.9 mL, IQR]) in BMS (postoperative survey [F test, 33.775; P = .000]) and (30.1 mL, median [20.5-34.1 mL, IQR] in non-BMS vs 46.6 mL, median [31.3-57.4 mL, IQR]) in BMS (12-month survey [F test, 14.001; P = .001]). The abdominal false lumen thrombosis percentage was higher in the BMS group than in the non-BMS group (25.6%, median [16.4%-58.9%, IQR] in non-BMS vs 54.0%, median [36.7%-65.3%, IQR] in the BMS group (F test, 6.318; P = .016). CONCLUSIONS: Following reintervention for chronic residual DeBakey type I aortic dissection, PETTICOAT abdominal dissection BMS effectively expanded the thoracic and abdominal true lumen and augmented false lumen thrombosis percentage during the first postoperative year.

Relationship between the extent of aortic replacement and stent graft for acute DeBakey type I aortic dissection and outcomes: Results from a medical center in Taiwan.

BACKGROUND: Total arch replacement (TAR) and/or stent graft implantation has been proposed as the primary surgical treatment for acute DeBakey type I aortic dissection. However, the suggestion was based on excellent outcomes of high-volume or aortic centers. How about the real results in most places around the world? The purpose of this study was intended to compared in-hospital mortality, major complications, and aortic remodeling between TAR and/or stent graft implantation in a medical center of northern Taiwan. METHODS: Between January 2008 and August 2017, 156 patients with acute type I aortic dissection underwent surgery at our institution, including proximal aortic replacement only (Group I, n = 72), concomitant TAR (Group II, n = 23), concomitant TAR extended with stent grafting (Group III, n = 45), and proximal aortic replacement with descending aortic stent grafting (Group IV, n = 16). RESULTS: No significant differences were found in underlying disease and preoperative presentations, including operative risk among four groups. Overall in-hospital mortality was 22.4% (13 patients in Group I, 9 in Group II, 12 in Group III, and 1 in Group IV). New-onset stroke occurred in 15 patients postoperatively (3 patients [5.2%] in Group I, 3 [21.4%] in Group II, and 9 [26.5%] in Group III after excluding 36 patients with documented preoperative cerebrovascular accident or cerebral malperfusion). Root reconstruction and TAR were significantly associated with in-hospital mortality. TAR was significantly associated with surgery-related stroke. Compared to those in Group I, true lumen expansion and false lumen shrinkage during 1-year aortic remodeling were significantly higher in Groups III and IV. Both TAR and descending aorta stent grafting were significantly associated with decreased risk of patent false lumen. CONCLUSIONS: Proximal aortic replacement remains the preferred surgical strategy for acute type I aortic dissection, with lower mortality and neurological complications. Proximal descending aorta stent grafting may benefit aortic remodeling, even without TAR.

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.

Clinical Outcomes of VasoRing Connector in Patients With Acute Type A Aortic Dissection.

BACKGROUND: Outcomes of acute type A aortic dissection repair may be improved when VasoRing connectors (VRC [Sunwei Technology, Taipei, Taiwan]) are used to facilitate aortic anastomosis. In the present study, we compared the results of acute type A aortic dissection repair using VRC and conventional suture technique. METHODS: A total of 68 patients who underwent acute type A aortic dissection repair by total arch replacement and antegrade frozen elephant trunk procedure at our institution were enrolled. Records of patients receiving aorta anastomosis with VRC (n = 33) and conventional suture (n = 35) were retrospectively compared. All the surgical results were collected and analyzed. RESULTS: The results showed that the VRC group exhibited significance in total operative time (326 ± 80 minutes versus 362 ± 34 minutes, p = 0.023), cardiopulmonary bypass time (97 ± 10 minutes versus 134 ± 15 minutes, p < 0.001), aortic cross-clamp time (97 ± 10 minutes versus 134 ± 15 minutes, p < 0.001), and circulatory arrest time (15 ± 4 minutes versus 50 ± 8 minutes, p < 0.001) compared with the suture group. Use of VRC for aortic anastomosis led to significantly less perioperative blood loss (442 ± 75 mL versus 849 ± 419 mL, p < 0.001) compared with conventional suture for aortic anastomosis There was no reoperation for postoperative bleeding in the VRC group whereas reoperation for postoperative bleeding occurred in 20% of the suture group (0% versus 20%, p = 0.011). Postoperative blood loss, amount of blood transfusion, and acute kidney injury requiring hemodialysis were also significantly less in the VRC group than the suture group. CONCLUSIONS: Use of VRC shortened operative time and improved bleeding control incorporating standard methods for aortic anastomoses during acute type A aortic dissection repair by total arch replacement and antegrade frozen elephant trunk procedure. Long-term follow-up and randomized comparison are needed to confirm VRC efficacy.

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.

Initial experience with percutaneous edge-to-edge transcatheter mitral valve repair in a tertiary medical center in Taiwan.

BACKGROUND: The transcatheter edge-to-edge mitral valve repair, using MitraClip, has been a safe and effective treatment for severe mitral regurgitation (SMR) in the westerners. However, the therapeutic results of the MitralClip in Taiwan remained elucidated. METHODS: Patients with symptomatic SMR were evaluated by the heart team. For those with high or prohibitive surgical risks, transcatheter mitral valve repair was performed in hybrid operation room. During procedure, continuous hemodynamic monitoring was conducted. Transthoracic echocardiography (TTE), blood tests, and six-minute walk test (6MWT) were performed before and 1-month after surgery. RESULTS: A total of 20 patients (73.4 ± 11.1 years, 85% male) with a mean Euroscore II of 13.2 ± 17.7% and a mean STS score of 8.7 ± 9.0% for mortality were enrolled. After a mean procedural time of 239 ± 95 min, an average of 1.8 ± 0.7 clips were used in each procedure. The procedural successful rate was 95% to achieve mild residual mitral regurgitation. Cardiac output was increased from 3.6 ± 0.9 to 4.6 ± 1.4 (p = 0.008) and V-wave of left atrial pressure declined from 24.4 ± 9.8 to 19.3 ± 7.1 (p = 0.030) immediately during the index procedure. There was no peri-procedural death, myocardial infarction, stroke or any events requiring emergent cardiac surgery. All patients experienced significant improvement in heart failure symptoms. The 6-min walk distance increased from 219.6 ± 118.4 m to 279.1 ± 111.6 (p = 0.04) at 1 month. The echocardiogram further showed significant improvements of mitral regurgitation, pulmonary artery systolic pressure, and the left ventricular end-diastolic volume. CONCLUSION: Trans-catheter edge-to-edge mitral valve repairs are safe and effective in Asians with symptomatic SMR, regarding the improvements of clinical symptoms and exercise capacities. MitraClips is also associated with reverse remodeling of pulmonary hypertension and left ventricular size in patients with SMR.

The Impact of Distal Stent Graft-Induced New Entry on Aortic Remodeling of Chronic Type B Dissection.

BACKGROUND: In chronic type B aortic dissection, late distal stent graft-induced new entry (SINE) has a possible negative role in long-term aortic remodeling. This study aimed to investigate the impact of SINE occurrence on survival by evaluating true and false lumen remodeling in thoracic and abdominal segments at midterm surveillance. METHODS: This study enrolled 65 patients with chronic type B aortic dissection (DeBakey type IIIb), who had received hybrid thoracic endovascular aortic repair (TEVAR) and had completed surveillance for at least 3 years. The 3-year survival rate was 84.7%. The patients were classified into non-SINE (n = 47) and SINE (n = 18) groups. Serial computed tomography scans were used to analyze volumetric change, true and false lumens, and thrombus volume from arch to aortic bifurcation level. RESULTS: The SINE event occurred at a median of 22.5 months. In the SINE group, there was a significant interruption of the abdominal true lumen expansion in the second year (median 0.01 [interquartile range (IQR), -0.03 to 0.12] in the non-SINE group versus median -0.04 [IQR, -0.12 to 0.04] in the SINE group; p = 0.014). There was a significantly worse thoracic false lumen remodeling in the SINE group compared with the non-SINE group in the third year after the SINE event occurred (median 0 [IQR, -0.09 to 0.05] in the non-SINE group versus median 0.06 [IQR, 0 to 0.13] in the SINE group; p = 0.038). CONCLUSIONS: For chronic aortic dissection, late occurrence of distal SINE could influence abdominal true lumen expansion and thoracic false lumen shrinkage. Early reintervention for distal SINE could improve aortic remodeling in chronic aortic dissection.

Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling.

NADPH oxidases (Noxes) produce ROS that regulate cell growth and death. NOX4 expression in cardiomyocytes (CMs) plays an important role in cardiac remodeling and injury, but the posttranslational mechanisms that modulate this enzyme are poorly understood. Here, we determined that FYN, a Src family tyrosine kinase, interacts with the C-terminal domain of NOX4. FYN and NOX4 colocalized in perinuclear mitochondria, ER, and nuclear fractions in CMs, and FYN expression negatively regulated NOX4-induced O2- production and apoptosis in CMs. Mechanistically, we found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation. Transverse aortic constriction activated FYN in the left ventricle (LV), and FYN-deficient mice displayed exacerbated cardiac hypertrophy and dysfunction and increased ROS production and apoptosis. Deletion of Nox4 rescued the exaggerated LV remodeling in FYN-deficient mice. Furthermore, FYN expression was markedly decreased in failing human hearts, corroborating its role as a regulator of cardiac cell death and ROS production. In conclusion, FYN is activated by oxidative stress and serves as a negative feedback regulator of NOX4 in CMs during cardiac remodeling.

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.

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.