Outcomes and Hemodynamic Performances of Transcatheter Aortic Valve Replacement with Two Generations of Self-Expanding Transcatheter Aortic Valves.

Background: The superiority of the new-generation self-expanding Evolut R compared with the first-generation CoreValve with regards to outcomes after transcatheter aortic valve replacement (TAVR) is unclear. The aim of this study was to investigate the hemodynamic and clinical performance of Evolut R compared with its direct predecessor, CoreValve, in a Taiwanese population. Methods: This study included all consecutive patients who underwent TAVR with either CoreValve or Evolut R between March 2013 and December 2020. Thirty-day Valve Academic Research Consortium-2 (VARC-2)-defined outcomes and hemodynamic performances were investigated. Results: There were no significant differences in baseline demographic characteristics between the patients receiving CoreValve (n = 117) or Evolut R (n = 117). Aortic valve-in-valve procedures for failed surgical bioprosthesis and procedures under conscious sedation were performed significantly more often with Evolut R. Pre-dilatation was performed significantly more often and contrast media volume was significantly higher with CoreValve. Stroke (0% vs. 4.3%, p = 0.024) and the need for emergent conversion to open surgery (0% vs. 5.1%, p = 0.012) were significantly lower in Evolut R than in CoreValve recipients. Evolut R significantly reduced 30-day composite safety endpoint (4.3% vs. 15.4%, p = 0.004). Conclusions: Advancements in transcatheter valve technologies have resulted in improved outcomes for patients undergoing TAVR with self-expanding valves. With the new-generation Evolut R, device success was high and the 30-day composite safety endpoint was significantly reduced after TAVR compared with CoreValve.

Impact of preprocedural mesenteric artery stenosis and mesenteric ischemia in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: We aimed to examine the incidence, etiologies, and consequences of acute mesenteric ischemia as well as the impact of preprocedural subclinical mesenteric artery stenosis in patients undergoing transcatheter aortic valve replacement. METHODS: Among prospective follow-up of 269 consecutive patients undergoing transcatheter aortic valve replacement, diagnosis of acute mesenteric ischemia was confirmed by abdominal computed tomography. Cumulative hazard of 1-year all-cause and cardiovascular mortality according to the absence or presence of mesenteric artery stenosis 70% or greater from preprocedural computed tomography angiography was analyzed. RESULTS: Acute mesenteric ischemia was confirmed in 7 patients (2.6%) during mid-term (median, 33.3 months, interquartile range, 15.0-61.0 months) follow-up. Thrombotic occlusions of previously stenotic mesenteric arteries account for 4 cases (57.1%), and embolic acute mesenteric ischemia constitute the rest (42.9%) of the cases. The mortality rate of acute mesenteric ischemia was 100%. At 30 days, death from acute mesenteric ischemia accounts for 40% of all-cause mortality and 67% of cardiovascular death. By multivariable analysis, higher Society of Thoracic Surgeons score and mesenteric artery stenosis 70% or greater were independently associated with acute mesenteric ischemia. Thirty-two patients (11.9%) with preprocedural mesenteric artery stenosis 70% or greater had an increased risk of all-cause mortality (adjusted hazard ratio, 3.78; 95% confidence interval, 1.74-8.19; P = .001) at 1 year after transcatheter aortic valve replacement. CONCLUSIONS: Acute mesenteric ischemia, an important cause of 30-day mortality, should be considered in patients who become clinically unstable after transcatheter aortic valve replacement, particularly but not exclusively in those with preexisting mesenteric artery stenosis. Mesenteric artery stenosis should be routinely assessed in all patients who are indicated for transcatheter aortic valve replacement considering the dismal prognosis of acute mesenteric ischemia.

Membranous septum length predicts conduction disturbances following transcatheter aortic valve replacement.

OBJECTIVES: Insufficient distance between membranous septum (MS) length and implant depth (ID) may aggravate mechanical compression of the conduction tissue by transcatheter aortic valve replacement (TAVR) prosthesis. We investigated the implication of MS length measured in the coronal view (coronal MS length) compared with infra-annular MS length from stretched vessel image to predict conduction disturbances following TAVR with CoreValve/Evolut R valves (Medtronic, Minneapolis, Minn). METHODS: Among 195 consecutive patients undergoing TAVR with CoreValve/Evolut R valves, we evaluated coronal, infra-annular MS lengths and ID, as well as MS length minus ID (ΔMSID) using pre-TAVR computed tomography and postprocedural angiography. RESULTS: Within 30 days, 6 (3.1%) required permanent pacemaker implantation and 31 (16.4%) developed left bundle branch block. When taking into account pre- and postprocedural parameters, multivariable logistic regression analysis revealed either coronal ΔMSID (odds ratio, 0.80; 95% confidence interval, 0.72-0.89; P < .001; cutoff point, 3.2 mm) or infra-annular ΔMSID (odds ratio, 0.84; 95% confidence interval, 0.76-0.92; P < .001; cutoff point, -0.2 mm) emerged as the only modifiable predictor of conduction disturbances. The area under the curve of coronal ΔMSID and infra-annular ΔMSID for predicting the occurrence of conduction disturbances were comparable (0.717 in coronal ΔMSID vs 0.708 in infra-annular ΔMSID; P = .761), but more patients could be guided by coronal MS length than infra-annular MS length (95.9% vs 87.2%; P = .002). CONCLUSIONS: Preprocedural assessment of MS length should be routinely adopted to determine the optimal ID to mitigate individual patient susceptibility to conduction disturbances after TAVR with self-expanding valves.

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement in Asian Patients.

BACKGROUND: Little is known about the incidence of prosthesis-patient mismatch (PPM) and its impact after transcatheter aortic valve replacement with self-expanding valves in an Asian population. We aimed to assess postprocedural effective orifice area with standardized methods and the impact of PPM on midterm outcomes after CoreValve or Evolut R (Medtronic) implantation in an Asian population. METHODS: Among 201 consecutive patients undergoing CoreValve or Evolut R implantation, PPM was assessed at 30 days and defined based on core laboratory measured indexed effective orifice area as severe (less than 0.65 cm2/m2) or moderate (0.65 to 0.85 cm2/m2). Multivariable regression models were utilized to examine predictors of PPM as well as mortality and rehospitalization for heart failure at midterm follow-up. RESULTS: Moderate and severe PPM were observed after self-expanding valves in 37 patients (18.4%) and 3 patients (1.5%), respectively. These 40 patients were included in the PPM group. Predictors of PPM included female sex, larger body surface area, and lower left ventricular ejection fraction. At midterm (median 30.4 months; interquartile range, 17 to 57.8) follow-up, patients with PPM had an increased risk of all-cause death (adjusted hazard ratio 1.95; 95% confidence interval, 1.08 to 3.53; P = .027), cardiovascular mortality (adjusted hazard ratio 3.38; 95% confidence interval, 1.04 to 10.99; P = .043), and rehospitalization for heart failure (adjusted hazard ratio 2.40; 95% confidence interval, 1.11 to 5.17; P = .025). CONCLUSIONS: Patient-prosthesis mismatch was associated with higher midterm mortality and rehospitalization for heart failure in an Asian population. The expected postprocedural effective orifice area for any given valve size may be helpful in preprocedural decision making to avoid PPM.

Optimal blood pressure for patients with end-stage renal disease following coronary interventions.

Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end-stage renal disease (ESRD) (eGFR < 15 ml/min/1.73m2 ) still unclear. The authors aimed to investigate the ideal achieved BP in ESRD patients with CAD after coronary intervention. Five hundred and seventy-five ESRD patients who had undergone percutaneous coronary interventions (PCIs) were enrolled and their clinical outcomes were analyzed according to the category of systolic BP (SBP) and diastolic BP (DBP) achieved. The clinical outcomes included major cardiovascular events (MACE) and MACE plus hospitalization for congestive heart failure (total cardiovascular (CV) event).The mean systolic BP was 135.0 ± 24.7 mm Hg and the mean diastolic BP was 70.7 ± 13.1 mm Hg. Systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg had the lowest MACE (11.0%; 13.2%) and total CV event (23.3%; 21.1%). Patients with systolic BP < 120 mm Hg had a higher risk of MACE (HR: 2.01; 95% CI: 1.17-3.46, p = .008) than those with systolic BP 140-149 mm Hg. Patients with systolic BP ≥ 160 mm Hg (HR: 1.84; 95% CI, 3.27-1.04, p = .04) and diastolic blood BP ≥ 90 mm Hg (HR: 2.19; 95% CI: 1.15-4.16, p = .02) had a higher risk of total CV event rate when compared to those with systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg. A J-shaped association between systolic (140-149 mm Hg) and diastolic (80-89 mm Hg) BP and decreased cardiovascular events for CAD was found in patients with ESRD after undergoing PCI in non-Western population.

Gal-1 (Galectin-1) Upregulation Contributes to Abdominal Aortic Aneurysm Progression by Enhancing Vascular Inflammation.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a vascular degenerative disease causing sudden rupture of aorta and significant mortality in elders. Nevertheless, no prognostic and therapeutic target is available for disease management. Gal-1 (galectin-1) is a ß-galactoside-binding lectin constitutively expressed in vasculature with roles in maintaining vascular homeostasis. This study aims to investigate the potential involvement of Gal-1 in AAA progression. Approach and Results: Gal-1 was significantly elevated in circulation and aortic tissues of Ang II (angiotensin II)-infused apoE-deficient mice developing AAA. Gal-1 deficiency reduced incidence and severity of AAA with lower expression of aortic MMPs (matrix metalloproteases) and proinflammatory cytokines. TNFα (tumor necrosis factor alpha) induced Gal-1 expression in cultured vascular smooth muscle cells and adventitial fibroblasts. Gal-1 deletion enhanced TNFα-induced MMP9 expression in fibroblasts but not vascular smooth muscle cells. Cysteinyl-labeling assay demonstrated that aortic Gal-1 exhibited susceptibility to oxidation in vivo. Recombinant oxidized Gal-1 induced expression of MMP9 and inflammatory cytokines to various extents in macrophages, vascular smooth muscle cells, and fibroblasts through activation of MAP (mitogen-activated protein) kinase signaling. Clinically, serum MMP9 level was significantly higher in both patients with AAA and coronary artery disease than in control subjects, whereas serum Gal-1 level was elevated in patients with AAA but not coronary artery disease when compared with controls. CONCLUSIONS: Gal-1 is highly induced and contributes to AAA by enhancing matrix degradation activity and inflammatory responses in experimental model. The pathological link between Gal-1 and AAA is also observed in human patients. These findings support the potential of Gal-1 as a disease biomarker and therapeutic target of AAA.

Association between Preoperative Nutritional Status and Clinical Outcomes of Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Malnutrition is associated with poor outcomes in patients with cancer, heart failure and chronic kidney disease. This study aimed to investigate the predictive value of the Controlling Nutritional Status (CONUT) score in coronary artery disease (CAD) patients. METHODS: We recruited a cohort of 3118 patients with CAD undergoing percutaneous coronary intervention (PCI) from 2005 to 2015. Nutritional status was evaluated using the CONUT score, with higher scores reflecting worse nutritional status. RESULTS: After adjustment for comorbidities and medication, an increased CONUT score was independently associated with a higher risk of acute myocardial infarction (AMI) (HR: 1.13; 95% CI: 1.03-1.24), cardiovascular (CV) death (HR: 1.18; 95% CI: 1.07-1.30), congestive heart failure (CHF) (HR: 1.11; 95% CI: 1.04-1.18), a major adverse cardiovascular event (MACE) (HR: 1.14; 95% CI: 1.07-1.22), and total CV events (HR: 1.11; 95% CI: 1.07-1.15). The subgroup analyses demonstrated that the association of the CONUT score existed independently of other established cardiovascular risk factors. In addition, CONUT significantly improved risk stratification for myocardial infarction (MI), cardiac death, CHF, MACEs and total CV events compared to conventional risk factors in CAD patients by the significant increase in the C-index (p < 0.05) and reclassification risk categories in cardiac death and MACEs. Conclusions The CONUT score improved the risk prediction of adverse events compared to traditional risk factors in CAD patients after percutaneous coronary intervention (PCI).

MicroRNA-132 targeting PTEN contributes to cilostazol-promoted vascular smooth muscle cell differentiation.

BACKGROUND AND AIMS: Cilostazol, beyond its antiplatelet effect, is also capable of promoting vascular smooth muscle cell (VSMC) differentiation. The aim of this study was to explore the potential role of PTEN, known to associate with VSMC differentiation, and its related microRNA (miRNA) in cilostazol-dependent effects. METHODS AND RESULTS: Microarray analysis in balloon-injured rat carotid arteries comparing with and without balloon injury revealed that miR-132 was differentially expressed. Bioinformatic analysis predicts PTEN as a novel target of miR-132. Western blot and quantitative real-time reverse transcription-polymerase chain reaction along with in situ hybridization documented that cilostazol treatment enhanced PTEN and reduced miR-132 expression in the neointima of balloon-injured arteries. Treatment of cultured rat VSMCs with cilostazol resulted in the up-regulation of PTEN mRNA and the down-regulation of miR-132, supporting an in vitro relevance. Co-transfection experiments showed that transfection of miR-132 mimic into VSMCs suppressed PTEN 3'UTR activities, further reflecting that PTEN is the direct target of miR-132. Over-expression of miR-132 in VSMCs led to an attenuation of cilostazol-induced PTEN and its downstream VSMC differentiation marker (calponin) expression, confirming the critical role of miR-132 in VSMC differentiation. Transient transfection studies demonstrated that cilostazol reduced the activity of miR-132 promoter, which was mediated via cyclic AMP response element-binding protein. Notably, the use of lentivirus to over-express miR-132 in the neointima of balloon-injured arteries could reverse the effect of cilostazol in vivo. CONCLUSIONS: These results suggest that miR-132 by targeting PTEN may be an important regulator in mediating cilostazol actions on VSMC differentiation.

Increase Carotid Flow by Double Sheath Connection Technique to Reduce Cerebral Ischemia for Transcatheter Aortic Valve Implantation through Transcarotid Approach.

PURPOSE: Transcarotid transcatheter aortic valve implantation (TAVI) is one alternative approach if unfavorable femoral access. However, this approach may cause cerebral vascular accidents (CVAs) by temporarily occluding common carotid artery (CCA). The purpose of this study is to develop a new method reducing cerebral ischemia during transcarotid TAVI. METHODS: We inserted an 8- and 18-Fr. sheath in CCA with tip toward brain and aortic arch, respectively, and connected their side arms to create a bypass flow. Medtronic CoreValve was then delivered and deployed in position after pre-TAVI balloon dilatation. RESULTS: Three patients received this implantation. There were no CVAs or transient ischemic attacks (TIAs) after the procedure and all patients had been followed up uneventfully for 1 year. CONCLUSION: Our technique is feasible and potentially reduces stroke in transcarotid TAVI.

Rosuvastatin suppresses atrial tachycardia-induced cellular remodeling via Akt/Nrf2/heme oxygenase-1 pathway.

Atrial fibrillation (AF) is associated with structural remodeling in atrial myocytes. Emerging evidence suggests that statin has a protective effect on AF through cholesterol-independent mechanisms. The aim of this study is to investigate whether heme oxygenase-1 (HO-1), a potent antioxidant system, mediates the suppressive effect of statin on atrial tachycardia-induced structural remodeling. Treatment of cultured atrium-derived myocytes (HL-1 cell line) with rosuvastatin enhanced HO-1 expression/activity and attenuated tachypacing-induced oxidative stress and myofibril degradation. Heme oxygenase-1 inhibitors and small-interfering RNA for HO-1 blocked the inhibitory effect of rosuvastatin on tachypacing-stimulated changes, suggesting the crucial role of HO-1 in mediating the effect of rosuvastatin. Time-dependent experiments and loss-of-function study demonstrated that Akt/Nrf2 pathways lay to the up-stream of HO-1 in this signaling cascade. Furthermore, the involvement of Akt/Nrf2/HO-1 pathway in the antioxidant effect of rosuvastatin was documented in an ex vivo tachypacing model. The suppressive effect of statin on atrial tachypacing-induced cellular remodeling is mediated via the activation of Akt/Nrf2/HO-1 signaling, which provides a possible explanation for the protective effect of statin on AF.

Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions.

BACKGROUND: Far infra-red (IFR) therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC) and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process. MATERIALS AND METHODS: Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocin (STZ)-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group). The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks. RESULTS: Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1(+)/Flk-1(+)) mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group). However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP(+)/CD31(+) double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H(2)O(2) production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice. CONCLUSIONS: Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ-induced diabetic mice, and these beneficial effects may derive from enhancement of EPC functions and homing process.

Effect of invasive strategy on different genders of Chinese patients with non-ST-elevation myocardial infarction.

OBJECTIVES: The aim of this study was to determine the impact of in-hospital revascularization on different genders and to compare the gender difference in short- and long-term prognosis of Chinese patients with non-ST-elevation myocardial infarction (NSTEMI). BACKGROUND: The benefit of invasive strategy between the genders of Asian ethnic populations with NSTEMI remains unclear. METHODS: A total of 343 consecutive NSTEMI patients were enrolled, 104 (30%) of them were women. All patients were followed up for at least 3 years or until the occurrence of a major event. The primary end point was all-cause death. The secondary end point was the combined occurrence of death or myocardial (re-)infarction (MI). RESULTS: The adjusted in-hospital and long-term clinical outcomes were similar between men and women. However, in-hospital revascularization significantly reduced long-term mortality and composite endpoint in men (P < 0.001), but not in women. After risk stratification by GRACE score, there was favorable effect of invasive strategy in high-risk women. In a multivariate Cox regression analysis, GRACE score (hazard ratio; HR, 1.017; P < 0.001) and in-hospital revascularization (HR, 0.516; P = 0.008) were the independent predictors of death or MI in men. However, only GRACE score was the independent predictor of composite endpoint in women (HR, 1.012; P = 0.004). CONCLUSIONS: In Asian ethnic patients with NSTEMI, the in-hospital and long-term prognosis were similar between men and women. In-hospital revascularization has a benefit in men and high-risk women for reducing the all-cause death at 1 and 3 years. Our data provide evidence supporting the guideline recommendation for an invasive strategy in high-risk women.

Cilostazol promotes vascular smooth muscles cell differentiation through the cAMP response element-binding protein-dependent pathway.

OBJECTIVE: Cilostazol, a potent type 3 phosphodiesterase inhibitor, has recently been found to reduce neointimal formation by inhibiting vascular smooth muscle cell (VSMC) proliferation. The aim of this study is to investigate whether cilostazol exerts an action on phenotypic modulation of VSMCs, another important process in the pathogenesis of neointimal formation. METHODS AND RESULTS: Cilostazol may convert VSMCs from a serum-induced dedifferentiation state to a differentiated state, as indicated by a spindle-shaped morphology and an increase in the expression of smooth muscle cell differentiation marker contractile proteins. The upregulation of contractile proteins by cilostazol involves the cAMP/protein kinase A (PKA) signaling pathway, because the cAMP analog mimicked and specific cAMP/PKA inhibitors opposed the effect of cilostazol. Furthermore, cilostazol-activated cAMP response element (CRE)-binding protein (CREB), including phosphorylation at Ser133 and its nuclear translocation. Deletion and mutational analysis of the contractile protein promoters along with chromatin immunoprecipitation using anti-CREB antibody showed that CRE is essential for cilostazol-induced contractile protein expression. Transfection of dominant-negative CREB (mutated Ser133) plasmid in VSMCs blocked cilostazol-stimulated contractile protein expression. In vivo, cilostazol upregulated contractile proteins and induced the activation of CREB in the neointima of balloon-injured arteries. CONCLUSIONS: Cilostazol promotes VSMC differentiation through the cAMP/PKA/CREB signaling cascade.

Association of adiponectin with future cardiovascular events in patients after acute myocardial infarction.

AIM: There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease risk, particularly in patients after acute myocardial infarction (AMI). The goal of this study was to determine whether plasma adiponectin levels could predict future cardiovascular events in patients after AMI, and to elucidate the role of adiponectin in cardioprotection. METHODS: A total of 102 patients with AMI were enrolled. Plasma adiponectin levels were examined from blood samples collected 18 months after AMI. All subjects were followed-up for 43+/-12 months. The primary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization due to unstable angina, nonfatal MI, revascularization with percutaneous coronary intervention or coronary artery bypass grafting, ischemic stroke, and cardiovascular death. RESULTS: A total of 30 MACE occurred, including one case of cardiovascular death, five cases of nonfatal MI, and nine cases of ischemic stroke. Patients with MACE had lower plasma adiponectin levels (p=0.013). In addition, adiponectin was positively associated with changes in left ventricular ejection fraction (p=0.005). All patients were divided into a high-adiponectin group (>or=6.46 microg/mL) and a low-adiponectin group (<6.46 microg/mL). The incidence of MACE was significantly reduced in the high-adiponectin group (p=0.021). In multivariate Cox regression analysis that included adiponectin, classical risk factors, and medications, adiponectin was an independent predictor of MACE in patients after AMI (HR, 0.821; 95% CI, 0.691 to 0.974; p=0.024). CONCLUSIONS: The results indicate a potential association between plasma adiponectin levels and future cardiovascular events in patients after AMI. Moreover, plasma adiponectin concentrations appear to play a pivotal role in atherothrombosis and cardioprotection.

Plasma heparin cofactor II activity is an independent predictor of future cardiovascular events in patients after acute myocardial infarction.

OBJECTIVES: This study tested the hypothesis that plasma heparin cofactor II (HCII) activity independently predicts cardiovascular events in patients after acute myocardial infarction (AMI) and attempted to elucidate the role of HCII in atherothrombosis. BACKGROUND: HCII inhibits thrombin activity by binding to dermatan sulfate and has been shown to be a novel and independent risk factor for atherosclerosis. However, there is limited data on the relation between plasma levels of HCII after AMI and future cardiovascular events. METHODS: A total of 110 consecutive patients (aged 63+/-11 years) with AMI were followed up for 42+/-12 months. Plasma HCII activity was determined from blood samples collected immediately after hospitalization. The primary end point was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization because of unstable angina, nonfatal MI, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting, ischemic stroke, and cardiovascular death. RESULTS: All patients were divided into three groups: a high-HCII group (>122%, n=35), a normal-HCII group (>98% and