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.

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.

Technical Characteristics and Feasibility of Coronary Angiography and Percutaneous Coronary Interventions Performed after Transcatheter Aortic Valve Replacement with Self-Expanding Valves.

BACKGROUND: Coronary angiography (CA) or percutaneous coronary intervention (PCI) after transcatheter aortic valve replacement (TAVR) may become technically challenging after implantation of the self-expanding Medtronic CoreValve (MCV) device, which extends above the coronary ostia. The aim of this study was to investigate the incidence and feasibility of CA or PCI and the outcomes of PCI after TAVR with the MCV device. METHODS: From July 2014 to April 2020, among 209 patients treated with TAVR with a MCV device, 14 (7%) underwent CA or PCI after the procedure at a mean duration of 28 ± 15 months at our institution. RESULTS: The mean age of the patients was 83 ± 6 years. Thirteen (93%) patients underwent CA due to angina symptoms with a positive noninvasive test, and 1 underwent CA for acute coronary syndrome. Most of the CA and PCI procedures were performed through a radial approach: 11 patients (79%) via the right radial artery, 1 (7%) the left radial artery, and 2 (14%) through the right femoral artery. CA of the left and right coronary arteries was successfully achieved in 13 patients (93%) with Judkin left (3.5 to 5) diagnostic catheters and in 11 patients (79%) with Judkin right (4) diagnostic catheters. The second-line catheter of choice was the Amplatz left (AL) 1 catheter for the right coronary artery and AL 2 for the left coronary artery. Procedural success was achieved in all 5 patients who underwent post-TAVR PCI without procedural or in-hospital complications. The use of a Guideliner microcatheter facilitated stent delivery in one patient. CONCLUSIONS: Coronary angiography or PCI following TAVR with a MCV device is feasible and safe, but requires understanding of the three-dimensional geometry of the prosthetic valve and its relationship to the coronary ostia.

Antithrombotic Treatment of Stable Coronary Artery Disease.

Coronary artery disease (CAD) is one of the leading causes of death in Taiwan. Despite the use of current guideline-recommended therapies for secondary prevention, the residual risk of recurrent cardiovascular events remains high in CAD, warranting the need for new treatment options. Antithrombotic drugs are one of the most important medical therapies for CAD. In this article, we review the unmet needs of the current antithrombotic agents and summarize the results of clinical trials with dual antiplatelet therapy in stable CAD. We also review data from a recent study demonstrating the benefits of a dual pathway inhibition strategy with antiplatelet and anticoagulant therapy, a new option for CAD treatment. Finally, we propose a treatment algorithm for choosing different antithrombotic regimens for CAD based on current scientific evidence and expert opinions.

Women had favourable reverse left ventricle remodelling after TAVR.

BACKGROUND: Being woman is associated with higher survival rates after transcatheter aortic valve replacement (TAVR) despite the increase in periprocedural complications. The left ventricle (LV) remodelling process that follows TAVR is considered to play an important role. We aim to investigate whether gender difference affects the process of LV remodelling after TAVR. MATERIALS AND METHODS: A total of 100 patients (50 men and 50 women) after TAVR were enrolled. Echocardiography was performed at baseline before the TAVR procedure and repeated upon discharge, and at three, nine and 12 months post-TAVR. RESULTS: Women exhibited an early regression of LV mass and the LV mass index (LVMi) decreased 12.0% from 148.3 ± 48.0 to 130.5 ± 43.7 g/m2 at just a median of 17 days after the procedure (P < .001). Almost one-half of the LVMi regression occurred by 17 days post-TAVR and the LVMi regressed 22.0% by 12 months post-TAVR. In contrast, the regression of LVMi in men seemed to be more gradual and the significant regression of LVMi from baseline began to be observed since three months later after TAVR. The LVMi reduction at nine months was 11.5% and achieved 15.4% over one year. Multivariable logistic regression analysis showed only the female sex, better LVEF and greater baseline LVMi were independently associated with greater LVMi regression after TAVR, indicating female gender is an independent predictor for favourable LV remodelling after TAVR. CONCLUSION: In conclusion, female patients with AS had favourable reverse remodelling with greater and earlier LV mass regression post-TAVR compared with the male patients.

Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease.

BACKGROUND: This study examines the predictive value of a novel systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) in coronary artery disease (CAD) patients. METHODS: A total of 5602 CAD patients who had undergone a percutaneous coronary intervention (PCI) were enrolled. They were divided into two groups by baseline SII score (high SII vs low SII) to analyse the relationship between SII groups and the long-term outcome. The primary outcomes were major cardiovascular events (MACE) which includes nonfatal myocardial infarction (MI), nonfatal stroke and cardiac death. Secondary outcomes included a composite of MACE and hospitalization for congestive heart failure. RESULTS: An optimal SII cut-off point of 694.3 × 109 was identified for MACE in the CAD training cohort (n = 373) and then verified in the second larger CAD cohort (n = 5602). Univariate and multivariate analyses showed that a higher SII score (≥694.3) was independently associated with increased risk of developing cardiac death (HR: 2.02; 95% CI: 1.43-2.86), nonfatal MI (HR: 1.42; 95% CI: 1.09-1.85), nonfatal stroke (HR: 1.96; 95% CI: 1.28-2.99), MACE (HR: 1.65; 95% CI: 1.36-2.01) and total major events (HR: 1.53; 95% CI: 1.32-1.77). In addition, the SII significantly improved risk stratification of MI, cardiac death, heart failure, MACE and total major events than conventional risk factors in CAD patients by the significant increase in the C-index (P < .001) and reclassification risk categories by significant NRI (P < .05) and IDI (P < .05). CONCLUSIONS: SII had a better prediction of major cardiovascular events than traditional risk factors in CAD patients after coronary intervention.

Sex difference in the prognostic role of body composition parameters in Taiwanese patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Evidence on association between body composition and outcomes of transcatheter aortic valve implantation (TAVI) is limited for Asian patients. This study investigated the prognostic role of body composition parameters in Taiwanese patients undergoing TAVI. MATERIALS AND METHODS: Data of consecutive patients undergoing TAVI for severe aortic stenosis between May 1, 2010 and August 31, 2019 were prospectively collected in this observational study. The association between body composition parameters (body mass index [BMI], body surface area [BSA], lean body mass [LBM], and LBM index) and cumulative mortality was analyzed using Cox proportional hazard regression model. RESULTS: A total of 221 patients (mean age 81.4 years), including 125 (56.6%) males, were included with median follow-up duration of 23.8 months. In males, multivariate analysis revealed that higher BMI (P = 0.035), BMI ≥ 20 kg/m2 (P = 0.026), and higher LBM index (P = 0.023) significantly predicted lower overall all-cause cumulative mortality. In females, none of the body composition parameters was significantly associated with all-cause cumulative mortality. Paradoxical association between BMI and estimated all-cause cumulative mortality was only significant among male patients. CONCLUSION: In Taiwanese TAVI patients, the prognostic effects of BMI and LBM index on cumulative mortality were only observed in males, not in females. Sex differences must be considered when stratifying risk among patients undergoing TAVI.

TIMI and GRACE Risk Scores Predict Both Short-Term and Long-Term Outcomes in Chinese Patients with Acute Myocardial Infarction.

BACKGROUND: Little is known about the long-term prognostic values of both thrombolysis in myocardial infarction (TIMI) and Global Registry of Acute Cardiac Events (GRACE) risk scores (RSs) to the Asian ethnicity. The purpose of this study is to compare the usefulness of these two scores in risk stratification and prediction of long-term (up to 3 years) outcomes for Chinese patients with myocardial infarction (MI). METHODS: We calculated the TIMI and GRACE RSs for 726 consecutive patients with MI [55.6% with ST-segment elevation (STEMI) and 44.4% with non-ST-segment elevation (NSTEMI)]. RESULTS: Although the risk profile of our population (median TIMI score = 5 for STEMI, 4 for NSTEMI, and median GRACE score = 164) was higher, the in-hospital mortality (7.1% for NSTEMI and 6.7% for STEMI) was comparable to that predicted by GRACE RS. The GRACE RS worked well in predicting short-term and long-term death (C-statistics range 0.710 to 0.789) and triple (death, MI, and stroke) endpoints (C-statistics range 0.695 to 0.764) in both subsets of MI. GRACE RS performed significantly better than the TIMIRS in predicting 3-year mortality in NSTEMI (p = 0.035) and 1-year and 3-year mortality in STEMI (p = 0.028 and 0.009, respectively). Stratification by tertiles of GRACERS furnished greater prognostic information versus risk assessment by the TIMI RS. CONCLUSIONS: The use of RSs revealed a fair to good discriminatory accuracy in predicting both short-term and long-term major adverse cardiac events in Asian patients with MI. Compared with the simpler TIMI RS, the GRACERS was more accurate in predicting long-term mortality.

Procedural Characteristics and Outcomes of Transcatheter Aortic Valve Implantation: A Single-Center Experience of the First 100 Inoperable or High Surgical Risk Patients with Severe Aortic Stenosis.

BACKGROUND: This is the first study of a Taiwanese population reporting transcatheter aortic valve implantation (TAVI) outcomes of the first 100 cases from a single center offering two different transcatheter heart valve technologies via six types of approaches. We herein report the 30-day and one-year outcomes in our first 100 TAVI patients at Taipei Veterans General Hospital. METHODS: From May 2010 to April 2016, 100 consecutive patients with severe aortic stenosis (AS) who were considered unsuitable or at high risk for surgical aortic valve replacement underwent TAVI. Patient outcomes were classified according to the Valve Academic Research Consortium-2 (VARC-2) definitions. The device performance was assessed using transthoracic echocardiography by independent investigators. RESULTS: The mean patient age was 81.1 years, where 54% were female, and the mean Logistic EuroSCORE was 21.5%. The Medtronic CoreValve was used in 84 patients and the Edwards Sapien or Sapien XT valve (ESV) in 16. The transfemoral approach was the most frequently used route (83%), followed by transapical (9%) access. Overall, there was no procedural death. The VARC-2 outcomes were as follows: device success, 95%; stroke, 1%; major vascular complication, 3%; a need for pacemaker implantation, 5.1%. At discharge, the incidence of postoperative mild, moderate or severe paravalvular leak was 30%, 3% and 0%, respectively. At one year, the all-cause mortality rate was 14.0%, and no valve-related dysfunction was observed. Through multivariable analysis, non-transfemoral access [hazard ratios (HR) 4.81; 95% confidence interval (CI) 1.66-14.09; p = 0.004] and advanced chronic kidney disease (stages 4-5), (HR 3.13; 95% CI 1.07-9.09; p = 0.036) were independently associated with an increased risk of one-year mortality. CONCLUSIONS: We demonstrated that TAVI shows good early and mid-term outcomes in terms of survival, technical success, valve-related adverse events and haemodynamic performance in high-risk patients with severe AS.

Protective role of heme oxygenase-1 in atrial remodeling.

Structural and electrical remodeling in the atrium constitutes the main feature of atrial fibrillation (AF), which is characterized by increased oxidative stress. Heme oxygenase-1 (HO-1) is a potent anti-oxidant system that may provide protection against various oxidative stress-related diseases. The aim of this study is to investigate whether HO-1 has a protective effect on AF-related remodeling. Cultured atrium-derived myocytes (HL-1 cell line) were used to evaluate tachypacing-induced oxidative stress, structural, and electrical remodeling. Transforming growth factor-ß (TGF-ß) was utilized to assess collagen (a main fibrosis-related protein) expression in atrial fibroblasts. Tachypacing in HL-1 myocytes and treatment of atrial fibroblasts with TGF-ß enhanced the expression of HO-1, both of which were mediated by the activation of nuclear factor erythroid-2-related factor 2. Over-expression of HO-1 in HL-1 cells attenuated tachypacing-induced oxidative stress, myofibril degradation, down-regulation of L-type calcium channel, and shortening of action potential duration. Furthermore, HO-1 over-expression in atrial fibroblasts blocked the up-regulation of collagen by TGF-ß, implicating a protective role of HO-1 in structural and electrical remodeling in the atrium. In vivo, HO-1(-/-) mice exhibited a higher degree of oxidative stress, myofibril degradation, and collagen deposit in their atria than wild-type mice. Moreover, burst atrial pacing induced a greater susceptibility to AF in HO-1(-/-) mice than in wild-type mice. In conclusion, a negative-feedback regulation of HO-1 in activated atrial myocytes and fibroblasts may provide protection against AF-related remodeling and AF development.

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.

Length polymorphism in heme oxygenase-1 and risk of CKD among patients with coronary artery disease.

The length polymorphism of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with cardiovascular events and mortality in high-risk populations. Experimental data suggest that heme oxygenase-1 protects against kidney disease. However, the association between this polymorphism and long-term risk of CKD in high-risk patients is unknown. We analyzed the allelic frequencies of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter in 386 patients with coronary artery disease recruited from January 1999 to July 2001 and followed until August 31, 2012. The S allele represents short repeats (<27), and the L allele represents long repeats (≥27). The primary renal end points consisted of sustained serum creatinine doubling and/or ESRD requiring long-term RRT. The secondary end points were major adverse cardiovascular events and mortality. At the end of study, the adjusted hazard ratios (95% confidence intervals) for each L allele in the additive model were 1.99 (1.27 to 3.14; P=0.003) for the renal end points, 1.70 (1.27 to 2.27; P<0.001) for major adverse cardiovascular events, and 1.36 (1.04 to 1.79; P=0.03) for mortality. With cardiac events as time-dependent covariates, the adjusted hazard ratio for each L allele in the additive model was 1.91 (1.20 to 3.06; P=0.01) for the renal end points. In conclusion, a greater number of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with higher risk for CKD, cardiovascular events, and mortality among patients with coronary artery disease.

Comparison of Bare-Metal Stent and Drug-Eluting Stent for the Treatment of Patients Undergoing Percutaneous Coronary Intervention for Unprotected Left Main Coronary Artery Disease - Long-Term Result from a Single Center Experience.

BACKGROUND: Percutaneous coronary intervention (PCI) has become an alternative treatment for left main (LM) coronary artery disease. The aim of our study was to compare long-term clinical outcomes of patients undergoing unprotected LM PCI with bare-metal stent (BMS) or drug-eluting stent (DES) in a high-risk population. METHODS AND RESULTS: We enrolled 223 consecutive patients with unprotected LM coronary artery disease undergoing PCI (mean age: 71.1 ± 11.2 years, 187 male), including 94 patients receiving BMS and 129 patients receiving DES. The patients receiving DES had a significantly higher SYNTAX score (p = 0.05). During the mean follow-up period of 2.5 years, there were 31 cardiovascular deaths (BMS: 21 cases, DES: 10 cases, p = 0.04 by log-rank test), 56 major adverse cardiovascular events (MACE, including cardiovascular death, non-fatal myocardial infarction (MI) and clinical-driven target lesion revascularization; BMS: 33 cases, DES: 23 cases, p = 0.03 by log-rank test) and 6 cases with definite/probable stent thrombosis (BMS: 5 cases, DES: 1 cases, p = 0.09). In multivariate Cox analysis, the use of DES was identified as an independent protective factor against cardiovascular death [hazard ratio (HR) = 0.34, 95% confidence interval (Cl) = 0.15-0.79, p = 0.01] and MACE (HR = 0.50, 95% CI = 0.28-0.88, p = 0.02). The clinical outcome analyses in propensity-score matched the cohort (87 matched pair of patients receiving BMS and DES) and yielded similar results. CONCLUSIONS: In the general practice among a high-risk population undergoing unprotected LM PCI, the use of DES appeared to be beneficial in reducing the risk of long-term cardiovascular death and MACE. KEY WORDS: Bare-mental stent; Drug-eluting stent; Left main coronary artery disease; Percutaneous coronary intervention.

The Impacts of In-Hospital Invasive Strategy on Long-Term Outcome in Elderly Patients with Non-ST-Elevation Myocardial Infarction.

BACKGROUND: The benefit of utilizing an invasive strategy in elderly Chinese patients with non-ST-elevation myocardial infarction (NSTEMI) remains unclear. The aim of this study was to determine whether in-hospital revascularization is associated with long-term prognosis in elderly Chinese patients with NSTEMI, as compared with younger patients. METHODS: All patients were followed up for at least 3 years or until the occurrence of a major event. The primary endpoint was all-cause mortality, and the secondary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including death, nonfatal MI, and ischemic stroke. RESULTS: A total of 343 consecutive NSTEMI patients (148 over the age of 75 years and 195 aged < 75 years) were enrolled. Coronary angiography was performed less frequently in elderly patients (66% vs. 76%; p = 0.027). Multiple logistic regression analysis confirmed the benefit of in-hospital revascularization in the elderly and younger patients, with a statistically significant reduction in the odds of all-cause death and MACE at 1 year and 3 years, respectively. In a multivariable Cox regression analysis, in-hospital revascularization was an independent predictor of future MACE not only in elderly patients [hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.38-0.97] but also in younger patients as well (HR, 0.51; 95% CI, 0.31-0.84). CONCLUSIONS: In Chinese patients with NSTEMI, in-hospital revascularization was associated with significant benefits at 1 year and 3 years in both younger and elderly groups. These results are consistent with the published literature and suggest that advanced age alone should not be regarded as a contraindication to invasive management following presentation with NSTEMI. KEY WORDS: Elderly; Invasive strategy; Myocardial infarction.

Sex and age differences of major cardiovascular events in patients after percutaneous coronary intervention.

BACKGROUND: Women usually have higher risk after receiving percutaneous coronary interventions (PCIs) than men with coronary artery disease (CAD). The aim of this study was to investigate the association of sex differences with future outcomes in CAD patients undergoing PCI, to assess the role of age, and to extend observed endpoints to stroke and congestive heart failure. METHODS: Six thousand six hundred forty-seven patients with CAD who received successful PCIs. The associations between clinic outcomes and sex were analyzed. The primary outcome was major cardiovascular events (MACE), including cardiac death, nonfatal myocardial infraction, and nonfatal stroke. The secondary outcome was MACE and hospitalization for heart failure (total CV events). RESULTS: During a mean of 52.7 months of follow-up, 4833 men and 1614 women received PCI. Univariate and multivariate analyses showed that women were independently associated with an increased risk of cardiac death (HR, 1.78; 95% CI, 1.32-2.41), hospitalization for heart failure (HR, 1.53; 95% CI, 1.23-1.89), MACE (HR, 1.34; 95% CI, 1.10-1.63), and total CV events (HR, 1.39; 95% CI, 1.20-1.62). In the subgroup analysis, women aged under 60 years had higher cardiovascular risks than men of the same age category. CONCLUSION: Women with CAD after successful PCI had poorer cardiovascular outcomes than men. Additionally, younger women (aged <60 years) were especially associated with a higher risk of developing future adverse cardiovascular outcomes.

Feasibility of Coronary Access Following Redo-TAVR for Evolut Failure: A Computed Tomography Simulation Study.

BACKGROUND: Coronary accessibility following redo-transcatheter aortic valve replacement (redo-TAVR) is increasingly important, particularly in younger low-risk patients. This study aimed to predict coronary accessibility after simulated Sapien-3 balloon-expandable valve implantation within an Evolut supra-annular, self-expanding valve using pre-TAVR computed tomography (CT) imaging. METHODS: A total of 219 pre-TAVR CT scans from the Evolut Low-Risk CT substudy were analyzed. Virtual Evolut and Sapien-3 valves were sized using CT-based diameters. Two initial Evolut implant depths were analyzed, 3 and 5 mm. Coronary accessibility was evaluated for 2 Sapien-3 in Evolut implant positions: Sapien-3 outflow at Evolut node 4 and Evolut node 5. RESULTS: With a 3-mm initial Evolut implant depth, suitable coronary access was predicted in 84% of patients with the Sapien-3 outflow at Evolut node 4, and in 31% of cases with the Sapien-3 outflow at Evolut node 5 (P<0.001). Coronary accessibility improved with a 5-mm Evolut implant depth: 97% at node 4 and 65% at node 5 (P<0.001). When comparing 3- to 5-mm Evolut implant depth, sinus sequestration was the lowest with Sapien-3 outflow at Evolut node 4 (13% versus 2%; P<0.001), and the highest at Evolut node 5 (61% versus 32%; P<0.001). CONCLUSIONS: Coronary accessibility after Sapien-3 in Evolut redo-TAVR relates to the initial Evolut implant depth, the Sapien-3 outflow position within the Evolut, and the native annular anatomy. This CT-based quantitative analysis may provide useful information to inform and refine individualized preprocedural CT planning of the initial TAVR and guide lifetime management for future coronary access after redo-TAVR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02701283.

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.