Publications by authors named "Hsien-Li Kao"

94 Publications

Development of an Efficient and Sensitive Chemical Derivatization-Based LC-MS/MS Method for Quantifying Gut Microbiota-Derived Metabolites in Human Plasma and Its Application in Studying Cardiovascular Disease.

J Proteome Res 2021 Jul 31;20(7):3508-3518. Epub 2021 May 31.

School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.

Recently, the gut microbiota has been found to be associated with many diseases, such as inflammatory bowel disease, depression, Parkinson's disease, cancer, metabolic syndrome, and cardiovascular disease (CVD). Among various gut microbiota-derived metabolites (GMs), short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (TRP) metabolites are the most frequently discussed metabolites. LC-MS/MS shows advantages in quantifying the levels of metabolites with good sensitivity and selectivity; however, the poor ionization efficiency and polar characteristics of SCFAs make their analysis challenging, especially when analyzing plasma samples with low SCFA concentrations. Moreover, without characteristic fragment ions for unconjugated BAs and different detection ion modes for TRP metabolites and BAs, GM analysis is complex and time-consuming. To overcome these problems, we developed a derivatization method combined with LC-MS/MS to enhance the sensitivity and LC retention of GMs. Through derivatization with 3-nitrophenylhydrazine (3-NPH), 7 SCFAs, 9 bile acids, and 6 tryptophan metabolites can be simultaneously analyzed via separation within 14 min on a reversed-phase C18 column. For accurate quantification, C-3NPH-labeled standards were used as one-to-one internal standards. This derivatization approach was optimized and then validated. We further applied this method to investigate the targeted GM profile in patients with CVD. The results showed a significant reduction in plasma butyrate levels in CVD patients compared with healthy controls, suggesting its potentially protective role in CVD. In summary, this work provides a sensitive and effective LC-MS/MS method for simultaneously quantifying gut microbiota-related metabolites in human plasma, which could benefit various future gut microbiota-related studies.
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http://dx.doi.org/10.1021/acs.jproteome.1c00147DOI Listing
July 2021

Assessing the Impact of Transcatheter Aortic Valve Implantation on Cardiac Catheterisation: A Multicentric Study.

Heart Lung Circ 2021 Mar 31. Epub 2021 Mar 31.

Department of Cardiology, National University Heart Centre, Singapore.

Background: The success rate of coronary angiography (CA) after transcatheter aortic valve implantation (TAVI) is variable. Our aim was to investigate CA difficulty, outcomes, and predictors of difficult CA after TAVI.

Method: This was an international multicentric retrospective cohort study that included patients with TAVI and subsequent CA between January 2010 and December 2019. Difficulty with CA was graded as 1 (normal), 2 (partial engagement, complete vessel opacification), 3 (partial engagement, incomplete vessel opacification), and 4 (unsuccessful angiography). Patients were grouped as (a) "easy" (grade 1 for left and right) or (b) "difficult" (grade >1 for either). We compared baseline characteristics and outcomes, and performed multivariate logistic regression for predictors of difficult CA.

Results: Of 96 patients included (mean age 77.4±8.7 years, 48 [50%] male), 88 (92%) had successful CA. Right CA was successful in 80 (83%) patients and left CA in 91 (95%) (p<0.0001). The "difficult" group (n=41 [43%]) had higher Society of Thoracic Surgery (STS) scores (7.6±4.9 vs 5.4±4.0; p=0.022), smaller annulus perimeters (72.4±5.4 mm vs 76.2±9.4 mm; p=0.049), greater use of self-expanding valves (83% vs 18%; p<0.0001), increased valve size (26.8±2.1 mm vs 25.6±3.0 mm; p=0.032), and increased oversizing for area (44.3%±17.4% vs 23.6%±22.0%; p=0.0002) and perimeter (17.5%±8.2% vs 7.1%±10.8%; p<0.0001). There was no difference in outcomes except for increased major bleeding (7.3% vs 0.0%; p=0.042). The strongest predictor for "difficult" CA was self-expanding valves when compared to balloon-expandable valves (adjusted odds ratio [aOR], 15.23; 95% confidence interval [CI], 2.27-102.40). Society of Thoracic Surgery score was borderline predictive (aOR, 1.26; 95% CI, 1.04-1.52).

Conclusions: Our results show that after TAVI, CA success rate is high, right CA is more difficult than left, self-expanding valves predispose to difficult CA, and STS score weakly predicts difficult CA. This study is hypothesis-generating and more research is required to confirm these findings.
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http://dx.doi.org/10.1016/j.hlc.2021.02.014DOI Listing
March 2021

Sex differences in patients undergoing transcatheter aortic valve replacement in Asia.

Open Heart 2021 01;8(1)

Department of Cardiology, Sichuan University West China Hospital, Chengdu, China.

Objectives: Transcatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.

Methods: Patients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.

Results: Eight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p<0.01); however, 30-day stroke and mortality (women vs men: 1.5% vs 1.6%, p=0.95% and 4.3% vs 3.4%, p=0.48) were similar. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements (11.2% vs 9.0%, p=0.52) were also similar as was 1-year survival (women vs men: 85.6% vs 88.2%, p=0.25). The only predictors of 30-day mortality were major vascular injury in women and age in men.

Conclusions: Asian women had significantly smaller stature and anatomy with some differences in clinical profiles. Despite more frequent major vascular complications, women had similar 30-day stroke or mortality rates. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements were similar as was 1-year survival.
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http://dx.doi.org/10.1136/openhrt-2020-001541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798412PMC
January 2021

Rationale and design of the ADAPT-TAVR trial: a randomised comparison of edoxaban and dual antiplatelet therapy for prevention of leaflet thrombosis and cerebral embolisation after transcatheter aortic valve replacement.

BMJ Open 2021 01 5;11(1):e042587. Epub 2021 Jan 5.

Division of Cardiology, Asan Medical Center, Songpa-gu, Seoul, The Republic of Korea

Introduction: Optimal antithrombotic strategy following transcatheter aortic valve replacement (TAVR) is still unknown. We hypothesised that the direct factor Xa inhibitor edoxaban can potentially prevent subclinical leaflet thrombosis and cerebral embolisation compared with conventional dual antiplatelet therapy (DAPT) in patients undergoing TAVR.

Methods And Analysis: The ADAPT-TAVR trial is an international, multicentre, randomised, open-label, superiority trial comparing edoxaban-based strategy and DAPT strategy in patients without an indication for oral anticoagulation who underwent successful TAVR. A total of 220 patients are randomised (1:1 ratio), 1-7 days after successful TAVR, to receive either edoxaban (60 mg daily or 30 mg daily if patients had dose-reduction criteria) or DAPT using aspirin (100 mg daily) plus clopidogrel (75 mg daily) for 6 months. The primary endpoint was an incidence of leaflet thrombosis on four-dimensional, volume-rendered cardiac CT imaging at 6 months post-TAVR. The key secondary endpoints were the number of new lesions and new lesion volume on brain diffusion-weighted MRI and the changes in neurological and neurocognitive function assessment between immediate post-TAVR and 6 months of study drug administration. Detailed clinical information on thromboembolic and bleeding events were also assessed.

Ethics And Dissemination: Ethic approval has been obtained from the Ethics Committee/Institutional Review Board of Asan Medical Center (approval number: 2017-1317) and this trial is also approved by National Institute of Food and Drug Safety Evaluation of Republic of Korea (approval number: 31511). Results of this study will be disseminated in scientific publication in reputed journals.

Trial Registration Number: NCT03284827.
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http://dx.doi.org/10.1136/bmjopen-2020-042587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786793PMC
January 2021

Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis.

Int J Mol Sci 2020 Nov 19;21(22). Epub 2020 Nov 19.

Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan.

Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.
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http://dx.doi.org/10.3390/ijms21228729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699263PMC
November 2020

Long-term outcomes and left ventricular diastolic function of sarcomere mutation-positive and mutation-negative patients with hypertrophic cardiomyopathy: a prospective cohort study.

Eur Heart J Cardiovasc Imaging 2020 Nov 22. Epub 2020 Nov 22.

Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan S. Rd, Zhongzheng Dist., Taipei 10002, Taiwan.

Aims: Hypertrophic cardiomyopathy (HCM) is an inheritable disease that leads to sudden cardiac death and heart failure (HF). Sarcomere mutations (SMs) have been associated with HF. However, the differences in ventricular function between SM-positive and SM-negative HCM patients are poorly characterized.

Methods And Results : Of the prospectively enrolled 374 unrelated HCM patients in Taiwan, 115 patients underwent both 91 cardiomyopathy-related gene screening and cardiovascular magnetic resonance (45.6 ± 10.6 years old, 76.5% were male). Forty pathogenic/likely pathogenic mutations were identified in 52 patients by next-generation sequencing. The SM-positive group were younger at first cardiovascular event (P = 0.04) and progression to diastolic HF (P = 0.02) with higher N-terminal pro-brain natriuretic peptide (NT-proBNP) [New York Heart Association (NYHA) Class III/IV symptoms with left ventricular ejection fraction > 55%] than the SM-negative group (P < 0.001). SM-positive patients had a greater extent of late gadolinium enhancement (P = 0.01), larger left atrial diameter (P = 0.03), higher normalized peak filling rate (PFR) and PFR ratio, and a greater reduction in global longitudinal strain than SM-negative patients (all P ≤ 0.01). During mean lifelong follow-up time (49.2 ± 15.6 years), SM-positive was a predictor of earlier HF (NYHA Class III/IV symptoms) after multivariate adjustment (hazard ratio 3.5; 95% confidence interval 1.3-9.7; P = 0.015).

Conclusion: SM-positive HCM patients had a higher extent of myocardial fibrosis and more severe ventricular diastolic dysfunction than those without, which may contribute to earlier onset of advanced HF, suggesting the importance of close surveillance and early treatment throughout life.
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http://dx.doi.org/10.1093/ehjci/jeaa317DOI Listing
November 2020

Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery.

Microbiome 2020 11 19;8(1):162. Epub 2020 Nov 19.

Department of Internal Medicine, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan.

The capability of gut microbiota in degrading foods and drugs administered orally can result in diversified efficacies and toxicity interpersonally and cause significant impact on human health. Production of atherogenic trimethylamine N-oxide (TMAO) from carnitine is a gut microbiota-directed pathway and varies widely among individuals. Here, we demonstrated a personalized TMAO formation and carnitine bioavailability from carnitine supplements by differentiating individual TMAO productivities with a recently developed oral carnitine challenge test (OCCT). By exploring gut microbiome in subjects characterized by TMAO producer phenotypes, we identified 39 operational taxonomy units that were highly correlated to TMAO productivity, including Emergencia timonensis, which has been recently discovered to convert γ-butyrobetaine to TMA in vitro. A microbiome-based random forest classifier was therefore constructed to predict the TMAO producer phenotype (AUROC = 0.81) which was then validated with an external cohort (AUROC = 0.80). A novel bacterium called Ihubacter massiliensis was also discovered to be a key microbe for TMA/TMAO production by using an OCCT-based humanized gnotobiotic mice model. Simply combining the presence of E. timonensis and I. massiliensis could account for 43% of high TMAO producers with 97% specificity. Collectively, this human gut microbiota phenotype-directed approach offers potential for developing precision medicine and provides insights into translational research. Video Abstract.
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http://dx.doi.org/10.1186/s40168-020-00912-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676756PMC
November 2020

High dose escalation of intracoronary adenosine in the assessment of fractional flow reserve: A retrospective cohort study.

PLoS One 2020 15;15(10):e0240699. Epub 2020 Oct 15.

College of Medicine, National Taiwan University, Taipei, Taiwan.

Maximal hyperaemia for fractional flow reserve (FFR) may not be achieved with the current recommended doses of intracoronary adenosine. Higher doses (up to 720 μg) have been reported to optimize hyperaemic stimuli in small dose-response studies. Real-world data from a large cohort of patients is needed to evaluate FFR results and the safety of high-dose escalation. This is a retrospective study aimed to evaluate the safety and frequency of FFR ≤0.8 after high-dose escalation of intracoronary adenosine. Data were extracted from the medical databases of two university hospitals. Increasing doses (100, 200, 400, 600, and 800 μg) of adenosine were administered as intracoronary boluses until FFR ≤0.8 was achieved or heart block developed. The percentage of FFR ≤0.8 after higher-dose escalation was compared with those at conventional doses, and the predictors for FFR ≤0.8 after higher doses were analysed. In the 1163 vessels of 878 patients, 402 vessels (34.6%) achieved FFR ≤0.8 at conventional doses and 623 vessels (53.6%) received high-dose escalation. An additional 84 vessels (13.5%) achieved FFR ≤0.8 after high-dose escalation. No major complications developed during high-dose escalation. Borderline FFR (0.81-0.85) at the conventional dose, stenosis >60%, and triple-vessel disease increased the likelihood of FFR ≤0.8 after high-dose escalation, but chronic kidney disease decreased it. For vessels of borderline FFR at conventional doses, 46% achieved FFR ≤0.8 after high-dose escalation. In conclusion, High-dose escalation of intracoronary adenosine increases the frequency of FFR ≤0.8 without major complications. It could be especially feasible for borderline FFR values near the 0.8 diagnostic threshold.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240699PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561200PMC
December 2020

Transcatheter aortic valve implantation during the COVID-19 pandemic: Clinical expert opinion and consensus statement for Asia.

J Card Surg 2020 Sep 27;35(9):2142-2146. Epub 2020 Jul 27.

Department of Cardiology, Queen Elizabeth Hospital, Kowloon, Hong Kong.

Objectives: The impact of the COVID-19 pandemic on the treatment of patient with aortic valve stenosis is unknown and there is uncertainty on the optimal strategies in managing these patients.

Methods: This study is supported and endorsed by the Asia Pacific Society of Interventional Cardiology. Due to the inability to have face to face discussions during the pandemic, an online survey was performed by inviting key opinion leaders (cardiac surgeon/interventional cardiologist/echocardiologist) in the field of transcatheter aortic valve implantation (TAVI) in Asia to participate. The answers to a series of questions pertaining to the impact of COVID-19 on TAVI were collected and analyzed. These led subsequently to an expert consensus recommendation on the conduct of TAVI during the pandemic.

Results: The COVID-19 pandemic had resulted in a 25% (10-80) reduction of case volume and 53% of operators required triaging to manage their patients with severe aortic stenosis. The two most important parameters used to triage were symptoms and valve area. Periprocedural changes included the introduction of teleconsultation, preprocedure COVID-19 testing, optimization of protests, and catheterization laboratory set up. In addition, length of stay was reduced from a mean of 4.4 to 4 days.

Conclusion: The COVID-19 pandemic has impacted on the delivery of TAVI services to patients in Asia. This expert recommendation on best practices may be a useful guide to help TAVI teams during this period until a COVID-19 vaccine becomes widely available.
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http://dx.doi.org/10.1111/jocs.14722DOI Listing
September 2020

Temporal Change in Paravalvular Leakage after Transcatheter Aortic Valve Replacement with a Self-Expanding Valve: Impact of Aortic Valve Calcification.

Acta Cardiol Sin 2020 Mar;36(2):140-147

Department of Internal Medicine.

Background: In patients undergoing transcatheter aortic valve replacement (TAVR), the severity of paravalvular leakage (PVL) may change during follow-up, however its mechanism is poorly understood. We aimed to explore temporal changes in PVL and possible predictors following TAVR.

Methods: A retrospective analysis was performed of all patients who had received a self-expanding valve. Multi-detector computed tomography was performed as pre-TAVR evaluation, including assessment of aortic valve calcification (AVC). The patients received transthoracic echocardiography at baseline and 30 days, 6 months, and 1 year after TAVR.

Results: In total, 93 patients who had received a self-expanding valve during TAVR were identified. Various degrees of PVL were seen in 63 patients, with moderate/severe PVL in 21 (22.6%). In multivariate analysis, the predictors of moderate/severe PVL were: chronic pulmonary disease, high degree of AVC, and an increased annulus perimeter. After 1 year of follow-up, PVL deteriorated from mild to moderate in 2 patients, while an improvement of ≥ 1 grade was seen in 25 patients. Of 21 patients with post-TAVR moderate/severe PVL, 9 had an improvement of ≥ 1 grade and 12 did not. The degree of AVC was significantly lower in those with PVL improvement (Agatston score 3068 ± 1816 vs. 6418 ± 3222; p = 0.01). AVC was a good predictor for an improvement in PVL, and the area under the receiver operating characteristic curve was 0.82 (95% confidence interval = 0.63-1.00, p = 0.01), with a cut-off value of 5210.

Conclusions: In this study, 43% (9/21) of the patients with moderate/severe PVL after self-expanding TAVR had an improvement of ≥ 1 grade within 1 year, and a low degree of AVC was predictive of this improvement.
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http://dx.doi.org/10.6515/ACS.202003_36(2).20190709BDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062810PMC
March 2020

miR-26a attenuates cardiac apoptosis and fibrosis by targeting ataxia-telangiectasia mutated in myocardial infarction.

J Cell Physiol 2020 09 28;235(9):6085-6102. Epub 2020 Jan 28.

Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Apoptosis and fibrosis play a vital role in myocardial infarction (MI) induced tissue injury. Although microRNAs have been the focus of many studies on cardiac apoptosis and fibrosis in MI, the detailed effects of miR-26a is needed to further understood. The present study demonstrated that miR-26a was downregulated in ST-elevation MI (STEMI) patients and oxygen-glucose deprivation (OGD)-treated H9c2 cells. Downregulation of miR-26a was closely correlated with the increased expression of creatine kinase, creatine kinase-MB and troponin I in STEMI patients. Further analysis identified that ataxia-telangiectasia mutated (ATM) was a target gene for miR-26a based on a bioinformatics analysis. miR-26a overexpression effectively reduced ATM expression, apoptosis, and apoptosis-related proteins in OGD-treated H9c2 cells. In a mouse model of MI, the expression of miR-26a was significantly decreased in the infarct zone of the heart, whereas apoptosis and ATM expression were increased. miR-26a overexpression effectively reduced ATM expression and cardiac apoptosis at Day 1 after MI. Furthermore, we demonstrated that overexpression of miR-26a improved cardiac function and reduced cardiac fibrosis by the reduced expression of collagen type I and connective tissue growth factor (CTGF) in mice at Day 14 after MI. Overexpression of miR-26a or ATM knockdown decreased collagen I and CTGF expression in cultured OGD-treated cardiomyocytes. Taken together, these data demonstrate a prominent role for miR-26a in linking ATM expression to ischemia-induced apoptosis and fibrosis, key features of MI progression. miR-26a reduced MI development by affecting ATM expression and could be targeted in the treatment of MI.
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http://dx.doi.org/10.1002/jcp.29537DOI Listing
September 2020

Efficacy and Safety of Renal Denervation for Patients with Uncontrolled Hypertension in Taiwan: 3-Year Results From the Global SYMPLICITY Registry-Taiwan (GSR-Taiwan).

Acta Cardiol Sin 2019 Nov;35(6):618-626

Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Department of Internal Medicine, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: It is unclear whether renal denervation (RDN) can safely result in blood pressure (BP) reductions in Asian hypertensive patients and whether such reductions would be sustainable. The study is to assess the safety and efficacy of RDN achieved by either main renal artery ablation using the Symplicity Flex catheter or main plus branch renal artery ablations using the Symplicity Spyral catheter in Taiwanese uncontrolled hypertensive patients enrolled in the Global SYMPLICITY Registry (GSR) with 3 years of follow-up.

Methods: The GSR is a prospective, open-label, and all-comer registry to evaluate the safety and effectiveness of RDN in patients with uncontrolled hypertension worldwide.

Results: Among 26 patients enrolled (mean age, 59.1 ± 13.8 years), 8 were treated with the Symplicity Flex catheter, and 18 were treated with the Symplicity Spyral catheter. Baseline office systolic BP was 168.2 ± 19.8 mmHg and diastolic BP was 89.0 ± 14.3 mmHg. Office BP reductions following RDN were sustained throughout the follow-up periods of up to 3 years in the Symplicity Flex group and 2 years in the Symplicity Spyral group. In the Symplicity Flex group, the office systolic BP reductions were 14.9 ± 14.7 mmHg and 29.7 ± 25.9 mmHg at 3 months and 3 years, respectively (both p < 0.05 from baseline). In the Symplicity Spyral group, the office systolic BP reductions were 21.2 ± 28.7 mmHg and 42.4 ± 10.7 mmHg at 3 months and 2 years, respectively (both p < 0.05 from baseline). There were no significant changes in heart rate or antihypertensive medication classes. Three protocol-defined adverse events occurred in 2 patients, including new-onset end-stage renal disease, stroke, and hospitalization for new-onset heart failure.

Conclusions: Given the susceptibility of Asian populations to hypertension, RDN, as a safe antihypertensive procedure with long-lasting BP-lowering effects, could reliably serve as an alternative or complementary BP-lowering strategy for patients with uncontrolled hypertension in Taiwan and other Asian countries.
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http://dx.doi.org/10.6515/ACS.201911_35(6).20190826ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859098PMC
November 2019

Acute Femoral Occlusion After Adjunctive Angio-Seal Usage in Vascular Closure Following Transcatheter Aortic Valve Replacement.

JACC Case Rep 2019 Dec 4;1(4):549-552. Epub 2019 Dec 4.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

We report 3 patients with acute femoral occlusion after adjunctive Angio-Seal use during transfemoral transcatheter aortic valve replacement. All occlusions were recanalized by applying elaborative strategies for chronic total occlusion recanalization. Our experience reminds operators to cautiously use the Angio-Seal as a bailout treatment, especially in patients with high-risk clinical features. ().
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http://dx.doi.org/10.1016/j.jaccas.2019.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288705PMC
December 2019

Advances in CrossBoss/Stingray use in antegrade dissection reentry from the Asia Pacific Chronic Total Occlusion Club.

Catheter Cardiovasc Interv 2020 12 26;96(7):1423-1433. Epub 2019 Nov 26.

Department of Cardiovascular Medicine, Toyohashi Heart Centre, Toyohashi, Aichi, Japan.

Antegrade dissection reentry with Stingray device (Boston Scientific, Marlborough, MA) accounts for 20-34% of the chronic total occlusion (CTO) cases in the various hybrid operators' CTO registries and is an important component of CTO crossing algorithms. The Stingray device can facilitate antegrade dissection and reentry, however its use is low outside North America and Europe. The Asia Pacific CTO Club along with three experience Stingray operators from the US, Europe and India, created an algorithm guiding use of the CrossBoss and Stingray catheter. This APCTO Stingray algorithm defines when to use the CrossBoss and Stingray device recommending a reduction in CrossBoss use except for in-stent restenosis lesions and immediate transition from knuckle wiring to the Stingray device. When antegrade wiring fails, choice of Stingray-facilitated reentry versus parallel wiring depends on operator experience, device availability, cost concerns, and anatomical factors. When the antegrade wire enters the subintimal space, we recommend using a rotational microcatheter to produce a channel and deliver the Stingray balloon-so called the "bougie technique." We recommend early switch to Stingray rather than persisting with single wire redirection or parallel wire. We recommend choosing a suitable reentry zone based on preprocedural computer tomography or angiogram, routine use of stick and swap, routine use of Subintimal TRAnscatheter Withdrawal (STRAW) through the Stingray balloon, and the multi stick and swap technique. We believe these techniques and algorithm can facilitate incorporation of the Stingray balloon into the practice of CTO interventionists globally.
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http://dx.doi.org/10.1002/ccd.28607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754104PMC
December 2020

Comparative Effectiveness and Safety of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome or Percutaneous Coronary Intervention.

Acta Cardiol Sin 2019 Sep;35(5):508-521

Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University.

Background: There remains insufficient evidence to determine the optimal antithrombotic strategy in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) or percutaneous coronary interventions (PCIs), especially in Asian populations.

Objectives: This study aimed to examine the real-world patterns of antithrombotic treatment among these patients and to compare the effectiveness and safety of different antithrombotic regimens.

Methods: A retrospective cohort study was conducted in AF patients presenting with a new ACS or PCI during 2006/1/1-2016/4/1. Three antithrombotic regimens were compared: dual antiplatelet therapy (DAPT, as the reference group), triple therapy (TT: DAPT plus an oral anticoagulant), and dual therapy (DT: single antiplatelet plus an oral anticoagulant). The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCEs) and bleeding. Treatment effect was estimated using a Cox proportional hazards model. Inverse probability of treatment weighting was used to balance baseline characteristics among comparison groups.

Results: Overall, 532 patients were included. At discharge from the index hospitalization, DAPT was the most common antithrombotic therapy, followed by TT and DT. No significant difference in MACCEs was found among the different antithrombotic regimens. However, DT was associated with a lower risk of any bleeding [adjusted hazard ratio 0.20 (95% confidence interval, 0.06-0.75)] than DAPT.

Conclusions: In the study population, DAPT was the most commonly prescribed antithrombotic regimen for cardio-cerebrovascular disease prevention. The effectiveness outcomes were comparable across different antithrombotic strategies. The lower risk of bleeding with DT compared with DAPT warrants further investigation.
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http://dx.doi.org/10.6515/ACS.201909_35(5).20190311ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760126PMC
September 2019

Guiding Principles for Chronic Total Occlusion Percutaneous Coronary Intervention.

Circulation 2019 07 29;140(5):420-433. Epub 2019 Jul 29.

Freeman Hospital and Newcastle University, Newcastle upon Tyne, United Kingdom (M.E.).

Outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have improved because of advancements in equipment and techniques. With global collaboration and knowledge sharing, we have identified 7 common principles that are widely accepted as best practices for CTO-PCI.  1. Ischemic symptom improvement is the primary indication for CTO-PCI.  2. Dual coronary angiography and in-depth and structured review of the angiogram (and, if available, coronary computed tomography angiography) are key for planning and safely performing CTO-PCI.  3. Use of a microcatheter is essential for optimal guidewire manipulation and exchanges.  4. Antegrade wiring, antegrade dissection and reentry, and the retrograde approach are all complementary and necessary crossing strategies. Antegrade wiring is the most common initial technique, whereas retrograde and antegrade dissection and reentry are often required for more complex CTOs.  5. If the initially selected crossing strategy fails, efficient change to an alternative crossing technique increases the likelihood of eventual PCI success, shortens procedure time, and lowers radiation and contrast use.  6. Specific CTO-PCI expertise and volume and the availability of specialized equipment will increase the likelihood of crossing success and facilitate prevention and management of complications, such as perforation.  7. Meticulous attention to lesion preparation and stenting technique, often requiring intracoronary imaging, is required to ensure optimum stent expansion and minimize the risk of short- and long-term adverse events. These principles have been widely adopted by experienced CTO-PCI operators and centers currently achieving high success and acceptable complication rates. Outcomes are less optimal at less experienced centers, highlighting the need for broader adoption of the aforementioned 7 guiding principles along with the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, and training.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.039797DOI Listing
July 2019

Retrograde Versus Antegrade Approach for Coronary Chronic Total Occlusion in an Algorithm-Driven Contemporary Asia-Pacific Multicentre Registry: Comparison of Outcomes.

Heart Lung Circ 2020 Jun 2;29(6):894-903. Epub 2019 Jul 2.

Prince of Wales Hospital, Hong Kong, China.

Background: The use of a retrograde approach and algorithm-driven CTO (chronic total occlusion) percutaneous coronary intervention (PCI) has become widespread, and many registries have reported good results. This study established a new algorithm and applied it to current CTO practice and collected a CTO registry to document the results. It compared the outcomes of a retrograde versus antegrade approach in a contemporary multicentre CTO registry.

Methods: Between 1 January 2016 and 31 December 2016, consecutive patients who underwent CTO PCI performed by eight high-volume CTO operators were included in a registry.

Results: During this period, 485 patients with 497 CTOs were treated with technical and procedural success rates of 93.8% and 89.9%, respectively. Antegrade and retrograde technical success was 95.9% and 91.2% (p = 0.03), respectively. Procedural success for antegrade and retrograde was 94.4% and 84.6%, respectively (p < 0.001). The pure retrograde success rate was 80% and pure antegrade success rate was 75%. Technical success in different Japanese Chronic Total Occlusion (JCTO) score groups was 100% (JCTO 0), 96.2% (JCTO 1), 95.3% (JCTO 2), and 92.5% (JCTO ≥ 3), with no statistical difference in success rates between different JCTO scores. In-hospital major adverse cardiac event (MACE) was 3.8% and more common in the retrograde group (6.6% vs 1.5%).

Conclusions: The retrograde approach, when used by experienced operators who have been well trained in retrograde approach, can produce higher retrograde success in complex CTO lesions. The use of an algorithm approach can improve procedural efficiency, reduce contrast and radiation dosage, and reduce the time spent in failure mode. These tools remain vital to the development of future CTO PCI.
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http://dx.doi.org/10.1016/j.hlc.2019.05.188DOI Listing
June 2020

Intentional combination of ProGlide and Angio-Seal for femoral access haemostasis in transcatheter aortic valve replacement.

Int J Cardiol 2019 10 23;293:76-79. Epub 2019 May 23.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Background: To describe and evaluate the intentional combination of Angio-Seal (AS) and Perclose ProGlide (PP) in achieving haemostasis in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR).

Methods: This study cohort was divided into two groups: dual PP versus one AS with one PP (AS + PP) used for common femoral artery haemostasis. The baseline, procedural characteristics and all outcomes (defined according toVARC-2 criteria) were prospectively collected and retrospectively compared.

Results: Overall, a total of 151 consecutive patients (68 men; 80.9 ± 7.3 years old) were evaluated. Of these, 51 patients (33.8%) underwent TAVR using the dual PP, and 100 (66.2%) using one AS with one PP. There were no significant differences in the baseline characteristics of both patient groups, except higher incidence of chronic pulmonary disease in dual PP group (21.6% vs 7%, P = 0.009). Patients in AS + PP group had lower rate of arterial stricture (21.6% vs 8%, P = 0.017), arterial dissection (13.7% vs 4.0%), requiring endovascular intervention for puncture site issues (21.6% vs 9.0%, P = 0.031). Less procedural time (139.8 ± 36.9vs97.9 ± 31.4 min, P < 0.001) & contrast medium consumption (223.9 ± 88.3vs174.1 ± 49.7 ml, P < 0.001) were also observed in AS+PP group. There were no statistically significant differences between 2 groups in regards of closure device failure, major and minor vascular complications, nor major and minor bleeding.

Conclusions: Intentional combination of one PP and one AS for femoral access haemostasis in patients undergoing TAVR is feasible and safe, with low risk of vascular and bleeding complications.
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http://dx.doi.org/10.1016/j.ijcard.2019.05.055DOI Listing
October 2019

Chronic Total Occlusion Wiring: A State-of-the-Art Guide From The Asia Pacific Chronic Total Occlusion Club.

Heart Lung Circ 2019 Oct 25;28(10):1490-1500. Epub 2019 Apr 25.

Wellington Hospital, Wellington, New Zealand.

Objective: Despite the advances in wire technology and development of algorithm-driven methodology for chronic total occlusion (CTO) intervention, there is a void in the literature about the technical aspects of CTO wiring. The Asia Pacific CTO Club, a group of 10 experienced operators in the Asia Pacific region, has tried to fill this void with this state-of-the-art review on CTO wiring.

Methods: This review explains, for proximal cap puncture: choices of wires, shaping of the wire, use of dual lumen catheter, and method of step-down of wire penetration force for successful wiring. In wiring the CTO body, the techniques of loose tissue tracking, intentional intimal plaque tracking, and intentional subintimal wiring are described in detail. For distal lumen wiring, a blunt distal cap, presence of a distal cap side branch, calcium, and sharp tapered distal stump predict cap toughness, and wire penetration force should be stepped-up in these cases. The importance of choosing between redirection, parallel wiring, and Stingray (Boston Scientific, Marlborough, MA, USA) for angiographic guidance is discussed along with which will be more successful. On the retrograde side, the problems encountered with distal cap puncture and methods to overcome these problems are explained. The method of wiring the CTO body through a retrograde approach depending on the morphology of the CTO is described. Different reverse controlled antegrade and retrograde tracking (CART) wiring methods - including end balloon wiring, side balloon entry, and conventional reverse CART - are explained in detail.

Conclusion: This is a systematic CTO wiring review, which is believed to be beneficial for CTO operators worldwide.
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http://dx.doi.org/10.1016/j.hlc.2019.04.004DOI Listing
October 2019

Quantification of cardiac pumping mechanics in rats by using the elastance-resistance model based solely on the measured left ventricular pressure and cardiac output.

Pflugers Arch 2019 07 23;471(7):935-947. Epub 2019 Mar 23.

Department of Physiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei, 100, Taiwan.

The cardiac pumping mechanics can be characterized by both the maximal systolic elastance (E) and theoretical maximum flow (Q), which are generated using an elastance-resistance model. The signals required to fit the elastance-resistance model are the simultaneously recorded left ventricular (LV) pressure and aortic flow (Q), followed by the isovolumic LV pressure. In this study, we evaluated a single-beat estimation technique for determining the E and Q by using the elastance-resistance model based solely on the measured LV pressure and cardiac output. The isovolumic LV pressure was estimated from the measured LV pressure by using a non-linear least-squares approximation technique. The measured Q was approximated by an unknown triangular flow (Q), which was generated by using a fourth-order derivative of the LV pressure. The Q scale was calibrated using the cardiac output. Values of E and Q obtained using Q were compared with those of E and Q obtained from the measured Q. Healthy rats and rats with chronic kidney disease or diabetes mellitus were examined. We found that the LV E and Q can be approximately calculated using the assumed Q, and they strongly correlated with the corresponding values derived from Q (P < 0.0001; n = 78): E = 51.9133 + 0.8992 × E (r = 0.8257; P < 0.0001); Q = 2.4053 + 0.9767 × Q (r = 0.7798; P < 0.0001). Our findings suggest that the proposed technique can be a useful tool for determining E and Q by using a single LV pressure pulse together with cardiac output.
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http://dx.doi.org/10.1007/s00424-019-02270-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591189PMC
July 2019

Improvement of Pituitary Function after Carotid Revascularization in Patients with Abnormal Cerebral Perfusion - A Pilot Study.

Acta Cardiol Sin 2018 Nov;34(6):472-480

Division of Cardiology.

Background: Brain ischemia may affect hypothalamic-pituitary axis function, which may influence the outcomes of patients with internal carotid artery (ICA) stenosis/occlusion. The objective of this study was to determine the influence of successful carotid revascularization on pituitary function in patients with severe ICA stenosis/occlusion.

Methods: This study was conducted from April 2009 to December 2014. Patients receiving successful endovascular interventions for severe ICA stenosis/occlusion were enrolled. The patients were divided into 2 groups: group 1 with abnormal ipsilateral cerebral perfusion, and group 2 without. Endocrine profiles were measured before and > 1 year after the procedure. Computed tomography perfusion studies were used to assess brain perfusion.

Results: Thirty-seven patients received successful interventions. Three patients were excluded due to re-stenosis before 1 year. There were 23 and 11 patients in group 1 and 2, with mean ages of 68 and 69 years, respectively. In the female patients, follicular stimulating hormone (FSH) and luteinizing hormone (LH) increased significantly (p = 0.043) after the interventions with a stable estradiol level in group 1. In contrast, FSH, LH and estradiol showed a decreasing trend in group 2. In the male patients, FSH and LH increased significantly (p < 0.01) after the interventions with a stable testosterone level in group 1, while testosterone showed a decreasing trend in group 2. Thyroid stimulating hormone increased significantly in the women in both groups, and in the men in group 1.

Conclusions: Successful revascularization for severe ICA stenosis/occlusion may improve their pituitary function, especially FSH and LH levels.
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http://dx.doi.org/10.6515/ACS.201811_34(6).20180818ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236569PMC
November 2018

Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice.

Gut 2019 08 30;68(8):1439-1449. Epub 2018 Oct 30.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Objective: The gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance.

Design: A pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation.

Results: The OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT.

Conclusion: The OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment.

Trial Registration Number: NCT02838732; Results.
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http://dx.doi.org/10.1136/gutjnl-2018-317155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691853PMC
August 2019

Long-term Outcomes After Endovascular Recanalization in Patients with Chronic Carotid Artery Occlusion.

Am J Cardiol 2018 11 22;122(10):1779-1783. Epub 2018 Aug 22.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Successful carotid artery stenting may correct ipsilateral hemisphere hypoperfusion and improve neurocognitive function in patients with chronic internal carotid artery occlusion (ICAO). Its effect on long-term outcomes, however, has never been studied. From May 2004 to April 2015, endovascular recanalization for chronic ICAO was attempted in 118 consecutive patients (119 lesions; 98 men; 67 ± 10 years old) with either recurrent neurologic events or objectively impaired ipsilateral hemisphere perfusion. Technical success in recanalization was achieved in 70 lesions (59%, 70/119). 3-months cumulative any stroke or death rate was 5% (6/119; 4 in recanalized group, 2 in failure group), including 2 periprocedural ischemic stroke, 2 intracranial hemorrhage, and 2 subarachnoid hemorrhage. In recanalized patients without periprocedural complication, 1-year reocclusion rate was 15% (10/65). Up to 7 years after procedure, cumulative events of transient ischemic attack (TIA), or any stroke, or death were 17 in recanalized group, compared with 23 in failure group (hazard ratio 0.51, 95% confidence interval 0.27 to 0.97; p = 0.04). The difference became more significant after excluding patients with periprocedure events (hazard ratio 0.41, 95% confidence interval 0.20 to 0.84, p = 0.015). In conclusions, the technical success and periprocedural complication rates of endovascular recanalization for chronic ICAO were acceptable. The cumulative event rates of any stroke or death up to 7 years were more favorable in patients after successful recanalization, compared to those in patients after failed procedure.
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http://dx.doi.org/10.1016/j.amjcard.2018.07.049DOI Listing
November 2018

Inhibition of Semicarbazide-sensitive Amine Oxidase Reduces Atherosclerosis in Cholesterol-fed New Zealand White Rabbits.

Sci Rep 2018 06 18;8(1):9249. Epub 2018 Jun 18.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Inflammation, oxidative stress, and the formation of advanced glycated end-products (AGEs) are important components of atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation. Its enzymatic activity, semicarbazide-sensitive amine oxidase (SSAO), can catalyze oxidative deamination reactions to produce hydrogen peroxide and aldehydes, leading to the subsequent generation of AGEs. This study aimed to investigate the effect of VAP-1/SSAO inhibition on atherosclerosis. In our study, immunohistochemical staining showed that atherosclerotic plaques displayed higher VAP-1 expression than normal arterial walls in apolipoprotein E-deficient mice, cholesterol-fed New Zealand White rabbits and humans. In cholesterol-fed rabbits, VAP-1 was expressed on endothelial cells and smooth muscle cells in the thickened intima of the aorta. Treatment with PXS-4728A, a selective VAP-1/SSAO inhibitor, in cholesterol-fed rabbits significantly decreased SSAO-specific hydrogen peroxide generation in the aorta and reduced atherosclerotic plaques. VAP-1/SSAO inhibition also lowered blood low-density lipoprotein cholesterol, reduced the expression of adhesion molecules and inflammatory cytokines, suppressed recruitment and activation of macrophages, and decreased migration and proliferation of SMC. In conclusion, VAP-1/SSAO inhibition reduces atherosclerosis and may act through suppression of several important mechanisms for atherosclerosis.
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http://dx.doi.org/10.1038/s41598-018-27551-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006253PMC
June 2018

Inhibition of semicarbazide-sensitive amine oxidase reduces atherosclerosis in apolipoprotein E-deficient mice.

Transl Res 2018 07 27;197:12-31. Epub 2018 Mar 27.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Inflammation, oxidative stress, and formation of advanced glycated end products (AGEs) and advanced lipoxidation end products (ALEs) are important for atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation and has semicarbazide-sensitive amine oxidase (SSAO) activity, which catalyzes oxidative deamination to produce hydrogen peroxide and aldehydes, leading to generation of AGEs and ALEs. However, the effect of VAP-1/SSAO inhibition on atherosclerosis remains controversial, and no studies used coronary angiography to evaluate if plasma VAP-1/SSAO is a biomarker for coronary artery disease (CAD). Here, we examined if plasma VAP-1/SSAO is a biomarker for CAD diagnosed by coronary angiography in humans and investigated the effect of VAP-1/SSAO inhibition by a specific inhibitor PXS-4728A on atherosclerosis in cell and animal models. In the study, VAP-1/SSAO expression was increased in plaques in humans and in apolipoprotein E (ApoE)-deficient mice, and colocalized with vascular endothelial cells and smooth muscle cells (SMCs). Patients with CAD had higher plasma VAP-1/SSAO than those without CAD. Plasma VAP-1/SSAO was positively associated with the extent of CAD. In ApoE-deficient mice, VAP-1/SSAO inhibition reduced atheroma and decreased oxidative stress. VAP-1/SSAO inhibition attenuated the expression of adhesion molecules, chemoattractant proteins, and proinflammatory cytokines in the aorta, and suppressed monocyte adhesion and transmigration across human umbilical vein endothelial cells. Consequently, the expression of markers for macrophage recruitment and activation in plaques was decreased by VAP-1/SSAO inhibition. Besides, VAP-1/SSAO inhibition suppressed proliferation and migration of A7r5 SMC. Our data suggest that plasma VAP-1/SSAO is a novel biomarker for the presence and the extent of CAD in humans. VAP-1/SSAO inhibition by PXS-4728A is a potential treatment for atherosclerosis.
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http://dx.doi.org/10.1016/j.trsl.2018.03.001DOI Listing
July 2018

Prevalence and outcome of patients with non-ST segment elevation myocardial infarction with occluded "culprit" artery - a systemic review and meta-analysis.

Crit Care 2018 Feb 9;22(1):34. Epub 2018 Feb 9.

Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan.

Background: The aim was to determine the prevalence and impact of an occluded "culprit" artery (OCA) in patients with non-ST segment elevation myocardial infarction (NSTEMI).

Methods: We searched PubMed, EMBASE, and Web of Science, with no language restrictions, up to 1 Jul. 2016. Observational cohorts or clinical trials of adult NSTEMI were eligible for inclusion to determine the prevalence if the proportion of OCA on coronary angiography was reported. Studies were further eligible for inclusion to determine the outcome if the association between OCA and clinical endpoints was reported.

Results: Among the 60,898 patients with NSTEMI enrolled in 25 studies, 17,212 were found to have OCA. The average proportion of OCA in NSTEMI was 34% (95% CI 30-37%). Patients with OCA were more likely to have left circumflex artery as their culprit artery (odds ratio (OR) 1.65, 95% CI 1.15-2.37, p = 0.007), and this was associated with lower left ventricular ejection fraction (standard mean difference -0.29, 95% CI -0.34 to -0.34, p < 0.001), higher peak enzyme level (standard mean difference 0.43, 95% CI 0.27-0.58, p < 0.001), and higher risk for cardiogenic shock (OR 1.66, 95% CI 1.35-2.04, p < 0.001), compared with patients with a non-occlusive culprit artery. Death rate (OR 1.72, 95% CI 1.49-1.98, p < 0.001) and recurrent myocardial infarction (OR 1.7, 95% CI 1.06-2.75, p = 0.029) were also higher in patients with OCA, compared with patients with a non-occlusive culprit artery.

Conclusions: Patients with OCA comprised a substantial portion of the NSTEMI population. These patients present with more severe symptoms and worse clinical outcome. Whether these patients should be treated with more aggressive strategy warrants further study.
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http://dx.doi.org/10.1186/s13054-018-1944-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806289PMC
February 2018

Overview and proposed terminology for the reverse controlled antegrade and retrograde tracking (reverse CART) techniques.

EuroIntervention 2018 05;14(1):94-101

Department of Cardiovascular Medicine, The Cardiovascular Institute, Tokyo, Japan.

During recent years, equipment and techniques for percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) have improved significantly. The retrograde approach remains critical to the improved success of CTO PCI. Currently, the reverse controlled antegrade and retrograde tracking (CART) technique has become the dominant retrograde wire crossing technique. In this article, we propose a standardised terminology and classification for this technique divided into three subtypes: a) conventional reverse CART, usually involving the use of large balloons on the antegrade wire to achieve re-entry within the CTO segment; b) "directed" reverse CART, which is characterised by small antegrade balloon size and more active, intentional vessel tracking and penetration with a controllable retrograde wire, still within the CTO segment; and c) "extended" reverse CART, in which the intimal/subintimal dissection is extended proximal or distal to the CTO segment, achieving re-entry outside the CTO segment. The proposed standardised terminology will facilitate the communication, teaching and adoption of the reverse CART techniques.
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http://dx.doi.org/10.4244/EIJ-D-17-00867DOI Listing
May 2018

Collateral Channel Size and Tortuosity Predict Retrograde Percutaneous Coronary Intervention Success for Chronic Total Occlusion.

Circ Cardiovasc Interv 2018 01;11(1):e005124

From the Department of Internal Medicine, National Taiwan University Hospital, Taipei (C.-C.H., C.-S.H., Y.-H.C., M.-S.L., C.-F.Y., H.-L.K.); and Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu (C.-K. L., S.-W.M.).

Background: There is little evidence on how to select an interventional collateral channel (CC) in retrograde chronic total occlusion (CTO) percutaneous coronary intervention. We aimed to identify independent angiographic predictors of CC tracking and technical success in retrograde CTO percutaneous coronary intervention.

Methods And Results: From January 2012 to December 2015, a total of 216 consecutive retrograde CTO percutaneous coronary intervention attempts by a high-volume operator in a tertiary university-affiliated hospital were enrolled. The clinical, angiographic, and procedural details were collected. The characteristics analyzed included channel type, size, tortuosity, angle of attack, length to emerging point, and the Multicenter CTO Registry of Japan score. The Multicenter CTO Registry of Japan score was 4.2±0.8. A total of 242 CCs were attempted for intervention. CC tracking success rate was 83.5%, and the technical success rate (per CC) was 81.4%. The per-patient technical success rate was 91.2%, and the major procedural complication rate was 4.6%. The atrioventricular groove, epicardial, and septal CCs were used in 36 (14.9%), 84 (34.7%), and 122 (50.4%) tracking attempts, respectively. In multivariable analysis, only large channel size and lack of tortuosity were significant independent predictors of CC tracking and technical success. A new scoring system was developed, while large size was given 1 point and lack of tortuosity was given 2 points. The receiver-operating characteristic area by the new model to predict CC tracking and technical success were 0.800 and 0.752, respectively.

Conclusions: In retrograde CTO percutaneous coronary intervention, only size and tortuosity of a CC are independent angiographic predictors of CC tracking and technical success.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.117.005124DOI Listing
January 2018

Quantification of contractile mechanics in the rat heart from ventricular pressure alone.

Oncotarget 2017 Nov 10;8(56):96161-96170. Epub 2017 Oct 10.

Department of Physiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.

To quantitate the contractile mechanics of the heart, the ventricle is considered an elastic chamber with known end-systolic elastance ( ). can be calculated from a single pressure-ejected volume curve, which requires simultaneous records of left ventricular (LV) pressure and the aortic flow (). In clinical settings, it is helpful to evaluate patients' cardiac contractile status by using a minimally invasive approach to physiological signal monitoring, wherever possible, such as by using LV pressure alone. In this study, we evaluated a method for determining on the basis of the measured LV pressure and an assumed aortic flow with a triangular wave shape (). was derived using a fourth-order derivative of the LV pressure to approximate its corresponding . Values of obtained using were compared with those of obtained from the measured . Healthy rats (NC; = 28) and rats with type 1 diabetes (DM; = 26) and chronic kidney disease (CKD; = 20) were examined. The cardiodynamic conditions in both the DM and CKD groups were characterized by a decline in and . A significant regression line for was observed ( < 0.0001): = 2.6214 + 1.0209 × ( = 0.9870; = 74). Our finding indicates that the systolic pumping mechanics of the heart can be derived from a single LV pressure recording together with the assumed .
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http://dx.doi.org/10.18632/oncotarget.21815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707089PMC
November 2017

Carotid-cavernous fistula after endovascular intervention for chronic carotid artery total occlusion.

Catheter Cardiovasc Interv 2018 03 4;91(4):735-741. Epub 2017 Dec 4.

Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

Background And Purpose: In addition to head trauma and cranial surgery, endovascular intervention for chronic carotid artery occlusion (CAO) may also result in carotid-cavernous fistula (CCF). The management and prognosis of iatrogenic CCF during CAO recanalization have never been well described and discussed in the literature.

Materials And Methods: We conducted a retrospective analysis for CAO recanalization attempts in National Taiwan University Hospital and affiliated hospitals. Incidence and presentation, demographic and angiographic variables, and clinical follow-up of the development of iatrogenic CCF were carefully reviewed.

Results: A total of 138 consecutive de novo CAO endovascular recanalization attempts were reviewed. The technical success rate was 61.6% (85/138). Complication rate, including death, stroke, and intracranial or sub-arachnoid hemorrhage (ICH or SAH) was 4.3% (6/138). CCF developed in 11 patients (8.0%), and none resulted in death, stroke, or ICH/SAH within 30 days. Female gender and distal carotid artery reconstitution at communicating or ophthalmic segments were associated with development of CCF. Imaging follow-ups were performed in eight patients and none showed persistent CCF.

Conclusion: CCF may develop during chronic CAO endovascular recanalization attempts. It is usually self-limited and can be managed conservatively.
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http://dx.doi.org/10.1002/ccd.27392DOI Listing
March 2018
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