Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Acute coronary syndrome and sudden cardiac death are often caused by rupture and thrombosis of lipid-rich atherosclerotic coronary plaques (known as vulnerable plaques), many of which are non-flow-limiting. The safety and effectiveness of focal preventive therapy with percutaneous coronary intervention of vulnerable plaques in reducing adverse cardiac events are unknown. We aimed to assess whether preventive percutaneous coronary intervention of non-flow-limiting vulnerable plaques improves clinical outcomes compared with optimal medical therapy alone. METHODS: PREVENT was a multicentre, open-label, randomised controlled trial done at 15 research hospitals in four countries (South Korea, Japan, Taiwan, and New Zealand). Patients aged 18 years or older with non-flow-limiting (fractional flow reserve >0·80) vulnerable coronary plaques identified by intracoronary imaging were randomly assigned (1:1) to either percutaneous coronary intervention plus optimal medical therapy or optimal medical therapy alone, in block sizes of 4 or 6, stratified by diabetes status and the performance of percutaneous coronary intervention in a non-study target vessel. Follow-up continued annually in all enrolled patients until the last enrolled patient reached 2 years after randomisation. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischaemia-driven target-vessel revascularisation, or hospitalisation for unstable or progressive angina, assessed in the intention-to-treat population at 2 years. Time-to-first-event estimates were calculated with the Kaplan-Meier method and were compared with the log-rank test. This report is the principal analysis from the trial and includes all long-term analysed data. The trial is registered at ClinicalTrials.gov, NCT02316886, and is complete. FINDINGS: Between Sept 23, 2015, and Sept 29, 2021, 5627 patients were screened for eligibility, 1606 of whom were enrolled and randomly assigned to percutaneous coronary intervention (n=803) or optimal medical therapy alone (n=803). 1177 (73%) patients were men and 429 (27%) were women. 2-year follow-up for the primary outcome assessment was completed in 1556 (97%) patients (percutaneous coronary intervention group n=780; optimal medical therapy group n=776). At 2 years, the primary outcome occurred in three (0·4%) patients in the percutaneous coronary intervention group and in 27 (3·4%) patients in the medical therapy group (absolute difference -3·0 percentage points [95% CI -4·4 to -1·8]; p=0·0003). The effect of preventive percutaneous coronary intervention was directionally consistent for each component of the primary composite outcome. Serious clinical or adverse events did not differ between the percutaneous coronary intervention group and the medical therapy group: at 2 years, four (0·5%) versus ten (1·3%) patients died (absolute difference -0·8 percentage points [95% CI -1·7 to 0·2]) and nine (1·1%) versus 13 (1·7%) patients had myocardial infarction (absolute difference -0·5 percentage points [-1·7 to 0·6]). INTERPRETATION: In patients with non-flow-limiting vulnerable coronary plaques, preventive percutaneous coronary intervention reduced major adverse cardiac events arising from high-risk vulnerable plaques, compared with optimal medical therapy alone. Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for percutaneous coronary intervention to include non-flow-limiting, high-risk vulnerable plaques. FUNDING: The CardioVascular Research Foundation, Abbott, Yuhan Corp, CAH-Cordis, Philips, and Infraredx, a Nipro company.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Sex-Specific Left Ventricular and Aorta Size Cut-Off Values for Hemodynamically Significant Chronic Aortic Regurgitation　- Implications for Treatment in Asian Populations.

BACKGROUND: There are no sex-specific guidelines for chronic aortic regurgitation (AR). This retrospective study examined sex-specific differences and propose treatment criteria from an Asian AR cohort.Methods and Results: Consecutive 1,305 patients with moderate-severe AR or greater at 3 tertiary centers in Taiwan and Japan (2008-2022) were identified. Study endpoints were aortic valve surgery (AVS), all-cause death (ACD), and cardiovascular death (CVD). The median follow up was 3.9 years (interquartile range 1.3-7.1 years). Compared with men (n=968), women (n=337) were older, had more advanced symptoms, more comorbidities, larger indexed aorta size (iAortamax) and indexed left ventricular (LV) end-systolic dimension (LVESDi; P<0.001 for all). Symptomatic status was poorly correlated with the degree of LV remodeling in women (P≥0.18). Women received fewer AVS (P≤0.001) and men had better overall 10-year survival (P<0.01). Ten-year post-AVS survival (P=0.9) and the progression of LV remodeling were similar between sexes (P≥0.16). Multivariable determinants of ACD and CVD were age, advanced symptoms, iAortamax, LV ejection fraction (LVEF), LVESDi, LV end-systolic volume index (LVESVi), and Taiwanese ethnicity (all P<0.05), but not female sex (P≥0.05). AVS was associated with better survival (P<0.01). Adjusted LVEF, LVESDi, LVESVi, and iAortamaxcut-off values for ACD were 53%, 24.8 mm/m2, 44 mL/m2, and 25.5 mm/m2, respectively, in women and 52%, 23.4 mm/m2, 52 mL/m2, and 23.2 mm/m2, respectively, in men. CONCLUSIONS: Early detection and intervention using sex-specific cut-off values may improve survival in women with AR.

Who needs to be screened for primary aldosteronism?

The prevalence of patients with primary aldosteronism (PA) is about 5%-15% in hypertensive patients, and it is common cause of secondary hypertension in clinical practice. Two major causes of PA are noted, namely bilateral adrenal hyperplasia and aldosterone-producing adenoma, and the general diagnosis is based on three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation (Figure 1). The recommendation for screening patients is at an increased risk of PA, here we focus on which patients should be screened for PA, not only according to well-established guidelines but for potential patients with PA. We recommend screening for 1) patients with resistant or persistent hypertension, 2) hypertensive patients with hypokalemia (spontaneous or drug-induced), 3) young hypertensive patients (age <40 years), and 4) all hypertensive patients with a history of PA in first-degree relatives. Moreover, we suggest screening for 1) hypertensive patients themselves or first-degree relatives with early target organ damage, such as stroke and other diseases, 2) all hypertensive patients with a concurrent adrenal incidentaloma, 3) hypertensive patients with obstructive sleep apnea, 4) hypertensive patients with atrial fibrillation unexplained by structural heart defects and/or other conditions resulting in the arrhythmia, 5) hypertensive patients with anxiety and other psychosomatic symptoms, and 6) hypertensive patients without other comorbidities to maintain cost-effectiveness.

Aldosterone-to-renin ratio (ARR) as a screening tool for primary aldosteronism (PA).

The aldosterone-to-renin ratio (ARR) is the standard screening test for primary aldosteronism (PA). Because of the poor reproducibility of the ARR, repeat testing is recommended if the result is not compatible with the clinical condition. Various methods to measure renin are used in different hospitals in Taiwan, and the ARR cutoff values also differ among laboratories. The Task Force of Taiwan PA recommend using plasma renin activity (PRA) to calculate ARR instead of direct renin concentration (DRC) unless PRA is unavailable, because PRA is widely used in international guidelines and most studies.

How should anti-hypertensive medications be adjusted before screening for primary aldosteronism?

Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding ß-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.

Differentiation of Alkyl- and Plasmenyl-phosphatidylcholine by Endogenous Sphingomyelin RT-XLOGP3 Regression for Coronary Artery Disease Plasma Lipidomics Analysis.

Accurate identification between alkyl- and plasmenyl-phosphatidylcholine (PC(O-) and PC(P-)) isomers is a major analytical challenge in lipidomics studies due to a lack of structure-specific ions in conventional tandem mass spectrometry (MS/MS) methods and the absence of universal retention time (RT) references. Given the importance of PC(O-) and PC(P-), an easy-to-apply method for current research is urgently needed. In this study, we present a quadratic RT-XLOGP3SM regression model that uses endogenous sphingomyelin (SM) species in blood samples as retention time (RT) indicators to predict the RTs of PC(O-) and PC(P-) species by coupling their calculated partition coefficients based on XLOGP3. The prediction results were obtained with a root-mean-square error (RMSE) of 0.12 min (1.3%) for the RRHD (rapid resolution high definition) nonlinear LC condition. A lipidomic analysis with RT-XLOGP3SM regression was used to study lipid regulation in coronary artery disease (CAD) outpatient plasma samples, and we found that the types of exhibited regulation were highly dependent on the lipid subclasses in comparison to the healthy control group. In conclusion, given that the quadratic RT-XLOGP3SM regression model predicts the RTs of PC species based on the relative value of XLOGP3 and the RTs of endogenous SM species, it can be expected that most of the C18-based lipidomics analyses could apply this method to increase the identification ability of the PC(O-) and PC(P-) subclasses and to improve the understanding of their physiological functions.

Effects of short-term oral anticoagulation following surgical bioprosthetic aortic valve replacement.

BACKGROUND: Short-term oral anticoagulation (OAC) is recommended for patients after surgical bioprosthetic aortic valve replacement (bAVR); however, the potential benefits remain controversial. This study evaluated the effects of short-term OAC following bAVR. METHODS: From 2010 to 2017, total 450 patients who underwent bAVR were enrolled. The outcomes of patients who did (OAC group) and who did not receive OAC (without-OAC group) after bAVR were compared. Propensity-score matching (PSM) was used to adjust for potential confounders, and a 1:1 matched cohort was formed. The main outcomes were all-cause mortality and bioprosthetic valve dysfunction (BVD). RESULTS: A total of 175 (39%) patients received OAC after bAVR. The median follow-up period was 2.9 years, the median duration of OAC use was 4 months; 162 pairs of patients were identified after the PSM. There was no significant difference in the prevalence of 1-year embolism/ischemic stroke between the OAC and without-OAC group in PSM cohort (0.62% vs. 1.89% for embolism, p = 0.623; 0 vs. 1.23% for ischemic stroke, p = 0.499). The prevalence of 1-year intracranial hemorrhage (ICH) between OAC and without-OAC group was also comparable (0.62% vs. 0.62%, p = 1). The OAC group had a lower all-cause mortality (adjusted hazard ratio (aHR):0.488, 95% confidence interval (CI): 0.259-0.919). There was also a trend for reduced BVD in the OAC group (aHR: 0.661, 95% CI: 0.339-1.290). CONCLUSION: Our study demonstrated that short-term OAC use after bAVR was associated with lower all-cause mortality. The prevalence of 1-year embolism/ischemic stroke/ICH were comparable despite of OAC use.

Impact of post-implantation time on bioresorbable vascular scaffold outcomes for type C versus non-type C coronary lesions: A longer-term study.

BACKGROUND: We have demonstrated that bioresorbable vascular scaffold (BVS) for ACC/AHA type C lesions was associated with higher risks of long-term target lesion revascularization (TLR) and target lesion failure (TLF). We determined the specific time after which higher risks of BVS for type C lesions are reduced in a longer-term follow-up. METHODS: We analyzed data of 457 patients (59 ± 12 years, 87% male) with 714 BVS implanted for 529 lesions and a median follow-up of 56.4 (48.6-62.6) months. Patients with BVS for at least one type C lesion (N = 177) at index intervention and all non-type C lesions (N = 280) were compared for TLF (cardiac death, target vessel myocardial infarction, TLR). We specified the interactions between the non-type C versus type C group and the event-free survival times dichotomized at 24, 30, 32, 33, 36, and 39 months respectively. RESULTS: The type C group had more multivessel disease (86% versus 65%, p < 0.001), left anterior descending artery treated (68% versus 53%, p = 0.002), intravascular imaging used (48% vs. 25%, p < 0.001), and BVS (2.3 ± 0.9 vs. 1.1 ± 0.3, p < 0.001) implanted with a longer total length (57 ± 21 vs. 29 ± 8 mm, p < 0.001). The TLR or TLF was higher (both log-rank p < 0.05) in the type C than in the non-type C group. However, the risks of TLR (hazard ratio: 3.6, 95% CI = 1.1-11.6) and TLF (hazard ratio: 3.8, 95% CI = 1.2-12.1) for type C lesions only remained higher until 24 months post-BVS implantation. CONCLUSION: BVS provides a longer-term advantage, particularly for type C lesions with the majority requiring long stenting.

On-Table Catheter-Based Neurosalvage Performed by Cardiologists for Embolic Complication during an Endovascular Procedure.

Objectives: To report our experience and clinical results of neurosalvage techniques, performed by interventional cardiologists without moving the patient, to manage cerebral thromboembolic complications. Background: Iatrogenic emboli may be released during an endovascular procedure, causing permanent neurological complications and catastrophic outcomes. Methods: Between July 2013 and December 2017, a total of eight patients suffered from embolic complications during endovascular procedures (two radiofrequency catheter ablation, five coronary angiogram/angioplasty, and one subclavian artery angioplasty). Catheter-based neurosalvage was attempted by experienced interventional cardiologists promptly in the same catheterization room. Results: The embolized locations were the M1 segment of the middle cerebral artery in four patients, the M2/M3 segments in three, and the basilar artery in one. Access to the supra-aortic vessels was achieved. Local intra-arterial thrombolysis was given in five patients (63%) and balloon angioplasty in three (38%). Intra-arterial thrombectomy with a stent retriever was attempted in three patients but failed in one. A combination of different techniques was used in three patients (38%). Final thrombolysis in cerebral infarction grade 3 flow was achieved in seven patients (88%). Favorable clinical outcomes at 1-month follow-up (modified Rankin scale of 0-2) were observed in seven patients (88%), and none of the patients had died at 12 months. Conclusions: Our experience demonstrated that acute embolic complications during an endovascular procedure can be salvaged by interventional cardiologists with acceptable angiographic and clinical results.

Renal Impact of Culprit-Only versus Multi-Vessel Revascularization for Cardiogenic Shock Complicating Acute Myocardial Infarction: Systematic Review and Meta-Analysis.

Background: The optimal strategy of percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) complicated with cardiogenic shock (CS) remains controversial. We aimed to elucidate the renal and cardiovascular impact of culprit-only (C) revascularization versus additional interventions on non-infarct-related arteries. Methods: PubMed, Embase, MEDLINE, and Cochrane Library were searched for relevant literature. A total of 96,812 subjects [C-PCI: 69,986; multi-vessel (MV)-PCI: 26,826] in nine studies (one randomized control trial; eight observational cohort studies) were enrolled. Results: MV-PCI was associated with a higher kidney event rate [relative risk (RR): 1.29, 95% confidence interval (CI): 1.12-1.49; p < 0.001]. However, the all-cause mortality rate was comparable both during admission (RR: 1.07, 95% CI: 0.94-1.22; p = 0.30) and at one year (RR: 0.96, 95% CI: 0.79-1.16; p = 0.65). MV-PCI was associated with a greater risk of stroke (RR: 1.19, 95% CI: 1.08-1.32; p < 0.001) and bleeding events (RR: 1.27, 95% CI: 1.07-1.51; p = 0.006), but reduced risk of recurrent MI (RR: 0.89, 95% CI: 0.82-0.97; p = 0.009) and repeat revascularization (RR: 0.34, 95% CI: 0.16-0.71; p = 0.004). No increased risk of coronary artery bypass grafting was present (RR: 1.09, 95% CI: 0.38-3.17; p = 0.87). Conclusions: C-PCI was associated with a lower rate of renal dysfunction but not all-cause mortality in patients with CS complicating acute MI.

Lesion impacts on long-term outcomes in patients implanted with bioresorbable vascular scaffold.

BACKGROUND: Bioresorbable vascular scaffold (BVS) had been implanted to several kinds of complex coronary lesions in real-world practice. We tested if long-term outcomes of BVS for complex lesions would be worse than that for relatively simple lesions. METHODS: We analyzed 457 patients (59 ± 12 years, 87% male) with 714 BVS implanted for their 529 lesions and median follow-up of 32.7 (26.8-39.3) months. Complex group (N = 284) was defined as those with BVS for acute coronary syndrome, chronic total occlusion, bifurcation/ostial lesions, instent restenosis/hybrid with metallic stents, diffuse lesions (overlapped by 2 BVS with each â‰§ 18 mm), venous graft/left main lesions, or lesions after rotablation. We compared their outcomes with the remaining 173 patients as non-complex group. RESULTS: The complex group had more chronic kidney disease (7% vs. 2%), multivessel disease (78% vs. 65%), use of intravascular imaging (40% vs. 23%), and more BVS (1.8 ± 0.9 vs. 1.1 ± 0.3) with longer total lengths (47 ± 22 vs. 29 ± 8 mm) implanted than non-complex group (all p < 0.05). However, the long-term target lesion revascularization (TLR) or target lesion failure (TLF) was similar (log rank p > 0.05) between the two groups. Multivariate Cox regression analyses showed BVS for ACC/AHA type C lesions was independently associated with higher risks of TLR (hazard ratio: 2.7, 95% CI = 1.1-6.6) and TLF (hazard ratio: 2.6, 95% CI = 1.1-6.3). CONCLUSION: Comparable outcomes were found between BVS for complex and non-complex lesion category. However, higher risks of TLR and TLF for type C lesions still suggested the prognostic impact of lesion complexity on long-term outcomes of BVS.

2022 Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the Management of Hypertension.

Hypertension is the most important modifiable cause of cardiovascular (CV) disease and all-cause mortality worldwide. Despite the positive correlations between blood pressure (BP) levels and later CV events since BP levels as low as 100/60 mmHg have been reported in numerous epidemiological studies, the diagnostic criteria of hypertension and BP thresholds and targets of antihypertensive therapy have largely remained at the level of 140/90 mmHg in the past 30 years. The publication of both the SPRINT and STEP trials (comprising > 8,500 Caucasian/African and Chinese participants, respectively) provided evidence to shake this 140/90 mmHg dogma. Another dogma regarding hypertension management is the dependence on office (or clinic) BP measurements. Although standardized office BP measurements have been widely recommended and adopted in large-scale CV outcome trials, the practice of office BP measurements has never been ideal in real-world practice. Home BP monitoring (HBPM) is easy to perform, more likely to be free of environmental and/or emotional stress, feasible to document long-term BP variations, of good reproducibility and reliability, and more correlated with hypertension-mediated organ damage (HMOD) and CV events, compared to routine office BP measurements. In the 2022 Taiwan Hypertension Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS), we break these two dogmas by recommending the definition of hypertension as ≥ 130/80 mmHg and a universal BP target of < 130/80 mmHg, based on standardized HBPM obtained according to the 722 protocol. The 722 protocol refers to duplicate BP readings taken per occasion ("2"), twice daily ("2"), over seven consecutive days ("7"). To facilitate implementation of the guidelines, a series of flowcharts encompassing assessment, adjustment, and HBPM-guided hypertension management are provided. Other key messages include that: 1) lifestyle modification, summarized as the mnemonic S-ABCDE, should be applied to people with elevated BP and hypertensive patients to reduce life-time BP burden; 2) all 5 major antihypertensive drugs (angiotensin-converting enzyme inhibitors [A], angiotensin receptor blockers [A], ß-blockers [B], calcium-channel blockers [C], and thiazide diuretics [D]) are recommended as first-line antihypertensive drugs; 3) initial combination therapy, preferably in a single-pill combination, is recommended for patients with BP ≥ 20/10 mmHg above targets; 4) a target hierarchy (HBPM-HMOD- ambulatory BP monitoring [ABPM]) should be considered to optimize hypertension management, which indicates reaching the HBPM target first and then keeping HMOD stable or regressed, otherwise ABPM can be arranged to guide treatment adjustment; and 5) renal denervation can be considered as an alternative BP-lowering strategy after careful clinical and imaging evaluation.

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.

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, 13C6-3NPH-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.

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

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.

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

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.

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

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.

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

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.

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

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.