The Asia-Pacific Society of Cardiology (APSC) high-sensitivity troponin T (hs-TnT) consensus recommendations and rapid algorithm were developed to provide guidance for healthcare professionals in the Asia-Pacific region on assessing patients with suspected acute coronary syndrome (ACS) using a hs-TnT assay. Experts from Asia-Pacific convened in 2 meetings to develop evidence-based consensus recommendations and an algorithm for appropriate use of the hs-TnT assay. The Expert Committee defined a cardiac troponin assay as a high-sensitivity assay if the total imprecision is ≤10% at the 99th percentile of the upper reference limit and measurable concentrations below the 99th percentile are attainable with an assay at a concentration value above the assay’s limit of detection for at least 50% of healthy individuals. Recommendations for single-measurement rule-out/rule-in cutoff values, as well as for serial measurements, were also developed. The Expert Committee also adopted similar hs-TnT cutoff values for men and women, recommended serial hs-TnT measurements for special populations, and provided guidance on the use of point-of-care troponin T devices in individuals suspected of ACS. These recommendations should be used in conjunction with all available clinical evidence when making the diagnosis of ACS.
Network medicine can advance current medical practice by arising as response to the limitations of a reductionist approach focusing on cardiovascular (CV) diseases as a direct consequence of a single defect. This molecular-bioinformatic approach integrates heterogeneous “omics” data and artificial intelligence to identify a chain of perturbations involving key components of multiple molecular networks that are closely related in the human interactome. The clinical view of the network-based approach is greatly supported by the general law of molecular interconnection governing all biological complex systems. Recent advances in bioinformatics have culminated in numerous quantitative platforms able to identify CV disease modules underlying perturbations of the interactome. This might provide novel insights in CV disease mechanisms as well as putative biomarkers and drug targets. We describe the network-based principles and discuss their application to classifying and treating common CV diseases. We compare the strengths and weaknesses of molecular networks in comparison with the classical current reductionist approach, and remark on the necessity for a two-way approach connecting network medicine with large clinical trials to concretely translate novel insights from bench to bedside.
Background:Evaluate the safety and efficacy of guideline-recommended risk score-directed dual antiplatelet therapy (GD-DAPT) based on THE PRECISE-DAPT score after 2nd-generation drug-eluting stent (DES) implantation.
Methods and Results:We analyzed 5,131 patients pooled from 4 clinical trials. Patients were divided into 3 groups according to current recommendations on the duration of DAPT and their actual DAPT duration: GD-DAPT (n=2,183), shorter DAPT (n=1,540), longer DAPT (n=1,408). The primary endpoint was the rate of net adverse clinical events (NACE) during the first 12 months. The secondary endpoints were ischemic or bleeding events. Overall, GD-DAPT did not affect NACE (1.2% vs. 1.2% for shorter DAPT and 1.7% for longer DAPT) or bleeding events (0.6% vs. 0.5% and 0.9%), and there were fewer ischemic events (2.8% vs. 4.4% and 4.0%, P=0.03) than with shorter DAPT. Especially in acute coronary syndrome (ACS) patients, GD-DAPT had fewer NACE (1.5% vs. 1.4% and 4.2%; P=0.006) and bleeding events (0.8% vs. 0.5% and 2.8%; P=0.001) than longer DAPT as well as fewer ischemic events (2.8% vs. 4.4% and 4.7%; P=0.03) than shorter DAPT.
Conclusions:GD-DAPT did not affect NACE or bleeding events and reduced the number of ischemic events at 12 months compared with shorter DAPT. For ACS, GD-DAPT was associated with favorable outcomes compared with non-GD-DAPT. Therefore, GD-DAPT may optimize efficacy and safety.
Background:Stent thrombosis (ST) remains a severe complication following stent implantation. We previously reported the risk factors for ST after 2nd-generation drug-eluting stent (DES) in the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation DES Implantation) registry.
Methods and Results:In this subanalysis, we aimed to reveal the difference in ST between right coronary (RCA) and left (LCA) coronary arteries. A total of 307 patients with ST were divided into the RCA-ST group (n=93) and the LCA-ST group (n=214). Multivariate analysis revealed younger age (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.93–0.99, P=0.01), ostial lesion at the time of index percutaneous coronary intervention (OR 4.37, 95% CI 1.43–13.33, P=0.01), bifurcation lesion at the time of index PCI (OR 0.05, 95% CI 0.02–0.12, P<0.01), chronic total occlusion (CTO) lesion at the time of index PCI indication (OR 4.19, 95% CI 1.05–16.71, P=0.04), and use of prasugrel at the time of ST (OR 7.30, 95% CI 1.44–36.97, P=0.02) were significantly associated with RCA-ST.
Conclusions:Younger age, ostial or CTO lesion, and use of prasugrel at the time of ST were prominent factors in RCA-ST, whereas bifurcation lesion was associated with LCA-ST. We should pay attention to the differences between RCA-ST and LCA-ST to prevent ST.
Background:The risks of ventricular fibrillation (Vfib) associated with frequency-domain optical coherence tomography (OCT)/optical frequency domain imaging (OFDI) remain undetermined.
Methods and Results:We retrospectively studied the occurrence of Vfib during OCT/OFDI for unselected indications. The frequency of Vfib and patient and procedural characteristics were investigated. A total of 4,467 OCT/OFDI pullback examinations were performed in 1,754 patients (median of 2.0 [2.0–3.0] pullbacks for 1.0 [1.0–1.3] vessels). OCT/OFDI was performed during PCI in 899 patients (51.3%). The contrast injection volume per pullback was 14.4 (11.7–17.2) mL with a flow rate of 3.4 (3.2–3.5) mL/s. Vfib occurred in 31 pullbacks (0.69%) in 30 patients (1.7%). No cases of Vfib occurred when using low-molecular-weight dextran. On multivariate analysis, contrast volume was the only independent factor for predicting Vfib (odds ratio, 1.080; 95% confidence interval, 1.008–1.158, P=0.029). The best cutoff value of contrast volume for predicting Vfib was 19.2 mL (area under the curve, 0.713, P<0.001; diagnostic accuracy, 87.1%).
Conclusions:The present large, single-center registry study indicated that Vfib during OCT/OFDI was rare for unselected indications. Contrast injection volume used to displace blood should be limited to avoid Vfib.
Background:Previous studies have shown that pulsed electromagnetic fields (PEMF) stimulate angiogenesis and may be a potential treatment strategy to improve cardiac function after myocardial infarction (MI). This study explored the effects and its related mechanisms of PEMF in MI mice.
Methods and Results:MI mice were used in PEMF treatment (15 Hz 1.5 mT PEMF or 30 Hz 3.0 mT PEMF) for 45 min per day for 2 weeks. Furthermore, an in vivo Matrigel plug assay was used to observe the effect of PEMF in promoting angiogenesis. Compared with the sham PEMF group, PEMF treatment with 30 Hz 3.0 mT significantly improved heart function. PEMF treatment with 15 Hz 1.5 mT and 30 Hz 3.0 mT both increased capillary density, decreased infarction area size, increased the protein expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), Ser473-phosphorylated Akt (pSer473-Akt) and S1177-phosphorylated endothelial nitric oxide synthase (pS1177-eNOS), and increased the mRNA level of VEGF and hypoxia inducible factor 1-alpha (HIF-1α) in the infarct border zone. Additionally, treatment with 30 Hz 3.0 mT also increased protein and mRNA level of fibroblast growth factor 2 (FGF2), and protein level of β1 integrin, and shows a stronger therapeutic effect.
Conclusions:PEMF treatment could promote angiogenesis of the infarct border zone and improve cardiac function in MI mice. A treatment parameter of 30 Hz 3.0 mT is remarkably effective in MI mice. The effect is associated with the proangiogenic signaling pathways of HIF-1α/VEGF/Akt/eNOS or HIF-1α/FGF2/Akt/eNOS.
Background:Countermeasure development for early rehospitalization for heart failure (re-HHF) is an urgent and important issue in Western countries and Japan.
Methods and Results:Of 1,074 consecutive NARA-HF study participants with acute decompensated HF admitted to hospital as an emergency between January 2007 and December 2016, we excluded 291 without follow-up data, who died in hospital, or who had previous HF-related hospitalizations, leaving 783 in the analysis. During the median follow-up period of 895 days, 241 patients were re-admitted for HF. The incidence of re-HHF was the highest within the first 30 days of discharge (3.3% [26 patients]) and remained high until 90 days, after which it decreased sharply. Within 90 days of discharge, 63 (8.0%) patients were re-admitted. Kaplan-Meier analysis revealed that patients with 90-day re-HHF had worse prognoses than those without 90-day re-HHF in terms of all-cause death (hazard ratio [HR] 2.321, 95% confidence interval [CI] 1.654–3.174; P<0.001) and cardiovascular death (HR 3.396, 95% CI 2.153–5.145; P<0.001). Multivariate analysis indicated that only male sex was an independent predictor of 90-day re-HHF.
Conclusions:The incidence of early re-HHF was lower in Japan than in Western countries. Its predictors are not related to the clinical factors of HF, indicating that a new comprehensive approach might be needed to prevent early re-HHF.
Background:Although full-volume quantification of epicardial adipose tissue (EAT) is a predictor of LV diastolic dysfunction (LVDD), how localized EAT depots are linked to LVDD remains unclear. We evaluated the effect of local EAT depots on LV diastolic function parameters in patients with preserved LV ejection fraction (LVEF).
Methods and Results:From 423 consecutive patients who underwent cardiac CT angiography, we recruited 252 with sinus rhythm and normal LVEF. The EAT volume index (EATV/body surface area) and the localized EAT thickness around the right coronary artery (EATRCA), left anterior descending artery (EATLAD), left circumflex artery (EATLCX), right ventricle (EATRV), left ventricle (EATLV), right atrium (EATRA), and left atrium (EATLA) were measured using cardiac CT. In the LVDD group (n=71), the EATV index (75±30 vs. 64±28 mL/m2, P=0.010), EATLCX(10.7±3.8 vs. 9.4±3.4 mm, P=0.008), and EATLV(2.6±1.6 vs. 2.1±1.4 mm, P=0.024) were greater than in the non-LVDD group (n=181). In contrast, EATLCXand EATLVwere markedly associated with decreased lateral e’ and increased lateral E/e’. Multiple regression analysis indicated that EATLCXand EATLVwere strongly associated with LV diastolic function parameters.
Conclusions:Localized EAT depots are linked to altered mitral annular motion. Further study is warranted to clarify whether localized EAT depots are functionally linked to the clinical manifestations of LVDD.
Background:Midkine (MK), a heparin-binding protein, participates in multiple cellular processes, such as immunity, cellular growth and apoptosis. Overwhelming evidence indicates that MK plays an important role in various pathological processes, including chronic inflammation, autoimmunity, cancer, and infection. Recent studies demonstrated that MK may be involved in the development of atherosclerosis, yet the mechanism has not been fully explored. Therefore, this study aims to investigate the effect and mechanism of MK on macrophage cholesterol efflux.
Methods and Results:Using Oil Red O staining, NBD-cholesterol fluorescence labeling and enzymatic methods, it observed that MK markedly promoted macrophage lipid accumulation. Liquid scintillation counting (LSC) showed that MK decreased cholesterol efflux. Moreover, cell immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) showed that MK downregulated ATP-binding membrane cassette transport protein A1 (ABCA1) expression. Functional promotion of ABCA1 expression attenuated the inhibitory effects of MK on cholesterol efflux, which reduced lipid accumulation. Additionally, intervention of adenosine monophosphate activated protein (AMPK)-mammalian target of rapamycin (mTOR) signaling molecule by the AMPK activator, AICAR, increased p-AMPK and ABCA1 expression, decreased p-mTOR expression and promoted cholesterol efflux, resulting in an obvious reduction in intracellular lipid content.
Conclusions:These data suggest that MK reduces the expression of ABCA1, inhibits the efflux of cholesterol and promotes the accumulation of lipids in RAW264.7 macrophages, and AMPK-mTOR signaling is involved in MK-mediated regulation of cholesterol metabolism in RAW264.7 macrophages.
Background:Left ventricular non-compaction (LVNC) is a cardiomyopathy characterized by prominent trabeculae and intertrabecular recesses. We present the cases of 3 girls with the sameryanodine receptor type 2(RYR2) mutation who had phenotypes of both catecholaminergic polymorphic ventricular tachycardia (CPVT) and LVNC .
Methods and Results:Clinical characteristics and genetic background of the 3 patients were analyzed retrospectively. Age at onset was 5, 6, and 7 years, respectively. Clinical presentation included syncope during exercise in all 3 patients and cardiac arrest in 2 patients. LVNC diagnosis was confirmed on echocardiography according to previously defined criteria. Exercise stress testing provoked ventricular arrhythmia in two of the patients. Beta-blockers (n=3) and flecainide (n=2) were given, and an implantable cardioverter defibrillator was used in 1 patient. Genotyping identified the sameRYR2-R169Q missense mutation and no other CPVT- or LVNC-related gene mutations. Functional analysis of the mutation using HEK293 cells with single-cell Ca2+imaging and [3H]ryanodine binding analysis, indicated a gain of function: a reduced threshold for overload-induced Ca2+release from the sarcoplasmic reticulum and increased fractional Ca2+release.
Conclusions:The rare association of LVNC and CPVT phenotypes withRYR2mutations is less likely to be coincidental. Screening for life-threatening arrhythmias using exercise or pharmacologic stress tests is recommended in LVNC patients to prevent sudden cardiac death in those with preserved LV function.
Background:Right ventricular (RV) volumetric and functional assessments are both crucial for the management of patients with hypoplastic left heart syndrome (HLHS). 3-dimensional echocardiography (3DE) for volume measurements and 2D speckle-tracking echocardiography (2D-STE) for strain analysis are performed separately. 3D-STE is capable of evaluating those parameters simultaneously and providing principal strain (PS), unifying the concepts of myofiber orientation and contraction into a single, maximal contractile direction. However, the application of 3D-STE to HLHS has not been studied and so became the aim of our study.
Methods and Results:64 HLHS patients after Fontan palliation underwent 3D-STE analysis measuring RV end-diastolic volume index (EDVi), ejection fraction (EF), global PS (GPS), global circumferential strain (GCS), and global longitudinal strain (GLS). Volume measurements were compared between 3D-STE and 3DE, and strains were compared between 3D- and 2D-STE. EDVi and EF showed strong correlations between 3D-STE and 3DE (r=0.93 and 0.87, respectively). GCS and GLS showed moderate correlations between 3D- and 2D-STE (r=0.65 and 0.61, respectively). GPS showed highest magnitude and excellent correlation with EF (r=−0.95).
Conclusions:Simultaneous volumetric and functional assessment by 3D-STE was a useful method in this HLHS cohort. PS is a promising parameter for evaluating the RV function of HLHS, which could be useful during longitudinal follow-up.
Background:The waiting period for lung transplantation (LT) is approximately 3 years in Japan. The prognosis of patients with pulmonary arterial hypertension (PAH) awaiting LT is poor without LT. Patients at the present center often survive in the long term after registration for LT. The aim of this study was to elucidate why some patients survive in the long term by investigating changes in pulmonary artery pressure (PAP) after registration, and medication used.
Methods and Results:This study involved 57 patients with PAH who were enrolled in a registry for LT at Okayama University Hospital. We divided patients into 3 groups according to outcome: LT (n=27); death without LT (n=21); and survival without LT (n=9). The median interval from PAH diagnosis to epoprostenol treatment was shorter in the survival group (58 days) than in the LT group (378 days) and death group (545 days). Eight patients in the survival group, 13 in the LT group, and 13 in the death group underwent right heart catheterization after registration. Percent change in mean PAP after registration was significantly greater in the survival group (−32%) than in the LT group (−13%) and death group (1%; P<0.01).
Conclusions:Even after LT registration, patients who received epoprostenol infusion soon after diagnosis of PAH often had marked reduction in PAP and long-term survival without LT.
Background:This study aimed to evaluate the effect of the initial aortic valve replacement (AVR) strategy relative to a conservative strategy on long-term outcomes stratified by age among asymptomatic patients with severe aortic stenosis (AS).
Methods and Results:Among 1,808 asymptomatic severe AS patients in the CURRENT AS registry, there were 1,166 patients aged ≥75 years (initial AVR: n=124, and conservative: n=1,042), and 642 patients with age <75 years (initial AVR: n=167, and conservative: n=475). Median follow-up interval was 1,280 (interquartile range [IQR]: 1,012–1,611) days, and 1461 (IQR: 1,132–1,886) days in patients aged ≥ and <75 years, respectively. The favorable effect of the initial AVR strategy relative to conservative strategy for heart failure (HF) hospitalization was seen regardless of the age stratum (≥75 years: adjusted hazard ratio [HR] 0.13, 95% confidence interval [CI] 0.05–0.34, and <75 years: HR 0.37, 95% CI 0.14–0.99, interaction P=0.35). However, the lower mortality risk of the initial AVR strategy relative to conservative strategy was significant in patients aged ≥75 years, but not in patients <75 years, with significant interaction (HR 0.35, 95% CI 0.20–0.61, and HR 0.69, 95% CI 0.41–1.16, interaction P=0.016).
Conclusions:The benefit of initial AVR in reducing HF hospitalization in asymptomatic patients with severe AS was consistently seen regardless of age. The magnitude of mortality benefit of initial AVR was greater in super-elder patients than in non-super-elder patients.
Background:Few studies with a large sample size have been performed to evaluate the incidence, risk factors and prognostic value of new-onset atrial fibrillation (AF) in patients with infective endocarditis (IE).
Methods and Results:A total of 1,063 IE patients were included and 83 developed new AF. Compared with no-AF, the incidence of in-hospital death (6.0% vs. 22.9%, P<0.001) was higher in patients with new-onset AF. New-onset AF was independently associated with increased risk of in-hospital (adjusted odds ratio [OR]=3.92, P=0.001) and 1-year death (adjusted hazard ratio=2.91, P=0.001), while prior AF was not an independent factor. Kaplan-Meier curve analysis demonstrated new-onset AF mainly affected short-term death (180 days). Age (OR=1.04, P<0.001), rheumatic heart disease (OR=1.88, P=0.022), NYHA Class III or IV (OR=2.09, P=0.003), and left atrial diameter (LAD; OR=1.05, P=0.006) were independent risk factors for development of new AF.
Conclusions:New-onset AF, not prior AF, was a prognostic factor in IE patients, which was mainly associated with increased risk of short-term death. Patients with concomitant rheumatic heart disease, poor cardiac function, and larger LAD had higher risk of developing new AF.
Background:Cardiac conduction disturbance (CD) is the most frequent complication following transcatheter aortic valve replacement (TAVR). This study examined whether the anatomy of the membranous septum (MS) could provide useful information about the risk of CD following TAVR with a balloon-expandable valve (BEV).
Methods and Results:Among 132 consecutive patients, 106 (mean age, 85.6±5.1 years; 75 females) were included in the study. Using preoperative CT and angiography, MS length and implantation depth (ID) were assessed. The MS length minus the prosthesis ID was calculated (∆MSID). Correlation between CD, defined as new-onset left-bundle branch block (LBBB) or the need for permanent pacemaker (PPM) within 1 week after the procedure, and MS length were evaluated. A total of 19 patients (18%) developed CD following TAVR. MS length was significantly shorter in these patients than in those without CD (5.3±1.3 vs. 6.6±1.4; P<0.001), and was the important predictor of CD (odds ratio [OR]: 0.43, 95% confidence interval [CI]: 0.27–0.69, P<0.001). When considering the pre- and postprocedural parameters, the ∆MSID was smaller in patients with CD (−1.7±1.5 vs. 0.8±1.9, P<0.001), and emerged as the important predictor of CD (OR: 0.47, 95% CI: 0.33–0.69, P<0.001).
Conclusions:Short MS is associated with an increased risk of CD after TAVR with BEV.
Background:Given the rapid expansion in the use of transcatheter aortic valve implantation (TAVI), recent outcomes of surgical aortic valve replacement (SAVR) should be re-evaluated.
Methods and Results:Using the data from the Japan Cardiovascular Surgery Database of 160 enrolled hospitals, trends in elective isolated SAVR were evaluated until the introduction of TAVI in Japan. Trend analyses were performed over 4 periods: period 1, 2008–2009 (4,415 cases); period 2, 2010–2011 (4,861 cases); period 3, 2012–2013 (5,674 cases); and period 4, 2014–2015 (5,563 cases). Baseline risk, evaluated on JapanSCORE, increased significantly over the 4 periods, from a median of 1.56 (IQR, 0.99–2.61) in period 1 to 2.08 (IQR, 1.33–3.96) in period 4 (P<0.001, trend test). Despite the increased risk, the composite major complication and operative mortality rate decreased significantly (10.7% in period 1 to 9.2% in period 4, P=0.01). Using a risk-adjusted model, the OR of operative mortality was 1.61 (95% CI: 1.29–2.02) in period 1 (P<0.0001) compared with period 4. An increase in the use of bioprostheses was also observed, from 60.4% to 76.8% (P<0.001) over the 4 periods.
Conclusions:Even in a short 8-year period, SAVR outcomes improved in Japan. This should be taken into account when discussing the indications for aortic valve intervention.
Background:In Asia, little information is available about contemporary real-world treatment patterns for venous thromboembolism (VTE).
Methods and Results:Consecutive patients (n=11,414) from the Taiwan National Health Insurance Research Database with initial VTE and taking oral anticoagulants between May 1, 2014 and June 30, 2016 were included. The temporal trends of using oral anticoagulants and pharmacomechanical therapy during the study period were evaluated. The efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) vs. warfarin were compared. Propensity score analysis (NOACs n=3,647 vs. warfarin n=3,647) was used to balance covariates between groups, and Cox proportional hazards models with adjustment were used to estimate the risks of clinical outcomes. The use of NOACs increased from 0.3% to 60.2% for VTE treatment during the study period. Pharmacomechanical therapy was used in 9.60%, 8.22%, and 5.63% from 2014 through 2016. NOACs were associated with a 16% risk reduction (adjusted hazard ratio [aHR] 0.84, 95% confidence interval [CI] 0.77–0.93) in all-cause mortality and a 21% risk reduction (aHR 0.79, 95% CI 0.65–0.96) in recurrent VTE vs. warfarin. Overall, NOACs were associated with a lower risk of major bleeding compared with warfarin (aHR 0.804, 95% CI 0.648–0.998).
Conclusions:In real-world practice, NOACs have become the major anticoagulant used for Asians with VTE. Although NOACs had a lower risk of recurrent VTE and major bleeding compared with warfarin in Taiwan, we still need a large-scale randomized controlled trial to confirm the findings.