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We evaluated the clinical outcomes of prosthetic valve endocarditis in 2 major tertiary referral centers in Hong Kong. The study population comprised 80 consecutive Chinese patients who fulfilled the modified Duke criteria for prosthetic valve endocarditis from March 2000 to June 2007. The major clinical endpoints analyzed were hospital mortality, need for valve surgery, and relapse of prosthetic endocarditis. The mean age at presentation was 56 ± 13 years, with a slight male preponderance. There were 76 (95%) patients with involvement of a mechanical prosthesis; the majority (69%) had late prosthetic endocarditis. Major hospital complications occurred in 49 (61%) patients. The overall hospital mortality was 28% (22 patients). Thirty-four (42%) patients required valve surgery during index hospitalization, of whom 5 (15%) died due to uncontrolled sepsis. Factors associated with hospital mortality were older age at presentation, Staphylococcus aureus infection, embolic events, severe heart failure, valve surgery, and any major complication. On multivariate analysis, severe heart failure was the only independent predictor of hospital death. Among the 58 hospital survivors followed up for a mean of 48 ± 31 months, 6 (10%) developed late complications related to prosthetic valve endocarditis, with 5 documented cases of relapse. [ABSTRACT FROM PUBLISHER]

Level of Evidence: 1 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Abstract: Transradial cardiac catheterization and percutaneous coronary intervention are increasingly being performed worldwide in elective and emergency procedures, with many centers adopting the transradial route as their first choice of arterial access. One of the most common complications encountered during transradial procedures is radial artery spasm. This article reviews the current literature on the incidence, predisposing factors, preventive, and treatment measures for radial artery spasm. [Copyright &y& Elsevier]

Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70–0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55–0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66–0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68–0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57–0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40–0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48–0.86). This were consistent for left ventricular ejection fraction < 50% or ≥ 50%. In conclusion, in AMI managed with revascularization, both BB and ACEI/ARB were associated with a lower incidence of 12-month all-cause mortality. Combined BB and ACEI/ARB was associated with the lowest incidence of all-cause mortality and HF hospitalization. [ABSTRACT FROM AUTHOR]

A letters to the editor is presented in response to the article related to emergence of drug-coated balloon (DCB) as a viable therapeutic option for treating coronary artery disease (CAD) as the drug-eluting stent (DES) and also mentions authors response on the letter.

The article presents a case study of a 76-year-old male suffering from resistant hypertension treated with percutaneous renal denervation therapy.

The SYNTAX score is clinically validated to stratify number of lesions and pattern of CAD. A better understanding of the underlying molecular mechanisms influencing the pattern and complexity of coronary arteries lesions among CAD patients is needed. Human arterial biopsies from 49 patients (16 low-SYNTAX-score (LSS, <23), 16 intermediate-SYNTAX-score (ISS, 23 to 32) and 17 high-SYNTAX-score (HSS, >32)) were evaluated using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray. The data were validated by Next-Generation Sequencing (NGS). Primary VSMC from patients with low and high SYNTAX scores were isolated and compared using immunohistochemistry, qPCR and immunoblotting to confirm mRNA and proteomic results. The IL1B was verified as the top upstream regulator of 47 inflammatory DEGs in LSS patients and validated by another sets of patient samples using NGS analysis. The upregulated expression of IL1B was translated to increased level of IL1β protein in the LSS tissue based on immunohistochemical quantitative analysis. Plausibility of idea that IL1B in the arterial wall could be originated from VSMC was checked by exposing culture to proinflammatory conditions where IL1B came out as the top DEG (logFC = 7.083, FDR = 1.38 × 10−114). The LSS patient-derived primary VSMCs confirmed higher levels of IL1B mRNA and protein. LSS patients could represent a group of patients where IL1B could play a substantial role in disease pathogenesis. The LSS group could represent a plausible cohort of patients for whom anti-inflammatory therapy could be considered. [Display omitted] • IL1B expression in the arterial wall correlates with the low-SYNTAX-score (LSS) pattern of coronary artery disease. • IL1B was verified as the top upstream regulator in LSS samples, directly connected with 47 inflammatory differentially expressed genes (DEGs). • IL1B was the top DEG under proinflammatory conditions in vascular smooth muscle cell (VSMC) culture. • LSS patient-derived VSMCs showed higher levels of IL1B at the mRNA and protein levels compare to high-SYNTAX score. • LSS patients with elevated levels of IL1B represent a specific group where inflammation could play a substantial role in disease pathogenesis. [ABSTRACT FROM AUTHOR]

The authors discuss the use of drug-coated balloons (DCBs) as a therapeutic option in the treatment of small coronary vessels. Of particular interest is given to the BASKET-SMALL 2 study published in "The Lancet" by Raban V. Jeger and colleagues, which suggested that paclitaxel and iopromide-coated DCB were non-inferior to second-generation drug-eluting stent. The use of DCB beyond in-stent restenosis is suggested.

Objectives The purpose of this study was to examine the angiographic and clinical results of stent full metal jacket in treating long lesions using everolimus-eluting stents (EES). Background Data are lacking regarding the use of EES for this lesion subgroup. Methods From 2007 to 2011, 77 symptomatic patients who had severe coronary stenoses necessitating implantation of stents with total length longer than 60 mm were treated with overlapping EES. Results The mean age of patient was 61 ± 11 years with male predominance (66%). Diabetes mellitus was seen in 35 (45.5%) patients. Majority of patients had class III angina with normal heart function. On average, 3.1 stents were implanted per lesion; the mean stent size and length were 2.70 ± 0.28 mm and 82 ± 16 mm. Restudy angiography was performed on 71 patients (72 lesions) at 8.9 ± 2.5 months. Angiographic restenosis was seen in 9 (12.5%) lesions; the lesion length and late loss were 67 ± 15 mm and 0.4 ± 0.6 mm, respectively. The use of intravascular ultrasound has been found to be a predictor of less restenosis (P = 0.02; HR: 0.02; CI: 0.01-0.59). The in-hospital and 1 year major adverse cardiac event rates were 7.8% and 13%. The annual cardiac death rates were 2.6%, 3.4%, and 5.3% in the first 3 years. Conclusions The use of EES full metal jacket for long lesions is only associated with good short-term clinical and angiographic outcomes. Long-term follow-up has revealed a high cardiac death rate which may necessitate prolongation of dual antiplatelet therapy. (J Interven Cardiol 2013;26:22-28) [ABSTRACT FROM AUTHOR]

MADIT II Criteria for Implantable Cardioverter. Background: MADIT-II demonstrated that prophylactic implantation of an implantable cardioverter-defibrillator (ICD) device prevents sudden cardiac death (SCD) in patients with myocardial infarction (MI) and impaired left ventricular ejection fraction (LVEF). It remains unclear whether the MADIT-II criteria for ICD implantation are appropriate for Chinese patients. Methods and Results: We compared the clinical characteristics and outcome for a cohort of consecutive Chinese patients who satisfied MADIT-II criteria for ICD implantation with the original published MADIT-II population. Seventy consecutive patients who satisfied MADIT-II criteria but did not undergo ICD implantation (age: 67 years, male: 77%) were studied. Their baseline demographics were comparable with the original MADIT-II cohort with the exception of a higher incidence of diabetes mellitus. After follow-up of 35 months, most deaths (78%) were due to cardiac causes (72% due to SCD). The 2-year SCD rate (10.0%) was comparable with that of the MADIT-II conventional group (12.1%), but higher than the MADIT-II defibrillator group (4.9%). Similarly, the 2-year non-SCD rate was 3.0%, also comparable with the MADIT-II conventional group (4.6%), but lower than the MADIT-II defibrillator group (7.0%). Cox regression analysis revealed that advance NYHA function class (Hazard Ratio [HR]: 3.5, 95% Confidence Interval [CI]: 1.48–8.24, P = 0.004) and the lack of statin therapy (HR: 3.7, 95%CI: 1.35–10.17, P = 0.011) were independent predictors for mortality in the MADIT-II eligible patients. Conclusion: Chinese patients who satisfy MADIT-II criteria for ICD implantation are at similar risk of SCD and non-SCD as the original MADIT-II subjects. Implantation of an ICD in Chinese patients is appropriate. [ABSTRACT FROM AUTHOR]

Aging is the primary risk factor for cardiovascular disease (CVD), but the mechanisms underlying age-linked atherosclerosis remain unclear. We previously observed that long-lived vascular matrix proteins can acquire 'gain-of-function' isoDGR motifs that might play a role in atherosclerotic pathology. IsoDGR-specific mAb were generated and used for ELISA-based measurement of motif levels in plasma samples from patients with coronary artery diseases (CAD) and non-CAD controls. Functional consequences of isoDGR accumulation in age-damaged fibronectin were determined by bioassay for capacity to activate monocytes, macrophages, and endothelial cells (signalling activity, pro-inflammatory cytokine expression, and recruitment/adhesion potential). Mice deficient in the isoDGR repair enzyme PCMT1 were used to assess motif distribution and macrophage localisation in vivo. IsoDGR-modified fibronectin and fibrinogen levels in patient plasma were significantly enhanced in CAD and further associated with smoking status. Functional assays demonstrated that isoDGR-modified fibronectin activated both monocytes and macrophages via integrin receptor 'outside in' signalling, triggering an ERK:AP-1 cascade and expression of pro-inflammatory cytokines MCP-1 and TNFα to drive additional recruitment of circulating leukocytes. IsoDGR-modified fibronectin also induced endothelial cell expression of integrin β1 to further enhance cellular adhesion and matrix deposition. Analysis of murine aortic tissues confirmed accumulation of isoDGR-modified proteins co-localised with CD68+ macrophages in vivo. Age-damaged fibronectin features isoDGR motifs that increase binding to integrins on the surface of monocytes, macrophages, and endothelial cells. Subsequent activation of 'outside-in' signalling elicits a range of potent cytokines and chemokines that drive additional leukocyte recruitment to the developing atherosclerotic matrix. [Display omitted] • IsoDGR-modified plasma proteins are associated with coronary artery diseases (CAD). • IsoDGR:integrin binding on leukocytes and endothelium induces outside-in signalling, and monocyte and endothelium activation. • IsoDGR-modified fibronectin may initiate vascular inflammation in atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular magnetic resonance (CMR) sequences are commonly used to obtain a complete description of the function and structure of the heart, provided that accurate measurements are extracted from images. New methods of extraction of information are being developed, among them, deep neural networks are powerful tools that showed the ability to perform fast and accurate segmentation. Iq1n order to reduce the time spent by reading physicians to process data and minimize intra- and inter-observer variability, we propose a fully automatic multi-scan CMR image analysis pipeline. Methods: Sequence specific U-Net 2D models were trained to perform the segmentation of the left ventricle (LV), right ventricle (RV) and aorta in cine short-axis, late gadolinium enhancement (LGE), native T1 map, post-contrast T1, native T2 map and aortic flow sequences depending on the need. The models were trained and tested on a set of data manually segmented by experts using semi-automatic and manual tools. A set of parameters were computed from the resulting segmentations such as the left ventricular and right ventricular ejection fraction (EF), LGE scar percentage, the mean T1, T1 post, T2 values within the myocardium, and aortic flow. The Dice similarity coefficient, Hausdorff distance, mean surface distance, and Pearson correlation coefficient R were used to assess and compare the results of the U-Net based pipeline with intra-observer variability. Additionally, the pipeline was validated on two clinical studies. Results: The sequence specific U-Net 2D models trained achieved fast (≤ 0.2 s/image on GPU) and precise segmentation over all the targeted region of interest with high Dice scores (= 0.91 for LV, = 0.92 for RV, = 0.93 for Aorta in average) comparable to intra-observer Dice scores (= 0.86 for LV, = 0.87 for RV, = 0.95 for aorta flow in average). The automatically and manually computed parameters were highly correlated (R = 0.91 in average) showing results superior to the intra-observer variability (R = 0.85 in average) for every sequence presented here. Conclusion: The proposed pipeline allows for fast and robust analysis of large CMR studies while guaranteeing reproducibility, hence potentially improving patient's diagnosis as well as clinical studies outcome. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery.Methods: We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.9 years. We then correlated plasma proteins with left ventricular ejection fraction measured at 4 months post-MI and identified proteins potentially coregulated in post-MI HF using weighted gene co-expression network analysis. A Singapore cohort (IMMACULATE [Improving Outcomes in Myocardial Infarction through Reversal of Cardiac Remodelling]) of 223 patients post-MI, of which 33 patients were hospitalized for HF (median follow-up, 2.0 years), was used for further candidate enrichment of plasma proteins by using Fisher meta-analysis, resampling-based statistical testing, and machine learning. We then cross-referenced differentially expressed proteins with their differentially expressed genes from single-cell transcriptomes of nonmyocyte cardiac cells isolated from a murine MI model, and single-cell and single-nucleus transcriptomes of cardiac myocytes from murine HF models and human patients with HF.Results: In the CDCS cohort, 212 differentially expressed plasma proteins were significantly associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at 4 months post-MI. Weighted gene co-expression network analysis prioritized 63 of the 212 proteins that demonstrated significantly higher correlations among patients who developed post-MI HF in comparison with event-free controls (data set 1). Cross-cohort meta-analysis of the IMMACULATE cohort identified 36 plasma proteins associated with post-MI HF (data set 2), whereas single-cell transcriptomes identified 15 gene-protein candidates (data set 3). The majority of prioritized proteins were of matricellular origin. The 6 most highly enriched proteins that were common to all 3 data sets included well-established biomarkers of post-MI HF: N-terminal B-type natriuretic peptide and troponin T, and newly emergent biomarkers, angiopoietin-2, thrombospondin-2, latent transforming growth factor-β binding protein-4, and follistatin-related protein-3, as well.Conclusions: Large-scale human plasma proteomics, cross-referenced to unbiased cardiac transcriptomics at single-cell resolution, prioritized protein candidates associated with post-MI HF for further mechanistic and clinical validation. [ABSTRACT FROM AUTHOR]

Metabolic disorders in T2DM generate multiple sources of free radicals and oxidative stress that accelerate nonenzymatic degenerative protein modifications (DPMs) such as protein oxidation, disrupt redox signaling and physiological function, and remain a major risk factor for clinical diabetic vascular complications. In order to identify potential oxidative biomarkers in the blood plasma of patients with T2DM, we used LC-MS/MS-based proteomics to profile plasma samples from patients with T2DM and healthy controls. The results showed that human serum albumin (HSA) is damaged by irreversible cysteine trioxidation, which can be a potential oxidative stress biomarker for the early diagnosis of T2DM. The quantitative detection of site-specific thiol trioxidation is technically challenging; thus, we developed a sensitive and selective LC-MS/MS workflow that has been used to discover and quantify three unique thiol-trioxidized HSA peptides, ALVLIAFAQYLQQC(SO3H)PFEDHVK (m/z 1241.13), YIC(SO3H)ENQDSISSK (m/z 717.80) and RPC(SO3H)FSALEVDETYVPK (m/z 951.45), in 16 individual samples of healthy controls (n = 8) and individuals with diabetes (n = 8). Targeted quantitative analysis using multiple reaction monitoring mass spectrometry revealed impairment of the peptides with m/z 1241.13, m/z 717.80 and m/z 951.45, with significance (P < 0.02, P < 0.002 and P < 0.03), in individuals with diabetes. The results demonstrated that a set of three HSA thiol-trioxidized peptides, which are irreversibly oxidatively damaged in HSA in the plasma of patients with T2DM, can be important indicators and potential biomarkers of oxidative stress in T2DM. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnoea (OSA) is an emerging risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study.Methods: A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. Using the same portable diagnostic device, OSA was defined as an apnoea-hypopnoea index of ≥15 events per hour.Results: A total of 1961 patients were analysed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3kg/m2 for Indians and 25.4kg/m2 for Chinese to 28.6kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian (36.1%) patients. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve (AUC) for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161).Conclusion: There was significant ethnic variation in the prevalence of OSA in patients with ACS. The magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients. [ABSTRACT FROM AUTHOR]

Background Chronic total occlusions remain one of the biggest challenges for interventional cardiologists and the high risk of restenosis and stent thrombosis is still a major problem. Drug-coated balloons showed favorable results for the treatment of in-stent restenosis and other lesion types. The aim of this study was to evaluate the feasibility and outcome of a drug-coated balloon only approach for chronic total occlusion. Methods We included 34 patients with a native chronic total occlusion treated only by drug-coated balloons. A visual residual stenosis of 30% or less without major dissection was considered a satisfactory percutaneous intervention result according to the German Consensus Group recommendations for drug-coated balloon use. We collected clinical and procedural data. Angiograms were conducted during the procedure and at follow-up. Quantitative coronary analysis was performed and mean and minimal lumen diameter and late luminal changes were assessed. Results The recanalization was considered satisfactory in 79.4% (n = 27). Restenosis occurred in 11.8% (n = 4) and reocclusion in 5.9% (n = 2). Out of the 27 patients with a satisfactory initial result, 3.7% (n = 1) had reocclusion and 3.7% (n = 1) had restenosis. In the subgroup without satisfactory result (n = 7), restenosis occurred in 3 patients (42.9%) and reocclusion in 1 patient (14.3%). A luminal increase was found in 67.6% (n = 23) and mean late luminal gain was 0.11 ± 0.49 mm. Angina class improved significantly (p < 0.001). There was no death or myocardial infarction. Conclusions Drug-coated balloon angioplasty without stenting is a feasible and well-tolerated treatment method for chronic total occlusions if the predilatation result is good. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the mid-term angiographic result of T-stenting with small protrusion (TAP) as the bailout strategy for treating coronary bifurcation lesions. From 2009 to 2012, symptomatic patients who had severe coronary bifurcation stenoses were treated with one-stent strategy using drug-eluting stents, with kissing balloon inflation performed whenever side branch (SB) impingement occurred. TAP was performed if residual diameter stenosis of SB was ≥75 %, presence of ≥type B dissection or flow impairment was observed in the SB. Seventy-one patients (83 % male, mean age of 61 ± 12 years) were recruited into the study. MEDINA classification 1,1,1 lesions were observed in over 60 % of patients. The mean stent size and length in the main vessel (MV) and SB were 2.86 ± 0.43 and 30 ± 12, and 2.45 ± 0.26 and 16 ± 6 mm, respectively. Restudy angiography was performed on 64 (90 %) patients at 9.2 ± 3.9 months. Angiographic restenosis was observed in 8 (12.5 %) patients with late lumen loss in the MV and SB being 0.22 ± 0.19 and 0.34 ± 0.37 mm, respectively. The use of TAP as the bailout technique for treating coronary bifurcation lesions is associated with good angiographic outcomes, in terms of late lumen loss and restenosis, at 9 months. [ABSTRACT FROM AUTHOR]

Abstract: Secretion of bioactive mediators regulates cell interactions with the microenvironment in tissue homeostasis and wound healing processes. We assessed the cardiomyocyte secretory response to hypoxia with the aim of identifying key mediators of tissue pathology and repair after ischemic heart attack. We profiled the secretome of rat H9C2 cardiomyoblast cells subjected to 16h hypoxia followed by 24h re-oxygenation using iTRAQ and label-free quantitative proteomics. A total of 860 and 2007 proteins were identified in the iTRAQ and label-free experiments respectively. Among these proteins, 1363 were identified as being secreted proteins, including mediators of critical cellular functions that were modulated by hypoxia/re-oxygenation stress (SerpinH1, Ppia, Attractin, EMC1, Postn, Thbs1, Timp1, Stip1, Robo2, Fat1). Further analysis indicated that hypoxia is associated with angiogenesis, inflammation, and remodeling of the extracellular matrix (ECM), whereas subsequent re-oxygenation was instead associated with modified secretion of proteins involved in suppression of inflammation, ECM modification, and decreased output of anti-apoptosis proteins. These data indicate that hypoxia and subsequent re-oxygenation modify the cardiomyocyte secretome in order to mitigate cellular injury and promote healing. The identified changes in cardiomyocyte secretome advance our current understanding of cardiac biology in ischemia/reperfusion injury and may lead to the identification of novel prognostic biomarker. Biological significance: Cardiovascular diseases (CVDs) are the leading cause of death globally. Myocardial infarction (MI) resulting from ischemic heart disease represents a substantial component of CVD-associated mortality, and is associated with obstruction of blood flow to the myocardium. Restoration of blood flow through the occluded coronary artery is the current most effective therapy to limit infarct size and preserve cardiac function after acute myocardial infarction. However, this treatment does not prevent subsequent development of heart failure in some patients. Reperfusion following ischemia causes additional cell death and increase in infarct size, a phenomenon called myocardial ischemia/reperfusion (I/R) injury. In order to advance our current understanding of cardiac biology in ischemia/reperfusion injury, we assessed the cardiomyocyte secretory response to hypoxia with the aim of identifying key mediators of tissue pathology and repair after ischemic heart attack. We profiled the secretome of rat H9C2 cardiomyoblast cells subjected to 16h hypoxia followed by 24h re-oxygenation using LC–MS/MS-based iTRAQ and label-free quantitative proteomics approaches. We identified many secreted proteins as mediators of critical cellular functions that were modulated by hypoxia and re-oxygenation stress. Further analysis of these modulated secretory proteins indicated that hypoxia is associated with angiogenesis, inflammation, and remodeling of the extracellular matrix (ECM), whereas subsequent re-oxygenation/reperfusion was instead associated with modified secretion of proteins involved in suppression of inflammation, ECM modification, and decreased output of anti-apoptosis proteins. These data indicate that hypoxia and subsequent re-oxygenation modify the cardiomyocyte secretome in order to mitigate cellular injury and promote healing. The identified changes in cardiomyocyte secretome may lead to the identification of novel prognostic biomarkers secreted from injured heart tissues into the circulation of patients with cardiovascular disease. [Copyright &y& Elsevier]

The role of the second-generation zotarolimus-eluting stent RESOLUTE in small-vessel coronary artery disease is unclear. The aim of this study was examine the angiographic results of RESOLUTE in de novo coronary lesions of ≥50 % diameter stenosis in target vessels ≤2.5 mm. From August 2008 to April 2010, 142 symptomatic patients with 159 lesions who fitted the inclusion criteria were treated with RESOLUTE. The mean age of patients was 66 ± 10 years, with male predominance (66 %). Diabetes mellitus was found in 62 (43.7 %) patients, whereas multivessel disease was observed in 105 (73.9 %). The mean stent size and length used were 2.33 ± 0.13 and 22 ± 8 mm, respectively. Follow-up angiography was performed on 143 (89.9 %) lesions in 127 (89.4 %) patients at a mean of 10.3 ± 3.6 months. Angiographic restenosis was found in 9 (6.3 %) lesions; the late loss was 0.26 ± 0.34 mm. At 1-year follow-up there were four cardiovascular deaths, two nonfatal myocardial infarctions, and six repeated revascularizations. The resultant major adverse cardiac event rate was 8.5 %. The use of RESOLUTE to treat small-vessel disease is associated with good clinical and angiographic outcomes at 1 year. [ABSTRACT FROM AUTHOR]

Background: Long-term β-blockade therapy is beneficial in post-myocardial infarct (MI) patients with left ventricular (LV) dysfunction; nevertheless, its benefit in post-MI patients with preserved LV function remains unclear. The objective of this study is to investigate the effects of long-term β-blockade therapy on the clinical outcomes in post-MI patients with preserved LV function. Hypothesis: The beneficial effects of long-term β-blockade therapy in post-MI patients with impaired LV function may extend to those with preserved LV function. Methods: Of 617 consecutive post-MI patients referred for cardiac rehabilitation program, 208 patients (age: 62.7 ± 0.8 years; male: 76%) with preserved LV function (ejection fraction ≥ 50%), negative exercise stress test, and on angiotensin-converting enzyme inhibition were studied. Results: Baseline characteristics were comparable between patients on β-blocker (n = 154) and not on β-blocker (n = 54). After a mean follow-up of 58.5 ± 2.7 months, 14 patients not on β-blocker (26%) and 14 patients on β-blocker (9%) died with hazard ratio (HR) of 2.5 (95% confidence interval [CI]: 1.25–6.42, P = 0.01). Likewise, patients not on β-blocker had a higher incidence of cardiac death (HR: 3.0, 95% CI: 1.07–12.10, P = 0.04), and non-sudden cardiac death (HR: 10.1, 95% CI: 1.82–89.65, P = 0.01), but not sudden cardiac death compared with patients on β-blocker (HR: 1.6, 95% CI: 0.34–7.61, P = 0.54). A Cox regression analysis revealed that only advanced age (≥75 years; HR: 2.55, 95% CI: 1.18–5.49, P = 0.02) and the absence of β-blocker (HR: 2.41, 95% CI: 1.14–5.09, P = 0.02) were independent predictors for mortality. Conclusion:β -blocker use was associated with a decrease in overall mortality and cardiac death in post-MI patients with preserved LV function. (PACE 2010; 33:675–680) [ABSTRACT FROM AUTHOR]

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention., Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P <0.05 was considered statistically significant., Results: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P =0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P =0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P =0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours., Conclusions: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723., Competing Interests: L.T. is on the Astra Zeneca international advisory board of management of adverse events with the new antibody drug conjugate T-DXd in Asian patients with metastatic breast cancer, Roche Singapore immunotherapy in early stage NSCLC patient journey advisory board. L.T. has received a Philips speaker honorarium in kind and a Siemens Healthineers speaker honorarium. Y.K.K. has received research funding from Amgen, Astra Zeneca, Abbott Vascular, Bayer, Boston Scientific, Shockwave Medical, and Novartis (via institution); consulting fees from Abbott Vascular, Medtronic, Novartis, and Peijia Medical; and speaker fees from Shockwave Medical, Abbott Vascular, Boston Scientific, Medtronic, Alvimedica, Biotronik, Orbus Neich, Amgen, Novartis, Astra Zeneca, Microport, Terumo, and Omnicare. Y.K.K. is also cofounder and owns equity in Trisail, for which OrbusNeich is an investor. D.J.H. has received consultant fees from Faraday Pharmaceuticals Inc and Boehringer Ingelheim International GmbH, honoraria from Servier, and research funding from Astra Zeneca and Merck Sharp & Dohme Corp. C.Y.C. has received speaker fees from Novartis and consultancy fees from Boston Scientific and Philips. The other authors report no conflicts.

This study aim to investigate if remote intensive coaching for the first 6 months post-AMI will improve adherence to the twice-a-day antiplatelet medication, ticagrelor. Between July 8, 2015, to March 29, 2019, AMI patients were randomly assigned to remote intensive management (RIM) or standard care (SC). RIM participants underwent 6 months of weekly then two-weekly consultations to review medication side effects and medication adherence coaching by a centralized nurse practitioner team, whereas SC participants received usual cardiologist face-to-face consultations. Adherence to ticagrelor were determined using pill counting and serial platelet reactivity measurements for 12 months. A total of 149 (49.5%) of participants were randomized to RIM and 152 (50.5%) to SC. Adherence to ticagrelor was similar between RIM and SC group at 1 month (94.4 ± 0.7% vs. 93.6±14.7%, p = 0.537), 6 months (91.0±14.6% vs. 90.6±14.8%, p = 0.832) and 12 months (87.4±17.0% vs. 89.8±12.5%, p = 0.688). There was also no significant difference in platelet reactivity between the RIM and SC groups at 1 month (251AU*min [212-328] vs. 267AU*min [208-351], p = 0.399), 6 months (239AU*min [165-308] vs. 235AU*min [171-346], p = 0.610) and 12 months (249AU*min [177-432] vs. 259AU*min [182-360], p = 0.678). Sensitivity analysis did not demonstrate any association of ticagrelor adherence with bleeding events and major adverse cardiovascular events. RIM, comprising 6 months of intensive coaching by nurse practitioners, did not improve adherence to the twice-a-day medication ticagrelor compared with SC among patients with AMI. A gradual decline in ticagrelor adherence over 12 months was observed despite 6 months of intensive coaching., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The COVID -19 pandemic impacted acute myocardial infarction (AMI) attendances, ST-elevation myocardial infarction (STEMI) treatments, and outcomes. We collated data from majority of primary percutaneous coronary intervention (PPCI)-capable public healthcare centres in Singapore to understand the initial impact COVID-19 had on essential time-critical emergency services. We present data comparisons from 'Before Disease Outbreak Response System Condition (DORSCON) Orange', 'DORSCON Orange to start of circuit breaker (CB)', and during the first month of 'CB'. We collected aggregate numbers of weekly elective PCI from four centres and AMI admissions, PPCI, and in-hospital mortality from five centres. Exact door-to-balloon (DTB) times were recorded for one centre; another two reported proportions of DTB times exceeding targets. Median weekly elective PCI cases significantly decreased from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (34 vs 22.5, P = 0.013). Median weekly STEMI admissions and PPCI did not change significantly. In contrast, the median weekly non-STEMI (NSTEMI) admissions decreased significantly from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (59 vs 48, P = 0.005) and were sustained during CB (39 cases). Exact DTB times reported by one centre showed no significant change in the median. Out of three centres, two reported significant increases in the proportion that exceeded DTB targets. In-hospital mortality rates remained static. In Singapore, STEMI and PPCI rates remained stable, while NSTEMI rates decreased during DORSCON Orange and CB. The severe acute respiratory syndrome (SARS) experience may have helped prepare us to maintain essential services such as PPCI during periods of acute healthcare resource strain. However, data must be monitored and increased pandemic preparedness measures must be explored to ensure that AMI care is not adversely affected by continued COVID fluctuations and future pandemics., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI., Methods: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity., Findings: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality., Interpretation: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality., Funding: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore., Competing Interests: M.Y.C. receives speaker's fees and research grants from Astra Zeneca, Abbott Technologies and Boston Scientific. S.N. has received research grant support from AstraZeneca, Amgen, Anthera, Cerenis, Eli Lilly, Esperion, InfraReDx, LipoScience; The Medicines Company, New Amsterdam Pharma, Novartis, Resverlogix, Roche, and Sanofi-Regeneron; he has received consulting fees from Akcea, Amarin, Anthera, AstraZeneca, Boehringer-Ingelheim, CSL Behring, Eli Lilly, Esperion, Omthera, Merck, Resverlogix, Sanof-Regeneron, Takeda, and Vaxxinity. N.W.S.C. has received research grant support from NUHS Seed Fund and National Medical Research Council Research Training Fellowship., (© 2023 The Author(s).)

Background: Considerable evidence links dietary salt intake with the development of hypertension, left ventricular hypertrophy, and increased risk of stroke and coronary heart disease. Despite extensive epidemiological and basic science interrogation of the relationship between high salt (HS) intake and blood pressure, it remains unclear how HS impacts endothelial cell (EC) and vascular structure in vivo. This study aims to elucidate HS-induced vascular pathology using a differential systemic decellularization in vivo approach., Methods: We performed systematic molecular characterization of the endothelial glycocalyx and EC proteomes in mice with HS (8%) diet-induced hypertension versus healthy control animals. Isolation of eGC and EC compartments was achieved using differential systemic decellularization in vivo methodology. Altered protein expression in hypertensive compared to normal mice was characterized by liquid chromatography tandem mass spectrometry. Proteomic results were validated using functional assays, microscopic imaging, and histopathologic evaluation., Results: Proteomic analysis revealed a significant downregulation of eGC and associated proteins in HS diet-induced hypertensive mice (among 1696 proteins identified in this group, 723 were markedly decreased in abundance, while only 168 were increased in abundance. Bioinformatic analysis indicated substantial derangement of the eGC layer, which was subsequently confirmed by fluorescent and electron microscopy assessment of vessel damage ex vivo. In the EC fraction, HS-induced hypertension significantly altered protein mediators of contractility, metabolism, mechanotransduction, renal function, and the coagulation cascade. In particular, we observed dysregulation of integrin subunits α2, α2b, and α5, which was associated with arterial wall inflammation and substantial infiltration of CD68+ monocyte-macrophages. Consequently, HS-induced hypertensive mice also displayed reduced vascular integrity of multiple organs including lungs, kidneys, and heart., Conclusions: These findings provide novel molecular insight into HS-induced structural changes in eGC and EC composition that may increase cardiovascular risk and potentially guide the development of new diagnostics and therapeutic interventions.

Background: The World Health Organization declared coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. We report a patient with acute myocardial infarction (AMI) who presented late due to fears of contracting COVID-19., Case Summary: A 65-year-old man with a history of hypertension presented late to the emergency department (ED) with AMI. He gave a 2-month history of exertional angina but avoided seeking medical consult due to fears of contracting COVID-19. On the day of admission, he had 4 h of severe chest pain before presenting to the ED. He was hypotensive and tachycardic on arrival. Electrocardiogram showed inferolateral ST-elevation myocardial infarction. Chest radiograph revealed widened superior mediastinum and bedside echocardiogram revealed inferoseptal and inferolateral hypokinesia with features of cardiac tamponade. An urgent computed tomography aortogram showed possible left ventricular (LV) wall perforation with resulting haemopericardium and cardiac tamponade. Subsequent coronary angiogram showed 100% occlusion of mid left circumflex artery and a contained LV wall rupture was confirmed with LV ventriculogram. He was transferred to a tertiary centre and underwent successful emergency surgical repair., Discussion: Our index case demonstrates the impact of the COVID-19 pandemic on health seeking behaviour due to fears of contracting COVID-19 and the ensuing impact of delayed medical intervention. Cardiologists worldwide are seeing an alarming rate of rare complications of AMI in patients who present late. Physicians need to be aware of this phenomenon and have an active role to play in public education., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)