Moe K.T.,National Heart Center |
Wong P.,National University of Singapore
Annals of the Academy of Medicine Singapore | Year: 2010
The diagnosis and management of patients with acute coronary syndrome (ACS) have evolved dramatically over the past decade. Biomarkers play an important role in the diagnosis of ACS, especially in unstable angina and non-ST-segment elevation myocardial infarction. Among these, cardiac troponin and creatine kinase appear to be the most sensitive and specific markers of myocardial injury. Recent studies have revealed several novel biomarkers. Elevated levels of C-reactive protein and interleukin-6 are strong independent markers of increased mortality among patients with ACS. However, the ideal biomarkers that offer early detection, risk stratification, selection of therapy, monitoring disease progression, and treatment efficacy remain to be elucidated. This review assesses limitations and contemporary needs for biomarkers in the context of diagnosis of ACS. It also discusses the newly developing technologies for novel biomarkers or novel biomarker protein signatures discovery, and importance of point-of-care testing for future management.
Verma S.,Center for Molecular Medicine National Institute of Immunology |
Mehta A.,Center for Molecular Medicine National Institute of Immunology |
Mehta A.,National Heart Center |
Shaha C.,Center for Molecular Medicine National Institute of Immunology
PLoS ONE | Year: 2011
Background: Cytochrome P450s (CYP450s) are hemoproteins catalysing diverse biochemical reactions important for metabolism of xenobiotics and synthesis of physiologically important compounds such as sterols. Therefore, they are functionally important for survival of invading pathogens. One such opportunistic pathogen Leishmania donovani causes visceral leishmaniasis worldwide, which is an important public health problem due to significant disease burden. The parasite genome database, Gene DB, annotates 3 CYP450s in Leishmania, however, the functional role of cytochrome P450 enzymes in Leishmania spp. remains elusive. Methodology/Principal Findings: A CYP450-like gene cloned from Leishmania donovani was identified as a novel CYP450, the CYP5122A1. Upon co-localization with organelle specific markers, CYP5122A1 distribution was shown to be localized in the promastigote ER, mitochondria and the glycosomes. Replacement of one allele of CYP5122A1 with either neomycin or hygromycin gene by homologous recombination in Leishmania promastigotes induced substantial reduction of CYP5122A1 expression. These parasites showed impaired growth, lower mitochondrial Ca 2+ and membrane potential resulting in low ATP generation. Also, these parasites were less infective in vitro and in vivo than their wild-type counterparts as assessed by incubation of Leishmania promastigotes with macrophages in vitro as well as through administration of parasites into hamsters. The HKOs were more susceptible to drugs like miltefosine and antimony, but showed reduced sensitivity to amphotericin B. Removal of two alleles of CYP5122A1 did not allow the parasites to survive. The mutant parasites showed 3.5 times lower ergosterol level as compared to the wild-type parasites when estimated by Gas chromatography/mass spectrometry. Complementation of CYP5122A1 through episomal expression of protein by using pXG-GFP+2 vector partially rescued CYP5122A1 expression and restored ergosterol levels by 1.8 times. Phenotype reversal included restored growth pattern and lesser drug susceptibility. Conclusions/Significance: In summary, this study establishes CYP5122A1 as an important molecule linked to processes like cell growth, infection and ergosterol biosynthesis in Leishmania donovani. © 2011 Verma et al.
Agasthian T.,11 Hospital Drive |
Lin S.J.,National Heart Center
Asian Cardiovascular and Thoracic Annals | Year: 2010
We reviewed our experience of video-assisted thoracoscopic thymectomy for myasthenia gravis and thymomas in 119 patients, aged 12-83 years, who were treated between 1998 and 2007. Disease severity was graded using the Osserman classification. To prevent rupture of the tumor capsule and tumor seeding, thymomas were resected using a modified no-touch technique. Thymoma diameters were 10-90mm (mean, 50 mm). There were no operative deaths, 12 (10%) patients had complications, and 87 (73.1%) improved by 1 or more Osserman grades postoperatively. After follow-up of 1.9-10 years (mean, 4.9 years), 74 (62%) patients remained asymptomatic, with 21% in complete stable remission. Using multivariate regression analysis, there were no statistical differences in median pre-and postoperative Osserman grades with regards to age, sex, duration of symptoms, and presence of thymoma. Videoassisted thoracoscopic thymectomy for myasthenia gravis and selected thymomas can achieve long-term clinical outcomes comparable to those of standard approaches. © 2010 SAGE Publications.
Liew R.,National Heart Center |
Chiam P.T.L.,National Heart Center
Annals of the Academy of Medicine Singapore | Year: 2010
Many patients who survive an acute myocardial infarction (AMI) remain at risk of recurrent cardiac events and sudden cardiac death after discharge, despite optimal medical treatment. Assessment of the degree of left ventricular dysfunction and residual myocardial ischaemia is useful to identify the patients at greatest risk. In addition, there is increasing evidence that a number of other cardiovascular tests can be used to detect autonomic dysfunction and myocardial substrate abnormalities postAMI that increase the risk of life-threatening ventricular arrhythmias. These investigations include ECG-based tests (signal averaged ECG and T-wave alternans), Holter-based recordings (heart rate variability and heart rate turbulence) and imaging techniques (echocardiography and cardiac magnetic resonance), as well as invasive electrophysiological testing. This article reviews the current evidence for the use of these additional cardiac investigations among survivors of AMI to aid in their risk stratification for malignant ventricular arrhythmias and sudden cardiac death.
Du X.,Tianjin Medical University |
Soon J.L.,National Heart Center
Journal of Cardiology | Year: 2011
Background: Aortic stenosis (AS) is the most common valvular disease in adult cardiac surgery and its incidence continues to rise. Increasingly older patients are being referred for coronary artery bypass grafting (CABG) with mild to moderate AS. Concomitant aortic valve replacement (AVR) for patients with moderate or severe AS undergoing CABG is warranted regardless of symptoms. Concomitant AVR remains contentious in patients with less than moderate severity AS undergoing CABG. Materials and methods: We review the contemporary literature aiming to resolve this dilemma in clinical practice. The assessment of these patients is reviewed. Considerations include identifying the rapid progressors, and balancing the risks of concomitant valve surgery against the potential prognostic gains. Results: Pathophysiological links between degenerative calcific AS and coronary artery disease suggest that the disease is an active, progressive process with mutually shared risk factors. Statins, however, offer limited protection against AS, despite its established role in coronary artery disease. Age, atherosclerosis risk, valve morphology, motion, and hemodynamics identify the rapid progressors, whilst the patients' general comorbidities and life expectancy influence the risk-benefit profile of concomitant operations. Conclusion: A precise echocardiographic quantification of the stenotic grade is mandatory before adopting any therapeutic strategy. Concomitant AVR for moderate AS is recommended if surgical risk is not prohibitive. Concomitant AVR for mild AS in 'rapid progressors' (i.e. moderate-severe valve calcification) may be considered, but patients should have reasonable life expectancy exceeding 5 years. Moderately restricted leaflet motions, gradient increase of >10. mm. Hg per year, and aortic jet velocity increase >0.4. m/s per year further supports intervention. Comorbidities increasing atherosclerotic burden and renal dialysis accelerate AS progression and increase surgical risk. Procedural advances in interventional cardiology and minimally invasive cardiac surgery may further expand the options available for these patients. © 2011 Japanese College of Cardiology.
Elkehili I.M.,National Heart Center
Arab journal of nephrology and transplantation | Year: 2012
The cause of the metabolic syndrome (MS) is incompletely understood but represents a complex interaction between genetic, environmental, and metabolic factors, clearly including diet, and level of physical activity. The prevalence of MS is continuously increasing in the general population. Recently it has been found that MS is also common in renal transplant recipients (RTRs). The aim of this study was to determine the prevalence and characteristics of MS in a group of Libyan renal transplant recipients, using two different diagnostic criteria. This study was conducted at the Nephrology Department of the National Heart Center, Tripoli, Libya. We determined the prevalence of MS in a group of renal transplant recipients using both the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria and the International Diabetes Federation (IDF) criteria. All patients were more than six months post transplantation. Patients with Pre-transplant diabetes mellitus were excluded from the analysis. By using the NCEP-ATP III criteria 26 out of 91 patients (28.6%) had the metabolic syndrome. MS was commoner in females than males, affecting 12 out of 35 females (34.3%) and 14 out of 56 males (25%). Using the IDF criteria the metabolic syndrome was diagnosed in 23 patients (25.3%). In this group of patients the most common component of the metabolic syndrome was high blood pressure and the least common was impaired glucose tolerance and diabetes. The prevalence of MS in our renal transplant patients is high, affecting females more than males. Key words: International Diabetes Federation; Metabolic Syndrome; NCEP-ATP III; Renal Transplant Recipients.
Narita T.,National Heart Center |
Suzuki K.,Queen Mary, University of London
Heart Failure Reviews | Year: 2014
Heart failure remains a major cause of death and disability, requiring rapid development of new therapies. Bone marrow-derived mesenchymal stem cell (MSC)-based therapy is an emerging approach for the treatment of both acute and chronic heart failure. Following successful experimental studies in a range of models, more than 40 clinical trials of MSC-based therapy for heart failure have now been registered, and the results of completed clinical trials so far have shown feasibility and safety of this approach with therapeutic potential suggested (though preliminarily). However, there appear to be several critical issues to be solved before this treatment could become a widespread standard therapy for heart failure. In this review, we comprehensively and systemically summarize a total of 73 preclinical studies and 11 clinical trial reports published to date. By analyzing the data in these reports, (1) improvement in the cell delivery method to the heart in order to enhance donor cell engraftment, (2) elucidation of mechanisms underpinning the therapeutic effects of the treatment differentiation and/or treatment secretion, and (3) validation of the utility of allogeneic MSCs which could enhance the efficacy and expand the application/indication of this therapeutic approach are highlighted as future perspectives. These important respects are further discussed in this review article with referencing latest scientific and clinical information. © 2014, Springer Science+Business Media New York.
Chiam P.T.L.,National Heart Center |
Ruiz C.E.,New Hill
JACC: Cardiovascular Interventions | Year: 2011
Surgical treatment of mitral regurgitation (MR) has evolved from mitral valve replacement (MVR) to repair (MVRe), because MVRe produces superior long-term outcomes. In addition, MVRe can be achieved through minimally invasive approaches. This desire for less invasive approaches coupled with the fact that a significant proportion of patientsespecially elderly persons or those with significant comorbidities or severe left ventricular (LV) dysfunction, are not referred for surgery, has driven the field of percutaneous MVRe. Various technologies have emerged and are at different stages of investigation. A classification of percutaneous MVRe technologies on the basis of functional anatomy is proposed that groups the devices into those targeting the leaflets (percutaneous leaflet plication, percutaneous leaflet coaptation, percutaneous leaflet ablation), the annulus (indirect: coronary sinus approach or an asymmetrical approach; direct: true percutaneous or a hybrid approach), the chordae (percutaneous chordal implantation), or the LV (percutaneous LV remodeling). The percutaneous edge-to-edge repair technology has been shown to be noninferior to open repair in a randomized clinical trial (EVEREST II [Endovascular Valve Edge-to-Edge REpair Study]). Several other technologies employing the concepts of direct and indirect annuloplasty and LV remodeling have achieved first-in-man results. Most likely a combination of these technologies will be required for satisfactory MVRe. However, MVRe is not possible for many patients, and MVR will be required. Surgical MVR is the standard of care in such patients, although percutaneous options are under development. © 2011 American College of Cardiology Foundation.
Tong A.K.T.,Singapore General Hospital |
Tan S.-Y.,Singapore General Hospital |
Go Y.-Y.,National Heart Center |
Lam W.W.C.,Singapore General Hospital
Canadian Journal of Cardiology | Year: 2014
A man presented with shortness of breath, and a globular heart was seen on a chest radiograph. An echocardiogram showed masses at the atrioventricular grooves. Computed tomography (CT) coronary angiography and fluorine-18 (18F) fluorodeoxyglucose positron emission tomography (FDG-PET)/CT confirmed coronary aneurysms with hypermetabolic perivascular masses at the coronary arteries and right internal iliac artery. Histologic features were highly suspicious for IgG4-related disease (IgG4-RD). IgG4-RD is a recently recognized fibroinflammatory condition, and FDG-PET/CT can provide information about the disease pattern, which may suggest IgG4-RD, as well as the optimal biopsy site. © 2014 Canadian Cardiovascular Society.
Pang P.Y.K.,National Heart Center |
Chiam P.T.L.,National Heart Center |
Chua Y.L.,National Heart Center |
Sin Y.K.,National Heart Center
European Journal of Cardio-thoracic Surgery | Year: 2012
Transcatheter aortic valve implantation (TAVI) has emerged as a viable alternative endovascular technique in selected patients with severe aortic stenosis, who are either inoperable or at high risk for surgical aortic valve replacement. We report a case of delayed displacement and rotation of an aortic bioprosthesis, 43 days after successful TAVI via the transfemoral approach, with the patient surviving the subsequent open heart surgery required for device retrieval. © The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.