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Coronary artery calcium and you - do you know where you stand?

Chin SP, Ng CK, Sim KH

Indian Heart J, 2007 May-Jun;59(3):211-3.
PMID: 19124927
Fulltext Managing congestive heart failure in a general hospital in Malaysia. Are we keeping pace with evidence?

Chin SP, Sapari S, How SH, Sim KH

Med J Malaysia, 2006 Aug;61(3):278-83.
PMID: 17240575 MyJurnal

Evidence-based heart failure management now includes beta-blockers and spironolactone in addition to diuretics and angiotensin-converting enzyme inhibitors. We aim to determine if these recommendations had been applied in practice for acute and chronic stable heart failure, and what difficulties there might be. Data from 80 consecutive patients hospitalized for decompensated heart failure ('acute') between May and July 2003 were analyzed at admission, upon discharge and at 12 weeks follow-up; along with 74 cardiology clinic out-patients with stable congestive heart failure ('chronic'- no decompensation or admission in previous six months). Less than half of study patients with prior left ventricular dysfunction were on ACE-inhibitors (47%), diuretics (39%), ATII antagonists, spironolactone or digoxin (5% each). All 'acute' patients were commenced on diuretics and ACE-inhibitors in hospital. Six patients died or transferred to another center. Compliance with clinic appointment at 12 weeks was 85% despite telephone reminders. Drug prescription at 12 weeks was significantly lower for diuretics and ACE-inhibitors compared to prescription at discharge (all p < 0.05) but higher compared to patients with chronic HF. Diuretics and ACE inhibitors remain under-utilized for patients with recurrent heart failure. Use of spironolactone and beta-blocker is slow due to limited medical experience and funding. Clinic non-attendance is significant and due to patient factors.
Computed tomography scan for cardiac interventions

Sim KH, Ong TK, Chin SP, Wong M

Indian Heart J, 2007 Mar-Apr;59(2 Suppl B):B25-32.
PMID: 19153433
Fulltext Pleural effusions: role of commonly available investigations

How SH, Chin SP, Zal AR, Liam CK

Singapore Med J, 2006 Jul;47(7):609-13.
PMID: 16810434

Previous studies have reported high rates of undetermined causes of pleural effusions. We aimed to find out the proportion of pleural effusions in which the aetiology is uncertain despite commonly available investigations.
Fulltext Secretome profile of TNF-α-induced human umbilical cord mesenchymal stem cells unveils biological processes relevant to skin wound healing

Tai L, Saffery NS, Chin SP, Cheong SK

Regen Med, 2023 Nov;18(11):839-856.
PMID: 37671699 DOI: 10.2217/rme-2023-0085

Aim: To profile and study the proteins responsible for the beneficial effect of the TNF-α-induced human umbilical cord mesenchymal stem cells (hUCMSCs) secretome in wound healing. Methods: The hUCMSCs secretome was generated with (induced) or without (uninduced) TNF-α and was subsequently analyzed by liquid chromatography-mass spectrometry, immunoassay and in vitro scratch assay. Results: Proteomic analysis revealed approximately 260 proteins, including 51 and 55 unique proteins in the induced and uninduced secretomes, respectively. Gene ontology analysis disclosed that differential proteins in the induced secretome mainly involved inflammation-related terms. The induced secretome, consisting of higher levels of FGFb, VEGF, PDGF and IL-6, significantly accelerated wound closure and enhanced MMP-13 secretion in HaCaT keratinocytes. Conclusion: The secretome from induced hUCMSCs includes factors that promote wound closure.
Fulltext Preclinical assessments of safety and tumorigenicity of very high doses of allogeneic human umbilical cord mesenchymal stem cells

Chin SP, Saffery NS, Then KY, Cheong SK

In Vitro Cell Dev Biol Anim, 2024 Mar;60(3):307-319.
PMID: 38421574 DOI: 10.1007/s11626-024-00852-z

Human umbilical cord-mesenchymal stem cells (hUC-MSCs) have been widely investigated as a new therapeutic agent to treat injuries and inflammatory-mediated and autoimmune diseases. Previous studies have reported on the safety of low-dose infusion of hUC-MSCs, but information on the cell behaviour at higher doses and frequency of injection of the cells remains uncertain. The aim of the present study was to demonstrate the safety and efficacy of hUC-MSCs by Cytopeutics® (Selangor, Malaysia) from low to an extremely high dose in different monitoring periods in healthy BALB/c mice as well as assessing the tumorigenicity of the cells in B-NDG SCID immunocompromised mice. Umbilical cord from two healthy human newborns was obtained and the isolation of the hUC-MSCs was performed based on previous established method. Assessment of the cells at different doses of single or multiple administrations was performed on healthy BALB/c mice in dose range finding, sub-acute (7 d and 28 d) and sub-chronic periods (90 d). Tumorigenicity potential of Cytopeutics® hUC-MSCs was also evaluated on B-NDG immunocompromised mice for 26 wk. Single or multiple administrations of Cytopeutics® hUC-MSCs up to 40 × 106 cells per kilogramme of body weight (kg BW) were found to have no adverse effect in terms of clinical symptoms, haematology and other laboratory parameters, and histology examination in healthy BALB/c mice. hUC-MSCs were also found to reduce pro-inflammatory cytokines (IL-6 and TNF-α) in a dose-dependent manner. No sign of tumor formation was observed in B-NDG mice in the 26-wk tumorigenicity assessment. Single or multiple administration of allogenic Cytopeutics® hUC-MSCs was safe even at very high doses, is non-tumorigenic and did not cause adverse effects in mice throughout the evaluation periods. In addition, Cytopeutics® hUC-MSCs exhibited immunomodulatory effect in a dose-dependent manner.
Fulltext Flavonoids with M1 muscarinic acetylcholine receptor binding activity

Swaminathan M, Chee CF, Chin SP, Buckle MJ, Rahman NA, Doughty SW, et al.

Molecules, 2014 Jun 27;19(7):8933-48.
PMID: 24979399 DOI: 10.3390/molecules19078933

Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer's disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki=40-110 µM), comparable to that of acetylcholine (Ki=59 µM). Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.
The National Stem Cell Therapy Patient Registry of Malaysia--measuring clinical outcomes of stem cell therapy

Loke SC, Chin SP, Sivanandam S, Goh PP, Ng RK, Saw KY, et al.

Stem Cell Rev Rep, 2010 Dec;6(4):507-11.
PMID: 20669056 DOI: 10.1007/s12015-010-9176-8

Very few registries worldwide focus on clinical outcomes of stem cell therapy (SCT) as the large number of applications and rapid development of the field complicates registry design considerably. The National Stem Cell Therapy Patient Registry of Malaysia aims to accommodate this by using a main protocol which covers the overall design and administration of the registry, and condition-specific sub-protocols which deal with outcome measures. The registry will start with a few sub-protocols covering existing modes of SCT in Malaysia, with new sub-protocols released periodically as the need arises.
Cryopreserved mesenchymal stromal cell treatment is safe and feasible for severe dilated ischemic cardiomyopathy

Chin SP, Poey AC, Wong CY, Chang SK, Teh W, Mohr TJ, et al.

Cytotherapy, 2010;12(1):31-7.
PMID: 19878080 DOI: 10.3109/14653240903313966

Bone marrow (BM) mesenchymal stromal cells (MSC) represent a novel therapy for severe heart failure with extensive myocardial scarring, especially when performed concurrently with conventional revascularization. However, stem cells are difficult to transport in culture media without risk of contamination, infection and reduced viability. We tested the feasibility and safety of off-site MSC culture and expansion with freeze-controlled cryopreservation and subsequent rapid thawing of cells immediately prior to implantation to treat severe dilated ischemic cardiomyopathy.
Fulltext Acute stroke patients with high BMI are less likely to have severe disability at initial presentation

Choo WS, Foo S, Tan E, Thayaparan FS, Chung YY, Raman S, et al.

Med J Malaysia, 2009 Mar;64(1):34-6.
PMID: 19852318 MyJurnal

This is a prospective study to determine the severity of disability and prognosis of acute stroke patients related to their Body Mass index (BMI). A total of 79 consecutive CT-scan-proven acute stroke patients who were admitted to Hospital Tuanku Ja'afar, Seremban between November 2006 and April 2007 were recruited (male:female 49:30; mean age 62.7 years; ischemic stroke 70, intracerebral bleed 9). The patients were divided according to BMI less than 25 (Group A) and equal or greater than 25 (Group B). Severity of disability was measured between 24-48 hours by modified Rankin's score. Patients were followed up after one month. Thirty-seven patients had severe disability (Rankin Score 5). Twenty-nine patients had adverse outcomes including 11 deaths and 18 rehospitalizations or prolonged hospital/nursing home stay. 34.3% of Group B had severe disability compared to 56.8% of Group A (chi2 P = 0.046). Conversely 42.9% of Group B had adverse events at one month compared to 31.8% of Group A (chi2 P = 0.312). There were no statistical differences between high- and low-BMI groups for gender ratio, smoking, hypertension, diabetes, prior cardiovascular disease, mean age, mean lipid profile and blood pressure. When comparing patients with Rankin Score 1-4 versus 5, age and BMI were statistically significant between the two groups. By multivariate analysis only age is independent predictor for severe disability (P < 0.05). The results of this pilot study should be confirmed in larger prospective multicentre trial.
Fulltext Acute coronary syndrome (ACS) registry--leading the charge for National Cardiovascular Disease (NCVD) Database

Chin SP, Jeyaindran S, Azhari R, Wan Azman WA, Omar I, Robaayah Z, et al.

Med J Malaysia, 2008 Sep;63 Suppl C:29-36.
PMID: 19230244

Coronary artery disease is one of the most rampant non-communicable diseases in the world. It begins indolently as a fatty streak in the lining of the artery that soon progresses to narrow the coronary arteries and impair myocardial perfusion. Often the atherosclerotic plaque ruptures and causes sudden thrombotic occlusion and acute ST-elevation myocardial infarction (STEMI), non-ST-elevation MI (NSTEMI) or unstable angina (UA). This phenomenon is called acute coronary syndrome (ACS) and is the leading cause of death not only in Malaysia but also globally. In order for us to tackle this threat to the health of our nation we must arm ourselves with reliable and accurate information to assess current burden of disease resources available and success of current strategies. The acute coronary syndrome (ACS) registry is the flagship of the National Cardiovascular Disease Database (NCVD) and is the result of the dedicated and untiring efforts of doctors and nurses in both public and private medical institutions and hospitals around the country, ably guided and supported by the National Heart Association, the National Heart Foundation, the Clinical Research Centre and the Ministry of Health of Malaysia. Analyses of data collected throughout 2006 from 3422 patients with ACS admitted to the 12 tertiary cardiac centres and general hospitals spanning nine states in Malaysia in this first report has already revealed surprising results. Mean age of patients was 59 years while the most consistent risk factor for STEMI was active smoking. Utilization of medications was high generally. Thirty-day mortality for STEMI was 11%, for NSTEMI 8% and UA 4%. Thrombolysis (for STEMI only) reduced in-hospital and 30-day mortality by nearly 50%. Percutaneous coronary intervention or PCI also reduced 30-day mortality for patients with non-ST elevation MI and unstable angina. The strongest determinants of mortality appears to be Killip Class and age of the patient. Fewer women received thrombolysis or underwent PCI on same admission although women make up 25% of the cohort.
Fulltext Serum cancer antigen 125 in patients with pleural effusions

How SH, Liam CK, Jamalludin AR, Chin SP, Zal AB

Med J Malaysia, 2006 Dec;61(5):558-63.
PMID: 17623956 MyJurnal

We studied the prevalence of raised serum CA125 in patients with pleural effusions and explored factors affecting its level. Sixty four patients with benign effusions and 36 patients with malignant effusions admitted to the University Malaya Medical Centre from May 2001 to January 2002 were included in the study. There were no significant differences in age, gender and ethnicity of the patients with benign and malignant effusions. There was also no difference in the frequency of the side of pleural effusion between the two groups but compared to benign effusions, a higher proportion of malignant effusions was moderate to large in size (66% versus 39%, p = 0.011). Serum CA125 levels were above 35U/dL in 83.3% and 78.1% of patients with malignant and benign effusions, respectively (p = 0.532). All patients with underlying malignancy and 95.3% of patients with benign effusions had pleural fluid CA125 levels above 35U/dL (p = 0.187). The median levels of CA125 were higher in the pleural fluid than in the serum in all aetiological groups. Higher serum CA125 levels were more likely to be found in patients with moderate to large effusions (p = 0.015), malignant effusions (p = 0.001) and in female patients (0.016). Serum CA125 level showed significant correlation with pleural fluid CA125 level (r = 0.532, p < 0.001) but not with pleural fluid total white blood cell count (r = -0.092, p = 0.362), red blood cell count (r = -0.082, p = 0.417) and lactate dehydrogenase level (r = 0.062, p = 0.541). We conclude that serum CA125 is commonly elevated in patients with benign and malignant pleural effusions.
Fulltext Feasibility and accuracy of 64-row MDCT coronary imaging from a centre with early experience: a review and comparison with established centres

Ong TK, Chin SP, Chan WL, Liew CK, Seyfarth MT, Liew HB, et al.

Med J Malaysia, 2005 Dec;60(5):629-36.
PMID: 16515115

The accuracy of multi-detector computed tomographic (MDCI) coronary angiography (CTA) is dependant on image quality as well as the experience of the operator. Established centers have reported negative predictive values of over 95%. The aim of our study was to investigate the accuracy and feasibility of CTA for the assessment of haemodynamically significant coronary stenosis in a center with very early experience (<6 months) utilizing the improved spatial and temporal resolutions of the latest generation 64-row MDCI scanner. One hundred and twenty eight patients (93 male, 35 female; mean age 56.2 +/- 9.5 years) with suspected or known coronary artery disease underwent both CIA and conventional coronary angiographv (CCA). The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for stenoses > or =50% by CIA compared to CCA were 70%, 97%, 70% and 97% respectively. Evaluation of main and proximal segments in patients with good quality images (78% of patients) produced values of 94%, 95%, 74% and 99% respectively. The improved spatial and temporal resolutions of 64-row MJ) CT provided a high negative predictive value in assessing significant coronary artery stenosis even in a centre with very early experience. However, new centers embarking on CTA might not be able to reproduce the results reported by more experienced centers.
Fulltext In Silico and In Vitro Analysis of Bacoside A Aglycones and Its Derivatives as the Constituents Responsible for the Cognitive Effects of Bacopa monnieri

Ramasamy S, Chin SP, Sukumaran SD, Buckle MJ, Kiew LV, Chung LY

PLoS One, 2015;10(5):e0126565.
PMID: 25965066 DOI: 10.1371/journal.pone.0126565

Bacopa monnieri has been used in Ayurvedic medicine to improve memory and cognition. The active constituent responsible for its pharmacological effects is bacoside A, a mixture of dammarane-type triterpenoid saponins containing sugar chains linked to a steroid aglycone skeleton. Triterpenoid saponins have been reported to be transformed in vivo to metabolites that give better biological activity and pharmacokinetic characteristics. Thus, the activities of the parent compounds (bacosides), aglycones (jujubogenin and pseudojujubogenin) and their derivatives (ebelin lactone and bacogenin A1) were compared using a combination of in silico and in vitro screening methods. The compounds were docked into 5-HT1A, 5-HT2A, D1, D2, M1 receptors and acetylcholinesterase (AChE) using AutoDock and their central nervous system (CNS) drug-like properties were determined using Discovery Studio molecular properties and ADMET descriptors. The compounds were screened in vitro using radioligand receptor binding and AChE inhibition assays. In silico studies showed that the parent bacosides were not able to dock into the chosen CNS targets and had poor molecular properties as a CNS drug. In contrast, the aglycones and their derivatives showed better binding affinity and good CNS drug-like properties, were well absorbed through the intestines and had good blood brain barrier (BBB) penetration. Among the compounds tested in vitro, ebelin lactone showed binding affinity towards M1 (Ki = 0.45 μM) and 5-HT2A (4.21 μM) receptors. Bacoside A and bacopaside X (9.06 μM) showed binding affinity towards the D1 receptor. None of the compounds showed any inhibitory activity against AChE. Since the stimulation of M1 and 5-HT2A receptors has been implicated in memory and cognition and ebelin lactone was shown to have the strongest binding energy, highest BBB penetration and binding affinity towards M1 and 5-HT2A receptors, we suggest that B. monnieri constituents may be transformed in vivo to the active form before exerting their pharmacological activity.
Fulltext Dynamics and binding interactions of peptide inhibitors of dengue virus entry

Isa DM, Chin SP, Chong WL, Zain SM, Rahman NA, Lee VS

J Biol Phys, 2019 03;45(1):63-76.
PMID: 30680580 DOI: 10.1007/s10867-018-9515-6

In this study, we investigate the binding interactions of two synthetic antiviral peptides (DET2 and DET4) on type II dengue virus (DENV2) envelope protein domain III. These two antiviral peptides are designed based on the domain III of the DENV2 envelope protein, which has shown significant inhibition activity in previous studies and can be potentially modified further to be active against all dengue strains. Molecular docking was performed using AutoDock Vina and the best-ranked peptide-domain III complex was further explored using molecular dynamics simulations. Molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) was used to calculate the relative binding free energies and to locate the key residues of peptide-protein interactions. The predicted binding affinity correlated well with the previous experimental studies. DET4 outperformed DET2 and is oriented within the binding site through favorable vdW and electrostatic interactions. Pairwise residue decomposition analysis has revealed several key residues that contribute to the binding of these peptides. Residues in DET2 interact relatively lesser with the domain III compared to DET4. Dynamic cross-correlation analysis showed that both the DET2 and DET4 trigger different dynamic patterns on the domain III. Correlated motions were seen between the residue pairs of DET4 and the binding site while binding of DET2 results in anti-correlated motion on the binding site. This work showcases the use of computational study in elucidating and explaining the experiment observation on an atomic level.
Fulltext High Dose of Intravenous Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells (CLV-100) Infusion Displays Better Immunomodulatory Effect among Healthy Volunteers: A Phase 1 Clinical Study

Chin SP, Mohd-Shahrizal MY, Liyana MZ, Then KY, Cheong SK

Stem Cells Int, 2020;2020:8877003.
PMID: 33061992 DOI: 10.1155/2020/8877003

Background: Mesenchymal stem cells (MSCs) express growth factors and other cytokines that stimulate repair and control the immune response. MSCs are also immunoprivileged with low risk of rejection. Umbilical cord-derived MSCs (UCMSCs) are particularly attractive as an off-the-shelf allogeneic treatment in emergency medical conditions. We aim to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs (CLV-100) by Cytopeutics® (Selangor, Malaysia) in healthy volunteers, and to determine the effective dose at which an immunomodulatory effect is observed. Methodology. Umbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents, and grandparents) were screened for genetic mutations, infections, cancers, and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 and followed up for 6 months. We measured cytokines using ELISA including anti-inflammatory cytokines interleukin 1 receptor antagonist (IL-1RA), interleukin 10 (IL-10), pro-/anti-inflammatory cytokine interleukin 6 (IL-6), and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α).
Results: 11 healthy subjects (LD, n = 5; HD, n = 6; mean age of 55 ± 13 years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study especially in vital parameters and routine blood tests. At 6 months, the HD group had significantly higher levels of anti-inflammatory markers IL1-RA (705 ± 160 vs. 306 ± 36 pg/mL; p = 0.02) and IL-10 (321 ± 27 vs. 251 ± 28 pg/mL; p = 0.02); and lower levels of proinflammatory marker TNF-α (74 ± 23 vs. 115 ± 15 pg/mL; p = 0.04) compared to LD group.
Conclusion: Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with a high-dose infusion.
Toward activated homology models of the human M1 muscarinic acetylcholine receptor

Chin SP, Buckle MJ, Chalmers DK, Yuriev E, Doughty SW

J Mol Graph Model, 2014 Apr;49:91-8.
PMID: 24631873 DOI: 10.1016/j.jmgm.2014.02.002

Structure-based virtual screening offers a good opportunity for the discovery of selective M1 muscarinic acetylcholine receptor (mAChR) agonists for the treatment of Alzheimer's disease. However, no 3-D structure of an M1 mAChR is yet available and the homology models that have been previously reported are only able to identify antagonists in virtual screening experiments. In this study, we generated a homology model of the human M1 mAChR, based on the crystal structure of an M3 mAChR as the template. This initial model was modified, using the agonist-bound crystal structure of a β2-adrenergic receptor as a guide, to give two possible activated structures. The T192 side chain was adjusted in both structures and one of the structures also had the whole of transmembrane (TM) 5 rotated and tilted toward the inner channel of the transmembrane region. The binding sites of all three structures were then refined by induced-fit docking (IFD) with acetylcholine. Virtual screening experiments showed that all three refined models could efficiently differentiate agonists from decoy molecules, with the TM5-modified models also giving good agonist/antagonist selectivity. The whole range of agonists and antagonists was observed to bind within the orthosteric site of the structure obtained by IFD refinement alone, implying that it has inactive state character. In contrast, the two TM5-modified structures were unable to accommodate the antagonists, supporting the proposition that they possess activated state character.
Fulltext Acute coronary syndrome in women of reproductive age

Idris N, Aznal SS, Chin SP, Wan Ahmad WA, Rosman A, Jeyaindran S, et al.

Int J Womens Health, 2011;3:375-80.
PMID: 22140324 DOI: 10.2147/IJWH.S15825

There is scarce or no data on prevalence and presentation of acute coronary syndrome (ACS) among women of reproductive age. Furthermore, whether women of reproductive age presenting with ACS have the same risk factors as men and older women is not known.
Intramyocardial and intracoronary autologous bone marrow-derived mesenchymal stromal cell treatment in chronic severe dilated cardiomyopathy

Chin SP, Poey AC, Wong CY, Chang SK, Tan CS, Ng MT, et al.

Cytotherapy, 2011 Aug;13(7):814-21.
PMID: 21526902 DOI: 10.3109/14653249.2011.574118

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) may improve cardiac function following myocardial infarction. MSC can differentiate into cardiomyocytes and endothelial cells while exerting additional paracrine effects. There is limited information regarding the efficacy of route for MSC treatment of severe dilated cardiomyopathy (DCM). The aim of this study was to demonstrate the clinical safety, feasibility and efficacy of direct intramyocardial and intracoronary administration of autologous bone marrow-derived MSC treatment for no-option patients with chronic severe refractory DCM.
METHODS: Ten symptomatic patients with DCM and refractory cardiac function, despite maximum medical therapy, were selected. Five had ischemic DCM deemed unlikely to benefit from revascularization alone and underwent bypass operations with concurrent intramyocardial MSC injection (group A). Two patients had previous revascularization and three had non-ischemic DCM and received intracoronary MSC injection (group B).
RESULTS: Group A and B patients received 0.5-1.0 × 10(6) and 2.0-3.0 × 10(6) MSC/kg body weight, respectively. All patients remained alive at 1 year. There were significant improvements from baseline to 6 and 12 months in left ventricular ejection fraction and other left ventricular parameters. Scar reduction was noted in six patients by 12 months.
CONCLUSIONS: Autologous bone marrow MSC treatment is safe and feasible for treating chronic severe refractory DCM effectively, via intracoronary or direct intramyocardial administration at prescribed doses.
Synergistic effects of intracoronary infusion of autologous bone marrow-derived mesenchymal stem cells and revascularization procedure on improvement of cardiac function in patients with severe ischemic cardiomyopathy

Chin SP, Maskon O, Tan CS, Anderson JE, Wong CY, Hassan HHC, et al.

Stem Cell Investig, 2021;8:2.
PMID: 33575315 DOI: 10.21037/sci-2020-026

Background: Ischemic cardiomyopathy (ICM) is a leading cause of cardiovascular mortality worldwide. It is defined as abnormal enlargement of the left ventricular (LV) cavity with poor LV function due to coronary artery disease. Currently available established treatments are palliative whereby blood supply is recovered to ischemic regions but fails to regenerate heart tissues. Mesenchymal stem cells (MSCs) offer a promising treatment for ICM given their regenerative and multipotent characteristics. This study aims to investigate the effect of MSCs infusion with concurrent revascularization in patients with severe ICM compared to receiving only revascularization procedure or MSCs infusion.
Methods: Twenty-seven patients with history of anterior myocardial infarction (MI) and baseline left ventricular ejection fraction (LVEF) of less than 35% were recruited into this study. Patients who are eligible for revascularization were grouped into group A (MSCs infusion with concurrent revascularization) or group B (revascularization only) while patients who were not eligible for revascularization were allocated in group C to receive intracoronary MSCs infusion. LV function was measured using echocardiography.
Results: Patients who received MSCs infusion (either with or without revascularization) demonstrated significant LVEF improvements at 3, 6 and 12 months post-infusion when compared to baseline LVEF within its own group. When comparing the groups, the magnitude of change in LVEF from baseline for third visits i.e., 12 months post-infusion was significant for patients who received MSCs infusion plus concurrent revascularization in comparison to patients who only had the revascularization procedure.
Conclusions: MSCs infusion significantly improves LV function in ICM patients. MSCs infusion plus concurrent revascularization procedure worked synergistically to improve cardiac function in patients with severe ICM.

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