Displaying publications 21 - 40 of 50 in total

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  1. Md Idris N, Chiam YK, Varathan KD, Wan Ahmad WA, Chee KH, Liew YM
    Med Biol Eng Comput, 2020 Dec;58(12):3123-3140.
    PMID: 33155096 DOI: 10.1007/s11517-020-02268-9
    Coronary artery disease (CAD) is an important cause of mortality across the globe. Early risk prediction of CAD would be able to reduce the death rate by allowing early and targeted treatments. In healthcare, some studies applied data mining techniques and machine learning algorithms on the risk prediction of CAD using patient data collected by hospitals and medical centers. However, most of these studies used all the attributes in the datasets which might reduce the performance of prediction models due to data redundancy. The objective of this research is to identify significant features to build models for predicting the risk level of patients with CAD. In this research, significant features were selected using three methods (i.e., Chi-squared test, recursive feature elimination, and Embedded Decision Tree). Synthetic Minority Over-sampling Technique (SMOTE) oversampling technique was implemented to address the imbalanced dataset issue. The prediction models were built based on the identified significant features and eight machine learning algorithms, utilizing Acute Coronary Syndrome (ACS) datasets provided by National Cardiovascular Disease Database (NCVD) Malaysia. The prediction models were evaluated and compared using six performance evaluation metrics, and the top-performing models have achieved AUC more than 90%. Graphical abstract.
  2. Tan LK, Liew YM, Lim E, Abdul Aziz YF, Chee KH, McLaughlin RA
    Med Biol Eng Comput, 2018 Jun;56(6):1053-1062.
    PMID: 29147835 DOI: 10.1007/s11517-017-1750-7
    In this paper, we develop and validate an open source, fully automatic algorithm to localize the left ventricular (LV) blood pool centroid in short axis cardiac cine MR images, enabling follow-on automated LV segmentation algorithms. The algorithm comprises four steps: (i) quantify motion to determine an initial region of interest surrounding the heart, (ii) identify potential 2D objects of interest using an intensity-based segmentation, (iii) assess contraction/expansion, circularity, and proximity to lung tissue to score all objects of interest in terms of their likelihood of constituting part of the LV, and (iv) aggregate the objects into connected groups and construct the final LV blood pool volume and centroid. This algorithm was tested against 1140 datasets from the Kaggle Second Annual Data Science Bowl, as well as 45 datasets from the STACOM 2009 Cardiac MR Left Ventricle Segmentation Challenge. Correct LV localization was confirmed in 97.3% of the datasets. The mean absolute error between the gold standard and localization centroids was 2.8 to 4.7 mm, or 12 to 22% of the average endocardial radius. Graphical abstract Fully automated localization of the left ventricular blood pool in short axis cardiac cine MR images.
  3. Chan SP, Mumtaz M, Ratnasingam J, Tan ATB, Lim SC, Rosman A, et al.
    PMID: 37292224 DOI: 10.51866/cpg.255
    Insulin degludec/insulin aspart (IDegAsp) co-formulation provides both basal and mealtime glycaemic control in a single injection. The glucose level-lowering efficacy of IDegAsp is reported to be superior or non-inferior to that of the currently available insulin therapies with a lower rate of overall hypoglycaemia and nocturnal hypoglycaemia. An expert panel from Malaysia aims to provide insights into the utilisation of IDegAsp across a broad range of patients with type 2 diabetes mellitus (i.e. treatment-naive or insulin-naive patients or patients receiving treatment intensification from basal-only regimens, premixed insulin and basal-bolus insulin therapy). IDegAsp can be initiated as once-daily dosing for the main meal with the largest carbohydrate content with weekly dose adjustments based on patient response. A lower starting dose is recommended for patients with cardiac or renal comorbidities. Dose intensification with IDegAsp may warrant splitting into twice-daily dosing. IDegAsp twice-daily dosing does not need to be split at a 50:50 ratio but should be adjusted to match the carbohydrate content of meals. The treatment of patients choosing to fast during Ramadan should be switched to IDegAsp early before Ramadan, as a longer duration of titration leads to better glycated haemoglobin level reductions. The pre-Ramadan breakfast/lunch insulin dose can be reduced by 30%-50% and taken during sahur, while the preRamadan dinner dose can be taken without any change during iftar. Education on the main meal concept is important, as carbohydrates are present in almost all meals. Patients should not have a misconception of consuming more carbohydrates while taking IDegAsp.
  4. Leong CO, Lim E, Tan LK, Abdul Aziz YF, Sridhar GS, Socrates D, et al.
    Magn Reson Med, 2019 02;81(2):1385-1398.
    PMID: 30230606 DOI: 10.1002/mrm.27486
    PURPOSE: To evaluate a 2D-4D registration-cum-segmentation framework for the delineation of left ventricle (LV) in late gadolinium enhanced (LGE) MRI and for the localization of infarcts in patient-specific 3D LV models.

    METHODS: A 3-step framework was proposed, consisting of: (1) 3D LV model reconstruction from motion-corrected 4D cine-MRI; (2) Registration of 2D LGE-MRI with 4D cine-MRI; (3) LV contour extraction from the intersection of LGE slices with the LV model. The framework was evaluated against cardiac MRI data from 27 patients scanned within 6 months after acute myocardial infarction. We compared the use of local Pearson's correlation (LPC) and normalized mutual information (NMI) as similarity measures for the registration. The use of 2 and 6 long-axis (LA) cine-MRI scans was also compared. The accuracy of the framework was evaluated using manual segmentation, and the interobserver variability of the scar volume derived from the segmented LV was determined using Bland-Altman analysis.

    RESULTS: LPC outperformed NMI as a similarity measure for the proposed framework using 6 LA scans, with Hausdorrf distance (HD) of 1.19 ± 0.53 mm versus 1.51 ± 2.01 mm (endocardial) and 1.21 ± 0.48 mm versus 1.46 ± 1.78 mm (epicardial), respectively. Segmentation using 2 LA scans was comparable to 6 LA scans with a HD of 1.23 ± 0.70 mm (endocardial) and 1.25 ± 0.74 mm (epicardial). The framework yielded a lower interobserver variability in scar volumes compared with manual segmentation.

    CONCLUSION: The framework showed high accuracy and robustness in delineating LV in LGE-MRI and allowed for bidirectional mapping of information between LGE- and cine-MRI scans, crucial in personalized model studies for treatment planning.

  5. Goldhaber SZ, Ageno W, Casella IB, Chee KH, Schellong S, Singer DE, et al.
    J Thromb Thrombolysis, 2021 Aug 28.
    PMID: 34453675 DOI: 10.1007/s11239-021-02463-x
    RE-COVERY DVT/PE is a two-phase, international, observational study of anticoagulant therapy in patients with deep vein thrombosis and/or pulmonary embolism (DVT/PE). The objective of the second phase was to compare the safety and effectiveness of dabigatran versus a vitamin K antagonist (VKA) over 1 year of follow-up. Primary safety and effectiveness outcomes were major or clinically relevant nonmajor bleeding events (MBE/CRNMBEs) and symptomatic recurrent venous thromboembolism (VTE) (including deaths related to recurrent VTE). To minimize bias due to unbalanced patient characteristics, only patients in an overlapping range of estimated propensity scores were included (analytic set), and propensity score weighting was applied to compare outcomes. Outcome analysis used an as-treated approach, censoring patients after they stopped or switched their initial anticoagulant. Overall, 3009 patients enrolled from 2016 to 2018 were eligible: 60% were diagnosed with DVT alone, 21% with PE alone, and 19% with DVT plus PE. The analytic set consisted of 2969 patients. The incidence rate in %/year (95% confidence interval [CI]) of MBE/CRNMBEs was 2.63 (1.79-3.74) with dabigatran versus 4.48 (3.23-6.06) with warfarin; hazard ratio 0.63 (95% CI 0.32-1.25). For symptomatic recurrent nonfatal or fatal VTE the incidence rate was 1.53 (0.91-2.42) with dabigatran versus 2.01 (1.21-3.14) with VKAs; hazard ratio 0.78 (95% CI 0.30-2.02). In conclusion, we found lower annualized rates of MBE/CRNMBEs with dabigatran than VKA, although the difference was not statistically significant. Annualized rates of symptomatic VTE or related mortality were similar with dabigatran and VKA. These observational results with 1 year of follow-up reflect those of the randomized clinical trials. Trial registration: ClinicalTrials.gov identifier NCT02596230, first registered November 4, 2015.
  6. Ageno W, Casella IB, Chee KH, Schellong S, Schulman S, Singer DE, et al.
    J Thromb Thrombolysis, 2021 Apr;51(3):561-570.
    PMID: 32851572 DOI: 10.1007/s11239-020-02239-9
    In randomized clinical trials (RCTs) of nonvitamin K antagonist oral anticoagulants (NOACs) for acute venous thromboembolism (VTE), ~ 12-13% of patients were elderly and ~ 26% had mild-to-moderate renal impairment. Observational studies are not restricted by the selection and treatment criteria of RCTs. In this ancillary analysis of the RE-COVERY DVT/PE global observational study, we aimed to describe patient characteristics, comorbidities, and anticoagulant therapy for subgroups of age (
  7. Chee KH, Amudha K, Hussain NA, Haizal HK, Choy AM, Lang CC
    PMID: 14608517
    Conventional diuretic agents are very effective agents in relieving volume overload and congestive symptoms in chronic heart failure (CHF). However, they are associated with activation of the renin-angiotensin system (RAS) and the sympathetic nervous system and a reduction in glomerular filtration rate, all of which have been associated with adverse outcomes in CHF. Therefore, there is an increasing interest in drugs that target the natriuretic system without neurohormonal activation and deterioration of renal function. In this review, we will discuss the underlying rationale and evidence behind currently pursued strategies that target the natriuretic system. This includes the administration of natriuretic peptides (NPs) and strategies that potentiate the NP system, such as neutral endopeptidase inhibition. We will also highlight some potentially important interactions of these strategies with drugs that target the RAS.
  8. Ahmad F, Sadiq MA, Chee KH, Mahmood Zuhdi AS, Wan Ahmad WA
    J Coll Physicians Surg Pak, 2014 Jun;24(6):441-3.
    PMID: 24953923 DOI: 06.2014/JCPSP.441443
    Pulmonary hypertension is frequently associated with atrial septal defect and various connective tissue disorders. This case describes a 74-year-old woman who presented with symptoms of heart failure and concomitant involvement of salivary glands and keratoconjunctivitis. An echocardiogram demonstrated ostium secundum atrial septal defect with left to right shunt and severe pulmonary hypertension. Laboratory investigations confirmed the diagnosis of Sjögren's syndrome (SS) with positive anti-nuclear factor and centromere SS-A/Ro pattern. Anti-Ro (SS-A) was found positive. Atrial septal defect was closed through transcatheter route with significant improvement in clinical outcome. This case report suggests a possible association of atrial septal defect with primary Sjögren's syndrome in an adult patient.
  9. Beshir SA, Yap LB, Sim S, Chee KH, Lo YL
    J Pharm Pharm Sci, 2017;20(1):365-377.
    PMID: 29145930 DOI: 10.18433/J3TP9Q
    PURPOSE: To assess the predicted rate and the factors associated with bleeding events among patients with non-valvular atrial fibrillation (NVAF) receiving dabigatran therapy.

    METHODS: This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified using pharmacy supply database or novel oral anticoagulant (NOAC) registry. Demographics, clinical data and laboratory test results were extracted from the medical records of the patients or electronic databases. The main outcome measure is the occurrence of a bleeding event. Bleeding events were classified into major bleeding, clinically relevant non-major bleeding, or minor bleeding, according to the International Society on Thrombosis and Haemostasis criteria. We consider clinically relevant non-major bleeding events or major bleeding events as clinically relevant bleeding events. An occurrence of any bleeding event was recorded from the initiation of NOAC therapy until the death of a patient, or the date of permanent discontinuation of NOAC use, or the last day of data collection. The predicted rate of dabigatran-induced bleeding events per 100 patient-years was estimated.

    RESULTS: During a median follow-up period of 18 months, 73 patients experienced 90 bleeding events. Among these patients, 25 including 4 fatal cases, experienced major bleeding events. The predicted rate per 100 patient-years of follow-up of any bleeding events was 9.0 [95% CI 6.9 to 11.1]; clinically relevant bleeding events 6.0 [95% CI 4.8 to 8.3], and major bleeding events 3.0 [95% CI 1.9 to 4.2]. The independent risk factor for clinically relevant bleeding events is prior bleeding. While prior bleeding or congestive heart failure is linked with major bleeding events.

    CONCLUSIONS: The predicted rate for dabigatran-induced major bleeding episodes is low but these adverse events carry a high fatality risk. Preventive measures should target older patients who have prior bleeding or congestive heart failure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  10. Kuan WC, Chee KH, Kasim S, Lim KK, Dujaili JA, Lee KK, et al.
    J Med Econ, 2024;27(1):607-617.
    PMID: 38557412 DOI: 10.1080/13696998.2024.2337563
    AIM: This study aimed to examine the validity of EQ-5D-5L among HFrEF patients in Malaysia, and to explore the measurement equivalence of three main language versions.

    METHODS: We surveyed HFrEF patients from two hospitals in Malaysia, using Malay, English or Chinese versions of EQ-5D-5L. EQ-5D-5L dimensional scores were converted to utility scores using the Malaysian value set. A confirmatory factor analysis longitudinal model was constructed. The utility and visual analog scale (VAS) scores were evaluated for validity (convergent, known-group, responsiveness), and measurement equivalence of the three language versions.

    RESULTS: 200 HFrEF patients (mean age = 61 years), predominantly male (74%) of Malay ethnicity (55%), completed the admission and discharge EQ-5D-5L questionnaire in Malay (49%), English (26%) or Chinese (25%) languages. 173 patients (86.5%) were followed up at 1-month post-discharge (1MPD). The standardized factor loadings and average variance extracted were ≥ 0.5 while composite reliability was ≥ 0.7, suggesting convergent validity. Patients with older age and higher New York Heart Association (NYHA) class reported significantly lower utility and VAS scores. The change in utility and VAS scores between admission and discharge was large, while the change between discharge and 1MPD was minimal. The minimal clinically important difference for utility and VAS scores was ±0.19 and ±11.01, respectively. Malay and English questionnaire were equivalent while the equivalence of Malay and Chinese questionnaire was inconclusive.

    LIMITATION: This study only sampled HFrEF patients from two teaching hospitals, thus limiting the generalizability of results to the entire heart failure population.

    CONCLUSION: EQ-5D-5L is a valid questionnaire to measure health-related quality of life and estimate utility values among HFrEF patients in Malaysia. The Malay and English versions of EQ-5D-5L appear equivalent for clinical and economic assessments.

  11. Leong CO, Liew YM, Bilgen M, Abdul Aziz YF, Chee KH, Chiam YK, et al.
    J Magn Reson Imaging, 2016 Jul 15.
    PMID: 27418150 DOI: 10.1002/jmri.25390
    To propose a cardiac motion tracking model that evaluates wall motion abnormality in postmyocardial infarction patients. Correlation between the motion parameter of the model and left ventricle (LV) function was also determined.
  12. Khalid A, Lim E, Chan BT, Abdul Aziz YF, Chee KH, Yap HJ, et al.
    J Magn Reson Imaging, 2019 04;49(4):1006-1019.
    PMID: 30211445 DOI: 10.1002/jmri.26302
    BACKGROUND: Existing clinical diagnostic and assessment methods could be improved to facilitate early detection and treatment of cardiac dysfunction associated with acute myocardial infarction (AMI) to reduce morbidity and mortality.

    PURPOSE: To develop 3D personalized left ventricular (LV) models and thickening assessment framework for assessing regional wall thickening dysfunction and dyssynchrony in AMI patients.

    STUDY TYPE: Retrospective study, diagnostic accuracy.

    SUBJECTS: Forty-four subjects consisting of 15 healthy subjects and 29 AMI patients.

    FIELD STRENGTH/SEQUENCE: 1.5T/steady-state free precession cine MRI scans; LGE MRI scans.

    ASSESSMENT: Quantitative thickening measurements across all cardiac phases were correlated and validated against clinical evaluation of infarct transmurality by an experienced cardiac radiologist based on the American Heart Association (AHA) 17-segment model.

    STATISTICAL TEST: Nonparametric 2-k related sample-based Kruskal-Wallis test; Mann-Whitney U-test; Pearson's correlation coefficient.

    RESULTS: Healthy LV wall segments undergo significant wall thickening (P 50% transmurality) underwent remarkable wall thinning during contraction (thickening index [TI] = 1.46 ± 0.26 mm) as opposed to healthy myocardium (TI = 4.01 ± 1.04 mm). For AMI patients, LV that showed signs of thinning were found to be associated with a significantly higher percentage of dyssynchrony as compared with healthy subjects (dyssynchrony index [DI] = 15.0 ± 5.0% vs. 7.5 ± 2.0%, P 

  13. Beshir SA, Aziz Z, Yap LB, Chee KH, Lo YL
    J Clin Pharm Ther, 2018 Apr;43(2):209-219.
    PMID: 29030869 DOI: 10.1111/jcpt.12634
    WHAT IS KNOWN AND OBJECTIVE: Bleeding risk scores (BRSs) aid in the assessment of oral anticoagulant-related bleeding risk in patients with atrial fibrillation. Ideally, the applicability of a BRS needs to be assessed, prior to its routine use in a population other than the original derivation cohort. Therefore, we evaluated the performance of 6 established BRSs to predict major or clinically relevant bleeding (CRB) events associated with the use of oral anticoagulant (OAC) among Malaysian patients.

    METHODS: The pharmacy supply database and the medical records of patients with non-valvular atrial fibrillation (NVAF) receiving warfarin, dabigatran or rivaroxaban at two tertiary hospitals were reviewed. Patients who experienced an OAC-associated major or CRB event within 12 months of follow-up, or who have received OAC therapy for at least 1 year, were identified. The BRSs were fitted separately into patient data. The discrimination and the calibration of these BRSs as well as the factors associated with bleeding events were then assessed.

    RESULTS: A total of 1017 patients with at least 1-year follow-up period, or those who developed a bleeding event within 1 year of OAC use, were recruited. Of which, 23 patients experienced a first major bleeding event, whereas 76 patients, a first CRB event. Multivariate logistic regression results show that age of 75 or older, prior bleeding and male gender are associated with major bleeding events. On the other hand, prior gastrointestinal bleeding, a haematocrit value of less than 30% and renal impairment are independent predictors of CRB events. All the BRSs show a satisfactory calibration for major and CRB events. Among these BRSs, only HEMORR2 HAGES (C-statistic = 0.71, 95% CI 0.60-0.82, P 

  14. Yong YL, Tan LK, McLaughlin RA, Chee KH, Liew YM
    J Biomed Opt, 2017 12;22(12):1-9.
    PMID: 29274144 DOI: 10.1117/1.JBO.22.12.126005
    Intravascular optical coherence tomography (OCT) is an optical imaging modality commonly used in the assessment of coronary artery diseases during percutaneous coronary intervention. Manual segmentation to assess luminal stenosis from OCT pullback scans is challenging and time consuming. We propose a linear-regression convolutional neural network to automatically perform vessel lumen segmentation, parameterized in terms of radial distances from the catheter centroid in polar space. Benchmarked against gold-standard manual segmentation, our proposed algorithm achieves average locational accuracy of the vessel wall of 22 microns, and 0.985 and 0.970 in Dice coefficient and Jaccard similarity index, respectively. The average absolute error of luminal area estimation is 1.38%. The processing rate is 40.6 ms per image, suggesting the potential to be incorporated into a clinical workflow and to provide quantitative assessment of vessel lumen in an intraoperative time frame.
  15. Chee KH, Azman W
    Int J Clin Pract, 2009 May;63(5):722-5.
    PMID: 18028390
    Peripartum cardiomyopathy (PPCM) is an uncommon form of congestive heart failure, afflicting obstetric patients around the time of delivery. The epidemiology of PPCM is infrequently reported. To the best of our knowledge, there has been no report from Asia.
  16. Chee KH, Siaw FS, Chan CG, Chong WP, Imran ZA, Haizal HK, et al.
    Int J Clin Pract, 2005 Jun;59(6):628-31.
    PMID: 15924588
    This single centre study was designed to demonstrate feasibility, safety and efficacy of the Vivant Z stent (PFM AG, Cologne, Germany). Patients with de novo lesion were recruited. Coronary angioplasty was performed with either direct stenting or after balloon predilatation. Repeated angiogram was performed 6 months later or earlier if clinically indicated. Between January to June 2003, a total of 50 patients were recruited (mean age 55.8 +/- 9 years). A total of 52 lesions were stented successfully. Mean reference diameter was 2.77 mm (+/-0.59 SD, range 2.05-4.39 mm) with mean target lesion stenosis of 65.5% (+/-11.6 SD, range 50.1-93.3%). Forty-six lesions (88.5%) were American College of Cardiologist/American Heart Association class B/C types. Direct stenting was performed in 18 (34.6%) lesions. Mean stent diameter was 3.18 mm (+/-0.41 SD, range 2.5-4 mm), and mean stent length was 14.86 mm (+/-2.72 SD, range 9-18 mm). The procedure was complicated in only one case which involved the loss of side branch with no clinical sequelae. All treated lesions achieved Thrombolysis In Myocardial Infarction 3 flow. Mean residual diameter stenosis was 12.2% (+/-7.55 SD, range 0-22.6%) with acute gain of 1.72 mm (+/-0.50 SD, range 0.5-2.8). At 6 months, there was no major adverse cardiovascular event. Repeated angiography after 6 months showed a restenosis rate of 17% (defined as >50% diameter restenosis). Mean late loss was 0.96 mm (+/-0.48 SD) with loss index of 0.61 (+/-0.38 SD). The restenosis rate of those lesions less than 3.0 mm in diameter was 22.2% compared with 6.25% in those lesions more than 3.0 mm in diameter. The Vivant Z stent was shown to be safe and efficacious with low restenosis rate in de novo coronary artery lesion.
  17. Amudha K, Chee KH, Tan KS, Tan CT, Lang CC
    Int J Clin Pract, 2003 Jun;57(5):369-72.
    PMID: 12846339
    Atherosclerosis is a progressive, disseminated condition that affects all the vascular beds. Peripheral arterial disease (PAD), a manifestation of atherosclerosis, measured non-invasively in the legs by ankle-brachial index (ABI) is associated with increased cardiovascular morbidity and mortality. Though several studies in the western industrialised countries have shown that PAD is widely prevalent in the general older population at risk, not much data are available in the South East Asian developing countries. We have conducted an epidemiological survey on the prevalence of PAD in high-risk patients at an urban hospital in Malaysia. A total of 301 consecutive patients aged 32-90 years were recruited during their follow-up clinic visits for established cardiovascular disease, ischaemic stroke or diabetes mellitus > or = 5 years. All participants underwent ABI measurement and were subjected to the Edinburgh claudication questionnaire to assess leg symptoms. The prevalence of PAD in our high-risk population was 23%, of which only 27% were symptomatic with the classical intermittent claudication. All the patients with PAD were diagnosed at the time of the study. PAD was found in 33% of patients with pre-existent cardiovascular disease, 28% in patients with ischaemic stroke and 24% in diabetic patients. PAD was also highly prevalent among the younger patients. Our study has shown that PAD is highly prevalent among high-risk Malaysian patients and is not necessarily a disease of older age. Only 27% of these patients were symptomatic. All the subjects with PAD were diagnosed at the time of the study, which would suggest it is an unrecognised and underdiagnosed condition, even in patients with atherosclerotic risk factors.
  18. Beshir SA, Chee KH, Lo YL
    Int J Clin Pharm, 2016 Oct;38(5):1182-90.
    PMID: 27450507 DOI: 10.1007/s11096-016-0350-1
    Background Oral anticoagulant therapy is indicated for the prevention of stroke or other thromboembolic events. Premature discontinuation of oral anticoagulants may increase the risk of thromboembolism resulting in adverse sequelae. There are sparse data on the prevalence and the predictors of dabigatran discontinuation in Malaysian patients with atrial fibrillation. Objectives Determine the reasons and identify associated factors for abrupt discontinuation of dabigatran, assess the switching pattern and the occurrence of thromboembolic events after dabigatran discontinuation. Setting A university-affiliated tertiary hospital in Kuala Lumpur, Malaysia. Methods The clinical and demographic data of a cohort who were initiated with dabigatran between 2010 and 2012 at the University of Malaya Medical Centre were reviewed until the date of death or on 31st December 2013. Those patients who discontinued dabigatran were further followed up until 31st December 2015 to determine the occurrence of any thromboembolic event. Main outcome measure Permanent discontinuation of dabigatran for more than 8 weeks. Results 26 (14 %) of a cohort of 192 patients discontinued dabigatran therapy during a median follow-up period of 20 (range 3-45) months. About one-half of the discontinuation occurred within the first 6 months of dabigatran use. The three most cited reasons for discontinuation are bleeding events (19 %), high out-of-pocket drug payment (19 %) and cardioversion (19 %). Heart failure [adjusted odds ratio 3.699 (95 % confidence interval 1.393-9.574)] or chronic kidney disease [adjusted odds ratio 5.211 (95 % confidence interval 1.068-23.475)] were found to be independent risk factors for abrupt dabigatran discontinuation. Patients who discontinued dabigatran received warfarin (38 %), antiplatelet agents (16 %) or no alternative antithrombotic therapy (46 %). Five of the 26 patients who discontinued dabigatran developed an ischaemic stroke within 3-34 months after discontinuation. Conclusion Abrupt dabigatran discontinuation without an alternative oral anticoagulant increases the risk of thromboembolic events. As adverse drug events and renal impairment contribute substantially to the premature discontinuation of dabigatran, it is important to identify and monitor patients at risk to reduce dabigatran discontinuation rate especially during the first six months of dabigatran therapy.
  19. Leong CN, Dokos S, Andriyana A, Liew YM, Chan BT, Abdul Aziz YF, et al.
    Int J Numer Method Biomed Eng, 2020 01;36(1):e3291.
    PMID: 31799767 DOI: 10.1002/cnm.3291
    Myocardial infarct extension, a process involving the enlargement of infarct and border zone, leads to progressive degeneration of left ventricular (LV) function and eventually gives rise to heart failure. Despite carrying a high risk, the causation of infarct extension is still a subject of much speculation. In this study, patient-specific LV models were developed to investigate the correlation between infarct extension and impaired regional mechanics. Subsequently, sensitivity analysis was performed to examine the causal factors responsible for the impaired regional mechanics observed in regions surrounding the infarct and border zone. From our simulations, fibre strain, fibre stress and fibre stress-strain loop (FSSL) were the key biomechanical variables affected in these regions. Among these variables, only FSSL was correlated with infarct extension, as reflected in its work density dissipation (WDD) index value, with high WDD indices recorded at regions with infarct extension. Impaired FSSL is caused by inadequate contraction force generation during the isovolumic contraction and ejection phases. Our further analysis revealed that the inadequacy in contraction force generation is not necessarily due to impaired myocardial intrinsic contractility, but at least in part, due to inadequate muscle fibre stretch at end-diastole, which depresses the ability of myocardium to generate adequate contraction force in the subsequent systole (according to the Frank-Starling law). Moreover, an excessively stiff infarct may cause its neighbouring myocardium to be understretched at end-diastole, subsequently depressing the systolic contractile force of the neighbouring myocardium, which was found to be correlated with infarct extension.
  20. Leong CO, Leong CN, Liew YM, Al Abed A, Aziz YFA, Chee KH, et al.
    Int J Numer Method Biomed Eng, 2021 08;37(8):e3501.
    PMID: 34057819 DOI: 10.1002/cnm.3501
    Infarct extension involves necrosis of healthy myocardium in the border zone (BZ), progressively enlarging the infarct zone (IZ) and recruiting the remote zone (RZ) into the BZ, eventually leading to heart failure. The mechanisms underlying infarct extension remain unclear, but myocyte stretching has been suggested as the most likely cause. Using human patient-specific left-ventricular (LV) numerical simulations established from cardiac magnetic resonance imaging (MRI) of myocardial infarction (MI) patients, the correlation between infarct extension and regional mechanics abnormality was investigated by analysing the fibre stress-strain loops (FSSLs). FSSL abnormality was characterised using the directional regional external work (DREW) index, which measures FSSL area and loop direction. Sensitivity studies were also performed to investigate the effect of infarct stiffness on regional myocardial mechanics and potential for infarct extension. We found that infarct extension was correlated to severely abnormal FSSL in the form of counter-clockwise loop at the RZ close to the infarct, as indicated by negative DREW values. In regions demonstrating negative DREW values, we observed substantial fibre stretching in the isovolumic relaxation (IVR) phase accompanied by a reduced rate of systolic shortening. Such stretching in IVR phase in part of the RZ was due to its inability to withstand the high LV pressure that was still present and possibly caused by regional myocardial stiffness inhomogeneity. Further analysis revealed that the occurrence of severely abnormal FSSL due to IVR fibre stretching near the RZ-BZ boundary was due to a large amount of surrounding infarcted tissue, or an excessively stiff IZ.
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