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  1. Juhan N, Zubairi YZ, Mahmood Zuhdi AS, Mohd Khalid Z
    BMJ Open, 2023 Nov 03;13(11):e066748.
    PMID: 37923353 DOI: 10.1136/bmjopen-2022-066748
    OBJECTIVES: Despite extensive advances in medical and surgical treatment, cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Identifying the significant predictors will help clinicians with the prognosis of the disease and patient management. This study aims to identify and interpret the dependence structure between the predictors and health outcomes of ST-elevation myocardial infarction (STEMI) male patients in Malaysian setting.

    DESIGN: Retrospective study.

    SETTING: Malaysian National Cardiovascular Disease Database-Acute Coronary Syndrome (NCVD-ACS) registry years 2006-2013, which consists of 18 hospitals across the country.

    PARTICIPANTS: 7180 male patients diagnosed with STEMI from the NCVD-ACS registry.

    PRIMARY AND SECONDARY OUTCOME MEASURES: A graphical model based on the Bayesian network (BN) approach has been considered. A bootstrap resampling approach was integrated into the structural learning algorithm to estimate probabilistic relations between the studied features that have the strongest influence and support.

    RESULTS: The relationships between 16 features in the domain of CVD were visualised. From the bootstrap resampling approach, out of 250, only 25 arcs are significant (strength value ≥0.85 and the direction value ≥0.50). Age group, Killip class and renal disease were classified as the key predictors in the BN model for male patients as they were the most influential variables directly connected to the outcome, which is the patient status. Widespread probabilistic associations between the key predictors and the remaining variables were observed in the network structure. High likelihood values are observed for patient status variable stated alive (93.8%), Killip class I on presentation (66.8%), patient younger than 65 (81.1%), smoker patient (77.2%) and ethnic Malay (59.2%). The BN model has been shown to have good predictive performance.

    CONCLUSIONS: The data visualisation analysis can be a powerful tool to understand the relationships between the CVD prognostic variables and can be useful to clinicians.

  2. Juhan N, Zubairi YZ, Khalid ZM, Mahmood Zuhdi AS
    Iran J Public Health, 2020 Sep;49(9):1642-1649.
    PMID: 33643938 DOI: 10.18502/ijph.v49i9.4080
    Background: Identifying risk factors associated with mortality is important in providing better prognosis to patients. Consistent with that, Bayesian approach offers a great advantage where it rests on the assumption that all model parameters are random quantities and hence can incorporate prior knowledge. Therefore, we aimed to develop a reliable model to identify risk factors associated with mortality among ST-Elevation Myocardial Infarction (STEMI) male patients using Bayesian approach.

    Methods: A total of 7180 STEMI male patients from the National Cardiovascular Disease Database-Acute Coronary Syndrome (NCVD-ACS) registry for the years 2006-2013 were enrolled. In the development of univariate and multivariate logistic regression model for the STEMI patients, Bayesian Markov Chain Monte Carlo (MCMC) simulation approach was applied. The performance of the model was assessed through convergence diagnostics, overall model fit, model calibration and discrimination.

    Results: A set of six risk factors for cardiovascular death among STEMI male patients were identified from the Bayesian multivariate logistic model namely age, diabetes mellitus, family history of CVD, Killip class, chronic lung disease and renal disease respectively. Overall model fit, model calibration and discrimination were considered good for the proposed model.

    Conclusion: Bayesian risk prediction model for CVD male patients identified six risk factors associated with mortality. Among the highest risks were Killip class (OR=18.0), renal disease (2.46) and age group (OR=2.43) respectively.

  3. 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.
  4. Mahmood Zuhdi AS, Krackhardt F, Waliszewski MW, Ismail MD, Boxberger M, Wan Ahmad WA
    Cardiol Res Pract, 2018;2018:8053168.
    PMID: 29686890 DOI: 10.1155/2018/8053168
    Objective: Coronary revascularization in chronic total occlusion (CTO) is associated with improved clinical outcomes. The choice of the coronary stent is crucial in maintaining long-term vessel patency after CTO revascularization. We investigated the efficacy and safety of polymer-free ultrathin strut sirolimus-probucol coated drug-eluting stents (PF-SES) for CTO lesions.

    Methods: Patients with CTO lesions treated with PF-SES were identified from the prospective multicenter international ISAR 2000 registry. The primary endpoint was clinically driven target lesion revascularization (TLR) at 9 months. Secondary endpoints were 9-month major adverse cardiac events (death, myocardial infarction, or TLR) (MACE) and the occurrence of stent thrombosis.

    Results: A total of 111 patients with CTO lesions (n=127) were available for analysis. The 9-month clinical follow-up rate was 91%. The mean reference vessel diameter and lesion length were 2.76 mm ± 0.40 and 26.8 mm ± 13.1, respectively. The overall DAPT duration was 9.7 ± 2.8 months. Only one (1%) in-hospital MI was reported. The TLR and MACE rates at 9 months were 2% (2/101) and 5.9% (6/101), respectively. The 9-month accumulated rates of definite or probable stent thrombosis was 0% (0/101).

    Conclusion: Revascularizations for CTO with PF-SES are associated with low rates of TLR and MACE at 9 months with no stent thrombosis. These initial findings need to be compared with results of other new generation DES of larger studies.

  5. Venkatason P, Zaharan NL, Ismail MD, Wan Ahmad WA, Mahmood Zuhdi AS
    Eur J Clin Pharmacol, 2018 Jul;74(7):953-960.
    PMID: 29582106 DOI: 10.1007/s00228-018-2451-3
    PURPOSE: Information is lacking on prescribing of preventative cardiovascular pharmacotherapies for patients with non-ST elevation myocardial infarction (NSTEMI) in the Asian region. This study examined the prescribing rate of these pharmacotherapies, comparing NSTEMI to STEMI, and variations across demographics and clinical factors within the NSTEMI group in the multi-ethnic Malaysian population.

    METHODS: This is a retrospective analysis of the Malaysian National Cardiovascular Disease Database-Acute Coronary Syndrome registry from year 2006 to 2013 (n = 30,873). On-discharge pharmacotherapies examined were aspirin, ADP-antagonists, statins, ACE-inhibitors, angiotensin-II-receptor blockers, and beta-blockers. Multivariate logistic regression was used to calculate adjusted odds ratio of receiving individual pharmacotherapies according to patients' characteristics in NSTEMI patients (n = 11,390).

    RESULTS: Prescribing rates for cardiovascular pharmacotherapies had significantly increased especially for ADP-antagonists (76%) in NSTEMI patients. More than 85% were prescribed statins and antiplatelets but rates remained significantly lower compared to STEMI. Women and those over 65 years old were less likely to be prescribed these pharmacotherapies compared to men and younger NSTEMI patients. Chinese and Indians were more likely to receive selected pharmacotherapies compared to Malays (main ethnicity). Geographical variations were observed; East Malaysian (Malaysian Borneo) patients were less likely to receive these compared to Western region of Malaysian Peninsular. Underprescribing in patients with risk factors such as diabetes were observed with other co-morbidities influencing prescribing selectively.

    CONCLUSION: This study uncovers demographic and clinical variations in cardiovascular pharmacotherapies prescribing for NSTEMI. Concerted efforts by policy makers, specialty societies, and physicians are required focusing on elderly, women, Malays, East Malaysians, and high-risk patients.

  6. Mahmood Zuhdi AS, Zeymer U, Waliszewski M, Spiecker M, Ismail MD, Boxberger M, et al.
    Springerplus, 2016;5:373.
    PMID: 27066381 DOI: 10.1186/s40064-016-2014-y
    Paclitaxel-coated balloon (PCB) angioplasty in small vessel de novo lesions has favourable outcome and appears to be an alternative to stent implantation. However there is limitted data on its use specifically in small vessel acute coronary syndrome (ACS).
  7. Tong KL, Mahmood Zuhdi AS, Wan Ahmad WA, Vanhoutte PM, de Magalhaes JP, Mustafa MR, et al.
    Int J Mol Sci, 2018 May 15;19(5).
    PMID: 29762500 DOI: 10.3390/ijms19051467
    Circulating microRNAs (miRNAs) hold great potential as novel diagnostic markers for acute coronary syndrome (ACS). This study sought to identify plasma miRNAs that are differentially expressed in young ACS patients (mean age of 38.5 ± 4.3 years) and evaluate their diagnostic potentials. Small RNA sequencing (sRNA-seq) was used to profile plasma miRNAs. Discriminatory power of the miRNAs was determined using receiver operating characteristic (ROC) analysis. Thirteen up-regulated and 16 down-regulated miRNAs were identified in young ACS patients. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) validation showed miR-183-5p was significantly up-regulated (8-fold) in ACS patients with non-ST-segment elevated myocardial infarction (NSTEMI) whereas miR-134-5p, miR-15a-5p, and let-7i-5p were significantly down-regulated (5-fold, 7-fold and 3.5-fold, respectively) in patients with ST-segment elevated myocardial infarction (STEMI), compared to the healthy controls. MiR-183-5p had a high discriminatory power to differentiate NSTEMI patients from healthy controls (area under the curve (AUC) of ROC = 0.917). The discriminatory power for STEMI patients was highest with let-7i-5p (AUC = 0.833) followed by miR-134-5p and miR-15a-5p and this further improved (AUC = 0.935) with the three miRNAs combination. Plasma miR-183-5p, miR-134-5p, miR-15a-5p and let-7i-5p are deregulated in STEMI and NSTEMI and could be potentially used to discriminate the two ACS forms.
  8. Wan Ahmad WA, Nakayoshi T, Mahmood Zuhdi AS, Ismail MD, Zainal Abidin I, Ino Y, et al.
    Heart Vessels, 2020 Apr;35(4):463-473.
    PMID: 31587103 DOI: 10.1007/s00380-019-01516-9
    Recent clinical trials have raised concerns about the safety and efficacy of ABSORB™ bioresorbable vascular scaffolds (BVS). The difference in the vascular healing process between SYNERGY™ bioabsorbable polymer-coated everolimus-eluting stents (BP-EES) and BVS remains unclear. The aim of the ENHANCE study was to compare vascular healing on BP-EES versus BVS by optical coherence tomography (OCT) and coronary angioscopy (CAS) at 4- and 12-month follow-ups. This is a prospective, non-randomized, single center clinical trial. Thirteen eligible patients with multivessel disease were enrolled. BP-EES and BVS were simultaneously implanted in the same patients, but in different coronary vessels. Imaging follow-up with both OCT and CAS was completed in 11 patients at 12 months. Neointimal coverage rates were similar between the two groups based on OCT measurements. The neointimal thickness of BP-EES was significantly thicker at the 12th month than at the 4th month, whereas the neointimal thickness of BVS did not change between the measurements taken at the 4th and 12th month. Existence of intra-stent thrombus was significantly higher in the BVS group, compared to the BP-EES group. On the other hand, CAS revealed that red-thrombi and yellow-plaque were more frequently observed in BVS at 4 months and up to 12-month follow-ups than in BP-EES. These findings suggested that the evidence of instability remained up to 12 months in the vascular healing with BVS, compared to that with BP-EES. Vascular healing of the stented wall was recognized at the very early phase after BP-EES implantation. However, vascular healing with BVS was still incomplete after 12 months.
  9. Prasad M, Wan Ahmad WA, Sukmawan R, Magsombol EB, Cassar A, Vinshtok Y, et al.
    Coron Artery Dis, 2015 May;26(3):194-200.
    PMID: 25734606 DOI: 10.1097/MCA.0000000000000218
    OBJECTIVE: Medically refractory angina remains a significant health concern despite major advances in revascularization techniques and emerging medical therapies. We aimed to determine the safety and efficacy of extracorporeal shockwave myocardial therapy (ESMT) in managing angina pectoris.

    METHODS: A single-arm multicenter prospective study was designed aiming to determine the safety and efficacy of ESMT. Patients of functional Canadian Cardiovascular Society class II-IV, despite stable and optimal medical management, with documented myocardial segments with reversible ischemia and/or hibernation on the basis of echocardiography/single-photon emission computerized tomography (SPECT) were enrolled from 2010 to 2012. A total of 111 patients were enrolled, 33 from Indonesia, 21 from Malaysia, and 57 from Philippines. Patients underwent nine cycles of ESMT over 9 weeks. Patients were followed up for 3-6 months after ESMT treatment. During follow-up, patients were subjected to clinical evaluation, the Seattle Angina Questionnaire, assessment of nitrate intake, the 6-min walk test, echocardiography, and SPECT.

    RESULTS: The mean age of the population was 62.9±10.9 years. The summed difference score on pharmacologically induced stress SPECT improved from 9.53±17.87 at baseline to 7.77±11.83 at follow-up (P=0.0086). Improvement in the total Seattle Angina Questionnaire score was seen in 83% of patients (P<0.0001). Sublingual nitroglycerin use significantly decreased (1.14±1.01 tablets per week at baseline to 0.52±0.68 tablets per week at follow-up; P=0.0215). There were no changes in left ventricular function on echocardiography (0.33±9.97, P=0.93). The Canadian Cardiovascular Society score improved in 74.1% of patients.

    CONCLUSION: This multicenter prospective trial demonstrated that ESMT is both a safe and an efficacious means of managing medically refractory angina.

  10. Ali RM, Abdul Kader MASK, Wan Ahmad WA, Ong TK, Liew HB, Omar AF, et al.
    JACC Cardiovasc Interv, 2019 Mar 25;12(6):558-566.
    PMID: 30898253 DOI: 10.1016/j.jcin.2018.11.040
    OBJECTIVES: The aim of this randomized controlled trial was to investigate a novel sirolimus-coated balloon (SCB) compared with the best investigated paclitaxel-coated balloon (PCB).

    BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging. PCBs are an established treatment option outside the United States with a Class I, Level of Evidence: A recommendation in the European guidelines. However, their efficacy is better in bare-metal stent (BMS) ISR compared with drug-eluting stent (DES) ISR.

    METHODS: Fifty patients with DES ISR were enrolled in a randomized, multicenter trial to compare a novel SCB (SeQuent SCB, 4 μg/mm2) with a clinically proven PCB (SeQuent Please Neo, 3 μg/mm2) in coronary DES ISR. The primary endpoint was angiographic late lumen loss at 6 months. Secondary endpoints included procedural success, major adverse cardiovascular events, and individual clinical endpoints such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis.

    RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.21 ± 0.54 mm in the PCB group versus 0.17 ± 0.55 mm in the SCB group (p = NS; per-protocol analysis). Clinical events up to 12 months also did not differ between the groups.

    CONCLUSIONS: This first-in-man comparison of a novel SCB with a crystalline coating shows similar angiographic outcomes in the treatment of coronary DES ISR compared with a clinically proven PCB. (Treatment of Coronary In-Stent Restenosis by a Sirolimus [Rapamycin] Coated Balloon or a Paclitaxel Coated Balloon [FIM LIMUS DCB]; NCT02996318).

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