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  1. Koh HP, Nagarajah JR, Hassan H, Ross NT
    World J Emerg Med, 2024;15(6):433-440.
    PMID: 39600808 DOI: 10.5847/wjem.j.1920-8642.2024.077
    BACKGROUND: Bleeding outcomes are crucial primary safety endpoints in studies involving thrombolytic agents. This study aimed to determine the incidence, characteristics and mortality outcomes of bleeding following ST-elevation myocardial infarction (STEMI) thrombolysis in an Asian population.

    METHODS: This single-centre retrospective study included all STEMI patients who received thrombolytic therapy from 2016 to 2020 in a Malaysian tertiary hospital. Total population sampling was used in this study. The primary outcome was bleeding events post-thrombolysis, categorised using the Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria. Inferential statistics were used to determine the associations between relevant variables.

    RESULTS: Data from 941 patients were analysed. A total of 156 (16.6%) STEMI patients bled post-thrombolysis. Major, minor, and minimal TIMI occurred in 7 (0.7%), 17 (1.8%), and 132 (14.0%) patients, respectively. Age 65 years (P=0.031) and Malaysian Chinese (P=0.008) were associated with a higher incidence of bleeding post-thrombolysis. Conversely, foreigners (P=0.032) and current smoker (P=0.007) were associated with a lower incidence of bleeding. Both TIMI major (P<0.001) and TIMI minor (P<0.001) were associated with a higher incidence of all-cause in-hospital mortality among STEMI patients. TIMI minor bleeding was significantly higher in the streptokinase recipients. The bleeding sites were comparable between streptokinase and tenecteplase recipients, except for a significantly higher incidence of gastrointestinal bleeding in the streptokinase recipients (P=0.027).

    CONCLUSION: In our Asian population, the incidence of total bleeding events following STEMI thrombolysis is comparable to that previously reported. The development of TIMI major and minor bleeding complications is associated with higher mortality.

  2. Koh HP, Md Redzuan A, Mohd Saffian S, R Nagarajah J, Ross NT, Hassan H
    Am J Emerg Med, 2022 Oct;60:9-14.
    PMID: 35872375 DOI: 10.1016/j.ajem.2022.07.021
    INTRODUCTION: Some guidelines had recommended "thrombolysis first" in ST-elevated myocardial infarction (STEMI) during the Coronavirus Disease 2019 (COVID-19) outbreak. The impact of COVID-19 solely on STEMI thrombolysis is lacking as most studies reported outcomes related to percutaneous coronary intervention (PCI) setting. Thus, this study aimed to assess the impact of the COVID-19 pandemic on STEMI thrombolysis outcomes and the Emergency Department's performance in a non-PCI capable centre.

    METHODS: This single-centre retrospective study analysed data on consecutive STEMI patients who received thrombolytic therapy from May 2019 to December 2020 (20 months) in a non-PCI capable tertiary hospital. Total population sampling was used in this study. We compared all patients' characteristics and outcomes ten months before and during the pandemic. Regression models were used to assess the impact of COVID-19 pandemic on door-to-needle time (DNT), mortality, bleeding events, and the number of overnight stays.

    RESULTS AND DISCUSSION: We analysed 323 patients with a mean age of 52.9 ± 12.9 years and were predominantly male (n = 280, 88.9%). There was a 12.5% reduction in thrombolysis performed during the pandemic. No significant difference in timing from symptoms onset to thrombolysis and DNT was observed. In-hospital mortality was significantly higher during the pandemic (OR 2.02, 95% CI 1.02-4.00, p = 0.044). Bleeding events post thrombolysis remained stable and there was no significant difference in the number of overnight stays during the pandemic.

    CONCLUSION: STEMI thrombolysis cases were reduced during the COVID-19 pandemic, with an inverse increase in mortality despite the preserved Emergency Department performance in timely thrombolysis.

  3. Koh HP, Md Redzuan A, Mohd Saffian S, Hassan H, R Nagarajah J, Ross NT
    Intern Emerg Med, 2023 Jun;18(4):1169-1180.
    PMID: 36648707 DOI: 10.1007/s11739-023-03202-1
    Pharmacological reperfusion remains the primary strategy for ST-elevation myocardial infarction (STEMI) in low- and medium-income countries. Literature has reported inconsistent incidences and outcomes of failed thrombolysis (FT). This study aimed to identify the incidence, mortality outcomes and predictors of FT in STEMI pharmacological reperfusion. This single-centre retrospective cohort study analyzed data on consecutive STEMI patients who received thrombolytic therapy from 2016 to 2020 in a public tertiary hospital. Total population sampling was used in this study. Logistic regression analyses were used to assess independent predictors of the mortality outcomes and FT. We analyzed 941 patients with a mean age of 53.0 ± 12.2 years who were predominantly male (n = 846, 89.9%). The in-hospital mortality was 10.3% (n = 97). FT occurred in 86 (9.1%) patients and was one of the predictors of mortality (aOR 3.847, p 
  4. Koh HP, Jagan N, George D, Mazlan-Kepli W, Mohamed S, Lim HT, et al.
    J Thromb Thrombolysis, 2021 Oct;52(3):836-847.
    PMID: 33748900 DOI: 10.1007/s11239-021-02426-2
    There is a wide variation on the efficacy of three-factor Prothrombin Complex Concentrate (3F-PCC) in warfarin reversal. We aimed to determine the efficacy and safety of 3F-PCC in warfarin reversal. This multicentre prospective study analysed data from adult patients on warfarin who received 3F-PCC (Prothrombinex-VF®) for anticoagulation reversal between June 2019 to October 2020. Purposive sampling was used in this study. Study endpoints included target INR achievement, adverse drug reactions (ADRs), and in-hospital all-cause mortality. Logistic regression analyses were used to assess independent predictors of study endpoints. One-hundred thirty-seven patients with a median age of 68 (59-76) years were recruited, who were predominantly male (59.9%, n = 82). A total of 102 patients required 3F-PCC for life-threatening (40.9%, n = 56) and clinically significant bleeding (33.6%, n = 46). Initial INRs ranged from 1.55 to undetectable high (> 26). All patients had INR reduction, of which 62% (n = 85) achieved target INR, whereas 12.4% (n = 17) achieved INR below the target range. Median INR was reduced from 4.76 (3.14-8.32) to 1.54 (1.27-1.88) post-3F-PCC (p 
  5. Wan Ahmad WA, Mohd Ghazi A, Abdul Ghapar AK, Muthusamy TS, Liew HB, Zainal Abidin I, et al.
    Malays J Med Sci, 2023 Feb;30(1):49-66.
    PMID: 36875198 DOI: 10.21315/mjms2023.30.1.5
    Globally, heart failure with preserved ejection fraction (HFpEF) is quickly becoming the dominant form of heart failure (HF) in ageing populations. However, there are still multiple gaps and challenges in making a firm diagnosis of HFpEF in many low-to-middle income Asian countries. In response to this unmet need, the Malaysian HFpEF Working Group (MY-HPWG) gathered and reviewed evidence surrounding the use of different diagnostic modalities indicated for patients with HFpEF to identify diagnostic tools that could be conveniently accessed across different healthcare settings. As a result, five recommendation statements were proposed and an accompanying algorithm was developed, with the aim of improving the diagnostic rate of HFpEF. The MY-HPWG recommends using more easily accessible and non-invasive tools, such as natriuretic peptide (NP) biomarkers and basic echocardiogram (ECHO), to ensure timely HFpEF diagnosis in the primary and secondary care settings, and prompt referral to a tertiary care centre for more comprehensive assessments in uncertain cases.
  6. Dauw J, Charaya K, Lelonek M, Zegri-Reiriz I, Nasr S, Paredes-Paucar CP, et al.
    Circ Heart Fail, 2024 Jan;17(1):e011105.
    PMID: 38179728 DOI: 10.1161/CIRCHEARTFAILURE.123.011105
    BACKGROUND: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload.

    METHODS: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms.

    RESULTS: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P<0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P<0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P<0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P=0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P=0.852).

    CONCLUSIONS: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.

  7. Wan Ahmad WA, Abdul Ghapar AK, Zainal Abidin HA, Karthikesan D, Ross NT, S K Abdul Kader MA, et al.
    ESC Heart Fail, 2024 Apr;11(2):727-736.
    PMID: 38131217 DOI: 10.1002/ehf2.14608
    AIMS: Heart failure (HF) is a growing health problem, yet there are limited data on patients with HF in Malaysia. The Malaysian Heart Failure (MY-HF) Registry aims to gain insights into the epidemiology, aetiology, management, and outcome of Malaysian patients with HF and identify areas for improvement within the national HF services.

    METHODS AND RESULTS: The MY-HF Registry is a 3-year prospective, observational study comprising 2717 Malaysian patients admitted for acute HF. We report the description of baseline data at admission and outcomes of index hospitalization of these patients. The mean age was 60.2 ± 13.6 years, 66.8% were male, and 34.3% had de novo HF. Collectively, 55.7% of patients presented with New York Heart Association (NYHA) Class III or IV; ischaemic heart disease was the most frequent aetiology (63.2%). Most admissions (87.3%) occurred via the emergency department, with 13.7% of patients requiring intensive care, and of these, 21.8% needed intubation. The proportion of patients receiving guideline-directed medical therapy increased at discharge (84.2% vs. 93.6%). The median length of stay (LOS) was 5 days, and in-hospital mortality was 2.9%. Predictors of LOS and/or in-hospital mortality were age, NYHA class, estimated glomerular filtration rate, and comorbid anaemia. LOS and in-hospital mortality were similar regardless of ejection fraction.

    CONCLUSIONS: The MY-HF Registry showed that the HF population in Malaysia is younger, predominantly male, and ischaemic-driven and has good prospects with hospitalization for optimization of treatment. These findings suggest a need to reassess current clinical practice and guide resource allocation to improve patient outcomes.

  8. Dauw J, Lelonek M, Zegri-Reiriz I, Paredes-Paucar CP, Zara C, George V, et al.
    ESC Heart Fail, 2021 Dec;8(6):4685-4692.
    PMID: 34708555 DOI: 10.1002/ehf2.13666
    AIMS: Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively.

    METHODS AND RESULTS: The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study is an international, multicentre, non-randomized, open-label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N-terminal pro-B-type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in-hospital mortality, and length of hospitalization.

    CONCLUSIONS: The ENACT-HF study will investigate whether a step-wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload.

  9. Chowdhury R, Noh MFM, Ismail SR, van Daalen KR, Kamaruddin PSNM, Zulkiply SH, et al.
    JMIR Res Protoc, 2022 Feb 10;11(2):e31885.
    PMID: 35142634 DOI: 10.2196/31885
    BACKGROUND: Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse.

    OBJECTIVE: The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results.

    METHODS: By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire.

    RESULTS: Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models.

    CONCLUSIONS: The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action.

    INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/31885.

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