Nephrolithiasis is associated with the severity of coronary artery calcification, but not with coronary artery stenosis.

PURPOSE: Emerging data have indicated that nephrolithiasis is possibly associated with subclinical coronary artery disease (CAD). Considering that a significant proportion of obstructive CAD in non-elderly individuals occurs in those without detectable calcium score (CACS), this study aimed to investigate whether nephrolithiasis is still associated with CAD as assessed by coronary computed tomography (CT)-derived luminal stenosis [using Gensini score (GS)]. METHODS: A total of 1170 asymptomatic adults without known CAD who underwent health examinations were recruited. Nephrolithiasis was assessed using abdominal ultrasonography (US). Individuals with a self-reported stone history, but no evidence of nephrolithiasis were excluded. The CACS and GS were measured using 256-slice coronary CT. RESULTS: Nearly half of these patients had a CACS > 0 (48.1%), and a higher prevalence of nephrolithiasis was observed than in those who had zero CACS (13.1% vs. 9.7%). However, no significant intergroup difference in GS was detected. A greater proportion of stone formers than non-stone formers had a higher risk category, whereas no significant difference was noted in Gensini category. Multiple linear regression analyses showed that the CACS independently predicted the presence of nephrolithiasis after adjustment. Importantly, we found that stone formers had a nearly threefold higher risk than non-stone formers of developing severe coronary calcification (CAC > 400). CONCLUSIONS: Nephrolithiasis was significantly associated with coronary artery calcification presence and severity, but not coronary luminal stenosis in patients without known CAD. Accordingly, the relationship between stone disease and CAD remains controversial, and additional studies are imperative to validate these findings.

Blood pressure levels within normotensive range are independently associated with increased risk of arterial stiffness in adults without hypertension or prehypertension.

BACKGROUND AND AIMS: High blood pressure (BP) indices, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP) predict cardiovascular diseases and mortality. However, the association of these BP indices with arterial stiffness (AS) in the normotensive population (BP < 120/80 mmHg) remains unclear. METHODS AND RESULTS: Study participants who underwent health checkups at a tertiary referred center were recruited between November 2018 to December 2019. 2129 participants were enrolled after excluding those aged <18 years old, with elevated BP, history of hypertension, cardiovascular disease, and stroke, or with incomplete data. The brachial-ankle pulse wave velocity (baPWV) values were examined for evaluation of AS. Participants with higher blood pressure indices had significantly higher baPWV. Multiple linear regression revealed that all BP indices were positively associated with baPWV. According to the binary logistic regression analysis, participants in the higher SBP and MAP quartiles were significantly related to AS. The odds ratio (OR) for SBP Q2, Q3 and Q4 vs. Q1 were 6.06, 10.06 and 17.78 whereas the OR for MAP Q2, Q3 and Q4 vs. Q1 were: 5.07, 5.28 and 10.34. For DBP and PP, only participants belonging to the highest quartile were associated with AS(OR for DBP Q4 vs. Q1: 2.51; PP Q4 vs Q1: 1.94). CONCLUSIONS: BP indices were linearly related to the baPWV. Normotensive participants with higher quartiles of SBP, DBP, MAP, and PP, remained associated with increased AS. The SBP and MAP levels exhibited a more prominent relationship with AS.

2022 Taiwanese Dermatological Association (TDA), Taiwanese Association for Psoriasis and Skin Immunology (TAPSI), and Taiwan Society of cardiology (TSOC) joint consensus recommendations for the management of psoriatic disease with attention to cardiovascular comorbidities.

Psoriatic disease is a chronic inflammatory disorder with skin and joint manifestations. Due to the persistent inflammatory state exhibited by patients with psoriasis, multiple systemic comorbidities occur more frequently in patients with psoriasis than in the general population, and the risk of cardiovascular (CV) diseases is significantly increased. As the pathophysiology of psoriatic disease is becoming better understood, the sharing of underlying pathogenic mechanisms between psoriatic and CV diseases is becoming increasingly apparent. Consequently, careful attention to CV comorbidities that already exist or may potentially develop is needed in the management of patients with psoriasis, particularly in the screening and primary prevention of CV disease and in treatment selection due to potential drug-drug and drug-disease interactions. Furthermore, as the use of effective biologic therapy and more aggressive oral systemic treatment for psoriatic disease is increasing, consideration of the potential positive and negative effects of oral and biologic treatment on CV disease is warranted. To improve outcomes and quality of care for patients with psoriasis, the Taiwanese Dermatological Association, the Taiwanese Association for Psoriasis and Skin Immunology, and the Taiwan Society of Cardiology established a Task Force of 20 clinicians from the fields of dermatology, cardiology, and rheumatology to jointly develop consensus expert recommendations for the management of patients with psoriatic disease with attention to CV comorbidities.

The Effects of Post-Acute Care in Patients with Heart Failure in Taiwan: A Single Center Experience.

Background: The National Health Insurance Administration in Taiwan has promoted the heart failure post-acute care (HF-PAC) program as a means to provide proactive integrated care within the optimal treatment timeframe to enhance functional recovery after acute decompensated heart failure (HF). Objectives: The aim of this program was to reduce HF readmission rates, improved medication prescription rates, and improve the quality of life in HF patients. Methods: Patients who had a reduced left ventricular ejection fraction (LVEF) of ≤ 40% were included and followed up for 6 months after discharge. They underwent cardiac rehabilitation and physiological, and nutritional status evaluations. The main clinical outcomes of the HF-PAC program were guideline-directed medical therapy prescription rate and 6-month readmission rate. Results: A total of 122 patients were recruited from June 2018 to December 2020 at a medical center in southern Taiwan. The patients' activities of daily living, nutritional status, quality of life and LVEF were significantly improved during the HF-PAC program. More than 95% of the patients received guideline-directed medical prescriptions at the end of the HF-PAC program. The cardiovascular-related 6-month re-admission rate after the HF-PAC program ended was 27.7%, and it could be predicted by the New York Health Association functional class [hazard ratio (HR) 95% confidence interval (95% CI) = 4.12 (1.36-12.46)], value of the Mini Nutritional Assessment - Short Form [HR (95% CI) = 0.46 (0.31-0.68)] and LVEF [HR (95% CI) = 0.95 (0.91-0.99)]. Conclusions: By incorporating multidisciplinary healthcare teams, the HF-PAC program improves the guideline- directed medical therapy prescription rate, thus improving patients' cardiac function, physical activity recovery, the quality of life, and also reduces their readmission rate.

Management of Restenosis after Stenting in Left Main Coronary Artery Disease.

Background: The optimal alternative treatment strategy to coronary artery bypass graft surgery (CABG) for in-stent restenosis (ISR) in left main (LM) coronary artery disease remains uncertain. Methods: We retrospectively screened all intervention reports from an intervention database and extracted those mentioning an LM stent. We then manually confirmed reports involving LM ISR and divided them into two groups, those in which the patient received a new drug-eluting stent (new-DES) strategy, and those in which the patient received a drug-coated balloon (DCB) only. A composite endpoint of major adverse cardiovascular events (MACEs) and each individual endpoint were compared. We also performed a brief analysis of similar designed studies. Results: Between the new-DES (n = 40) and DCB-only (n = 22) groups, during median respective follow-up times of 581.5 and 642.5 days, no significant statistical differences were detected in MACEs (50.0% vs. 50.0%, p = 0.974), cardiovascular death (27.5% vs. 13.6%, p = 0.214), nonfatal myocardial infarction (30.0% vs. 31.8%, p = 0.835), or target lesion revascularization (35.0% vs. 45.5%, p = 0.542). We analyzed four similar studies and found comparable MACE findings (odds ratio: 0.85, 95% CI: 0.44-1.67). Conclusions: Our findings support both DCB angioplasty and repeat DES implantation for LMISR lesions in patients who were clinically judged to be unsuitable for CABG; the treatments achieved comparable clinical results in terms of MACEs in the medium term.

2023 Expert Consensus of the Taiwan Society of Cardiology on the Diagnosis and Treatment of Cardiac Amyloidosis.

Cardiac amyloidosis is one form of systemic amyloidosis caused by abnormal amyloid fibrils deposited in the extracellular space of the myocardium causing heart failure because of restrictive cardiomyopathy and conduction disturbances. The incidence and prevalence of cardiac amyloidosis are higher than previously noted, particularly among special populations. The most common forms of cardiac amyloidosis are light chain and transthyretin amyloid cardiomyopathy. Even though more than 70% of patients with systemic amyloidosis have cardiac amyloidosis, the diagnosis is often delayed, suggesting significant gaps in the knowledge of cardiac amyloidosis and a lack of multidisciplinary teamwork in our daily practice. The Taiwan Society of Cardiology Heart Failure Committee organized experts to draft the "Expert Consensus on the diagnosis and treatment of cardiac amyloidosis." This statement aims to help clinicians and healthcare professionals improve early diagnosis and management of cardiac amyloidosis in Taiwan. The expert panel met virtually to review the data and discuss the consensus statements. Our review provided practical information about diagnostic methods and algorithms, clinical clues and red-flag signs, cardiac amyloidosis per se and its comorbidities treatment modalities, and follow-up plans for asymptomatic transthyretin gene carriers. We especially innovate two acronyms, "HFpEF MUTED CALL" and "HFmrEF MUST COUNT", to help in the early diagnosis and screening of transthyretin amyloid cardiomyopathy as shown in the Central Illustration.

Rationale and Study Design of the TSOC-Fully Organized Registry for the Management of Symptomatic ACS Study (T-FORMOSA Study).

Background: Successful implementation of practice guidelines has been challenging in the treatment of acute coronary syndrome (ACS), leaving room for improvement. A nationwide registry can provide more information than that recorded in the National Health Insurance Research Database (NHIRD). Methods: We conducted a prospective, nationwide, multi-center ACS full spectrum registry involving 3600 patients admitted to hospitals within 24 hours of the onset of myocardial infarction with ST-segment elevation or ACS without ST-segment elevation. In total, 41 sites including medical centers and regional hospitals were selected across Taiwan. The data for each patient are collected at 3 time points for the main study: during hospitalization, 6 months, and 12 months after the discharge. The milestone for first patient in was reached on January 7, 2022, and complete enrollment is expected before October 2023. The primary aims of the main study are to determine the degree of guideline-directed medical therapies and to identify prognostic predictors associated with 1-year composite outcomes, including death, myocardial infarction, stroke, and unplanned coronary revascularization in ACS patients. Thereafter, the patient data will be analyzed every 3 to 5 years for up to 20 years after discharge using the NHIRD in the extended study. Conclusions: We hypothesized that a greater increase in the implementation of guideline-directed medical therapies can be observed. The results of the current study will add new and important information regarding a broad spectrum of ACS to drive further investigations.

2023 Guidelines of the Taiwan Society of Cardiology on the Diagnosis and Management of Chronic Coronary Syndrome.

Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of "stable CAD" may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.

2023 Consensus of Taiwan Society of Cardiology on the Pharmacological Treatment of Chronic Heart Failure.

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure.

Effects of Cilostazol on Angiogenesis in Diabetes through Adiponectin/Adiponectin Receptors/Sirtuin1 Signaling Pathway.

Cilostazol is an antiplatelet agent with vasodilating effects that functions by increasing the intracellular concentration of cyclic adenosine monophosphate. We have previously shown that cilostazol has favorable effects on angiogenesis. However, there is no study to evaluate the effects of cilostazol on adiponectin. We investigated the effects of cilostazol on angiogenesis in diabetes in vitro and in vivo through adiponectin/adiponectin receptors (adipoRs) and the sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) signaling pathway. Human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs) were cocultured under high glucose (HG) conditions. Adiponectin concentrations in the supernatants were significantly increased when HASMCs were treated with cilostazol but not significantly changed when only HUVECs were treated with cilostazol. Cilostazol treatment enhanced the expression of SIRT1 and upregulated the phosphorylation of AMPK in HG-treated HUVECs. By sequential knockdown of adipoRs, SIRT1, and AMPK, our data demonstrated that cilostazol prevented apoptosis and stimulated proliferation, chemotactic motility, and capillary-like tube formation in HG-treated HUVECs through the adipoRs/SIRT1/AMPK signaling pathway. The phosphorylation of downstream signaling molecules, including acetyl-CoA carboxylase (ACC) and endothelial nitric oxide synthase (eNOS), was downregulated when HUVECs were treated with a SIRT1 inhibitor. In streptozotocin-induced diabetic mice, cilostazol treatment could improve blood flow recovery 21-28 days after inducing hindlimb ischemia as well as increase the circulating of CD34+CD45dim cells 14-21 days after operation; moreover, these effects were significantly attenuated by the knockdown of adipoR1 but not adipoR2. The expression of SIRT1 and phosphorylation of AMPK/ACC and Akt/eNOS in ischemic muscles were significantly attenuated by the gene knockdown of adipoRs. Cilostazol improves HG-induced endothelial dysfunction in vascular endothelial cells and enhances angiogenesis in diabetic mice by upregulating the expression of adiponectin/adipoRs and its SIRT1/AMPK downstream signaling pathway.

Diverse Effects of Cilostazol on Proprotein Convertase Subtilisin/Kexin Type 9 between Obesity and Non-Obesity.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis. Cilostazol exerts favorable cellular and metabolic effects; however, the effect of cilostazol on the expression of PCSK9 has not been previously reported. Our study aimed to investigate the potential mechanisms of action of cilostazol on the expression of PCSK9 and lipid homeostasis. We evaluated the effects of cilostazol on the expression of PCSK9 in HepG2 cells and evaluated potential molecular mechanisms by measuring signaling molecules in the liver and serum lipid profiles in high-fat diet-induced obese mice and normal chow-fed mice. Cilostazol treatment significantly induced the messenger RNA and protein expression of PCSK9 in HepG2 cells and enhanced PCSK9 promoter activity. Chromatin immunoprecipitation assays confirmed that cilostazol treatment enhanced PCSK9 transcription by binding to peroxisome proliferator-activated receptor-γ (PPARγ) via the PPARγ DNA response element. PPARγ knockdown attenuated the stimulatory effect of cilostazol on PCSK9. In vitro, cilostazol treatment increased PCSK9 expression in vehicle-treated HepG2 cells but decreased PCSK9 expression in palmitic acid-treated HepG2 cells. In vivo, cilostazol treatment increased the serum levels of PCSK9 in normal mice but significantly reduced PCSK9 levels in obese mice. The expressions of PCSK9-relevant microRNAs also showed similar results. Clinical data showed that cilostazol treatment significantly reduced serum PCSK9 levels in patients with obesity. The obesity-dependent effects of cilostazol on PCSK9 expression observed from bench to bedside demonstrates the therapeutic potential of cilostazol in clinical settings.

2022 Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the Management of Hypertension.

Hypertension is the most important modifiable cause of cardiovascular (CV) disease and all-cause mortality worldwide. Despite the positive correlations between blood pressure (BP) levels and later CV events since BP levels as low as 100/60 mmHg have been reported in numerous epidemiological studies, the diagnostic criteria of hypertension and BP thresholds and targets of antihypertensive therapy have largely remained at the level of 140/90 mmHg in the past 30 years. The publication of both the SPRINT and STEP trials (comprising > 8,500 Caucasian/African and Chinese participants, respectively) provided evidence to shake this 140/90 mmHg dogma. Another dogma regarding hypertension management is the dependence on office (or clinic) BP measurements. Although standardized office BP measurements have been widely recommended and adopted in large-scale CV outcome trials, the practice of office BP measurements has never been ideal in real-world practice. Home BP monitoring (HBPM) is easy to perform, more likely to be free of environmental and/or emotional stress, feasible to document long-term BP variations, of good reproducibility and reliability, and more correlated with hypertension-mediated organ damage (HMOD) and CV events, compared to routine office BP measurements. In the 2022 Taiwan Hypertension Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS), we break these two dogmas by recommending the definition of hypertension as ≥ 130/80 mmHg and a universal BP target of < 130/80 mmHg, based on standardized HBPM obtained according to the 722 protocol. The 722 protocol refers to duplicate BP readings taken per occasion ("2"), twice daily ("2"), over seven consecutive days ("7"). To facilitate implementation of the guidelines, a series of flowcharts encompassing assessment, adjustment, and HBPM-guided hypertension management are provided. Other key messages include that: 1) lifestyle modification, summarized as the mnemonic S-ABCDE, should be applied to people with elevated BP and hypertensive patients to reduce life-time BP burden; 2) all 5 major antihypertensive drugs (angiotensin-converting enzyme inhibitors [A], angiotensin receptor blockers [A], ß-blockers [B], calcium-channel blockers [C], and thiazide diuretics [D]) are recommended as first-line antihypertensive drugs; 3) initial combination therapy, preferably in a single-pill combination, is recommended for patients with BP ≥ 20/10 mmHg above targets; 4) a target hierarchy (HBPM-HMOD- ambulatory BP monitoring [ABPM]) should be considered to optimize hypertension management, which indicates reaching the HBPM target first and then keeping HMOD stable or regressed, otherwise ABPM can be arranged to guide treatment adjustment; and 5) renal denervation can be considered as an alternative BP-lowering strategy after careful clinical and imaging evaluation.

Risk Management for Radiation-Induced Cardiovascular Disease (RICVD): The 2022 Consensus Statement of the Taiwan Society for Therapeutic Radiology and Oncology (TASTRO) and Taiwan Society of Cardiology (TSOC).

Advances in cancer management have significantly improved survival in patients with cancers. Cardiovascular complications of cancer treatment are becoming significant competing causes of death in these patients. Radiotherapy is an indispensable component of cancer treatment, and irradiation of the heart and vasculature during cancer radiotherapy is now recognized as a new risk factor for cardiovascular diseases. It is important to involve multidisciplinary expertise and provide practical recommendations to promote awareness, recognize risks, and provide adequate interventions without jeopardizing cancer control. In this consensus paper, experts from the Taiwan Society for Therapeutic Radiology and Oncology and Taiwan Society of Cardiology provide a focused update on the clinical practice for risk stratification and management of radiation-induced cardiovascular disease (RICVD). We believe that implementing RICVD care under a collaborative cardio-oncology program will significantly improve cancer treatment outcomes and will facilitate high quality clinical investigations.

Reduced-Dose Prasugrel versus Clopidogrel for Patients Undergoing Percutaneous Coronary Intervention.

Whether reduced-dose prasugrel has a better efficacy or safety than standard-dose clopidogrel remains unknown in patients undergoing percutaneous coronary intervention (PCI).A systematic search of PubMed, EMBASE, Google Scholar, and Cochrane Library from database inception to May 1, 2020 was performed to compare the clinical outcomes in patients with acute coronary syndrome or stable coronary artery disease undergoing PCI between those treated with reduced-dose prasugrel and clopidogrel. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using the fixed-effect or random-effect model if significant heterogeneity was observed. The primary efficacy endpoint was major adverse cardiovascular events (MACE), including cardiovascular (CV) death, myocardial infarction (MI), or ischemic stroke. The primary safety endpoint was all bleeding events.Overall, seven studies with 32,951 patients with PCI were included in the analysis. Reduced-dose prasugrel was associated with a lower risk of MACE than clopidogrel (OR 0.80, 95% CI 0.67-0.97). Except for MI (OR 0.74, 95% CI 0.56-0.98), the secondary efficacy endpoints of CV death, ischemic stroke, all-cause death, and stent thrombosis were similar. For the primary safety endpoint of all bleeding events, there was no significant difference between reduced-dose prasugrel and clopidogrel (OR 1.31, 95% CI 0.87-1.98), but the risk of minor bleeding was significantly higher in reduced-dose prasugrel (OR 1.73, 95% CI 1.25-2.41).In patients undergoing PCI, a lower risk of MACE was found in patients receiving reduced-dose prasugrel than in those with clopidogrel, but a higher risk of minor bleeding events was noted.

Addressing Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following COVID-19 Vaccination: A Mini-Review of Practical Strategies.

In response to the COVID-19 pandemic, several vaccines were developed and rolled out at unprecedented speed, and notwithstanding this rapid pace of development, the results from initial clinical trials involving tens of thousands of adult subjects generally indicated that most vaccines were remarkably effective and safe, with no major safety warnings noted. However, with more than 2 billion vaccination doses administered to date, reports of rare adverse events following immunization (AEFI) are beginning to emerge. In late February 2021, atypical thrombotic events following immunization with the adenoviral vector-based ChAdOx1 nCov-19 vaccine were first reported, and similar events have also been observed in recipients of the adenoviral vector-based Ad26.COV2.S vaccine and the mRNA-based BNT162b2 and mRNA-1273 vaccines. These manifestations of atypical thrombosis and thrombocytopenia following COVID-19 vaccine immunization are now collectively referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Although the reported incidence remains very low and does not affect the overall benefit of immunization, it is also true that if left untreated, VITT can be debilitating or even fatal. Therefore, this review seeks to provide a comprehensive overview regarding the incidence, pathogenesis, presentation, diagnosis, and treatment of VITT, as well as considerations for special populations, based on the currently available evidence in the literature. It is hoped that this will enhance awareness of this vaccine side effect, so that cases of VITT may be identified and treated in a timely and appropriate manner.

2021 TSOC Expert Consensus on the Clinical Features, Diagnosis, and Clinical Management of Cardiac Manifestations of Fabry Disease.

Fabry disease (FD) is an X-linked, rare inherited lysosomal storage disease caused by α-galactosidase A gene variants resulting in deficient or undetectable α-galactosidase A enzyme activity. Progressive accumulation of pathogenic globotriaosylceramide and its deacylated form globotriaosylsphingosine in multiple cell types and organs is proposed as main pathophysiology of FD, with elicited pro-inflammatory cascade as alternative key pathological process. The clinical manifestations may present with either early onset and multisystemic involvement (cutaneous, neurological, nephrological and the cardiovascular system) with a progressive disease nature in classic phenotype, or present with a later-onset course with predominant cardiac involvement (non-classical or cardiac variant; e.g. IVS4+919G>A in Taiwan) from missense variants. In either form, cardiac involvement is featured by progressive cardiac hypertrophy, myocardial fibrosis, various arrhythmias, and heart failure known as Fabry cardiomyopathy with potential risk of sudden cardiac death. Several plasma biomarkers and advances in imaging modalities along with novel parameters, cardiac magnetic resonance (CMR: native T1/T2 mapping) for myocardial tissue characterization or echocardiographic deformations, have shown promising performance in differentiating from other etiologies of cardiomyopathy and are presumed to be helpful in assessing the extent of cardiac involvement of FD and in guiding or monitoring subsequent treatment. Early recognition from extra-cardiac red flag signs either in classic form or red flags from cardiac manifestations in cardiac variants, and awareness from multispecialty team work remains the cornerstone for timely managements and beneficial responses from therapeutic interventions (e.g. oral chaperone therapy or enzyme replacement therapy) prior to irreversible organ damage. We aim to summarize contemporary knowledge based on literature review and the gap or future perspectives in clinical practice of FD-related cardiomyopathy in an attempt to form a current expert consensus in Taiwan.

Intra-Coronary Administration of Tacrolimus Improves Myocardial Perfusion and Left Ventricular Function in Patients with ST-Segment Elevation Myocardial Infarction (COAT-STEMI) Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Ischemia-reperfusion injury following acute ST-segment elevation myocardial infarction (STEMI) is strongly related to inflammation. However, whether intracoronary (IC) tacrolimus, an immunosuppressant, can improve myocardial perfusion is uncertain. METHODS: A multicenter double-blind randomized controlled trial was conducted in Taiwan from 2014 to 2017. Among 316 STEMI patients with Killip class ≤ 3 undergoing primary percutaneous coronary intervention (PCI), 151 were assigned to the study group treated with IC tacrolimus 2.5 mg to the culprit vessel before first balloon inflation, and the remaining 165 were assigned to the placebo group receiving IC saline only. The primary endpoint was percentage of post-PCI TIMI-3 flow. The primary composite endpoints included achievement of TIMI-3 flow, TIMI- myocardial perfusion (TMP) grade, or 90-min ST-segment resolution (STR). The secondary endpoints were left ventricular ejection fraction (LVEF) and 1-month/1-year major adverse cardio-cerebral vascular events (MACCEs) (defined as death, myocardial infarction, stroke, target-vessel revascularization or re-hospitalization for heart failure). RESULTS: Although post-PCI TIMI-3 epicardial flow and MACCE rate at 1 month and 1 year did not differ between the two groups, TMP grade (2.54 vs. 2.23, p < 0.001) and 90-min STR (67% vs. 61%, p < 0.001) were significantly higher in the tacrolimus-treated group than in the placebo group. The STEMI patients treated with tacrolimus also had significantly higher 3D LVEF and less grade 2 or 3 LV diastolic dysfunction at 9 months compared to those without. CONCLUSIONS: IC tacrolimus for STEMI improved coronary microcirculation and 9-month LV systolic and diastolic functions. However, the benefit of tacrolimus on clinical outcomes remains inconclusive due to insufficient patient enrollment.

Cardiovascular and Bleeding Risks in Acute Myocardial Infarction Newly Treated With Ticagrelor vs. Clopidogrel in Taiwan.

BACKGROUND: There are few data on ticagrelor in Asian patients. This study evaluated clinical outcomes with ticagrelor and clopidogrel in Taiwanese patients with acute myocardial infarction (AMI).Methods and Results:We used the Taiwan National Health Insurance Research Database to identify 27,339 AMI patients aged ≥18 years between January 2012 and December 2014, and only patients who survived greater than or equal to 30 days after AMI and took dual antiplatelet therapy were included. Cohorts of ticagrelor and clopidogrel were matched 1:8, based on propensity score matching, to balance baseline covariates. The primary efficacy endpoints were death from any cause, AMI, or stroke. The safety endpoints consisted of major gastrointestinal bleeding or intracerebral hemorrhage. Following propensity matching, the primary efficacy endpoint rate was 22% lower in the ticagrelor group than in the clopidogrel group (10.6% and 16.2%, respectively; adjusted HR, 0.779; 95% CI: 0.684-0.887). The safety endpoint rate was similar between the ticagrelor and clopidogrel groups (3.2% and 4.1% respectively; adjusted HR, 0.731; 95% CI: 0.522-1.026). CONCLUSIONS: In real-world AMI Taiwanese patients, ticagrelor seemed to offer better anti-ischemic protection than clopidogrel, without an increase in the rate of major bleeding. A large-scale randomized trial is needed to assess the efficacy and safety of ticagrelor in East Asian AMI patients.

Lipid Lowering Therapy for Acute Coronary Syndrome and Coronary Artery Disease: Highlights of the 2017 Taiwan Lipid Guidelines for High Risk Patients.

Intensive lipid lowering therapy is important in patients with acute coronary syndrome (ACS) and stable coronary artery disease (CAD). The 2017 Taiwan Lipid Guidelines for High Risk Patients was recently published. The guideline suggests that low-density lipoprotein cholesterol (LDL-C) should be the primary target, and that the treatment goal of LDL-C is < 70 mg/dL for patients with ACS or stable CAD. A lower target of < 55 mg/dL is appropriate for patients with ACS and diabetes mellitus. Non-high-density lipoprotein cholesterol (non-HDL-C) < 100 mg/dL can be considered as the secondary target after achieving the LDL-C goal for patients with a triglyceride level > 200 mg/dL. Statins are usually the first-line therapy. Moderate or high intensity statins are preferred, and up-titration to the highest recommended and tolerable dose to reach the target is necessary. Combination therapy with statins and other lipid-lowering drugs can also be considered. We hope the clinical outcomes of patients with ACS or CAD can be improved in Taiwan through the implementation of the guideline recommendations.

2017 Taiwan lipid guidelines for high risk patients.

In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG) levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, nicotinic acids (niacin), fibric acids derivatives (fibrates), and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS) and stable CAD, LDL-C < 70 mg/dL is the major target. A lower target of LDL-C <55 mg/dL can be considered in ACS patients with DM. After treating LDL-C to target, non-HDL-C can be considered as a secondary target for patients with TG ≥ 200 mg/dL. The suggested non-HDL-C target is < 100 mg/dL in ACS and CAD patients. For patients with ischemic stroke or transient ischemic attack presumed to be of atherosclerotic origin, statin therapy is beneficial and LDL-C < 100 mg/dL is the suggested target. For patients with symptomatic carotid stenosis or intracranial arterial stenosis, in addition to antiplatelets and blood pressure control, LDL-C should be lowered to < 100 mg/dL. Statin is necessary for DM patients with CV disease and the LDL-C target is < 70 mg/dL. For diabetic patients who are ≥ 40 years of age, or who are < 40 years of age but have additional CV risk factors, the LDL-C target should be < 100 mg/dL. After achieving LDL-C target, combination of other lipid-lowering agents with statin is reasonable to attain TG < 150 mg/dL and HDL-C >40 in men and >50 mg/dL in women in DM. LDL-C increased CV risk in patients with CKD. In adults with glomerular filtration rate (GFR) < 60 mL/min/1.73m2 without chronic dialysis (CKD stage 3-5), statin therapy should be initiated if LDL-C ≥ 100 mg/dL. Ezetimibe can be added to statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia.