Comprehensive comparative efficacy and safety of potent P2Y12 inhibitors in patients undergoing coronary intervention: A systematic review and meta-analysis.

Potent P2Y12 receptor antagonists have been used widely for patients undergoing percutaneous coronary intervention with different results. Benefits from different regimens various between trials. Randomized controlled trials (RCTs) have restrictive inclusion and exclusion criteria; thus, they may limit the generalizability of the findings to a broader population. This study was aimed to comprehensively investigate the outcomes of potent P2Y12 inhibitors in patients undergoing PCI, including RCTs and real-world evidence (RWE) studies. Multiple electronic databases were systemically reviewed and searched on compared potent P2Y12 inhibitors with clopidogrel. The primary efficacy end point was composite ischemic cardiovascular event and primary safety endpoint was major bleeding. Overall estimates of proportions and incidence rates with 95 % confidence intervals (CI) were calculated using fixed-effects models. Total 24 studies (140,986 patients) underwent coronary intervention were included in this meta-analysis, including 18 RCTs and 6 large cohort studies with propensity score matching. The potent P2Y12 inhibitors including cangrelor, prasugrel, and ticagrelor, significantly decreased the risk of composite adverse cardiovascular ischemic events (95 % CI 0.89-0.96, p < 0.001), but increased major bleeding (95 % CI 1.15-1.33, p < 0.001) or any bleeding (95 % CI 1.21-1.33, p < 0.001) compared with Clopidogrel. This meta-analysis merges RCTs and RWE studies and comprehensively evidences newer potent P2Y12 inhibitors are significantly more effective than clopidogrel in reduction of composite adverse thrombotic events, but the incidence of major or any bleeding was higher compared with clopidogrel.

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.

Antithrombotic Treatment of Stable Coronary Artery Disease.

Coronary artery disease (CAD) is one of the leading causes of death in Taiwan. Despite the use of current guideline-recommended therapies for secondary prevention, the residual risk of recurrent cardiovascular events remains high in CAD, warranting the need for new treatment options. Antithrombotic drugs are one of the most important medical therapies for CAD. In this article, we review the unmet needs of the current antithrombotic agents and summarize the results of clinical trials with dual antiplatelet therapy in stable CAD. We also review data from a recent study demonstrating the benefits of a dual pathway inhibition strategy with antiplatelet and anticoagulant therapy, a new option for CAD treatment. Finally, we propose a treatment algorithm for choosing different antithrombotic regimens for CAD based on current scientific evidence and expert opinions.

Percutaneous Coronary Intervention for Very Small Vessels With the Use of a Newer-Generation 2.0 mm Drug-Eluting Stent.

OBJECTIVES: The outcomes of treating coronary artery disease (CAD) in very small vessels <2.25 mm are sparse. The present study aimed to compare the safety and efficacy of the Resolute Onyx 2.0 mm drug-eluting stent (DES) (Medtronic) with the Onyx 2.25 mm DES for the treatment of CAD. METHODS: We retrospectively evaluated patients who underwent percutaneous coronary intervention (PCI) for CAD involving Onyx 2.0 mm DES (Onyx 2.0 group) and Onyx 2.25 mm DES (Onyx 2.25 group) in the 2 consecutive years from November 2016 to November 2018. Major adverse cardiac and cerebral event (MACCE) rate, defined as all-cause mortality, non-fatal myocardial infarction, stroke, and repeat revascularization for target-lesion failure, was reported. RESULTS: A total of 152 subjects with 160 lesions were enrolled. The baseline demographics, lesion characteristics, and procedural results between the two groups were similar. The lesions were significantly shorter (P<.01), fewer stents were consequently deployed (P=.04), and the total stent length was shorter (P<.01) in the Onyx 2.0 group vs the Onyx 2.25 group. At a median follow-up of 673 days, MACCE rate did not differ significantly between the two groups. Multivariate analysis identified the presence of atrial fibrillation, chronic kidney disease, and the use of statins to be independently associated with MACCE. CONCLUSIONS: Our data suggest that the use of the Onyx 2.0 mm DES to treat CAD in very small vessels (<2.25 mm) is feasible and safe, and the clinical outcomes were similar to those of the Onyx 2.25 mm group.

The Impact of Fractional Flow Reserve-Guided Coronary Revascularization in Patients with Coronary Stenoses of Intermediate Severity.

BACKGROUND: Previous studies have shown that the use of fractional flow reserve (FFR) in addition to angiography significantly reduced the rate of all major adverse cardiovascular events (MACE). However, this practice has not been widely accepted and limited outcome data exist about FFR-guided percutaneous coronary intervention (PCI) in Taiwan. The aim of the present study was to evaluate the possible impact of FFR-guided PCI in coronary stenoses of intermediate severity. METHODS: We performed a retrospective case-control study on 443 cases of intermediate coronary stenoses in 206 patients recruited from our computerized database. The study patients were divided into two groups: the FFR group (n = 101) and the angiography group (n = 105), matched with age, gender, clinical and angiographic lesion characteristics. In the angiography group, the indicated lesions had been treated with PCI by angiographic or anatomical assessment, whereas those patients in the FFR group underwent PCI of indicated lesions only if the FFR was < 0.80. The primary end point was the MACE rate regarding death, nonfatal myocardial infarction (MI), and target vessel failure at a mean follow-up of 418 days. RESULTS: The MACE rate was similar in both groups (6% in the angiography group and 3% in the FFR group, p = 0.06). However, FFR-guided PCI strategy prevented unnecessary revascularization in up to 75% of patients, and markedly reduced costs of the index hospitalization. Moreover, multivariate analysis found that the use of drug-eluting stent and statin therapy, and the presence of family history of premature coronary artery disease and periprocedural MI are independent predictors of clinical outcomes. CONCLUSIONS: FFR-guided intervention, compared to angiography-guided intervention for Taiwanese patients with coronary stenoses of intermediate severity, achieved similar clinical outcomes and provided cost-savings.

Circulating Adiponectin Levels Following Treatment Can Predict Late Clinical Outcomes in Chronic Heart Failure.

BACKGROUND: Circulating adiponectin concentration increases in patients with chronic heart failure (HF). We sought to explore the prognostic value of temporal changes in adiponectin concentration following treatment for chronic HF. METHODS: Serum adiponectin levels were measured at baseline and after a 3-month anti-failure treatment in 124 patients with symptomatic chronic systolic HF. Major adverse cardiac events (MACE) including death, heart transplantation, or hospitalization with worsening HF during a median follow-up period of 752 days were determined. RESULTS: Univariate and multivariate analysis showed that high levels of adiponectin after a 3-month treatment were associated with a 3.8-fold increased risk of MACE (p = 0.03), independent of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Moreover, the combining of circulating levels of adiponectin with NT-proBNP provided independent and additional prognostic value in identifying high risk patients with MACE during follow-up. CONCLUSIONS: Changes in adiponectin and NT-proBNP over time provide prognostic information. When adiponectin is used in conjunction with NT-proBNP in chronic HF, the prognostic value may be better than if each biomarker is used separately.

Endothelin-1-Induced Cell Hypertrophy in Cardiomyocytes is Improved by Fenofibrate: Possible Roles of Adiponectin.

AIM: Previous studies demonstrated that endothelin-1 (ET-1) can significantly increase the cell size and stimulate adiponectin expression in cultured human cardiomyocytes (HCM). The aim of the present study was to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor-α (PPARα) activator, on cell hypertrophy and adiponectin expression in vitro and in a rat model of daunorubicin-induced cardiomyopathy. METHODS: The cultured human cardiomyocytes (HCM) were stimulated with or without ET-1. The cell size and the protein expressions of PPARα and adiponectin were tested by confocal Immunofluorescence study and Western blot, respectively. To study the effects of PPARα activation on ET-1-induced cell hypertrophy and adiponectin protein synthesis, HCM were pretreated with fenofibrate or small interfering RNA (siRNA) of PPARα. Echocardiographic parameters were measured and immunohistochemistry study of myocardial adiponectin expression was conducted in the in vivo study. RESULTS: ET-1 significantly increased the cell size, dose-dependently suppressed the expression of PPARα, and enhanced the expression of adiponectin; whereas, such an increase of cell size and enhancement of adiponectin expression were inhibited by the pre-treatment with fenofibrate. Addition of siRNA of PPARα abolished the effects of fenofibrate. Moreover, we found that fenofibrate treatment can significantly improve the left ventricular function and reverse the myocardial expression of adiponectin. CONCLUSIONS: Our study shows that fenofibrate may protect against ET-1-induced cardiomyocyte hypertrophy and enhanced adiponectin expression through modulation of PPARα expression in vitro and limitation of daunorubicin cardiotoxicity in vivo, suggesting a novel mechanistic insight into the role of PPARα and adiponectin in cardiac hypertrophy and heart failure.

Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin.

Peroxisome proliferator-activated receptor α (PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARα activation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and explore its underlying mechanisms. Human cardiomyocytes (HCMs) were cultured with or without ET-1, whereafter the inhibitory effects of fenofibrate, a PPARα activator, on cell size and adiponectin protein were tested. We examined the activation of extracellular signal-regulated kinase (ERK) and p38 proteins caused by ET-1 and the inhibition of the ERK and p38 pathways on ET-1-induced cell size and adiponectin expression. Moreover, we investigated the interaction of PPARα with adiponectin and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assays and coimmunoprecipitation. ET-1 treatment significantly increased cell size, suppressed PPARα expression, and enhanced the expression of adiponectin. Pretreatment with fenofibrate inhibited the increase in cell size and enhancement of adiponectin expression. ET-1 significantly activated the ERK and p38 pathways, whereas PD98059 and SB205380, respectively, inhibited them. Our results suggest that activated PPARα can decrease activation of adiponectin and NF-κB and inhibit ET-1-induced cardiomyocyte hypertrophy.

Transradial versus transfemoral rotablation for heavily calcified coronary lesions in contemporary drug-eluting stent era.

BACKGROUND: Although radial access for drug-eluting stent (DES) combined with rotational atherectomy (RA) in patients with calcified coronary lesions may be associated with a lower risk of major bleeding complications and obtain favorable clinical results compared with femoral access, the long-term outcome data of this approach were limited in contemporary DES era. METHODS & RESULTS: This retrospective study sought to compare in-hospital and long-term outcomes for patients undergoing RA via the transradial (TR) and transfemoral (TF) route in 126 consecutive patients (59 radial, 67 femoral) from 2009 to 2014. TR RA procedures were performed in 44/62 (71%) by the three TR operators, compared with 15/64 (23%) by the four TF operators in the present study. Significantly smaller diameter guide catheters and burrs (1.39 ± 0.16 mm vs. 1.53 ± 0.24 mm, P = 0.001) were used in the TR group. Procedural success rates were similar in both TR and TF groups. There was a significantly less major access site bleeding complications in favor of radial artery access (2% vs. 16%, P = 0.012). The incidence of in-hospital death or myocardial infarction was low in both groups. Although a trend of lower adverse event rate was demonstrated in the TR group compared with the TF one, no statistical significance (21% vs. 27%, P = 0.135) was detected. CONCLUSIONS: Radial access, a useful alternative to femoral access for RA and DES, can be safely and successfully performed on up to 71% of the patients with heavily calcified coronary lesions needing RA by experienced TR operators.

Associations between endothelin-1 and adiponectin in chronic heart failure.

OBJECTIVES: Endothelin-1 (ET-1) induces cardiac hypertrophy, whereas adiponectin may elicit protective effects in the vasculature and myocardium. We therefore evaluated the relationship between plasma ET-1 and adiponectin levels in heart failure (HF) patients, and the association between adiponectin expression and ET-1-induced hypertrophy of human cardiomyocytes (HCM) in vitro. METHODS: One hundred seventeen patients with chronic HF were enrolled into this study. A group of 7 patients with end-stage HF undergoing heart transplantation was included in the histopathological study. Baseline clinical evaluations and laboratory measurements were performed. HCM cultures were studied to investigate the effect of ET-1 on cell size and adiponectin expression. RESULTS: Plasma ET-1, adiponectin, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased with the severity of HF. Higher New York Heart Association functional class, plasma ET-1, adiponectin, and NT-proBNP levels were significant predictors of adverse outcomes in these patients. The myocardial expression of adiponectin was significantly higher in the recipient hearts of patients undergoing emergency or urgent heart transplantation. In cell culture, ET-1 significantly increased cell size and adiponectin expression in HCM. CONCLUSIONS: Adiponectin was significantly elevated in HF and was significantly associated with ET-1. The study provides a basis for further investigation of ET-1 and adiponectin modulation as a therapeutic strategy for ventricular remodeling in HF.

Transradial approach in myocardial infarction.

OBJECTIVE: This study investigates the feasibility, efficacy, and safety of routine primary percutaneous coronary intervention via transradial approach in patients with acute ST-elevation myocardial infarction. METHODS AND RESULTS: From 2005 to 2007,122 consecutive patients with acute ST-elevation myocardial infarction within 12 hours, including those experiencing cardiogenic shock, were eligible for primary transradial PCI if the radial artery pulse could be felt. Efficacy, safety, and major adverse cardiac events regarding mortality, recurrent non-fatal myocardial infarction, and revascularization were recorded. Eighty-five of 122 patients underwent transradial PCI, and 37 had transfemoral PCI. Older women, haemodynamic instability, and the presence of severe chronic kidney disease (stages 4 and 5) or end-stage renal disease were significantly related to choice of transfemoral approach (P < 0.05). Glycoprotein IIb/IIIa inhibitors were used more often in patients who underwent transradial PCI than in those who underwent transfemoral PCI (37% vs 16%; P = 0.043). The incidence of major bleeding complications requiring blood transfusion was significantly higher in the transfemoral group (P = 0.004). A similar procedural success rate was achieved in both groups (P = 0.737). During follow-up of 580 days, the total major adverse cardiac events were similar in both groups (P = 0.299). CONCLUSIONS: Routine transradial primary PCI can be safely and successfully performed on up to 70% of acute ST-elevation myocardial infarction patients and, compared with transfemoral approach, is associated with a significantly reduced rate of major bleeding complications.

Effects of moderate alcohol consumption on inflammatory biomarkers.

OBJECTIVES: Although light to moderate alcohol consumption has been associated with lower all-cause and cardiovascular (CV) mortality, the underlying mechanisms are only partly understood. Evidence has emerged in recent years that atherosclerosis is an inflammatory disease. We hypothesize that beneficial effects of moderate alcohol consumption on CV mortality may be linked to antiinflammatory effects. METHODS AND RESULTS: The association between alcohol consumption and concentrations of high sensitivity C-reactive protein (hs-CRP) and fibrinogen were investigated. Six hundred and thirtysix eligible individuals apparently healthy were included. 393 (61.8%) were men and 243 (38.2%) were women. The mean ages for men and women were 51.5 +/- 12.4 y and 50.8 +/- 12.1 y, respectively. Daily alcohol intake showed an apparent U-shaped association with hs-CRP and fibrinogen values in men, with lowest levels at an alcohol intake of 20-70 g daily (0.139 +/- 0.116 mg/dl for hs-CRP and 274 +/- 51.7 mg/dl for fibrinogen). Proportional odds model analysis showed moderate alcohol consumption (20 to 70 g vs. no drinking per day, OR = 0.32, 95% CI: 0.14-0.74), and regular exercise (> or = 3 times/week vs. no, OR = 0.52, 95% CI: 0.35-0.77) were negatively correlated with elevated hs-CRP values. CONCLUSIONS: Our results parallel the demonstration of a U-shaped relationship between alcohol consumption and cardiovascular mortality, and suggest that anti-inflammatory effects of moderate alcohol intake may partly be linked to a low cardiovascular and overall mortality.

Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure.

BACKGROUND: The serum concentration of C-reactive protein (CRP) is mildly elevated in patients with chronic congestive heart failure (CHF), but this level falls well within the range found in healthy subjects. Standard clinical assays for CRP lack sensitivity within the low reference range and thus cannot be used effectively for routine clinical risk prediction. Because assays for high-sensitivity CRP (hsCRP) are now available, we can measure hsCRP to determine its predictive value for the prognosis of patients with CHF. METHODS: Serum levels of hsCRP in 108 patients with CHF and left ventricular ejection fraction (LVEF) <50% were examined. Major adverse cardiac events (death, heart transplantation, or hospitalization with worsening heart failure) during a median follow-up period of 403 days were determined. RESULTS: The concentrations of hsCRP in this study population were significantly increased with the severity of CHF. In a multivariate analysis, LVEF and serum levels of hsCRP were independent significant predictors for adverse outcomes in these patients (hazard ratio, 3.714, P =.024, and hazard ratio, 2.584, P =.047, respectively). However, hsCRP was minimally correlated with LVEF (r = -0.167, P =.084). Further analysis indicated that hsCRP might identify a different high-risk group and could improve risk stratification beyond that of LVEF. CONCLUSIONS: These findings suggest that an elevated level of hsCRP is an independent predictor of prognosis in CHF and can provide additional prognostic information for the risk stratification and treatment in patients with chronic CHF.

Implantation of a passive fixation dual chamber pacemaker in a patient with persistent left superior vena cava.

Electrode instability and displacement have been reported in patients who underwent pacemaker implantation via persistent left superior vena cava. An active-fixation system, and sometimes epicardial pacing, is necessary to maintain pacing stability. We report the case of a 76-year-old man with a left superior vena cava who required dual-chamber permanent pacing. Passive-fixation atrial and ventricular leads were successfully inserted and produced good long-term pacing and sensing. To the best of our knowledge, this is the first reported case of implantation of a dual-chamber pacemaker via persistent left superior vena cava in Taiwan.

The prognostic value of circulating soluble cell adhesion molecules in patients with chronic congestive heart failure.

BACKGROUND: Circulating soluble (s) cell adhesion molecules (CAMs) are elevated in patients with congestive heart failure (CHF) and may play an important role in the pathogenesis of CHF by mediating the cell-cell interactions of the immune response. However, clinical data about the prognostic value of sCAMs are sparse. The purpose of this study is to determine whether various sCAMs can provide prognostic information in patients with CHF. METHODS: We measured circulating levels of three sCAMs (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and sP-selectin) in 74 patients with symptomatic chronic CHF and left ventricular ejection fraction (LVEF) <50%. We compared these levels with those of a group of 19 age-matched control subjects. Major adverse cardiac events (death, heart transplantation or hospitalization with worsening CHF) during a median follow-up period of 240 days were determined. RESULTS: The concentrations of the three sCAMs in the 74 patients with CHF were significantly associated with one another. Their levels were higher than those of the control subjects and increased with the severity of CHF. Significantly higher sCAM levels were noted in those patients who had major adverse cardiac events during the follow-up period. There were significant negative correlations between LVEF and sCAMs. However, only high levels of sP-selectin were found to be an independent significant predictor of CHF by Cox proportional hazards analysis. CONCLUSIONS: These findings indicate that the levels of these three sCAMs increase with the severity of CHF and are related to clinical outcomes. Among them, high levels of sP-selectin can provide prognostic information independently in patients with CHF.

Development of an echocardiographic method for choosing the best fitting single-pass VDD lead.

To achieve stable single-lead VDD pacing, a selection of the electrode with the optimal distance between the lead tip and the floating atrial dipole (AV distance [AVD]) is important. The authors hypothesized that the size of the right heart chambers may affect atrial sensing, and that measurement of their internal dimension at end-diastole (RHIDd) in the apical four chamber view by transthoracic echocardiography may aid in choosing the proper AVD. Twenty-six consecutive cases that had undergone VDD pacer implantation using the conventional chest X ray were examined retrospectively by the echocardiographic method. The chest x-ray method properly selected a lead with optimal atrial sensing, defined as minimum P wave amplitude > or = 1.0 mV, for only 20 (77%) of 26 patients. By comparing these results with their respective RHIDd, a cut-off point of 13 cm was obtained that indicated a criterion for choosing the proper AVD. The indication was that if the RHIDd was > or = 13 cm, a lead with an AVD of 15.5/16 cm should have been used; if the RHIDd was < 13 cm, a lead with an AVD of 13/13.5 cm should have been chosen. Using the echocardiographic method, all six patients who had suboptimal atrial sensing could be identified and classified as having missized (four undersized; two oversized) permanent leads. In conclusion, the described method provides a promising preoperative assessment of the best fitting electrode length in single lead VDD pacing. A prospective study is ongoing to verify its applicability.