The Clinical Impact of β-Blocker Therapy on Patients With Chronic Coronary Artery Disease After Percutaneous Coronary Intervention

Background and Objectives@#The outcome benefits of β-blockers in chronic coronary artery disease (CAD) have not been fully assessed. We evaluated the prognostic impact of β-blockers on patients with chronic CAD after percutaneous coronary intervention (PCI). @*Methods@#A total of 3,075 patients with chronic CAD were included from the Grand DrugEluting Stent registry. We analyzed β-blocker prescriptions, including doses and types, in each patient at 3-month intervals from discharge. After propensity score matching, 1,170 pairs of patients (β-blockers vs. no β-blockers) were derived. Primary outcome was defined as a composite endpoint of all-cause death and myocardial infarction (MI). We further analyzed the outcome benefits of different doses (low-, medium-, and high-dose) and types (conventional or vasodilating) of β-blockers. @*Results@#During a median (interquartile range) follow-up of 3.1 (3.0–3.1) years, 134 (5.7%) patients experienced primary outcome. Overall, β-blockers demonstrated no significant benefit in primary outcome (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.63–1.24), all-cause death (HR, 0.87; 95% CI, 0.60–1.25), and MI (HR, 1.25; 95% CI, 0.49–3.15). In subgroup analysis, β-blockers were associated with a lower risk of all-cause death in patients with previous MI and/ or revascularization (HR, 0.38; 95% CI, 0.14–0.99) (p for interaction=0.045). No significant associations were found for the clinical outcomes with different doses and types of β-blockers. @*Conclusions@#Overall, β-blocker therapy was not associated with better clinical outcomes in patients with chronic CAD undergoing PCI. Limited mortality benefit of β-blockers may exist for patients with previous MI and/or revascularization.

Prasugrel-based De-Escalation of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With STEMI

Background and Objectives@#De-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events (NACEs) after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. Whether the benefits of de-escalation are sustained in highly thrombotic conditions such as ST-elevation myocardial infarction (STEMI) is unknown. We aimed to assess the efficacy and safety of de-escalation therapy in patients with STEMI or non-STsegment elevation ACS (NSTE-ACS). @*Methods@#This is a pre-specified subgroup analysis of the HOST-REDUCE-POLYTECH-ACS trial. ACS patients were randomized to prasugrel de-escalation (5 mg daily) or conventional dose (10 mg daily) at 1-month post-percutaneous coronary intervention. The primary endpoint was a NACE, defined as a composite of all-cause death, non-fatal myocardial infarction, stent thrombosis, clinically driven revascularization, stroke, and bleeding events of grade ≥2 Bleeding Academic Research Consortium (BARC) criteria at 1 year. @*Results@#Among 2,338 patients included in the randomization, 326 patients were diagnosed with STEMI. In patients with NSTE-ACS, the risk of the primary endpoint was significantly reduced with de-escalation (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48– 0.89; p=0.006 for de-escalation vs. conventional), mainly driven by a reduced bleeding. However, in those with STEMI, there was no difference in the occurrence of the primary outcome (HR, 1.04; 95% CI, 0.48–2.26; p=0.915; p for interaction=0.271). @*Conclusions@#Prasugrel dose de-escalation reduced the rate of NACE and bleeding, without increasing the rate of ischemic events in NSTE-ACS patients but not in STEMI patients.

Long-term efficacy of vasodilating β-blocker in patients with acute myocardial infarction: nationwide multicenter prospective registry

Background/Aims@#Long-term benefit of vasodilating β-blockers is unknown. This study aimed to investigate the long-term benefit of vasodilating β-blockers over conventional β-blockers in patients with acute myocardial infarction (AMI). @*Methods@#Using nationwide prospective multicenter Korean Acute Myocardial Infarction Registry data, we analyzed 3-year clinical outcomes of 7,269 patients with AMI who received percutaneous coronary intervention (PCI) and β-blocker therapy. Patients were classified according to treatment strategy (vasodilating β-blockers vs. conventional β-blockers). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), and hospitalization for heart failure (HF) at 3 years. Secondary outcomes were each component of the primary outcome. Propensity score matching was performed to adjust for differences of baseline characteristics. @*Results@#In 3,079 pairs (6,158 patients) of propensity score-matched patients, the primary outcome occurred significantly less in the vasodilating β-blockers group compared with the conventional β-blockers group (7.6% vs. 9.8%, p = 0.003). Among the secondary outcomes, cardiac death occurred significantly less in the vasodilating β-blockers group than in the conventional group (3.5% vs. 4.8%, p = 0.015). The incidence rates of MI (2.4% vs. 3.0%, p = 0.160) or hospitalization for HF (2.6% vs. 3.2%, p = 0.192) were not significantly different between the two groups. @*Conclusions@#Vasodilating β-blocker therapy was associated with better clinical outcomes compared with conventional β-blocker therapy in AMI patients undergoing PCI during 3 years follow-up. Vasodilating β-blockers could be recommended preferentially for these patients.

SYNTAX Score and SYNTAX Score II Can Predict the Clinical Outcomes of Patients with Left Main and/or 3-Vessel Disease Undergoing Percutaneous Coronary Intervention in the Contemporary Cobalt-Chromium Everolimus-Eluting Stent Era

BACKGROUND AND OBJECTIVES@#The impact of SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery score (SS) and SS II in patients who receive percutaneous coronary intervention with second-generation everolimus-eluting stents (EES) has not been fully validated.@*METHODS@#The SS, SS II were calculated in 1,248 patients with left main and/or 3-vessel disease treated with EES. Patient-oriented composite endpoint (POCE; all-cause death, any myocardial infarction (MI), any revascularization) and target lesion failure (TLF: cardiac death, target-vessel MI, target lesion revascularization) were analyzed.@*RESULTS@#The mean SS was 21.1±9.6. Three-year POCE increased according to the SS group (15.2% vs. 19.9% vs. 27.4% for low (≤22), intermediate (≥23, ≤32), high (≥33) SS groups, p<0.001). By multivariate Cox proportional hazard analysis, SS group was an independent predictor of 3-year POCE (hazard ratio, 1.324; 95% confidence interval, 1.095–1.601; p=0.004). The receiver operating characteristic curves revealed that the SS II was superior to the SS for 3-year POCE prediction (area under the curve [AUC]: 0.611 vs. 0.669 for SS vs. SS II, p=0.019), but not for 3-year TLF (AUC: 0.631 vs. 0.660 for SS vs. SS II, p=0.996). In subgroup analysis, SS II was superior to SS in patients with cardiovascular clinical risk factors, and in those presenting as stable angina.@*CONCLUSIONS@#The usefulness of SS and SS II was still valid in patients with left main and/or 3-vessel disease. SS II was superior to SS for the prediction of patient-oriented outcomes, but not for lesion-oriented outcomes.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00698607ClinicalTrials.gov Identifier: NCT01605721

SYNTAX Score and SYNTAX Score II Can Predict the Clinical Outcomes of Patients with Left Main and/or 3-Vessel Disease Undergoing Percutaneous Coronary Intervention in the Contemporary Cobalt-Chromium Everolimus-Eluting Stent Era

BACKGROUND AND OBJECTIVES: The impact of SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery score (SS) and SS II in patients who receive percutaneous coronary intervention with second-generation everolimus-eluting stents (EES) has not been fully validated.METHODS: The SS, SS II were calculated in 1,248 patients with left main and/or 3-vessel disease treated with EES. Patient-oriented composite endpoint (POCE; all-cause death, any myocardial infarction (MI), any revascularization) and target lesion failure (TLF: cardiac death, target-vessel MI, target lesion revascularization) were analyzed.RESULTS: The mean SS was 21.1±9.6. Three-year POCE increased according to the SS group (15.2% vs. 19.9% vs. 27.4% for low (≤22), intermediate (≥23, ≤32), high (≥33) SS groups, p<0.001). By multivariate Cox proportional hazard analysis, SS group was an independent predictor of 3-year POCE (hazard ratio, 1.324; 95% confidence interval, 1.095–1.601; p=0.004). The receiver operating characteristic curves revealed that the SS II was superior to the SS for 3-year POCE prediction (area under the curve [AUC]: 0.611 vs. 0.669 for SS vs. SS II, p=0.019), but not for 3-year TLF (AUC: 0.631 vs. 0.660 for SS vs. SS II, p=0.996). In subgroup analysis, SS II was superior to SS in patients with cardiovascular clinical risk factors, and in those presenting as stable angina.CONCLUSIONS: The usefulness of SS and SS II was still valid in patients with left main and/or 3-vessel disease. SS II was superior to SS for the prediction of patient-oriented outcomes, but not for lesion-oriented outcomes.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00698607ClinicalTrials.gov Identifier: NCT01605721

Antithrombotic Strategy in Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention

Choosing antithrombotic regimens for patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) with stent placement is challenging. Until recently, the guidelines recommended warfarin-based triple therapy, which causes frequent major bleeding events in up to 12% of patients during the first year of treatment. The WOEST trial, however, revealed that dual therapy, by without aspirin, resulted in significantly lower bleeding risks with similar thromboembolic events to triple therapy. Subsequently, efforts to seek the optimal dual therapy regimens, especially with the combination of a non-vitamin K antagonist oral anticoagulant (NOAC), were initiated. This review highlights the evidence for dual therapy using an NOAC for patients with AF who underwent PCI, with an emphasis on reduced bleeding risk.

Clinical and Angiographic Outcomes of the First Korean-made Sirolimus-Eluting Coronary Stent with Abluminal Bioresorbable Polymer

BACKGROUND AND OBJECTIVES: This trial evaluated the safety and efficacy of the Genoss drug-eluting coronary stent. METHODS: This study was a prospective, multicenter, randomized trial with a 1:1 ratio of Genoss drug-eluting stent (DES)™ and Promus Element™. Inclusion criteria were the presence of stable angina, unstable angina, or silent ischemia. Angiographic inclusion criteria were de novo coronary stenotic lesion with diameter stenosis >50%, reference vessel diameter of 2.5–4.0 mm, and lesion length ≤40 mm. The primary endpoint was in-stent late lumen loss at 9-month quantitative coronary angiography follow-up. Secondary endpoints were in-segment late lumen loss, binary restenosis rate, death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis during 9 months of follow-up. RESULTS: We enrolled 38 patients for the Genoss DES™ group and 39 patients for the Promus Element™ group. In-stent late lumen loss at 9 months was not significantly different between the 2 groups (0.11±0.25 vs. 0.16±0.43 mm, p=0.567). There was no MI or stent thrombosis in either group. The rates of death (2.6% vs. 0%, p=0.494), TLR (2.6% vs. 2.6%, p=1.000), and TVR (7.9% vs. 2.6%, p=0.358) at 9 months were not significantly different. CONCLUSION: This first-in-patient study of the Genoss DES™ stent showed excellent angiographic outcomes for in-stent late lumen loss and major adverse cardiac events over a 9-month follow-up.

Development of a Rabbit Model for a Preclinical Comparison of Coronary Stent Types In-Vivo

Along with the development of innovative stent designs, preclinical trials in animal models are essential. Many animal models have been used and appear to yield comparable results to clinical trials despite substantial criticisms about their validity. Among the animal models, porcine coronary artery models have been the standard models for the preclinical evaluation of endovascular devices. However, rapid growth rate, high body weight potential, and the propensity to develop granulomatous inflammatory reactions are major limitations of the porcine coronary artery model. Compared with porcine coronary artery models, the comparative rabbit iliac artery model has the advantages of being small and easy to handle and relatively inexpensive. Furthermore, the rabbit model has been known to reliably reflect human restenosis histopathologically and have major advantages such as pairwise comparison, which makes each animal serve as its own control subject, therefore, maximizing its statistical power for comparative testing. However, despite the widespread use of this model, a systematic description of the procedure and harvest protocols has never been published. This article describes the surgical procedure, stent implantation procedure, method for tissue harvesting, and how measurements are performed. Although the results of animal models may not perfectly extrapolate to humans, the comparative rabbit iliac artery model may be a useful tool for assessing and comparing the efficacy of new coronary stents with conventional stent systems. This thorough description of the techniques required for vascular access, stent implantation, tissue preparation, and measurement, should aid investigators wishing to begin using the comparative rabbit iliac artery model.

PPARgamma modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury

Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to vascular injury such as angioplasty. Protein kinase G (PKG) has an important role in the process of VSMC phenotype switching. In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, could modulate VSMC phenotype through the PKG pathway to reduce neointimal hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone inhibited the phenotype change of VSMCs from a contractile to a synthetic form. The platelet-derived growth factor (PDGF)-induced reduction of PKG level was reversed by rosiglitazone treatment, resulting in increased PKG activity. This increased activity of PKG resulted in phosphorylation of vasodilator-stimulated phosphoprotein at serine 239, leading to inhibited proliferation of VSMCs. Interestingly, rosiglitazone did not change the level of nitric oxide (NO) or cyclic guanosine monophosphate (cGMP), which are upstream of PKG, suggesting that rosiglitazone influences PKG itself. Chromatin immunoprecipitation assays for the PKG promoter showed that the activation of PKG by rosiglitazone was mediated by the increased binding of Sp1 on the promoter region of PKG. In vivo experiments showed that rosiglitazone significantly inhibited neointimal formation after balloon injury. Immunohistochemistry staining for calponin and thrombospondin showed that this effect of rosiglitazone was mediated by modulating VSMC phenotype. Our findings demonstrate that rosiglitazone is a potent modulator of VSMC phenotype, which is regulated by PKG. This activation of PKG by rosiglitazone results in reduced neointimal hyperplasia after angioplasty. These results provide important mechanistic insight into the cardiovascular-protective effect of PPARgamma.

A randomized, prospective, two-center comparison of sirolimus-eluting stent and zotarolimus-eluting stent in acute ST-elevation myocardial infarction: the SEZE trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The zotarolimus-eluting stent has shown larger in-stent late lumen loss compared to sirolimus-eluting stents in previous studies. However, this has not been thoroughly evaluated in ST elevation myocardial infarction.</p><p><b>METHODS</b>This was a prospective, randomized, controlled trial evaluating angiographic outcomes in patients presenting with ST elevation myocardial infarction, treated with zotarolimus-eluting stents or sirolimus-eluting stents. From March 2007 to February 2009, 122 patients were randomized to zotarolimus-eluting stents or sirolimus-eluting stents in a 1:1 fashion. The primary endpoint was 9-month in-stent late lumen loss confirmed by coronary angiography, and secondary endpoints were percent diameter stenosis, binary restenosis rate, major adverse cardiac events (a composite of cardiac death, non-fatal myocardial infarction, and target vessel revascularization), and late-acquired incomplete stent apposition.</p><p><b>RESULTS</b>Angiographic in-stent late lumen loss was significantly higher in the zotarolimus-eluting stent group compared to the sirolimus-eluting stent group ((0.49 ± 0.65) mm vs. (0.10 ± 0.46) mm, P = 0.001). Percent diameter stenosis at 9-month follow-up was also larger in the zotarolimus-eluting stent group ((30.0 ± 17.9)% vs. (17.6 ± 14.0)%, P < 0.001). In-segment analysis showed similar findings. There were no significant differences in binary restenosis rate, major adverse cardiac events, and late-acquired incomplete stent apposition.</p><p><b>CONCLUSIONS</b>Compared to sirolimus-eluting stents, the zotarolimus-eluting stent is associated with significantly higher in-stent late lumen loss at 9-month angiographic follow-up in the treatment of ST elevation myocardial infarction. Although there was no significant difference in 1-year clinical outcomes, the clinical implication of increased late lumen loss should be further studied.</p>

Lack of Association Between Low Density Lipoprotein Particle Size and On-Treatment Platelet Reactivity in Patients With Coronary Artery Disease

BACKGROUND AND OBJECTIVES: Small dense low density lipoproteins (sd-LDL) are a risk factor for coronary artery disease and are known to stimulate platelet function in vitro. This study aimed to evaluate whether high proportion of sd-LDL is associated with high on-treatment platelet reactivity (HOPR). SUBJECTS AND METHODS: From January 2009 to March 2010, 439 subjects (mean age: 64.3+/-9.7, Male : Female=306 : 133) were enrolled from the low density LIPOProtein-cholesterol Size measurement Registry with coronary artery disease, who had undergone elective percutaneous coronary intervention and measured both LDL particle size and on-treatment platelet reactivity (OPR). Mean LDL particle size was measured by gradient gel electrophoresis (Quantimetrix, Lipoprint(TM)) and OPR by the VerifyNow(TM) system (aspirin and P2Y12). RESULTS: Between pattern A (large, buoyant LDL dominant) and B (sd-LDL dominant) population, there were no significant difference in OPR to aspirin (441.3+/-71.9 vs. 434.07+/-63.45 aspirin reaction units, p=0.351) or clopidogrel (237.9+/-87.3 vs. 244.9+/-80.7 P2Y12 reaction units, p=0.465). There was no difference in LDL particle size between patients with HOPR compared with non-HOPR patients (aspirin: 26.8+/-0.5 vs. 26.7+/-0.6 nm, p=0.078, clopidogrel: 26.7+/-0.6 vs. 26.8+/-0.5 nm, p=0.857). Pearson's correlation coefficients between LDL particle size and platelet reactivity were not statistically significant (aspirin assay: r=0.080, p=0.098, P2Y12 assay: r=-0.027, p=0.568). CONCLUSION: There was no significant association between LDL particle size and OPR in patients with coronary artery disease.

Clinical Characteristics of Coronary Drug-Eluting Stent Fracture: Insights from a Two-Center DES Registry

Stent fracture (SF) has been implicated as a risk factor for in-stent restenosis, but its incidence and clinical characteristics are not well established. Therefore we investigated the conditions associated with stent fracture and its clinical presentation and outcome. Between 2004 and 2007, consecutive cases of SF were collected from the Seoul National University Hospital. Clinical characteristics and outcome of patients with fractured stents were compared with a ten-fold cohort of age and gender matched controls (n = 236). A total of 4,845 patients received percutaneous coronary intervention and 3,315 patients (68.4%) underwent angiographic follow-up. Twenty-eight fractured stents were observed in 24 patients. The incidence of SF was 0.89% for sirolimus-eluting stents (SES) and 0.09% for paclitaxel-eluting stents. Chronic kidney disease, stent implantation in the right coronary artery (RCA), and SES use were independent predictors of drug-eluting stent fracture by multivariate analysis. SF was significantly associated with binary restenosis (11.4% vs 41.7%, P < 0.001) and increased risk of target lesion revascularization (8.1% vs 33.3%, P = 0.001). Patients with SF but without significant restenosis showed excellent outcome despite only medical treatment. In conclusion, SF is associated with increased rates of restenosis and repeat revascularization. Significant risk factors include chronic kidney disease, RCA intervention, and SES use.

Clinical Characteristics of Coronary Drug-Eluting Stent Fracture: Insights from a Two-Center DES Registry

Stent fracture (SF) has been implicated as a risk factor for in-stent restenosis, but its incidence and clinical characteristics are not well established. Therefore we investigated the conditions associated with stent fracture and its clinical presentation and outcome. Between 2004 and 2007, consecutive cases of SF were collected from the Seoul National University Hospital. Clinical characteristics and outcome of patients with fractured stents were compared with a ten-fold cohort of age and gender matched controls (n = 236). A total of 4,845 patients received percutaneous coronary intervention and 3,315 patients (68.4%) underwent angiographic follow-up. Twenty-eight fractured stents were observed in 24 patients. The incidence of SF was 0.89% for sirolimus-eluting stents (SES) and 0.09% for paclitaxel-eluting stents. Chronic kidney disease, stent implantation in the right coronary artery (RCA), and SES use were independent predictors of drug-eluting stent fracture by multivariate analysis. SF was significantly associated with binary restenosis (11.4% vs 41.7%, P < 0.001) and increased risk of target lesion revascularization (8.1% vs 33.3%, P = 0.001). Patients with SF but without significant restenosis showed excellent outcome despite only medical treatment. In conclusion, SF is associated with increased rates of restenosis and repeat revascularization. Significant risk factors include chronic kidney disease, RCA intervention, and SES use.

Evaluation of Local Flow Conditions in Jailed Side Branch Lesions Using Computational Fluid Dynamics

BACKGROUND AND OBJECTIVES: Lesions of vascular bifurcation and their treatment outcomes have been evaluated by anatomical and physiological methods, such as intravascular ultrasound and fractional flow reserve (FFR). However, local changes in flow dynamics in lesions of bifurcation have not been well evaluated. This study aimed at evaluating changes in the local flow patterns of bifurcation lesions. MATERIALS AND METHODS: Eight (n=8) representative simulation-models were constructed: 1 normal bifurcation, 5 main-branch (MB) stenting models with various side-branch (SB) stenoses (ostial or non-ostial 75% diameter stenosis with 1- or 2-cm lesion lengths, ostial 75% diameter stenosis caused by carina shift), and 2 post-kissing models (no or 50% SB residual stenosis). Pressure, velocity, and wall shear stress (WSS) profiles around the bifurcation sites were investigated using computational fluid dynamics. RESULTS: Post-stenting models revealed significant pressure drop in the SB (FFR<0.75), excluding the carina shift model (FFR=0.89). In the post-kissing models, there was no significant pressure drop. All post-stenting models revealed eccentric low velocity flow patterns and areas of low WSS, primarily in the lateral wall on distal MB. Post-kissing angioplasty improved pressure drop in the SB but resulted in alteration of flow distribution in the MB. In the carina shift model, kissing ballooning resulted in deteriorated local flow conditions due to increased area of low velocity and WSS. CONCLUSION: This study suggests that the most commonly used bifurcation intervention strategy may cause local flow disturbances, which may partially explain high restenosis and event rates in patients with bifurcation lesions.

Evaluation of Local Flow Conditions in Jailed Side Branch Lesions Using Computational Fluid Dynamics

BACKGROUND AND OBJECTIVES: Lesions of vascular bifurcation and their treatment outcomes have been evaluated by anatomical and physiological methods, such as intravascular ultrasound and fractional flow reserve (FFR). However, local changes in flow dynamics in lesions of bifurcation have not been well evaluated. This study aimed at evaluating changes in the local flow patterns of bifurcation lesions. MATERIALS AND METHODS: Eight (n=8) representative simulation-models were constructed: 1 normal bifurcation, 5 main-branch (MB) stenting models with various side-branch (SB) stenoses (ostial or non-ostial 75% diameter stenosis with 1- or 2-cm lesion lengths, ostial 75% diameter stenosis caused by carina shift), and 2 post-kissing models (no or 50% SB residual stenosis). Pressure, velocity, and wall shear stress (WSS) profiles around the bifurcation sites were investigated using computational fluid dynamics. RESULTS: Post-stenting models revealed significant pressure drop in the SB (FFR<0.75), excluding the carina shift model (FFR=0.89). In the post-kissing models, there was no significant pressure drop. All post-stenting models revealed eccentric low velocity flow patterns and areas of low WSS, primarily in the lateral wall on distal MB. Post-kissing angioplasty improved pressure drop in the SB but resulted in alteration of flow distribution in the MB. In the carina shift model, kissing ballooning resulted in deteriorated local flow conditions due to increased area of low velocity and WSS. CONCLUSION: This study suggests that the most commonly used bifurcation intervention strategy may cause local flow disturbances, which may partially explain high restenosis and event rates in patients with bifurcation lesions.

Celecoxib Does Not Attenuate the Antiplatelet Effects of Aspirin and Clopidogrel in Healthy Volunteers

BACKGROUND AND OBJECTIVES: The prevalence of arthritis, which is often treated with celecoxib, is high in patients with coronary artery disease. Furthermore, celecoxib has been reported to reduce restenosis after coronary stenting by inhibiting expression of the proto-oncogene Akt. A concern is that celecoxib increases thrombogenicity by inhibiting the synthesis of prostacyclin in endothelial cells. However, it is not known whether the administration of celecoxib will attenuate the antiplatelet effects of aspirin and clopidogrel, which are used after stenting. We addressed this gap in our knowledge. SUBJECTS AND METHODS: We recruited healthy volunteers (n=40) and randomized them into five subgroups (n=8 for each group: aspirin, celecoxib, aspirin+celecoxib, aspirin+clopidogrel, and aspirin+clopidogrel+celecoxib). Each subject received their medications for 6 days and blood samples were taken on day 0 and day 7. Celecoxib (200 mg twice a day), and/or aspirin (100 mg daily), and/or clopidogrel (75 mg daily) were administered. We compared platelet function among subgroups using light transmittance aggregometry and arachidonic acid metabolite assays. RESULTS: Celecoxib treatment alone did not significantly affect platelet aggregation. The reduction in adenosine diphosphase (ADP)-induced platelet aggregation by aspirin+clopidogrel was not affected by addition of celecoxib (31.3+/-6.9% vs. 32.4+/-12.2%, p=0.83). Inhibition of collagen-induced platelet aggregation by aspirin+clopidogrel was not affected by addition of celecoxib (47.6+/-13.4% vs. 51.6+/-3.7%, p=0.69). Drug-induced changes in prostacyclin and thromboxane levels did not differ among treatment groups. CONCLUSION: Celecoxib treatment does not interfere with the antiplatelet effects of aspirin or clopidogrel, suggesting that celecoxib can be safely administered in combination with dual antiplatelet therapy in patients with coronary stenting without increased thrombogenicity.

Systolic Mitral Annular Velocity as a Simple Marker of Left Ventricular Peak Systolic dP/dt in Patients with Significant Mitral Regurgitation

BACKGROUND: Evaluating left ventricular (LV) contractile function in patients with mitral regurgitation (MR) is a difficult clinical problem. Although LV dP/dt measured by Doppler echocardiography has been shown to be a good marker for LV contractility, it is limited clinically due to the complexity of the measurement and the difficulty in obtaining appropriate Doppler tracings in patients with eccentric MR. We hypothesized that systolic mitral annulus velocity (S') can be a good marker of LV dP/dt. METHODS: We studied 62 patients (25 men, age: 47+/-15 years) who had 3+ or 4+ MR with normal LV systolic function (ejection fraction >50%). Two-dimensional and Doppler echocardiography was performed. LV dP/dt-Doppler was measured using MR jet tracing as previously reported. S' velocity was measured at the septal annulus using Doppler tissue imaging. In 10 patients undergoing mitral surgery, LV pressure was measured with micromanometer-tipped catheter and peak dP/dt-cath was calculated. RESULTS: Mean LV ejection fraction was 60+/-6% and regurgitant fraction was 59+/-15%. S' velocity correlated well with LV dP/dt-Doppler (r=0.50, p<0.01). In 10 patients who underwent LV catheterization, LV dP/dt-Doppler correlated well with peak dP/dt-cath (r=0.68, p=0.03). Whereas S' velocity could be measured in all patients, LV dP/dt-Doppler could not be measured in 31 patients (50%) due to eccentric jet direction. CONCLUSION: Systolic mitral annulus velocity is a simple and feasible marker of LV dP/dt and, therefore, may be useful for assessing myocardial contractile function in patients with MR.

Long-Term Effect of Angiotensin Converting Enzyme Inhibitor on Chronic Mitral Regurgitation

BACKGROUND AND OBJECTIVES: Angiotensin converting enzyme inhibitors (ACEI) have been suggested to be beneficial in regurgitant valvular heart disease by reducing both preload and afterload. Moreover their benefits have also been proven in acute mitral regurgitation (MR). However the role of long term administration of ACEI in chronic MR remains in dispute. SUBJECTS AND METHODS: One hundred patients with more than moderate degree MR (rheumatic MR or Mitral valve prolapse [MVP] MR) were identified from patients undergoing cardiac echocardiography between April 1984 and July 2002. Patients with co-morbid valvular heart disease more than mild degree were excluded from the study. The subjects were divided into the study group (who took ACEI) and the control group. Medical records and echocardiographic reports were reviewed and the etiology of MR, left ventricular end-diastolic dimensions (LVEDD), end-systolic dimensions (LVESD), left atrial dimensions, and ejection fraction (EF) changes were studied serially for both groups. RESULTS: The mean duration of follow-up was 5.0+/-3.2 years. There were no significant differences in age, blood pressure, or basal echocardiographic parameters between the rheumatic MR and MVP MR groups. In the MVP MR patients, the ACEI group showed a statistically significant increase in EF (p=0.007), decrease in LVESD (p=0.0014) and decrease in left atrial dimensions (p=0.01). However, in the rheumatic MR patients, the ACEI group showed no significant changes compared to those of the non-ACEI group. CONCLUSION: Long term ACEI therapy seems to be beneficial in mildly symptomatic MR due to mitral valve prolapse.

A Case of Coronary Vasospasm during Neck Surgery

Prinzmetal, or variant, angina is an unusual syndrome of cardiac pain, which is secondary to myocardial ischemia resulting from transient increases in coronary vasomotor tone or vasospasm. We experienced a 58-year-old male patient with an unusual ST segment using carotid sinus massage during neck surgery. A coronary angiography, with intravenous ergonovine provocation, showed a reversible coronary artery spasm with typical chest pain and ST segment elevation. This is a report of coronary vasospasm detected during neck surgery, and suggests the role of a dynamic sequential change in autonomic function as a key player in the mechanism behind coronary vasospasm.

A Case of Acute Suppurative Thyroiditis as a Complication of Acupuncture in Patient with a Benign Thyroid Nodule / 대한내분비학회지

Acute suppurative thyroiditis is an uncommon disease, and usually affects patients with preexisting thyroid gland pathology. Penetrating injury could provide an acquired channel for the infection to spread into the relatively infection-resistant thyroid gland. We describe the first case of acute suppurative thyroiditis, as a complication of acupuncture, in a patient with a benign thyroid nodule. A 54-year-old male received acupuncture on his neck for the treatment of a previously diagnosed thyroid nodule. Four days after the acupuncture, the patient was admitted due to severe pain of the anterior neck and odynophagia. Fever and tenderness over the thyroid gland were observed. Burkholderia cepacia was isolated from a culture dish of aspirate of the thyroid gland. A neck computed tomography scan showed an abscess in the thyroid gland. Antibiotic treatment, and repeated drainage of the abscess, ameliorated the symptoms of infection. Two weeks after admission, the patient was discharged without sequela. Acupuncture should be considered as a kind of penetrating injury, which may induce acute suppurative thyroiditis.