Ondansetron blocks wild-type and p.F503L variant small-conductance Ca2+-activated K+ channels.

Apamin-sensitive small-conductance Ca2+-activated K+ (SK) current ( IKAS) is encoded by Ca2+-activated K+ channel subfamily N ( KCNN) genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT syndrome (diLQTS), we screened for KCNN variants among patients with diLQTS, determined the properties of heterologously expressed wild-type (WT) and variant KCNN channels, and determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS. We searched 2,306,335 records in the Indiana Network for Patient Care and found 11 patients with diLQTS who had DNA available in the Indiana Biobank. DNA sequencing discovered a heterozygous KCNN2 variant (p.F503L) in a 52-yr-old woman presenting with corrected QT interval prolongation at baseline (473 ms) and further corrected QT interval lengthening (601 ms) after oral administration of ondansetron. That patient was also heterozygous for the p.S38G and p.P2835S variants of the QT-controlling genes KCNE1 and ankyrin 2, respectively. Patch-clamp experiments revealed that the p.F503L KCNN2 variant heterologously expressed in human embryonic kidney (HEK)-293 cells augmented Ca2+ sensitivity, increasing IKAS density. The fraction of total F503L-KCNN2 protein retained in the membrane was higher than that of WT KCNN2 protein. Ondansetron at nanomolar concentrations inhibited WT and p.F503L SK2 channels expressed in HEK-293 cells as well as native SK channels in ventricular cardiomyocytes. Ondansetron-induced IKAS inhibition was also demonstrated in Langendorff-perfused murine hearts. In conclusion, the heterozygous p.F503L KCNN2 variant increases Ca2+ sensitivity and IKAS density in transfected HEK-293 cells. Ondansetron at therapeutic (i.e., nanomolar) concentrations is a potent IKAS blocker. NEW & NOTEWORTHY We showed that ondansetron, a 5-HT3 receptor antagonist, blocks small-conductance Ca2+-activated K+ (SK) current. Ondansetron may be useful in controlling arrhythmias in which increased SK current is a likely contributor. However, its SK-blocking effects may also facilitate the development of drug-induced long QT syndrome.

Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing.

BACKGROUND: Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic. METHODS AND RESULTS: Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 milliseconds (95% confidence interval [CI], 14-37) during normokalemia and by 54 milliseconds (95% CI, 40-68) during hypokalemia (P=0.01) at a 1000-millisecond pacing cycle length. In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the pacing cycle length threshold of APD alternans, the pacing cycle length for wave-break induction, and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained ventricular fibrillation (from 3 of 9 hearts to 9 of 9 hearts; P=0.009). Short-term cardiac memory was assessed by the slope of APD80 versus activation time. The slope increased from 0.01 (95% CI, -0.09 to 0.12) at baseline to 0.34 (95% CI, 0.23-0.44) after apamin (P<0.001) during right ventricular pacing and from 0.07 (95% CI, -0.05 to 0.20) to 0.54 (95% CI, 0.06-1.03) after apamin infusion (P=0.045) during left ventricular pacing. Patch-clamp studies confirmed increased IKAS in isolated rabbit ventricular myocytes during hypokalemia (P=0.038). CONCLUSIONS: Hypokalemia activates IKAS to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. IKAS blockade prominently lengthens the APD at late activation sites and facilitates ventricular fibrillation induction.

The anticoagulation one year after ablation of atrial fibrillation in patients with atrial fibrillation (ALONE-AF) trial: Study protocol.

Background: The ideal long-term antithrombotic strategy for patients after successful catheter-based atrial fibrillation (AF) ablation is still uncertain. Presently, practices vary, and the advantages of oral anticoagulation (OAC) for the post-ablation population are not clearly established. To date, no randomized trials have addressed this therapeutic question. This study aimed to evaluate whether no OAC therapy is superior to apixaban in reducing the risk of stroke, systemic embolism, or major bleeding among patients without apparent recurrent atrial arrhythmias for at least 1 year after their AF ablation procedure. Methods: The ALONE-AF trial is a prospective, multicenter, open-label, randomized study with blinded outcome assessment. Patients with AF who have at least one non-gender stroke risk factor (as determined by the CHA2DS2-VASc score) and no documented recurrences of atrial arrhythmia for at least 12 months post-ablation will be randomly assigned to apixaban 5 mg b.i.d. or no OAC therapy. The primary endpoint is a composite outcome of stroke, systemic embolism, and major bleeding. Key secondary outcomes include clinically relevant non-major bleeding, all-cause mortality, myocardial infarction, transient ischemic attack, quality of life, and frailty analysis. Participants will be followed for a period of 2 years. The estimated total sample size is 840 subjects, with 420 subjects in each arm. Conclusion: The ALONE-AF trial aims to provide robust evidence for the optimal anticoagulation strategy for patients with stroke risk factors following successful AF ablation.

Standard-Intensity Versus Low-Intensity Anticoagulation with Warfarin in Asian Patients with Atrial Fibrillation: A Multi-Center, Randomized Controlled Trial.

Anticoagulation with warfarin in Asian patients with atrial fibrillation (AF) often has been decreased as an international normalized ratio (INR) of prothrombin time 1.6-2.6 due to fear of bleeding, although universal criteria recommend an INR of 2.0-3.0. In this randomized, open-label trial, low-intensity anticoagulation (INR 1.6-2.6) was compared with standard-intensity anticoagulation (INR 2.0-3.0) with warfarin. A total 616 patients with AF and at least 1 risk factor for stroke were randomized to low-intensity anticoagulation (n = 308) and standard-intensity anticoagulation (n = 308) groups. The intention-to-treat analysis was performed to determine differences. The baseline characteristics of the two groups were comparable. New-onset stroke occurred in 2 patients (0.44% per year) in the low-intensity group and 5 patients (1.05% per year) in the standard-intensity group (HR 0.42, 95% CI 0.08-2.15). Major bleeding occurred in 4 patients (0.89% per year) in the low-intensity group and 5 patients (1.06% per year) in the standard-intensity group (HR 0.84, 95% CI 0.22-3.11). The rate of the net clinical outcome (composite of stroke, systemic embolism, major bleeding, and death) was 1.33% per year in the low-intensity group compared with 2.12% per year in the standard-intensity group (HR 0.63, 95% CI 0.23-1.72). In Asian patients with AF, clinical outcomes were not different between low-intensity and standard-intensity anticoagulation with warfarin.

Net clinical benefit of oral anticoagulants in Korean atrial fibrillation patients with low to intermediate stroke risk: A report from the Clinical Survey on Stroke Prevention in patients with Atrial Fibrillation (CS-SPAF).

Background: The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non-gender CHA2DS2-VASc scores 0-1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non-gender CHA2DS2-VASc scores 0-1. Methods: This multi-center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-VKA oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0-1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. Results: We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed-up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37-4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56-5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score = 0). Conclusions: In the Korean AF cohort at non-gender CHA2DS2-VASc scores 0-1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1.

Impact of plaque components on no-reflow phenomenon after stent deployment in patients with acute coronary syndrome: a virtual histology-intravascular ultrasound analysis.

AIMS: We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relation between coronary plaque characteristics and no-reflow in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: A total of 190 consecutive ACS patients were imaged using VH-IVUS and analysed retrospectively. Angiographic no-reflow was defined as TIMI flow grade 0, 1, and 2 after stenting. Virtual histology-intravascular ultrasound classified the colour-coded tissue into four major components: fibrotic, fibro-fatty, dense calcium, and necrotic core (NC). Thin-cap fibroatheroma (TCFA) was defined as focal, NC-rich (≥10% of the cross-sectional area) plaques being in contact with the lumen in a plaque burden≥40%. Of the 190 patients studied at pre-stenting, no-reflow was observed in 24 patients (12.6%) at post-stenting. The absolute and %NC areas at the minimum lumen sites (1.6±1.2 vs. 0.9±0.8 mm2, P<0.001, and 24.5±14.3 vs. 16.1±10.6%, P=0.001, respectively) and the absolute and %NC volumes (30±24 vs. 16±17 mm3, P=0.001, and 22±11 vs. 14±8%, P<0.001, respectively) were significantly greater, and the presence of at least one TCFA and multiple TCFAs within culprit lesions (71 vs. 36%, P=0.001, and 38 vs. 15%, P=0.005, respectively) was significantly more common in the no-reflow group compared with the normal-reflow group. In the multivariable analysis, %NC volume was the only independent predictor of no-reflow (odds ratio=1.126; 95% CI 1.045-1.214, P=0.002). CONCLUSION: In ACS patients, post-stenting no-reflow is associated with plaque components defined by VH-IVUS analysis with larger NC and more TCFAs.

Clinical Implications of Heart Rate Control in Heart Failure With Atrial Fibrillation: Multi-Center Prospective Observation Registry (CODE-AF Registry).

Background: Atrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively). Methods: Echocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61-80 bpm, 81-110 bpm, and >110 bpm. Results: A total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61-80 bpm group: hazard ratio, 0.66; 95% CI, 0.46-0.94; p = 0.021; 81-110 bpm group: hazard ratio, 0.60; 95% CI, 0.40-0.90; p = 0.013). Especially, HFpEF patients with HR 81-110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011). Conclusion: In patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.

Validation of Biomarker-Based ABCD Score in Atrial Fibrillation Patients with a Non-Gender CHA2DS2-VASc Score 0-1: A Korean Multi-Center Cohort.

PURPOSE: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA2DS2-VASc score of 0-1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m²), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA2DS2-VASc score 0-1. MATERIALS AND METHODS: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0-1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. RESULTS: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA2DS2-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P-Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11-0.63, p=0.003). CONCLUSION: The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0-1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA2DS2-VASc score 0-1.

Comparison of effects of rosuvastatin and atorvastatin on plaque regression in Korean patients with untreated intermediate coronary stenosis.

BACKGROUND: Serial intravascular ultrasound (IVUS) was used to compare the effects of moderate doses of rosuvastatin and atorvastatin on plaque regression in patients with intermediate coronary stenosis. METHODS AND RESULTS: This was a prospective, randomized, and comparative study for lipid-lowering therapy with rosuvastatin 20mg (n=65) and atorvastatin 40mg (n=63) using serial IVUS (baseline and 11-month follow-up). Efficacy parameters included changes in total atheroma volume (TAV) and percent atheroma volume (PAV) from baseline to follow-up. Changes of TAV (-4.4±7.3 vs. -3.6±6.8mm(3), P=0.5) and PAV (-0.73±2.05 vs. -0.19±2.00%, P=0.14) from baseline to follow-up were not significantly different between the 2 groups. Plaque was increased in 15% in the rosuvastatin group and in 30% in the atorvastatin group at follow-up (P=0.064). The plaque increase group had higher baseline high-sensitivity C-reactive protein (hs-CRP; 1.28±2.70mg/dl vs. 0.54±1.16mg/dl, P=0.034) and higher follow-up low-density lipoprotein cholesterol (LDL-C) (78±24mg/dl vs. 63±21mg/dl, P=0.002) compared with the plaque non-increase group. Follow-up LDL-C (odds ratio [OR]=1.038, 95% confidence interval [CI]=1.003-1.060, P=0.036) and baseline hs-CRP (OR=1.025, 95%CI=1.001-1.059, P=0.046), not the type of statin, were the independent predictors of plaque increase at follow-up. CONCLUSIONS: Moderate doses of rosuvastatin and atorvastatin could contribute to effective plaque regression. Follow-up LDL-C and baseline hs-CRP are associated with plaque progression in patients with intermediate coronary stenosis.

Coronary artery responsiveness to ergonovine provocation in patients without vasospatic angina: a quantitative coronary angiography analysis.

Even patients without vasospastic angina show vasoconstriction after intracoronary ergonovine administration. We evaluated the determinants of coronary artery responsiveness to ergonovine in such patients.In 165 patients with no provoked electrocardiographic changes or ischemic chest pain during an intracoronary ergonovine test, total cholesterol, triglycerides (TG), high density lipoprotein cholesterol (HDL), and low density lipoprotein cholesterol (LDL) were correlated with the arterial luminal diameters before and after ergonovine infusion and after nitroglycerin injection by quantitative coronary angiography analysis.The mean and maximal basal tone (ie, percent change between baseline luminal diameter and diameter after nitroglycerin) were 7.0 ± 9.9% and 27.9 ± 10.8%, respectively. The mean and maximal responsiveness to ergonovine (ie, percent change between minimal diameter during ergonovine infusion and diameter after nitroglycerin) were 30.3 ± 13.6% and 52.7 ± 16.0%, respectively. The TG level (r = 0.191, P = 0.016) and TG/HDL ratio (r = 0.182, P = 0.021) were positively correlated with the basal tone, whereas LDL level (r = 0.155, P = 0.048) and LDL/HDL ratio (r = 0.172, P = 0.030) were positively correlated with the responsiveness to ergonovine. By multivariate analysis, LDL level, LDL/HDL ratio, and smoking were independent predictors of more than 50% responsiveness to ergonovine.Serum lipid profile and smoking influence the basal tone and responsiveness to ergonovine of coronary artery in patients without vaospastic angina.

Early statin therapy within 48 hours decreased one-year major adverse cardiac events in patients with acute myocardial infarction.

HMG-CoA reductase inhibitors (statins) reduce major adverse cardiac events (MACE) and mortality in patients with acute coronary syndrome. We investigated whether early statin therapy would be effective at reducing MACE in patients with acute myocardial infarction (AMI).A total of 1,159 patients were analyzed. They were grouped by initiation time of statin administration after admission as follows: group I; n = 945, ≤ 48 hours, group II; n = 214, > 48 hours.Cardiovascular risk factors and noncardiac comorbidities were not different between the two groups. ST-elevation MI as initial diagnosis was more prevalent in group I (68.4% versus 59.3%, P = 0.013). In-hospital mortality was not different in the two groups (0.8% versus 0.5%, P = 0.483). In one-year clinical follow-up, MACE and repercutaneous coronary intervention were lower in group I (17.8% versus 24.6%, P = 0.016, 10.2% versus 15.5%, P = 0.021, respectively). However, there was no difference in mortality (3.8% versus 4.7%, P = 0.319). In multivariate analysis, statin initiation within 48 hours after admission was an independent predictor of one-year MACE (OR 1.49, 95% CI = 1.00-2.21, P = 0.045).Consequently, early statin therapy within 48 hours after admission reduced MACE at one-year follow-up in patients with AMI.

Screening for Atrial Fibrillation Using a Single Lead ECG Monitoring Device.

Atrial fibrillation (AF) is the most common arrhythmia which needs management for stroke prevention. Therefore, it has emphasized the importance of screening for general population to detect AF earlier. We conducted screening for AF in the Chonbuk region in South Korea. Participants who were older than 50 years were enrolled. The screening test used a single lead electrocardiography (ECG) (KardiaBand, AliveCor, CA, USA). Diagnosis of AF was confirmed by electrophysiologists, if the single lead ECG demonstrated AF of more than 30 seconds. We analyzed the prevalence of AF and the characteristics of newly detected AF patients. A total of 2728 participants, 145 (5.3%) participants had already been diagnosed with AF before. The number of screening positive was 55. Among them, 40 participants were confirmed for AF. Male gender and age older than 70 years were the independent risk factors for AF among the screening positive participants. Most of newly detected AF patients were at high risk for stroke which had more than 2 points on the CHA2DS2-VASc score. We followed up with those patients and encouraged them to visit the hospital. As a result, 31 (77.5%) patients started to manage AF. The additional 1.2% of AF was detected by a screening test with a single lead ECG monitor device. Considering most participants of newly detected AF by screening were at high risk for stroke, it was thought that AF was still undertreated. Therefore, screening tests with simple mobile device might be useful for early detection of AF.

Introduction of Wearable Device in Cardiovascular Field for Monitoring Arrhythmia.

There has been increasing adoption of wearable smart devices in health care field and they enable non-invasive continuous monitoring of various cardiac parameters. Lots of studies have demonstrated that ambulatory monitoring devices were able to provide data for reliable diagnostics for arrhythmia. Distinguishing features of wearables such as ubiquitous continuous monitoring make it a convincing alternative to traditional diagnostic devices. Additionally, this revolutionary technology does not only enhance the diagnostic utility of wearable devices, but has also facilitated remote health care using IOT (internet of things) capability. In this review, the authors aim to present the state of current technologic development of smart wearables for detection of arrhythmia and comment on future perspectives with reviewing recent studies focused on clinical utility.

Factors Related to Major Bleeding After Ticagrelor Therapy: Results from the TICO Trial.

Background There is a lack of data on factors that are related to clinically relevant bleeding after ticagrelor treatment. We investigated the clinical and procedural factors related to major bleeding in patients with acute coronary syndrome treated with ticagrelor after coronary stent implantation. Methods and Results From the TICO (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome) randomized trial, a total of 2660 patients were included for the present study. Patients with major bleeding, defined by TIMI (Thrombolysis in Myocardial Infarction) major or Bleeding Academic Research Consortium type 3 or 5, were compared with those without major bleeding. On the basis of multivariable and receiver operating characteristic curve analyses, weight ≤65 kg, hemoglobin ≤12 g/dL, and estimated glomerular filtration rate <60 mL/min per 1.73 m2 were associated with an increased risk of major bleeding. In contrast, 3-month aspirin therapy with continued ticagrelor (versus 12-month aspirin and ticagrelor) was associated with a decreased risk of major bleeding. The lower risk of a net adverse clinical event (a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) in patients treated with 3-month aspirin therapy reported from the TICO trial remained valid in patients with any of these risk factors (hazard ratio, 0.59; 95% CI, 0.39-0.90; Pinteraction=0.74). Conclusions Low body weight, anemia, and chronic kidney disease were risk factors for major bleeding after ticagrelor therapy. Early aspirin discontinuation had a net clinical benefit among patients with a bleeding risk. Registration URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT02494895.

Long-term clinical course of patients with isolated myocardial bridge.

BACKGROUND: Myocardial bridge (MB) is regarded as a common benign lesion on coronary angiography (CAG). It is known to be harmless but may cause several cardiac events and recurrent hospitalization, so in the present study the long-term clinical course of patients with isolated MB and predictors of readmission were investigated. METHODS AND RESULTS: Total 684 patients (343 males, 60.5+/-11.2 years) with persistent chest pain without critical stenosis on CAG were enrolled. The patients were divided into 2 groups according to the presence of MB. Clinical follow-up was performed with respect to readmission after baseline CAG. At a mean follow-up of 37 months, 92 patients (13.3%) were re-admitted because of 79 recurrent chest pain refractory to medication (11.5%), 8 myocardial infarctions (1.2%), 1 life-threatening arrhythmia (0.1%) and 4 deaths (0.6%). There was a significant higher incidence of readmission in the MB group (P=0.038). In multivariate analysis, long MB (hazard ratio (HR) 2.780; 95% confidence interval (CI) 1.070-7.218, P=0.036) and spontaneous vasospasm in CAG (HR 2.335; 95%CI 1.055-5.171, P=0.037) were the predictors of readmission. Moreover, additional use of aspirin or statin decreased the readmission rate. CONCLUSIONS: This study suggests that MB on non-occlusive CAG is not benign and may cause recurrent chest pain, myocardial infarction or life-threatening arrhythmia. Especially, patients with a long MB and vasospasm on CAG need intensive medical therapy, including antiplatelet treatment.

Two-year clinical outcome after abciximab-coated stent implantation in patients with coronary artery disease.

BACKGROUND: Despite abciximab-coated stents having an inhibitory effect on coronary artery restenosis, the medium-term clinical outcome is unknown. METHODS AND RESULTS: This prospective, randomized study compared the effects of the abciximab-coated stent, which was implanted in 95 patients, with those of control bare metal stents (BMS) implanted in 93 patients for de novo coronary lesions. Stent implantation was performed without any complications associated with the procedure. The 6-month intravascular ultrasound analysis showed that the area of neointimal hyperplasia was significantly smaller in the abciximab-coated stent group compared with the control stent group (+2.0+/-1.6 mm(2) vs +3.4+/-1.7 mm(2), P=0.001). However, at 2-year clinical follow up, there were no statistically significant differences in the incidences of total major adverse cardiac events (16% vs 24%, P=0.19) and cardiac death (0% vs 1.1%, P=0.3), target vessel revascularization (16% vs 21%, P=0.4) or non-fatal myocardial infarction (0% vs 2.3%, P=0.16) in the abciximab-coated stent group compared with the control stent group. CONCLUSIONS: Although abciximab-coated stents are safe and inhibit neointimal hyperplasia, they have no superiority over BMS in 2-year clinical outcome.

Relation between plaque components and plaque prolapse after drug-eluting stent implantation--virtual histology-intravascular ultrasound.

BACKGROUND: It is not well known which plaque components are associated with the development of plaque prolapse (PP) and what are the major components in prolapsed plaque. The relationship between pre-stenting plaque components and post-stenting PP was assessed and the plaque components of prolapsed plaque were evaluated in patients who underwent drug-eluting stent (DES) implantation using virtual histology-intravascular ultrasound (VH-IVUS). METHODS AND RESULTS: The study group consisted of 132 patients who underwent DES implantation and pre- and post-stenting VH-IVUS. Of these patients, 68 patients had 76 PP lesions and 64 patients had 76 non-PP lesions. Intra-stent PP volume was 3.6+/-1.5 mm(3). Plaque volume was significantly greater and absolute fibrotic (FT) and necrotic core (NC) volumes were significantly greater in PP lesions compared with non-PP lesions. On multivariate analysis, absolute NC (odds ratios [OR]=1.14, P<0.001) and FT volume (OR =1.09, P<0.001) were independently associated with the development of PP. In intra-stent prolapsed plaque the FT component was greatest, but the NC component was also large, and %NC volume correlated positively with Deltacreatine kinase-MB (r=0.489, P<0.001) and Deltatroponin-I (r=0.679, P<0.001), and %FT volume correlated negatively with DeltaCK-MB (r=-0.539, P<0.001) and Deltatroponin-I. CONCLUSIONS: NC and FT components were associated with development of PP; and NC and FT components in prolapsed plaque were associated with cardiac enzyme elevation after DES implantation.

Protective Effect of Cilostazol Against Restraint Stress Induced Heart Failure in Post-Myocardial Infarction Rat Model.

Cilostazol, a phosphodiesterase III inhibitor, has antiplatelet and vasodilatory effects. It also has pleiotrophic effects including reduction of oxygen free radicals, positive chronotropic effect and inhibition of intracellular Ca2+ associated catecholamine secretion. The study was aimed to examine, in vivo, the effects of cilostazol treatments on myocardial function, myocardial remodeling, and neurohormonal status in myocardial infarction (MI) with restrained stress rat model. Male Sprague Dawley rats, subjected to coronary artery ligation to induce myocardial infarction (MI), received either a standard rat chow alone (control, n=5) or combined with cilostazol (cilostazol, n=5; 5 mg/kg×5 weeks). They were exposed to repeated restraint stress (2 h×2 times/day) for 10 days beginning 1 week after surgery. Left ventricular ejection fraction (LVEF), LV mass by heart weight/body weight ratio and level of tissue brain natriuretic peptide (BNP) expression by immunoblotting were determined. Plasma epinephrine and norepinephrine levels were also measured. Mean LVEF was higher in the cilostazol group than in the control group (66.9±14.3 vs 47.0±17.1, p<0.05) at 5 weeks after MI. However, LV mass and tissue BNP expression were significantly lower in the cilostazol than in the control group (p<0.05). Plasma epinephrine and norepinephrine levels were also lower in the cilostazol group compared with the control (p<0.05). Cilostazol preserves left ventricular systolic function and attenuates stress induced remodeling in postinfarct rats. Its beneficial effects were associated with reduced plasma catecholamine levels during postinfarct remodeling.