Jum Suk Ko

Effect of High Dose Rosuvastatin Loading before Primary Percutaneous Coronary Intervention on Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction

Background and Objectives High dose rosuvastatin loading before percutaneous coronary interventions (PCI) reduces the myocardial damage and the incidence of adverse cardiac events in patients with stable angina and acute coronary syndrome. However, no studies are present yet about rosuvastatin loading in patients with ST-segment elevation myocardial infarction (STEMI) in a primary PCI setting. Subjects and Methods A total of 475 patients who underwent primary PCI for STEMI were studied. The study population was divided into two groups with 208 patients in the statin group=40 mg rosuvastatin loading before primary PCI and 267 patients in the control group=no statin pretreatment. At median 3 days after PCI a single-photon emission computed tomography (SPECT) was performed with technetium 99m tetrofosmin For this study were compared infarct size, corrected Thrombolysis in Myocardial Infarction (TIMI) frame count and the myocardial blush grade (MBG) between the both groups. Results Baseline clinical and procedural characteristics were similar between the groups. Infarct size, as assessed by SPECT, was significantly smaller (19.0±15.9% vs. 22.9±16.5%, p=0.009) in the statin group than in the control group. Patients of the statin group showed a lower corrected TIMI frame count (28.2±19.3 vs. 32.6±21.4, p=0.020), and higher MBG (2.49±0.76 vs. 2.23±0.96, p=0.001) than the patients of the control group. The multivariate analysis revealed that rosuvastatin loading {odds ratio (OR) 0.61}, pain to balloon time (OR 2.05), anterior myocardial infarction (OR 3.89) and final the MBG (OR 2.93) were independent predictors of a large infarct size. Conclusion A high dose rosuvastatin loading before the primary PCI reduced the infarct size by microvascular myocardial perfusion improvement.

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.

Left Ventricular Thrombus Associated with Takotsubo Cardiomyopathy: A Cardioembolic Cause of Cerebral Infarction.

Takotsubo cardiomyopathy, also called stress-induced cardiomyopathy, usually occurs in patients with severe emotional or physiologic stress. The prognosis is favorable, and the wall motion abnormlities normalize within weeks. However, stress-induced cardiomyopathy is rarely assosicated with left ventricular thrombus and thromboembolic complications. Here, we report a case of stress-induced cardiomyopathy with left ventricular thrombus that embolized to cause cerebral infarction.

Effect of High Dose Rosuvastatin Loading before Percutaneous Coronary Intervention on Contrast-Induced Nephropathy

Background and Objectives Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality. This observational, non-randomized study evaluated the effect of rosuvastatin loading before percutaneous coronary intervention (PCI) on the incidence of CIN in patients with acute coronary syndrome (ACS). Subjects and Methods A total of 824 patients who underwent PCI for ACS were studied (408 patients in the statin group=40 mg rosuvastatin loading before PCI; 416 patients of control group=no statin pretreatment). Serum creatinine concentrations were measured before and 24 and 48 hours after PCI. The primary endpoint was development of CIN defined as an increase in serum creatinine concentration of ≥0.5 mg/dL or ≥25% above baseline within 72 hours after PCI. Results The incidence of CIN was significantly lower in the statin group than that in the control group (18.8% vs. 13.5%, p=0.040). The maximum percent changes in serum creatinine and estimated glomerular filtration rate in the statin group within 48 hours were significantly lower than those in the control group (5.84±22.59% vs. 2.43±24.49%, p=0.038; -11.44±14.00 vs. -9.51±13.89, p=0.048, respectively). The effect of rosuvastatin on preventing CIN was greater in the subgroups of patients with diabetes, high-dose contrast medium, multivessel stents, high baseline C-reactive protein, and myocardial infarction. A multivariate analysis revealed that rosuvastatin loading was independently associated with a decreased risk for CIN (odds ratio, 0.64; 95% confidence interval, 0.43-0.95, p=0.026). Conclusion High-dose rosuvastatin loading before PCI was associated with a significantly lower incidence of CIN in patients with ACS.

The Number of Endothelial Progenitor Cells is Decreased in Patients With Non-Dipper Hypertension

Background and Objectives Circulating endothelial progenitor cells (EPCs) play a key role in the maintenance of endothelial homeostasis and promote vascular repair. A reduced number of EPCs and the functional activity have been associated with several cardiovascular risk factors. However, the relationship between the number of EPCs and circadian rhythm of the blood pressure (BP) remains unclear. The purpose of the present study was to evaluate the relationship between the circadian rhythm of the BP and EPCs in patients with essential hypertension. Subjects and Methods A total of 45 patients with essential hypertension who were newly identified by outpatient BP measurements, underwent 24-hour ambulatory BP monitoring. Among the 45 patients with essential hypertension, 20 were classified as dippers (12 men and 8 women; mean age 48±14 years) and 25 as non-dippers (14 men and 11 women; mean age 52±18 years). The EPC count was isolated from the peripheral bloodstream and quantified by flow cytometry. Results The baseline clinical characteristics were similar between the dipper and non-dipper hypertensive patients. The circulating EPCs were statistically reduced in the non-dipper patients as compared to the dippers (104±60 vs. 66±47 EPCs per 106 mononuclear cells, p=0.027). The circulating EPC level correlated positively with the circadian changes in the systolic and diastolic BP (r=0.435, p=0.003, and r=0.310, p=0.038, respectively). Conclusion The present study demonstrated that the EPC count was reduced in the peripheral bloodstream in non-dipper hypertensive patients.

Rosuvastatin-induced high-density lipoprotein changes in patients who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome

BACKGROUND Clinical significance of statin-induced high-density lipoprotein cholesterol (HDL-C) changes is not well known. We investigated the factors affecting rosuvastatin-induced HDL-C changes and their correlation with 12-month major adverse cardiovascular events (MACE) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and percutaneous coronary intervention (PCI). MATERIALS AND METHODS We analyzed 556 consecutive NSTE-ACS patients who underwent PCI and received rosuvastatin 10mg before discharge. We measured serum lipids, including total cholesterol, triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and HDL-C at baseline and at 4 weeks. The relationship between on-treatment lipid levels, baseline lipid levels, and 12-month MACE was assessed. RESULTS Rosuvastatin treatment increased the mean HDL-C concentration by 1.1 ± 9.8 mg/dl (4.3 ± 23.0%). HDL-C was increased in 312 patients (56.1%), but decreased in 244 patients (43.9%) after statin treatment. Changes in HDL-C during first month were inversely correlated with baseline HDL-C levels (r=-0.379, p<0.001). The patients with increased HDL-C showed higher baseline TG levels but lower on-treatment TG levels. Changes in TG were correlated with changes in HDL-C (r=-0.212, p<0.001). The incidence of 12-month MACE according to changes in HDL-C was similar between the two groups (11.9% vs. 12.3%, p=0.875). Multivariate analysis revealed that baseline HDL-C level was the only significant predictor of rosuvastatin-induced HDL-C changes. CONCLUSION Baseline HDL-C concentration was an independent predictor of rosuvastatin-induced HDL-C changes. Statin-induced HDL-C changes did not predict 12-month MACE in patients with NSTE-ACS.

Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current

BACKGROUND Apamin-sensitive small-conductance calcium-activated potassium (SK) channels are gated by intracellular Ca(2+) through a constitutive interaction with calmodulin. OBJECTIVE We hypothesize that arrhythmogenic human calmodulin mutations impede activation of SK channels. METHODS We studied 5 previously published calmodulin mutations (N54I, N98S, D96V, D130G, and F90L). Plasmids encoding either wild-type or mutant calmodulin were transiently transfected into human embryonic kidney 293 cells that stably express subtype 2 of SK protein channels (SK2 cells). Whole-cell voltage-clamp recording was used to determine apamin-sensitive current densities. We also performed optical mapping studies in normal murine hearts to determine the effects of apamin in hearts with (n=7) or without (n=3) pretreatment with sea anemone toxin. RESULTS SK2 cells transfected with wild-type calmodulin exhibited an apamin-sensitive current density of 33.6 pA/pF (31.4-36.5 pA/pF) (median and confidence interval 25th-75th percentile), which was significantly higher than that observed for cells transfected with N54I (17.0 pA/pF [14.0-27.7 pA/pF]; P = .016), F90L (22.6 pA/pF [20.3-24.3 pA/pF]; P = .011), D96V (13.0 pA/pF [10.9-15.8 pA/pF]; P = .003), N98S (13.7 pA/pF [8.8-20.4 pA/pF]; P = .005), and D130G (17.6 pA/pF [13.8-24.6 pA/pF]; P = .003). The decrease in SK2 current densities was not associated with a decrease in membrane protein expression or intracellular distribution of the channel protein. Apamin increased the ventricular action potential duration at 80% repolarization (from 79.6 ms [63.4-93.3 ms] to 121.8 ms [97.9-127.2 ms]; P = .010) in hearts pretreated with anemone toxin but not in control hearts. CONCLUSION Human arrhythmogenic calmodulin mutations impede the activation of SK2 channels in human embryonic kidney 293 cells.

Comparison of the Infarct Size between the Loading of Ticagrelor and Clopidogrel in Patients with Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Background and Objectives Ticagrelor is considered a potent antiplatelet agent compared to clopidogrel. However, there are no studies regarding the effect of ticagrelor loading on infarct size in patients with ST-segment elevation myocardial infarction (STEMI) in a primary percutaneous coronary intervention (PCI) setting. Subjects and Methods In this single-center, randomized, open-label study, 188 patients who underwent primary PCI for STEMI were enrolled (92 patients in the clopidogrel group and 96 in the ticagrelor group) and compared the infarct size by technetium-99m (Tc-99m) tetrofosmin single-photon emission computed tomography (SPECT) and serial cardiac biomarker levels between the groups. SPECT was performed at a median of 2 days after PCI. Results Baseline clinical and procedural characteristics were similar between the groups. Infarct size on SPECT, was similar between the 2 groups (28.1%±34.5% vs. 32.8%±29.2%; p=0.169). At all time-points after PCI (8, 24, and 48 hours), the peak levels of creatine kinase-myocardial band (CK-MB) and troponin T were lower in the clopidogrel group. The clopidogrel group showed lower cumulative troponin T levels than the ticagrelor group (12.59±10.66 vs. 17.67±19.51 ng/mL; p=0.029). Conclusion Ticagrelor loading before primary PCI was not associated with reduced myocardial infarct size during the first 48 hours, compared to clopidogrel loading.

Carotid Atherosclerosis and Electrocardiographic Left Ventricular Hypertrophy in the General Population: The Namwon Study

This study aimed to investigate the relationship between carotid atherosclerosis and left ventricular hypertrophy on electrocardiogram (ECG-LVH) on adults living in the community. A total of 9,266 adults who participated in the Namwon Study were included in this analysis. Carotid atherosclerosis, including intima-media thickness (IMT) and plaques, were assessed using high-resolution B-mode ultrasound. ECG-LVH was determined using the Sokolow-Lyon voltage (SokV) and Cornell voltage (CorV) criteria. The prevalence of ECG-LVH was 12.7% using the SokV criteria and 9.7% using the CorV criteria. After full adjustment, compared to the lowest quartile of common carotid artery IMT (CCA-IMT), the odds ratios and 95% confidence intervals for ECG-LVH of the carotid IMT quartiles 2, 3, and 4 increased linearly as follows: 1.54 (1.24-1.90), 1.62 (1.31-2.02), and 1.91 (1.54-2.38), respectively, for the SokV criteria (p<0.001); and 1.33 (1.05-1.68), 1.41 (1.11-1.78), and 1.48 (1.16-1.88), respectively, for the CorV criteria (p=0.003). Positive associations between the carotid bulb IMT (CB-IMT) quartiles and the ECG-LVH were also observed, although the magnitudes of association between CB-IMT and ECG-LVH were slightly lower than those of CCA-IMT. However, no significant association between carotid plaques and ECG-LVH as defined by the SokV or CorV criteria was found. The present study demonstrated that increased carotid IMT, but not carotid plaques, is significantly associated with LVH defined by various ECG criteria in a large population.

Correlations between High Platelet Reactivity, Extent of Coronary Artery Disease, and Periprocedural Myonecrosis in Patients with Acute Coronary Syndrome

The purpose of the present study was to evaluate the correlations between high platelet reactivity (HPR) and the extent of coronary atherosclerosis and periprocedural myonecrosis in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). A total of 485 patients who underwent PCI for ACS was studied. HPR was defined as ≥230 platelet reactivity units (PRU) in point-of-care P2Y12 tested by the VerifyNow assay. The incidence of multi-vessel disease (MVD) was higher in patients with HPR than those with no HPR (56.2% vs 45.8%, p=0.023). PRU values progressively increased with the number of diseased coronary arteries (1-vessel disease 221.8±86.7; 2-vessel disease 239.3±90.1; 3-vessel disease 243.4±84.5; p=0.038 by ANOVA). Multivariate analysis revealed that HPR was independently associated with MVD (Odds ratio 1.48, 95% confidence interval 1.01-2.25, p=0.048). Patients with periprocedural myonecrosis showed significantly higher PRU values compared with those without myonecrosis (258.6±94.5 vs. 228.5±85.6, p=0.013). Multivariate analysis revealed that HPR was an independent predictor for periprocedural myonecrosis as defined as any creatine kinase-myocardial band isoenzyme elevation or troponin T elevation. In conclusion, HPR is associated with MVD and periprocedural myonecrosis in patients with ACS and PCI. Thus, platelet reactivity after treatment with clopidogrel might be associated not only with blood clot formation but also with increased coronary atherosclerotic burden.