Rosuvastatin Reduces Blood Viscosity in Patients with Acute Coronary Syndrome.

BACKGROUND AND OBJECTIVES: Wall shear stress contributes to atherosclerosis progression and plaque rupture. There are limited studies for statin as a major contributing factor on whole blood viscosity (WBV) in patients with acute coronary syndrome (ACS). This study investigates the effect of statin on WBV in ACS patients. SUBJECTS AND METHODS: We prospectively enrolled 189 consecutive patients (mean age, 61.3±10.9 years; 132 males; ST-segment elevation myocardial infarction, n=52; non-ST-segment elevation myocardial infarction, n=84; unstable angina n=53). Patients were divided into two groups (group I: previous use of statins for at least 3 months, n=51; group II: statin-naïve patients, n=138). Blood viscosities at shear rates of 1 s-1 (diastolic blood viscosity; DBV) and 300 s-1 (systolic blood viscosity; SBV) were measured at baseline and one month after statin treatment. Rosuvastatin was administered to patients after enrollment (mean daily dose, 16.2±4.9 mg). RESULTS: Baseline WBV was significantly higher in group II ([SBV: group I vs group II, 40.8±5.9 mP vs. 44.2±7.4 mP, p=0.003], [DBV: 262.2±67.8 mP vs. 296.9±76.0 mP, p=0.002]). WBV in group II was significantly lower one month after statin treatment ([SBV: 42.0±4.7 mP, p=0.012, DBV: 281.4±52.6 mP, p=0.044]). However, low-density lipoprotein cholesterol level was not associated with WBV in both baseline (SBV: R2=0.074, p=0.326; DBV: R2=0.073, p=0.337) and after one month follow up (SBV: R2=0.104, p=0.265; DBV: R2=0.112, p=0.232). CONCLUSION: Previous statin medication is an important determinant in lowering WBV in patients with ACS. However, one month of rosuvastatin decreased WBV in statin-naïve ACS patients.

Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Cyclic ADP-Ribose (cADPR) Mediate Ca2+ Signaling in Cardiac Hypertrophy Induced by ß-Adrenergic Stimulation.

Ca2+ signaling plays a fundamental role in cardiac hypertrophic remodeling, but the underlying mechanisms remain poorly understood. We investigated the role of Ca2+-mobilizing second messengers, NAADP and cADPR, in the cardiac hypertrophy induced by ß-adrenergic stimulation by isoproterenol. Isoproterenol induced an initial Ca2+ transients followed by sustained Ca2+ rises. Inhibition of the cADPR pathway with 8-Br-cADPR abolished only the sustained Ca2+ increase, whereas inhibition of the NAADP pathway with bafilomycin-A1 abolished both rapid and sustained phases of the isoproterenol-mediated signal, indicating that the Ca2+ signal is mediated by a sequential action of NAADP and cADPR. The sequential production of NAADP and cADPR was confirmed biochemically. The isoproterenol-mediated Ca2+ increase and cADPR production, but not NAADP production, were markedly reduced in cardiomyocytes obtained from CD38 knockout mice. CD38 knockout mice were rescued from chronic isoproterenol infusion-induced myocardial hypertrophy, interstitial fibrosis, and decrease in fractional shortening and ejection fraction. Thus, our findings indicate that ß-adrenergic stimulation contributes to the development of maladaptive cardiac hypertrophy via Ca2+ signaling mediated by NAADP-synthesizing enzyme and CD38 that produce NAADP and cADPR, respectively.

Beneficial effects of Korean traditional diets in hypertensive and type 2 diabetic patients.

The prevalence of metabolic syndrome, hypertension, and diabetes has been increasing rapidly in Korea. The rate of increase has paralleled the replacement of Korean traditional diets (KTD), which emphasize vegetables and fermented foods, with western style dietary patterns that are rich in animal foods and saturated fat. We aimed to investigate the efficacy of the KTD in controlling fasting plasma glucose, blood pressure, and cardiovascular disease risk factors in hypertensive and type 2 diabetic (T2D) patients. Forty-one patients (61.8±1.5 years) who were taking medications prescribed for respective diseases were recruited from the Chonbuk National University Hospital for participation in a 12-week, parallel, controlled clinical trial. The control group (n=20) was advised to "eat as usual," whereas the experimental KTD diet group (n=21) was fed the KTD three times a day for 12 weeks. At the end of the trial, both groups had lower body mass index, % body fat, and waist-hip ratio compared to the baseline values (P<.05). Compared to the control group, the KTD group had a greater mean change (P<.05) from the baseline for glycated hemoglobin (HbA1c) (-0.72% vs. -0.25%) and heart rate (-7.1 vs. +1.6). Regular consumption of the KTD for 12 weeks by hypertensive and T2D patients resulted in favorable changes in cardiovascular risk factors.

Different Characteristics between Patients with Apical and Non-Apical Subtypes of Stress-Induced Cardiomyopathy.

BACKGROUND: Stress-induced cardiomyopathy (SCM) is characterized by apical ballooning on echocardiography, but some of SCM patients show non-apical involvement and their characteristics are not well defined. METHODS: We investigated 56 patients that were diagnosed as SCM and divided them into 2 groups: apical ballooning syndrome (ABS, n = 49, 87.5%) and non-apical ballooning syndrome (N-ABS, n = 7, 12.5%) groups. Patients with N-ABS were significantly younger than those of the ABS group (52 ± 11 vs. 73 ± 10 years, p < 0.001). RESULTS: Types of preceding stressors and clinical presentation including chest pain, pulmonary edema, cardiogenic shock and in-hospital mortality were comparable between the two groups. In the N-ABS group, wall motion score index was significantly lower than in the ABS group (1.61 ± 0.35 vs. 1.93 ± 0.31, p = 0.016). On electrocardiogram (ECG), T-wave inversion (57.1% vs. 95.8%, p < 0.001) were less frequent in the N-ABS than in the ABS group. Furthermore, maximum QT and corrected QT (QTc) intervals in the N-ABS patients were significantly shorter than the ABS patients (QT, 419.9 ± 66.1 vs. 487.3 ± 79.6 ms, p = 0.038; QTc, 479.0 ± 61.9 vs. 568.0 ± 50.5 ms, p < 0.001). CONCLUSION: Patients with the N-ABS showed not only atypical echocardiographic findings, but also atypical clinical and ECG manifestations. Integrated consideration is needed to reach a diagnosis of the non-apical subtype of SCM.

Elevated coronary whole blood viscosity in acute coronary syndrome patients.

OBJECTIVES: As most clinical studies measure whole blood viscosity (WBV) from peripheral samples, potential differences in WBV obtained from the coronary arteries are often ignored. This study investigated differences in WBV measured from coronary artery specimens in patients with and without acute coronary syndrome (ACS). METHODS AND RESULTS: Consecutive patients with chest pain who underwent diagnostic coronary angiography were divided into two groups [non-ACS (n = 16), ACS (n = 22)]. The ACS group consisted of unstable angina (n = 13) and acute myocardial infarction (n = 9) patients. Two blood samples were obtained from each patient at the both coronary artery ostia prior to coronary angiography. Low-shear and high-shear blood viscosities (BVs) were measured at shear rates of 1 and 300 s-1, respectively, by a scanning capillary tube viscometer (Bio-Visco Inc., South Korea). Both low-shear and high-shear BVs obtained from peripheral, left and right coronary arteries were not different in both groups. Mean coronary low-shear WBV values obtained in ACS group were 29.2% higher than those in non-ACS group (295.3 ± 87.2 mP vs. 228.5 ± 69.2 mP, p = 0.016). Mean coronary high-shear WBV values obtained in ACS group were 15.6% higher than those in non-ACS group (42.9 ± 10.0 mP vs. 37.1 ± 4.6 mP, p = 0.036). CONCLUSIONS: Direct measurement of WBV from the coronary artery showed no differences with peripheral samples. Future larger studies are needed to clarify our results.

Infective Endocarditis due to Streptococcus Agalactiae in Young and Immunocompetent Woman: A Case of Structurally Normal Valve Endocarditis Presented with Major Stroke.

We describe here a 26-year-old woman who presented confusion and right hemiparesis due to embolic obstruction of left internal carotid artery and middle cerebral artery. Transthoracic echocardiography showed structurally normal mitral valve with hypermobile echogenic material suggesting vegetation. The vegetation was disappeared after antimicrobial treatment without surgery.

A randomized comparison of sirolimus- versus paclitaxel-eluting stent implantation in patients with diabetes mellitus: 4-year clinical outcomes of DES-DIABETES (drug-eluting stent in patients with DIABETES mellitus) trial.

OBJECTIVES: We compared 4-year efficacy and safety of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with diabetes mellitus (DM). BACKGROUND: Four-year comparison of SES with PES in diabetic patients has not been evaluated in a randomized manner. METHODS: This prospective, multicenter, randomized study compared SES (n = 200) and PES (n = 200) implantation in diabetic patients. We evaluated 4-year major adverse cardiac events (MACE) including death, myocardial infarction (MI), and target lesion revascularization (TLR). RESULTS: The 2 groups had similar baseline characteristics. At 2 years, TLR (3.5% vs. 11.0%, log-rank, p < 0.01) and MACE (3.5% vs. 12.5%, log-rank, p < 0.01) were significantly lower in SES versus PES group with no difference of death or MI. At 4 years there were no differences in death (3.0% vs. 5.0%, p = 0.45) or MI (1.5% vs. 1.0%, p = 0.99) between SES and PES group. The TLR (7.5% vs. 12.0%, log-rank, p = 0.10) and MACE (11.0% vs. 16.0%, log-rank, p = 0.10) were statistically not different between SES and PES group. At multivariate Cox regression, post-procedural minimal lumen diameter (hazard ratio [HR]: 0.44, 95% confidence interval [CI]: 0.24 to 0.81, p < 0.01), hypercholesterolemia (HR: 2.21, 95% CI: 1.29 to 3.79, p < 0.01), and use of intravascular ultrasound (HR: 0.51, 95% CI: 0.26 to 0.99, p = 0.049) were independent predictors of 4-year MACE. CONCLUSIONS: Superiority of SES over PES during 2 years was attenuated between 2 years and 4 years in diabetic patients. Use of intravascular ultrasound and larger post-procedural minimal lumen diameter were independent predictors of the improved long-term clinical outcomes.

Long-term safety and efficacy of sirolimus- vs. paclitaxel-eluting stent implantation for acute ST-elevation myocardial infarction: 3-year follow-up of the PROSIT trial.

BACKGROUND: Meta-analysis of randomized trials showed superior efficacy and similar safety of drug-eluting stent over bare-metal stent in acute ST-elevation myocardial infarction (STEMI) patients. However, long-term relative outcomes of sirolimus- (SES) vs. paclitaxel-eluting stent (PES) have not been fully evaluated in randomized studies. This study compared long-term safety and efficacy of these two stents in STEMI. METHODS: A total of 308 STEMI patients were randomly treated with SES (n = 154) or PES (n = 154). Three-year clinical outcomes were assessed. Primary outcome of interest was incidence of major adverse cardiac events (MACE) including death, myocardial infarction (MI), stent thrombosis or target vessel revascularization (TVR). Secondary outcome of interest was occurrence of very late stent thrombosis. RESULTS: Both groups had similar baseline characteristics. During follow-up, there was no difference between the two groups in terms of death (6.5% for SES and 10.4% for PES, p = 0.22), MI (2.6% vs. 3.9%, p = 0.75), stent thrombosis (1.9% vs. 3.2%, p = 0.72), TVR (3.9% vs. 8.4%, p = 0.15) and MACE (12.3% vs. 18.8%, p = 0.12). Eight patients in overall population had stent thrombosis: definite 3, probable 1, and possible 4. Cumulative incidence of stent thrombosis was gradually increased; 0.6% at 30 days, 0.6% at 1 year, 1.6% at 2 years, and 2.6% at 3 years. Very late stent thrombosis, definite or probable, occurred in 0.6% for both. CONCLUSION: Among non-selected STEMI patients who underwent primary angioplasty, both SES and PES might be safe and SES showed similar three-year clinical outcomes compared to PES.

Cardiovascular Behçet's Disease Presenting as a Subepicardial Hematoma: An Uneventful 2-Year Clinical Course.

Cardiovascular involvement in Behçet's disease is not uncommon and could be life-threatening. We describe here a 28-year-old man, who developed sudden onset chest pain during warfarinization due to deep vein thrombosis. Echocardiography and computed tomography showed a 60×60 mm-sized hematoma in the pericardial space compressing the right heart. Coronary angiography showed totally occluded proximal right coronary artery. The hematoma was located at the subepicardial plane of the right atrium on surgical view and successfully evacuated. Follow-up echocardiography revealed complete resolution of the hematoma. He is doing well for 24 months after surgery.

Periprocedural hemoglobin drop and contrast-induced nephropathy in percutaneous coronary intervention patients.

BACKGROUND AND OBJECTIVES: The development of contrast-induced nephropathy (CIN) is associated with an increased risk of death and late cardiovascular events after percutaneous coronary intervention (PCI). The relationship between CIN and hemoglobin drop has been controversial. The aim of this study was to evaluate the clinical usefulness of periprocedural hemoglobin drop as a nontraditional risk factor for CIN. SUBJECTS AND METHODS: Five-hundred thirty-seven patients who underwent PCI were divided into 2 groups: Group I (486 patients: patients who did not develop CIN) and Group II (51 patients: patients who developed CIN). All patients were administered iodixanol as contrast media during coronary angiography. CIN is defined as a rise in serum creatinine of >/=25% or >/=0.5 mg/dL above the baseline value within 48 hours after contrast administration. RESULTS: BASELINE CLINICAL AND CARDIOVASCULAR RISK FACTORS WERE NOT SIGNIFICANTLY DIFFERENT BETWEEN THE TWO GROUPS, EXCEPT FOR LOW ABDOMINAL CIRCUMFERENCE (GROUP I : Group II=87.9+/-9.0 cm : 81.2+/-15.1 cm, p=0.024), body weight (Group I : Group II=63.5+/-10.6 kg : 59.7+/-9.2 kg, p=0.008), body mass index (BMI) (Group I : Group II=24.4+/-3.4 kg/m(2) : 23.4+/-2.8 kg/m(2), p=0.032), pre-PCI hemoglobin (Group I : Group II=13.2+/-2.0 g/dL : 12.3+/-2.0 g/dL, p=0.003), and post-PCI hemoglobin (Group I : Group II=12.4+/-1.9 g/dL : 11.5+/-1.8 g/dL, p=0.001). Multiple logistic regression analysis showed that a periprocedural drop in hemoglobin (>1 g/dL) was an independent predictor of CIN, like other known risk factors. CONCLUSION: A periprocedural drop in hemoglobin of more than 1 g/dL is another important independent predictor for CIN, even in patients administered the lowest nephrotoxic contrast agent, iodixanol, during PCI.

Comparison of Triple antiplatelet therapy and dual antiplatelet therapy in patients at high risk of restenosis after drug-eluting stent implantation (from the DECLARE-DIABETES and -LONG Trials).

Although cilostazol has decreased restenosis and target lesion revascularization (TLR) after drug-eluting stent implantation, it is not known if this effect is durable at 2 years. We analyzed 2 randomized studies (Drug-Eluting stenting followed by Cilostazol treatment reduces LAte REstenosis in patients with DIABETES mellitus and Drug-Eluting Stenting Followed by Cilostazol treatment reduces LAte REstenosis in patients with LONG native coronary lesions trials) in which 900 patients were randomly assigned to triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol; triple group, n = 450) and dual antiplatelet therapy (aspirin and clopidogrel; standard group, n = 450) for 6 months in patients with diabetes or long lesions receiving drug-eluting stents. We evaluated 2-year major adverse cardiac events (MACEs) including death, myocardial infarction (MI), and TLR. Nine-month TLRs and MACEs were significantly decreased in the triple versus standard group. At 2 years, the triple group sowed significantly decreased TLRs (4.2% vs 9.1%, hazard ratio 0.45, 95% confidence interval 0.26 to 0.78, p = 0.004) and MACEs (5.6% vs 10.4%, hazard ratio 0.52, 95% confidence interval 0.32 to 0.84, p = 0.008) compared to the standard group with no differences in death and MI. In subgroup analysis, triple antiplatelet therapy decrease of 2-year TLR was favorable in all subgroups, especially in patients with paclitaxel-eluting stents, diabetes mellitus, small vessels, long lesions, and left anterior descending coronary artery lesions. In conclusion, compared to the standard group, initial benefit in decreases of 9-month TLRs and MACEs in the triple group was sustained at 2 years with no differences in death or MI. Triple antiplatelet therapy decrease of 2-year TLR was favorable in all subgroups, especially in patients with high-risk profiles.

Double coronary artery stent fracture with coronary artery microaneurysms.

Even though drug-eluting stent (DES) implantation is an effective treatment for coronary artery stenosis, there are growing concerns related to the real usefulness of DESs due to their increased incidence of thrombosis, stent fracture, and late stent malapposition in comparison to bare metal stents. We have previously reported a case of stent fractures and multiple microaneurysms in both the left anterior descending and left circumflex coronary arteries. In the present case, we demonstrate the ability of dual-source spiral computed tomography to evaluate the various complications of DESs.

Simple method of counterclockwise isthmus conduction block by comparing double potentials and flutter cycle length.

BACKGROUND AND OBJECTIVES: Local wide split double potentials are used as a parameter to determine complete conduction block during cavotricuspid isthmus ablation in patients with isthmus dependent atrial flutter. However, delayed slow conduction in that region can sometimes be very difficult to differentiate from complete block. Flutter cycle length (FCL) can be used to confirm isthmus conduction block, because FCL is a measure of conduction time around the tricuspid annulus (TA). This study was designed to determine which degree of splitting of the local electrograms is adequate to confirm complete isthmus block, using FCL as a reference. SUBJECTS AND METHODS: Cavotricuspid isthmus (CTI) ablation was performed in fifty consecutive patients. The interval between the pacing stimulus on the lateral side of the CTI and the first component of the double potentials on the block line (SD1) corresponded to the counterclockwise conduction time. The interval between the pacing stimulus and second component (SD2) represented the clockwise conduction time to the contralateral side of the ablation line. SD1 and SD2 were measured before and after complete isthmus block. RESULTS: An SD1+SD2 reaching 90% of the FCL identified the counterclockwise isthmus conduction block with 94% sensitivity and 100% specificity. CONCLUSION: If the sum of SD1 and SD2 following isthmus ablation was close to the FCL, complete conduction block was predicted with high diagnostic accuracy and positive predictive value for at least counterclockwise conduction.

Inhibition of ADP-ribosyl cyclase attenuates angiotensin II-induced cardiac hypertrophy.

AIMS: Here, we report the discovery of a small molecule inhibitor, 2,2'-dihydroxyazobenzene (DAB), of ADP ribosyl cyclase (ADPR-cyclase) and showed that this inhibitor attenuated angiotensin (Ang) II-induced hypertrophic responses. METHODS: and results The intracellular concentration of free Ca(2+) [Ca(2+)](i) in adult rat cardiomyocytes was measured by using a confocal microscope. Cardiac hypertrophy was induced by the two-kidney one-clip (2K1C) method. Hypertrophy was determined by de novo protein synthesis, cell volume, echocardiography, nuclear translocation of nuclear factor of activated T-cells, and transforming growth factor-beta1 protein expression. Treatment of cardiomyocytes with Ang II generated a biphasic [Ca(2+)](i) increase that included an initial Ca(2+)peak and sustained Ca(2+) rise via inositol trisphosphate and cyclic ADP-ribose (cADPR) formation, respectively. A cADPR antagonistic analogue, 8-Br-cADPR, and an ADPR-cyclase inhibitor, DAB, blocked the sustained Ca(2+) signal, but not the initial Ca(2+) rise. Furthermore, DAB significantly inhibited Ang II-mediated cADPR formation and hypertrophic responses in vitro. Echocardiography and histological examination revealed significant cardiac hypertrophy in 2K1C rats that was potently inhibited by treatment with DAB. In addition, the hypertrophic responses induced by Ang II in vitro were significantly increased by 2K1C, and DAB treatment reversed these hypertrophic responses to the levels of sham Control. CONCLUSION: ADPR-cyclase is an important mediator of cardiac hypertrophy, and inhibition of ADPR-cyclase by DAB may provide a new therapeutic strategy for cardiac diseases.

Disseminated multiple ostial stenoses in a young woman presenting as unstable angina.

A previously healthy 40-year-old woman presented as unstable angina. She had a family history of stroke as the only cardiovascular risk factor. Her blood pressure on admission was 150/90 mmHg. Laboratory study showed absolutely all negative markers of inflammation, autoimmune disorders, or atherosclerosis. Coronary angiography revealed subtotal ostial stenosis of the right coronary artery (RCA). Additionally, total occlusion of the ostium of the right subclavian artery and severe discrete ostial stenoses of left subclavian, celiac, superior mesenteric, both renal arteries were demonstrated on multidetector computed tomographic and magnetic resonance angiographies. She underwent stent implantation at the culprit lesion of RCA, and the left subclavian and both renal arteries. The fluorine-18-fluorodeoxyglucose positron-emission tomography-computed tomography showed slightly increased glucose metabolism at the proximal left subclavian artery. She is doing very well for 10 months during taking antiplatelet agents only.

Consecutively developed late stent malappositions following the implantation of two different kinds of drug-eluting stents associated with spontaneous healing.

We describe here a 63-year-old woman, who consecutively developed a stent-related coronary aneurysm of left circumflex artery, which was associated with spontaneous healing, and sequential late stent malapposition of left anterior descending artery following the implantation of two different kinds of drug-eluting stents, respectively. She did not experience any cardiac events for thirty eight months.

Incidence and predictors of drug-eluting stent fractures in long coronary disease.

BACKGROUND: Stent fractures after drug-eluting stent (DES) implantation have not been evaluated sufficiently in patients with long coronary artery disease. METHODS: This study comprised of 415 patients, who were enrolled in the Long-DES-II study and had a complete serial angiography both before and after procedure and also at follow-up. The lesions were > or =25 mm in length and were randomly treated with sirolimus-eluting stents (SES, 210 lesions) or paclitaxel-eluting stent (205 lesions). RESULTS: DES fracture was identified in 7 lesions (1.7%): 1 minor, 3 moderate, and 3 severe fractures. Most of the fractures occurred in patients who received SES (85.7%) and in the right coronary artery (RCA) lesions (71.4%). Lesions with fracture had a smaller minimal lumen diameter before procedure than lesions without fracture (0.38+/-0.55 vs. 0.71+/-0.46 mm, p=0.043). However, acute gain (2.28+/-0.39 vs. 1.44+/-0.60 mm, p=0.001) and late loss (0.81+/-0.49 vs. 0.42+/-0.50 mm, p=0.033) in analysis segment were greater in lesions with fracture. By multivariate analysis, the independent predictor of fracture was the RCA lesion (Odds ratio, 7.81; 95% CI, 1.45 approximately 42.04; p=0.017). Although one patient had an intermediate angiographic narrowing at the fracture site, there was no adverse cardiac event related with fracture. CONCLUSIONS: The incidence of stent fracture in long DES implantation was not common and was associated with SES implantation or RCA lesions. Fortunately, the clinical prognosis of DES fracture was somewhat benign.