Long-Term Clinical Outcomes of Iliac Artery Endovascular Therapy in the Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases (K-VIS ELLA) Registry.

BACKGROUND AND OBJECTIVES: Limited data are available regarding long-term clinical outcomes of iliac artery endovascular therapy (EVT) in real-world practice. This study investigated long-term outcomes according to Trans-Atlantic Inter-Society Consensus (TASC) classifications. METHODS: We analyzed data from 1,705 limbs of 1,364 patients from the retrospective cohort of the multicenter Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry. The primary endpoint was target lesion revascularization (TLR)-free survival. RESULTS: TASC A, B, C, and D lesions were present in 19.4%, 26.2%, 28.7%, and 25.7% of the treated limbs, respectively. The technical success rate was 96.2% and did not differ between TASC lesion types. Complications occurred in 6.8% of cases and more occurred in TASC D (11.8%). Iliac artery EVT showed a 5-year TLR-free survival of 89.2%. The TASC D group had the lowest TLR-free rate of 79.3%. TASC D (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.12-2.73; p=0.014), plain old balloon angioplasty (HR, 4.25; 95% CI, 2.03-8.88; p<0.001), current smoker (HR, 1.89; 95% CI, 1.26-2.83; p=0.002), previous bypass surgery (HR, 3.04; 95% CI, 1.28-7.19; p=0.011), combined femoropopliteal treatment (HR, 4.89; 95% CI, 3.19-7.50; p<0.001), combined below the knee treatment (HR, 2.20; 95% CI, 1.25-3.89; p=0.007), and complications (HR, 1.86; 95% CI, 1.07-3.24; p=0.028) were predictors for TLR. CONCLUSIONS: Iliac artery EVT achieved excellent technical success and 5-year TLR-free survival. TASC D showed a favorable but lower 5-year TLR-free survival rate and higher complication rate compared with other TASC groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Long-term Clinical Outcomes and Prognostic Factors After Endovascular Treatment in Patients With Chronic Limb Threatening Ischemia.

BACKGROUND AND OBJECTIVES: Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in real-world practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors. METHODS: From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention). RESULTS: Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p<0.001), end-stage renal disease (ESRD; HR, 2.340; p<0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471; p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3-4 years. CONCLUSIONS: In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Association between Body Mass Index and Clinical Outcomes of Peripheral Artery Disease after Endovascular Therapy: Data from K-VIS ELLA Registry.

BACKGROUND AND OBJECTIVES: Few studies have investigated the obesity paradox in clinical outcomes of peripheral artery disease (PAD). We investigated the association between body mass index (BMI) and clinical outcomes in PAD patients undergoing endovascular therapy (EVT). METHODS: Patients (n=2,914) from the retrospective Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry were categorized according to BMI: underweight (<18.5 kg/m², n=204), normal weight (18.5-25 kg/m², n=1,818), overweight (25-30 kg/m², n=766), or obese (≥30 kg/m², n=126). Groups were compared for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). RESULTS: The underweight and obese groups were older and had more frequent critical limb ischemia and infrapopliteal artery disease than the normal or overweight groups (all p<0.001). Hypertension and diabetes were more frequent and current smoking was less frequent in the overweight and obese groups than the underweight or normal weight groups (all p <0.001). The underweight group showed the higher rates of MACE and MALE at 3 years (17.2%, 15.7%) compared with the normal weight (10.8%, 11.7%), overweight (8.4%, 10.7%), or obese groups (8.7%, 14.3%) (log-rank p<0.001, p=0.015). In contrast, the risk of MACE was lower in the overweight than the normal weight group (adjusted hazard ratio, 0.706; 95% CI, 0.537-0.928). CONCLUSIONS: In PAD patients undergoing EVT, underweight was an independent predictor for MACE and MALE, whereas MACE risk was lower for overweight than normal weight patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Coronary calcification is associated with elevated serum lipoprotein (a) levels in asymptomatic men over the age of 45 years: A cross-sectional study of the Korean national health checkup data.

ABSTRACT: Lipoprotein a (Lp (a)) and coronary artery calcification (CAC) are markers of coronary artery and cardiovascular diseases. However, the association between Lp (a) and CAC in asymptomatic individuals remains unclear. In this study, we aimed to determine the influence of Lp (a) on CAC in asymptomatic individuals.We included 2019 asymptomatic Korean adults who underwent testing for a coronary artery calcium score (CACS) and Lp (a) at the Gangnam Severance Hospital Health Checkup Center in Korea from January 2017 to August 2019. Participants were divided into 2 groups: CACS = 0 and CACS > 0. Factors affecting the CACS were analyzed by sex. Because age is a major risk factor for atherosclerosis, ≥45 years in men and ≥55 years in women, we further divided participants into 4 subgroups (≥45 and <45 in men, ≥55 and <55 in women). Factors affecting the CACS in the 4 groups were analyzed.There was a positive correlation between the CACS and traditional cardiovascular risk factors. Lp (a) positively correlated with the CACS in men (P < .01) and remained significant after multivariable logistic regression (P < .01). The same result was observed in men aged ≥45 years (P < .01).Lp (a) is an independently associated factor of CAC and a marker of coronary atherosclerosis in asymptomatic men aged ≥45 years. In asymptomatic men aged ≥45 years, Lp (a) should be measured, and intensive Lp (a)-lowering treatment should be considered.

Outcomes and Associated Factors of Discrepant Coronary and Carotid Atherosclerosis.

Some patients exhibit discrepancies in carotid and coronary artery atherosclerosis. This study aimed to define the characteristics and prognosis of these discrepant patients and determine the best strategy to detect pan-vascular atherosclerosis. A database of 5,022 consecutively registered patients who underwent both coronary angiography and carotid ultrasonography, along with clinical and blood laboratory tests, echocardiography, and pulse wave velocity (PWV), was analyzed. The development of cerebro-cardiovascular (CV) events during the follow-up period was also evaluated. A significant proportion of patients (n = 1,741, 35%) presented with a discrepancy between carotid artery plaque and coronary artery disease (CAD). In patients without carotid plaque, male sex (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.20-2.41; P = 0.003), older age (OR, 1.03; 95% CI, 1.01-1.04; P = 0.002), smoking history (OR, 1.58; 95% CI, 1.13-2.20; P = 0.008), lower high-density lipoprotein (HDL) -cholesterol level (OR, 0.97; 95% CI, 0.96-0.98; P < 0.001), and lower common carotid artery end-diastolic velocity (CCA-EDV) (OR, 0.97; 95% CI, 0.95-0.99; P = 0.005) were independently related to the presence of CAD. In patients without CAD, increased PWV was independently related to the presence of carotid plaque. In survival analysis, patients with isolated CAD had a higher probability of composite CV events; those with isolated carotid plaque had a higher probability of heart failure (HF) and mortality than their counterpart groups (P < 0.05). Even in patients without carotid artery plaque, careful coronary evaluation is needed in older or male patients with smoking history, lower HDL-cholesterol level, or lower CCA-EDV. Carotid plaque may be a potential risk factor for HF.

Frequent Premature Atrial Contractions as a Poor Prognostic Factor in Cryptogenic Stroke Patients with Concomitant Non-Sustained Atrial Tachycardia.

In cryptogenic stroke patients, early detection of new-onset atrial fibrillation (AF) and recurrent stroke is required to prevent poor clinical outcomes. Therefore, we investigated the predictors of new-onset AF and recurrent stroke in cryptogenic stroke patients without previously diagnosed AF. In total, 390 patients who were diagnosed with stroke and non-sustained atrial tachycardia (NSAT) on 24-hour Holter monitoring were followed up to assess new-onset AF and recurrent stroke. The 5-year event-free survival as well as the predictors of recurrent stroke or new-onset AF were investigated. Based on receiver operating characteristic analysis, frequent premature atrial contractions (PACs) were defined as PACs >44 beats/day. The median follow-up period was 35 months. The composite event rate was 11.5%. In Kaplan-Meier analysis, the 5-year cumulative incidence of composite events was higher in cryptogenic stroke patients with frequent PACs than in those without frequent PACs. Multivariate analysis revealed that current smoking, increased left atrial volume index, and frequent PACs were poor prognostic predictors of composite event, and frequent PACs were an independent poor prognostic factor of new-onset AF in cryptogenic stroke patients. Therefore, frequent PACs might be associated with poor clinical outcomes (new-onset AF and recurrent stroke) in cryptogenic stroke patients with concomitant NSAT.

Different association between renal dysfunction and clinical outcomes according to the presence of diabetes in patients undergoing endovascular treatment for peripheral artery disease.

OBJECTIVE: Although chronic kidney disease (CKD) and diabetes are important prognostic factors in patients with peripheral artery disease, there are limited data regarding the outcomes of endovascular treatment (EVT) according to the severity of CKD, especially in the presence of diabetes. This study sought to compare clinical outcomes of lower limb EVT between patients with and patients without CKD according to the presence of diabetes. METHODS: Patients were enrolled from the Korean multicenter EVT registry and were divided according to the presence of diabetes, then further stratified by CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2). The primary outcome was major adverse limb events (MALEs; a composite of reintervention for target limb, reintervention for target vessel, and unplanned major amputation) at 2 years. RESULTS: A total of 3045 patients were eligible for analysis: 1277 nondiabetic patients (944 without CKD, 333 with CKD) and 1768 diabetic patients (951 without CKD, 817 with CKD). CKD was associated with a significantly increased risk of MALEs after EVT in diabetic patients (14.4% vs 9.9%; adjusted hazard ratio, 1.60; 95% confidence interval, 1.28-2.01; P < .001) but not in nondiabetic patients (7.6% vs 9.7%; adjusted hazard ratio, 0.78; 95% confidence interval, 0.53-1.14; P = .203; interaction P = .018). In analysis stratified by the severity of CKD among diabetic patients, end-stage renal disease was significantly associated with an increased risk of MALE. CONCLUSIONS: CKD was associated with a significantly higher risk of MALEs after EVT in diabetic patients but not in nondiabetic patients. The increased risk of MALEs was mainly driven by patients with end-stage renal disease.

Genetic relevance and determinants of mitral leaflet size in hypertrophic cardiomyopathy.

BACKGROUND: Whether mitral leaflet elongation is a primary phenotype of hypertrophic cardiomyopathy (HCM) is controversial. We investigated the genetic relevance and determinants of mitral leaflet size by performing extensive gene analyses in patients with HCM. METHODS: Anterior mitral leaflet (AML) lengths were measured in HCM patients (n = 211) and age- and sex-matched controls (n = 30) using echocardiography with hemodynamic and chamber geometric assessments. We analyzed 82 nuclear DNA (8 sarcomeric genes, 74 other HCM-associated genes) and mitochondrial DNA. Cardiac magnetic resonance imaging (CMR) was performed in the 132 HCM patients. RESULTS: Average indexed AML was significantly longer for HCM than for controls (17.2 ± 2.3 vs. 13.3 ± 1.6 mm/m2, P <  0.001). Average AML length correlated with body surface area (BSA), left ventricular (LV) end-systolic volume (P <  0.001) and LV mass by CMR (P < 0.001). Average indexed AML by BSA of pure-apical HCM was significantly shorter than other typed HCM (16.6 ± 2.0 vs. 17.4 ± 2.4 mm/m2, P = 0.025). Indexed AML was independently correlated with left atrial wall stress. The thin filament mutation group showed larger average AML (31.9 ± 3.8 vs. 29.6 ± 3.8 mm, P = 0.045), but this was not significant with the indexed value. No difference in AML size among subgroups was observed based on the presence of sarcomere protein or mitochondria-related gene variants (P > 0.05). CONCLUSION: AML elongation was a unique finding of HCM. However, the leaflet size was more related to chamber geometry and hypertrophy pattern rather than genetic factors within overt HCM.

Diagnostic accuracy of low-radiation coronary computed tomography angiography with low tube voltage and knowledge-based model reconstruction.

We aimed to evaluate the accuracy of coronary computed tomography angiography (CCTA) with a low-radiation protocol and iterative model reconstruction (IMR), in comparison with invasive coronary angiography (ICA). Sixty-one patients (45 males; mean age, 61.9 ± 9.2 years) with suspected coronary artery disease who underwent CCTA and ICA were retrospectively enrolled. CCTA was performed with low tube voltage (80 or 100 kVp), low tube current (100-200 mAs), prospective ECG triggering, and IMR using a 64-slice computed tomography scanner. Coronary artery disease was defined as luminal narrowing of >50%, as assessed using CCTA and ICA. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive value, and accuracy of CCTA were examined. The mean radiation dose of CCTA was 1.05 ± 0.36 mSv. No non-diagnostic segment was noted. The sensitivity, specificity, PPV, NPV, and accuracy of CCTA were 86.4%, 96.1%, 80.3%, 97.5%, and 94.6% on a per segment basis, 93.1%, 94.7%, 88.3%, 97.0%, and 94.2% on a per vessel basis, and 100%, 83.3%, 93.5%, 100%, and 95.1% on a per patient basis, respectively. In conclusion, a low-radiation CCTA protocol with IMR may be useful for diagnosing coronary artery disease, as it reduces the radiation dose while maintaining diagnostic accuracy.

Associates and Prognosis of Giant Left Atrium; Single Center Experience.

BACKGROUND: Left atrial (LA) remodeling develops as a result of longstanding pressure overload. However, determinants and clinical outcome of excessive remodeling, so called giant left atrium (GLA), are not clear. METHODS: Clinical characteristics of patients with GLA (antero-posterior diameter higher than 65 mm), including echo-Doppler parameters, and follow-up clinical outcomes from a tertiary referral hospital were investigated. RESULTS: Among 68519 consecutive primary patients who underwent echocardiography over a period of 10 years, data from 163 GLA cases (0.24%) were analyzed. Main causes were significant rheumatic mitral stenosis (n = 58, 36%); other causes comprised significant rheumatic mitral regurgitation (MR; n = 10, 6%), mitral valve (MV) prolapse or congenital mitral valvular disease (MVD) (n = 20, 12%), and functional MR (n = 25, 15%). However, mild rheumatic MV disease (n = 4, 3%) or left ventricular (LV) systolic or diastolic dysfunction without significant MR (n = 46, 28%) were also causes of GLA. During median follow-up of 22 months, 42 cases (26%) underwent composite events. MV surgery was related to lower rate of composite events. In multivariate analysis, MV surgery, elevated pulmonary arterial systolic pressure, and increased LA volume index were independent predictors of future events (p < 0.05) regardless of underlying diseases or history of MV surgery. CONCLUSION: Although rheumatic MVD with atrial fibrillation is the main contributor to GLA, longstanding atrial fibrillation with LV dysfunction but without MVD also could be related to GLA. Even in GLA state, accurate measurement of LA volume is crucial for risk stratification for future events, regardless of underlying disease.

Carotid Artery End-Diastolic Velocity and Future Cerebro-Cardiovascular Events in Asymptomatic High Risk Patients.

BACKGROUND AND OBJECTIVES: Prognostic value of additional carotid Doppler evaluations to carotid intima-media thickness (IMT) and plaque has not been completely evaluated. SUBJECTS AND METHODS: A total of 1119 patients with risk factors for, but without, overt coronary artery disease (CAD), who underwent both carotid ultrasound and Doppler examination were included in the present study. Parameters of interest included peak systolic and end-diastolic velocities, resistive indices of the carotid arteries, IMT, and plaque measurements. The primary end-point was all-cause cerebro-cardiovascular events (CVEs) including acute myocardial infarction, coronary revascularization therapy, heart failure admission, stroke, and cardiovascular death. Model 1 covariates comprised age and sex; Model 2 also included hypertension, diabetes and smoking; Model 3 also had use of aspirin and statin; and Model 4 also included IMT and plaque. RESULTS: The mean follow-up duration was 1386±461 days and the mean age of the study population was 60±12 years. Amongst 1119 participants, 43% were women, 57% had a history of hypertension, and 23% had diabetes. During follow-up, 6.6% of patients experienced CVEs. Among carotid Doppler parameters, average common carotid artery end-diastolic velocity was the independent predictor for future CVEs after adjustments for all models variables (HR 0.95 per cm/s, 95% confident interval 0.91-0.99, p=0.034 in Model 4) and significantly increased the predictive value of Model 4 (global χ(2)=59.0 vs. 62.8, p=0.029). CONCLUSION: Carotid Doppler measurements in addition to IMT and plaque evaluation are independently associated with future CVEs in asymptomatic patients at risk for CAD.

Circulating Microparticles and Coronary Plaque Components Assessed by Virtual Histology Intravascular Ultrasound of the Target Lesion in Patients with Stable Angina.

High levels of microparticles (MPs) circulate in the blood of patients with atherosclerotic diseases where they can serve as potential biomarkers of vascular injury and cardiovascular outcome. We used virtual histology intravascular ultrasound (VH-IVUS) to evaluate the relationship between the levels of circulating MPs and the coronary plaque composition in patients with stable angina. We included 35 patients with stable angina (22 men, age 64 ± 9 years) and a de novo target lesion. Preintervention gray-scale and VH-IVUS analysis was performed across the target lesion. Volumetric analysis was performed over a 10-mm-long segment centered at the minimum luminal site. Blood samples were obtained from the femoral artery before coronary angioplasty. MPs were measured using a solid-phase capture assay from a commercial kit. We divided participants into either a low MPs group or high MPs group based on the median value of MPs. There was no significant difference in baseline characteristics between the groups. The plaque burden and remodeling index were similar between the groups. The presence of VH-IVUS-derived thin-cap fibroatheroma was not different between the groups. The percentage of the necrotic core (NC) was significantly higher in the high MPs group than in the low MPs group, both in planar (17.0 ± 8.8% vs. 24.1 ± 6.9%, p = 0.012) and volumetric analyses (17.0 ± 4.8% vs. 22.1 ± 4.3%, p = 0.002). Circulating MPs were positively correlated with the percentage of the NC area at the minimal luminal site (r = 0.491, p = 0.003) and the percentage of the NC volume (r = 0.496, p = 0.002). Elevated levels of circulating MPs were associated with the amount of NC in the target lesion in those with stable angina, suggesting a potential role of circulating MPs as a biomarker for detecting unstable plaque in patients with stable angina.

MicroRNA-365 inhibits the proliferation of vascular smooth muscle cells by targeting cyclin D1.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of disease progression in atherosclerosis. Cell proliferation is regulated by cell cycle regulatory proteins. MicroRNAs (miR) have been reported to act as important gene regulators and play essential roles in the proliferation and migration of VSMCs in a cardiovascular disease. However, the roles and mechanisms of miRs in VSMCs and neointimal formation are far from being fully understood. In this study, cell cycle-specific cyclin D1 was found to be a potential target of miR-365 by direct binding. Through an in vitro experiment, we showed that exogenous miR-365 overexpression reduced VSMC proliferation and proliferating cell nuclear antigen (PCNA) expression, while miR-365 was observed to block G1/S transition in platelet-derived growth factor-bb (PDGF-bb)-induced VSMCs. In addition, the proliferation of VSMCs by various stimuli, including PDGF-bb, angiotensin II (Ang II), and serum, led to the downregulation of miR-365 expression levels. The expression of miR-365 was confirmed in balloon-injured carotid arteries. Taken together, our results suggest an anti-proliferative role for miR-365 in VSMC proliferation, at least partly via modulating the expression of cyclin D1. Therefore, miR-365 may influence neointimal formation in atherosclerosis patients.

Usefulness of metabolic syndrome score in the prediction of angiographic coronary artery disease severity according to the presence of diabetes mellitus: relation with inflammatory markers and adipokines.

BACKGROUND: It is a matter of debate whether metabolic syndrome (MS) improves cardiovascular risk prediction beyond the risk associated with its individual components. The present study examined the association of MS score with high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), resistin, adiponectin, and angiographic coronary artery disease (CAD) severity according to the presence of DM. In addition, the predictive value of various clinical and biochemical parameters were analyzed, including the MS score for angiographic CAD. METHODS: The study enrolled 363 consecutive patients (196 men, 62 ± 11 years of age) who underwent coronary angiography for evaluation of chest pain. Blood samples were taken prior to elective coronary angiography. MS was defined by the National Cholesterol Education Program criteria, with MS score defined as the numbers of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD severity was assessed using the Gensini score. RESULTS: Of the 363 patients studied, 174 (48%) had CAD and 178 (49%) were diagnosed with MS. When the patients were divided into 4 subgroups according to MS score (0-1, 2, 3, 4-5), IL-6 levels and the CAD severity as assessed by the Gensini score increased as MS scores increased. In contrast, adiponectin levels decreased significantly as MS scores increased. When subjects were divided into two groups according to the presence of DM, the relationships between MS score and IL-6, adiponectin, and Gensini score were maintained only in patients without DM. Age, smoking, DM, MS score, and adiponectin independently predicted angiographic CAD in the whole population. However, age is the only predictor for angiographic CAD in patients with DM. CONCLUSIONS: In the presence of DM, neither adipokines nor MS score predicted angiographic CAD. However, in non-diabetic patients, IL-6 and adiponectin showed progressive changes according to MS score, and MS score was an independent predictor of CAD in patients without DM.

Preventive effect of pretreatment with intravenous nicorandil on contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography (PRINCIPLE Study).

PURPOSE: To investigate the effect of pretreatment with intravenous nicorandil on the incidence of contrast-induced nephropathy (CIN) in patients with renal dysfunction undergoing coronary angiography. MATERIALS AND METHODS: This randomized controlled multicenter study enrolled a total of 166 patients (nicorandil n=81; control n=85) with an estimated glomerular filtration rate <60 mL/min. Nicorandil 12 mg dissolved in 100 mL of 0.9% saline was administered intravenously for 30 minutes just prior to coronary angiography in the nicorandil group. The same volume of only saline was given to the control group. The primary endpoint was the incidence of CIN, defined as >0.5 mg/dL increase or >25% rise in serum creatinine (SCr) concentration within 48 hours of contrast exposure compared to baseline. RESULTS: The final analysis included 149 patients (nicorandil n=73; control n=76). The baseline characteristics and the total volume of the used contrast (Iodixanol, 125.6±69.1 mL vs. 126.9±74.6 mL, p=0.916) were similar between the two groups. The incidence of CIN also did not differ between the nicorandil and control groups (6.8% vs. 6.6%, p=0.794). There was no difference between the two groups in the relative change in SCr from baseline to peak level within 48 hours after coronary angiography (-1.58±24.07% vs. 0.96±17.49%, p=0.464), although the nicorandil group showed less absolute change in SCr than the control group (-0.01±0.43 mg/mL vs. 0.02±0.31 mg/mL, p=0.005). CONCLUSION: Prophylactic intravenous infusion of nicorandil did not decrease the incidence of CIN in patients with renal dysfunction undergoing coronary angiography.

Prognostic significance of elevated lipoprotein(a) in coronary artery revascularization patients.

BACKGROUND: Although lipoprotein(a) [Lp(a)] has been considered a cardiovascular risk factor for many years, there is a paucity of data in regard to the potential risk of elevated Lp(a) in symptomatic patients with CAD. Therefore, we sought to evaluate whether elevated Lp(a) is associated with worse outcome in symptomatic patients with coronary artery disease (CAD), and to clarify the prognostic value of Lp(a) in the era of coronary artery revascularization. METHODS: 6252 consecutive subjects (59.2% male, mean age 61.2 ± 11.2 years) suspected of having CAD underwent coronary angiography. Laboratory values for lipid parameters including Lp(a) were obtained on the day of coronary angiography. Baseline risk factors, coronary angiographic findings, length of follow-up, and major adverse cardiovascular events (MACE), including cardiac death and non-fatal myocardial infarction were recorded. RESULTS: Over a mean follow-up period of 3.1 ± 2.2 years, there were 100 MACE (56 cardiac deaths and 44 non-fatal myocardial infarctions), with an event rate of 1.6%. In multivariate Cox regression analysis, elevated Lp(a) was a significant predictor of MACE [hazard ratio 1.773 (95% confidence interval 1.194-2.634, p=0.005)], and the addition of this factor to the model significantly increased the global х(2) value over traditional risk factors and CAD (from 79.1 to 88.7, p=0.003). CONCLUSIONS: Elevated Lp(a) is an independent prognostic risk factor for cardiovascular events, and moreover, has incremental prognostic value in symptomatic patients with coronary artery revascularization.

Left atrial strain assessed by speckle tracking imaging is related to new-onset atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Left atrial (LA) dysfunction was recently proposed as an important factor in the development of postoperative atrial fibrillation (POAF). LA strain analysis by 2-dimensional (2D) speckle tracking imaging is emerging as a new tool to evaluate LA function. We aimed to evaluate the correlation of LA dysfunction assessed by 2D speckle tracking imaging with the occurrence of POAF after coronary artery bypass grafting (CABG). METHODS: In this study, 53 patients (mean age 66 ± 9 years) undergoing elective isolated CABG were enrolled. Conventional transthoracic echocardiography and 2D speckle tracking strain analysis were performed before surgery. POAF was detected with continuous electrocardiography monitoring throughout hospitalization (mean duration 17 ± 10 days). RESULTS: POAF occurred in 13 of 53 patients (24%). Patients with POAF were significantly older than patients with normal sinus rhythm after surgery (71 ± 5 vs 64 ± 10 years, P = 0.026). Compared with patients with normal sinus rhythm, patients with POAF had a significantly larger LA volume index (32.6 ± 5.1 vs 27.3 ± 7.2 mL/m(2), P = 0.018), lower value of LA global strain (25.4 ± 10.4 vs 36.8 ± 7.6%, P = 0.001), and strain rate (1.2 ± 0.6 vs 1.6 ± 0.8 seconds, P = 0.024). By multivariate logistic regression analysis, only LA global strain (odds ratio, 1.12; 95% confidence interval, 1.00-1.24; P = 0.040) was an independent predictor of POAF after CABG. CONCLUSIONS: Preoperative LA global strain measured by 2D speckle tracking strain analysis is associated with the development of POAF after CABG.

Left ventricular hypercontractility immediately after tilting triggers a disregulated cardioinhibitory reaction in vasovagal syncope: echocardiographic evaluation during the head-up tilt test.

OBJECTIVES: Vasovagal syncope (VVS) has been believed to occur when mechanoreceptors are discharged by vigorous ventricular contraction. However, previous investigators have reported divergent observations regarding the presence of left ventricular (LV) hypercontractility in VVS. Because the autonomic nervous system can be promptly activated after certain stimuli, we postulated that instantaneously increased LV contractility at the time of venous pooling may trigger the disregulated vasovagal reaction in VVS. METHODS: Forty-seven patients (31 males, mean age 41 ± 18 years) with unexplained syncope were enrolled. Echocardiography was performed during the head-up tilt test (HUTT) as follows: baseline, passive tilting (0 and 20 min), and tilting with isoproterenol administration (5 and 10 min). Patients were divided into 2 groups according to the results of the HUTT; group 1 (n = 12) had a positive result and group 2 had a negative response. RESULTS: LV ejection fraction (LVEF), determined immediately after tilting, increased in group 1, whereas LVEF decreased in group 2 (p = 0.032). Although left atrial and LV volumes decreased similarly during the test, group 1 showed a progressive reduction in LVEF, while LVEF progressively increased in group 2 (p = 0.007). CONCLUSION: Patients with HUTT-induced VVS presented LV hypercontractions immediately after tilting and a subsequent decrease in LV contractility. An instantaneous activation of the sympathetic nervous system at the time of venous pooling may trigger an early disregulated vasovagal reflex via an increase in LV contractility in VVS.

Potential role of HMG CoA reductase inhibitor on oxidative stress induced by advanced glycation endproducts in vascular smooth muscle cells of diabetic vasculopathy.

Advanced glycation endproducts (AGEs)-induced vascular smooth muscle cell (VSMCs) proliferation and formation of reactive oxygen species (ROS) are emerging as one of the important mechanisms of diabetic vasculopathy but little is known about the antioxidative action of HMG CoA reductase inhibitor (statin) on AGEs. We hypothesized that statin might reduce AGEs-induced intracellular ROS of VSMCs and analyzed the possible mechanism of action of statin in AGEs-induced cellular signaling. Aortic smooth muscle cell of Sprague-Dawley rat (RASMC) culture was done using the different levels of AGEs stimulation in the presence or absence of statin. The proliferation of RASMC, ROS formation and cellular signaling was evaluated and neointimal formation after balloon injury in diabetic rats was analyzed. Increasing concentration of AGEs stimulation was associated with increased RASMC proliferation and increased ROS formation and they were decreased with statin in a dose-dependent manner. Increased NF-kappaB p65, phosphorylated ERK, phosphorylated p38 MAPK, cyclooxygenase-2, and c-jun by AGEs stimulation were noted and their expression was inhibited by statin. Neointimal formation after balloon injury was much thicker in diabetic rats than the sham-treated group but less neointimal growth was observed in those treated with statin after balloon injury. Increased ROS formation, subsequent activation of MAPK system and increased VSMC proliferation may be possible mechanisms of diabetic vasculopathy induced by AGEs and statin may play a key role in the treatment of AGEs-induced diabetic atherosclerosis.

Systemic immunosuppressive therapy inhibits in-stent restenosis in patients with renal allograft.

BACKGROUND: Cyclosporine is used routinely for prophylaxis for renal allograft rejection. In experimental animal studies, cyclosporine had been shown to inhibit smooth muscle cell proliferation during the arterial response to injury. We investigated whether systemic immunosuppression may inhibit in-stent restenosis in renal transplant patients undergoing coronary stenting. METHODS: From 1993 to 2003, 33 renal transplant patients with 45 coronary lesions and 37 dialysis patients with 52 lesions underwent coronary stenting using bare metal stents at our center. We followed all patients clinically for a mean period of 37 +/- 31 months and 40 patients angiographically at 14 +/- 15 months after coronary intervention. Cyclosporine was combined with corticosteroids in 32 patients and one patient received tacrolimus instead of cyclosporine. RESULTS: The baseline clinical and angiographical characteristics were similar and the success rate of the procedure was 100% in both groups. In renal transplant group, the mean dose of cyclosporine was 192.5 +/- 68 mg/day and the blood cyclosporine level at the time of procedure was 152.9 +/- 51.5 ng/mL. The rate of in-stent restenosis was 7.1% in renal transplant group and 57.1% in dialysis group (P < 0.0001). The mean late loss was 0.47 +/- 0.57 mm in renal transplant group when compared with 1.51 +/- 1.09 mm in dialysis group (P = 0.004). The overall rate of major adverse cardiac events (MACEs) was 6.1% in renal transplant group and 35.1% in dialysis group (P < 0.0001). CONCLUSIONS: Renal transplant patients receiving combined immunosuppressive agents showed markedly low rates of in-stent restenosis and MACE after coronary revascularization with stent. We consider that this result may be related to the ability of combined immunosuppressive therapy to inhibit inflammatory reaction and vascular smooth muscle cell proliferation induced by coronary stenting.