Eun Ho Choo

Benefit of β-blocker treatment for patients with acute myocardial infarction and preserved systolic function after percutaneous coronary intervention

Objective β-blockers are the standard treatment for myocardial infarction (MI) based on evidence from the pre-thrombolytic era. The aim of this study was to examine the effect of β-blocker treatment in patients with acute MI and preserved systolic function in the era of percutaneous coronary intervention (PCI). Methods We analysed a multicentre registry and identified 3019 patients who presented with acute MI between 2004 and 2009. Patients were treated with PCI, had left ventricular EFs ≥50% according to echocardiograms that were performed during the index PCI, and were alive at the time of discharge. The association between β-blocker use after discharge and mortality (all-cause death and cardiac death) within 3 years was examined. Results Patients who were not treated with β-blockers (n=595) showed higher rates of all-cause death and cardiac death compared to patients treated with β-blockers (10.8% vs 5.7%, p<0.001, 7.6% vs 2.6%, p<0001). The multivariate Cox proportional hazards model showed that β-blocker treatment was associated with a significant reduction in all-cause death (adjusted HR 0.633, 95% CI 0.464 to 0.863; p=0.004) and cardiac death (adjusted HR 0.47, 95% CI 0.32 to 0.70; p<0.001). Comparable results were obtained after propensity score matching. Conclusions β-blocker treatment was associated with reduced long term mortality in patients with acute MI and preserved systolic function who received PCI.

The impact of no-reflow phenomena after primary percutaneous coronary intervention: a time-dependent analysis of mortality.

BackgroundThe no-reflow phenomenon is a potential complication of primary percutaneous coronary intervention (PCI). Predictors of the no-reflow phenomenon and the impact on long-term mortality remain unclear. MethodsTwo thousand and seventeen patients with ST-segment elevation myocardial infarction (STEMI) who had undergone primary PCI were consecutively enrolled in the multicentre Acute Myocardial Infarction registry of Korea. The no-reflow phenomenon was diagnosed on the basis of angiographic criteria. The primary outcome was all-cause mortality. ResultsThe no-reflow phenomenon was diagnosed in 262 patients (13.0%). Independent predictors of no-reflow were older age, high Killip class, reduced pre-PCI thrombolysis in myocardial infarction flow grade, and longer stent length in the culprit vessel. During a median follow-up period of 4.1 years (interquartile range: 3.0–5.2 years), patients with no-reflow showed a higher rate of mortality than that observed in patients with reflow (30.2 vs. 18.3%, P<0.001). The multivariate Cox proportional hazards model identified the no-reflow phenomenon as an independent correlate of long-term mortality [adjusted hazard ratio (HR): 1.45; 95% confidence interval (CI): 1.12–1.86; P=0.004]. Time period-specific analyses demonstrated that the association between no-reflow and mortality was significant and stronger for short-term (<30 days) mortality (adjusted HR: 3.11; 95% CI: 1.91–5.05; P<0.001) but was not significant for longer-term mortality (≥30 days; adjusted HR: 1.12; 95% CI: 0.82–1.52; P=0.47). ConclusionIn patients with STEMI who had undergone primary PCI, the no-reflow phenomenon was an independent predictor of short-term but not long-term mortality.

Impact of Percutaneous Coronary Intervention for Chronic Total Occlusion in Non–Infarct-Related Arteries in Patients With Acute Myocardial Infarction (from the COREA-AMI Registry)

Chronic total occlusion (CTO) in a non-infarct-related artery (IRA) is an independent predictor of clinical outcomes in patients with acute myocardial infarction (AMI). This study evaluated the impact of successful percutaneous coronary intervention (PCI) for CTO of a non-IRA on the long-term clinical outcomes in patients with AMI. A total of 4,748 patients with AMI were consecutively enrolled in the Convergent Registry of Catholic and Chonnam University for AMI registry from January 2004 to December 2009. We enrolled 324 patients with CTO in a non-IRA. To adjust for baseline differences, propensity matching (96 matched pairs) was used to compare successful PCI and occluded CTO for the treatment of CTO in non-IRA. The primary clinical end points were all-cause mortality and a composite of the major adverse cardiac events, including cardiac death, MI, stroke, and any revascularization during the 5-year follow-up. Patients who received successful PCI for CTO of non-IRA had lower rates of all-cause mortality (16.7% vs 32.3%, hazard ratio 0.459, 95% CI 0.251 to 0.841, p = 0.012) and major adverse cardiac events (21.9% vs 55.2%, hazard ratio 0.311, 95% CI 0.187 to 0.516, p <0.001) compared with occluded CTO group. Subgroup analyses revealed that successful PCI resulted in a better mortality rate in patients with normal renal function compared to patients with chronic kidney disease (p = 0.010). In conclusion, successful PCI for CTO of non-IRA is associated with improved long-term clinical outcomes in patients with AMI.

Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage PolarizationClinical Perspective

Background: Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases. Methods: We generated tDCs by treating bone marrow–derived dendritic cells with tumor necrosis factor-&agr; and cardiac lysate from MI mice. We injected MI mice, induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation. Results: In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate–primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue–specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved left ventricular systolic function after myocardial tissue damage, and improved survival. Conclusions: This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair.

Effect of Pioglitazone in Combination with Moderate Dose Statin on Atherosclerotic Inflammation: Randomized Controlled Clinical Trial Using Serial FDG-PET/CT

Background and Objectives Non-statin therapy plus lower intensity statin might be an alternative in patients with coronary artery disease (CAD). A recent data suggested an anti-inflammatory therapy can reduce recurrent cardiovascular events and pioglitazone is also an intriguing inflammatory-modulating agent. However, limited data exist on whether pioglitazone on top of statins further attenuates plaque inflammation. Methods Statin-naïve patients with stable CAD and carotid plaques of ≥3 mm were randomly prescribed moderate dose atorvastatin (20 mg/day), or moderate dose atorvastatin plus pioglitazone (30 mg/day) for 3 months. The primary endpoint was the change in the arterial inflammation of the carotid artery measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) during 3 months. Results Of the 41 randomized patients, 33 underwent an evaluation by fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT; 17 atorvastatin plus pioglitazone and 16 atorvastatin patients). The addition of pioglitazone significantly improved the insulin sensitivity and increased the high-density lipoprotein cholesterol after 3 months. Although a reduction in the (FDG) uptake by pioglitazone on top of atorvastatin in carotid arteries with plaque showed marginally statistical significance in the entire patient group (atorvastatin plus pioglitazone; −0.10±0.07 and atorvastatin −0.06±0.04, p=0.058), pioglitazone showed a further reduction of the fluorodeoxyglucose (FDG) uptake among patients who had a baseline FDG uptake above the median (atorvastatin plus pioglitazone; −0.14±0.04 and atorvastatin −0.03±0.03, p<0.001). Conclusions Pioglitazone demonstrated marginally significant anti-inflammatory effects in addition to moderate dose atorvastatin. This may have been due to the lack of power of the study. However, pioglitazone may have an anti-inflammatory effect in those patients with high plaque inflammation (Trial registry at ClinicalTrials.gov, NCT01341730).

Low plasma renin activity is an independent predictor of near-term incidence of hypertension in Asian populations

ABSTRACT Background: Plasma renin activity is involved in the regulation of body salt content and blood pressure. However, there is a paucity of data regarding the association between low or high plasma renin activity and the development of hypertension. Method: We investigated the relation of baseline plasma renin activity to increases in blood pressure and the incidence of hypertension after four years in 2,146 non-hypertensive individuals from a community-based Korean population (mean age, 50 years), 58% of whom were women. We defined an “increase in blood pressure” as an increment of systolic blood-pressure ≥ 10 mmHg or initiation of antihypertensive drugs and defined “hypertension” as a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or the use of antihypertensive medications. Results: After 4 years, the increase in blood pressure had increased in 27.9% of the participants, and hypertension had developed in 17.9%. After adjustment, the lowest sex-specific tertile of plasma renin activity was an independent risk factor of an elevation in blood pressure (Adjusted Odds Ratio 1.37, 95% confidence interval 1.07–1.74, p = 0.011) and hypertension (Adjusted Odds Ratio 1.84, 95% confidence interval 1.36–2.50, p < 0.001) compared to the highest sex-specific tertile. The associations between the plasma renin activity and blood-pressure outcomes were evident in adults with especially high urine sodium excretion. Conclusion: Low plasma renin activity was associated with the development of hypertension in the middle-aged Asian population, especially in peoples with high sodium intake.

PS 02-10 Relationship of brachial-ankle pulse wave velocity and coronary atherosclerosis in asymptomatics: Evaluation by coronary CT angiography

Objective: We investigated the association of arterial stiffness, assessed by pulse wave velocity (PWV) with the prevalence, extent, and severity of coronary atheroma burden using coronary computed tomography angiography (CCTA) in community-dwelling Korean adults without chest pain. Design and Method: We analyzed 749 individuals without known or suspected coronary artery disease (CAD) undergoing CCTA. Participants were divided into two groups according to the mean value of PWV: 1455 cm/sec. Obstructive CAD, as measured by CCTA, was defined as maximum intra-luminal stenosis ≥ 50%. We compared the prevalence, extent, and severity of coronary atheroma burden, including coronary artery calcium score (CACS), atheroma burden obstructive score (ABOS), segment involvement score (SIS), and segment stenosis score (SSS) between groups. Multivariable logistic regression analysis was also performed to identify independent predictors of CAD. Results: Individuals with higher PWV possessed higher obstructive CAD (p < 0.001). Higher PWV was associated with greater degrees of CACS, ABOS, SIS, and SSS on CT scans (p < 0.001 for all). Multivariable analyses adjusted for conventional cardiovascular risk factors, including age, sex, and diabetes mellitus revealed that higher PWV was an independent predictor of obstructive CAD (odds ratio 2.694, confidence intervals 1.382–5.252, p = 0.004). Conclusions: Arterial stiffness assessed by PWV was associated with higher prevalence, extent, and severity of coronary atherosclerosis as well as increased risk of obstructive CAD in asymptomatics. Figure. No caption available.

MPS 14-02 Comparison of Decrease in Urinary Albumin Excretion According to Fimasartan Dosing of Evening versus Morning in Never-Treated Hypertensive Patients

Objective: Previous results indicated that some aldosterone receptor blockers (ARB) at evening administration, as opposed to upon morning, might improve the diurnal/nocturnal ratio of blood pressure and urinary albumin excretion (UAE). The bedtime dosing of fimasartan compared to morning dosing effects on blood pressure and UAE is still uncertain. Design and Method: Data from a 12-week prospective, randomized, open-label, blinded endpoint trial on 97 previously never-treated hypertensive patients, who were assigned to receive fimasartan (60 mg/day) as a monotherapy either on morning or evening, were included. Blood pressure was measured every 15 min during the day and every 30 min during the night for 24 consecutive hours before and after 3 months of treatment. Urinary excretion was calculated to use the urine albumin/creatinine ratio of morning spot urine. Results: The significant blood pressure reduction after 3 months of fimasartan (P < 0.001) was similar for both treatment times (10.8 and 10.2 mmHg reduction in the 24-h mean of systolic and diastolic blood pressure with morning administration; 7.4 and 10.9 mmHg with evening administration). Urinary albumin excretion was significantly reduced by 49% after awakening treatment and by 21% after bedtime treatment. Conclusions: Fimasartan significantly reduced the blood pressure, and urinary albumin excretion, however, the expected difference of dosing regimen evening versus morning effect on urinary albumin excretion was not detected. Figure. No caption available.

MPS 05-02 PULSE PRESSURE AND CORONARY STENOSIS IN CORONARY COMPUTED TOMOGRAPHIC ANGIOGRAPHY IN ASYMPTOMATIC TYPE 2 DIABETIC PATIENTS

Objective: Limited data exist regarding the prevalence, extent and severity of coronary artery disease (CAD) as well as clinical outcomes in asymptomatic diabetic patients according to pulse pressure. Design and Method: We enrolled 935 consecutive asymptomatic type 2 diabetic patients without known CAD. Coronary computed tomography angiography was used to evaluate the prevalence and severity of CAD. Brachial blood pressure was measured at baseline. Patients were assigned to quartile of pulse pressure (<40, 40–49, 50–59, and >=60 mmHg). Results: The prevalence of obstructive CAD (≥50% stenosis) was increased from the lowest quartile of patients (26.5%) to the highest quartile of patients (54.5%) (p = <0.001). The incidence of obstructive CAD in multivessel or left main CAD also increased across the quartiles (11.7% to 32.0%, p < 0.001). Increase of pulse pressure by 10 mmHg was an independent predictor of obstructive CAD after adjusting for risk factors including systolic blood pressure (adjusted odds ratio, 1.293; 95% confidence interval (CI), 1.07–1.57, p = 0.008). During a median follow-up of 3.1 years, the highest quartile of pulse pressure was associated with increased risk of cardiac death or myocardial infarction compared to the risk in the lowest quartile (0% vs. 5.2%, log rank p = 0.019). Conclusions: In asymptomatic type 2 diabetic patients, increased pulse pressure was associated with increased risk of CAD and poor clinical outcomes.

PS 11-03 Blood pressure at 1 year after myocardial infarction and mortality

Objective: In patients with coronary artery disease, a J-curve relationship has been reported between blood pressure (BP) and future cardiovascular events. However, this is controversial. We investigated the relationship between BP at 1 year after myocardial infarction (MI) and mortality. Design and Method: We analyzed a multicenter registry and identified 2,889 patients who presented with acute MI and were treated with percutaneous coronary intervention between 2004 and 2009. Patients survived for 1 year after MI and were measured blood pressure at 1 year. The association between BP at 1 year and mortality (all-cause death and cardiac death) within three years after BP measurement was examined. Cox proportional hazards models were fitted to examine the effects on mortality of blood pressure at 1 year and of blood pressure as a time-dependent covariate. Results: Among the 2,889 patients, 278 (9.6 %) experienced mortality (cardiac death: 94 [3.3%]) at 2.5 years (median) of follow-up after BP measurement at 1 year. The relationship between systolic BP or diastolic BP and mortality did not follow J-curve which were examined by cox proportional hazards using BP at 1 year as a time-dependent covariate. The mortality increased in patients with systolic BP > 150 mmHg or diastolic BP > 90 mmHg (13.8%, n = 319). In multivariate analysis, systolic BP > 150 mmHg or diastolic BP > 90 mmHg at 1 year were one of independent predictors of mortality (Adjusted Hazard Ratio [HR] 1.84, 95% Confidence interval [CI] 1.31–2.60, p = 0.001) and cardiac death (adjusted HR 2.11, 95% CI 1.17–3.81, p = 0.014). Conclusions: In stable post-MI patients at 1 year, high BP (systolic BP > 150 or diastolic BP > 90 mmHg) were associated wtih increased risk of mortality. Tight blood pressure control may be required to reduce the substantial risk for mortality beyond first year post-MI.