Clinical Implication of Hypoxic Liver Injury for Predicting Hypoxic Hepatitis and In-Hospital Mortality in ST Elevation Myocardial Infarction Patients

Purpose@#In this study, we aimed to determine the value of hypoxic liver injury (HLI) in the emergency room (ER) for predicting hypoxic hepatitis (HH) and in-hospital mortality in ST elevation myocardial infarction (STEMI) patients. @*Materials and Methods@#1537 consecutive STEMI patients were enrolled. HLI in the ER was defined as a ≥2-fold increase in serum aspartate transaminase (AST). HH was defined as a ≥20-fold increase in peak serum transaminase. Patients were divided into four groups according to HLI and HH status (group 1, no HLI or HH; group 2, HLI, but no HH; group 3, no HLI, but HH; group 4, both HLI and HH). @*Results@#The incidences of HLI and HH in the ER were 22% and 2%, respectively. In-hospital mortality rates were 3.1%, 11.8%, 28.6%, and 47.1% for groups 1, 2, 3, and 4, respectively. Patients with HLI and/or HH had worse Killip class, higher cardiac biomarker elevations, and lower left ventricular ejection fraction. Multivariate logistic regression analysis showed that HLI in the ER was an independent predictor of HH [odds ratio 2.572, 95% confidence interval (CI) 1.166–5.675, p=0.019]. The predictive value of HLI in the ER for the development of HH during hospitalization was favorable [area under the curve (AUC) 0.737, 95% CI 0.643–0.830, sensitivity 0.548, specificity 0.805, for cut-off value AST >80]. Furthermore, in terms of in-hospital mortality, predictive values of HLI in the ER and HH during hospitalization were comparable (AUC 0.701 for HLI at ER and AUC 0.674 for HH). @*Conclusion@#Among STEMI patients, HLI in the ER is a significant predictor for the development of HH and mortality during hospitalization (INTERSTELLAR ClinicalTrials.gov number, NCT02800421).

Clinical Implication of Hypoxic Liver Injury for Predicting Hypoxic Hepatitis and In-Hospital Mortality in ST Elevation Myocardial Infarction Patients

Purpose@#In this study, we aimed to determine the value of hypoxic liver injury (HLI) in the emergency room (ER) for predicting hypoxic hepatitis (HH) and in-hospital mortality in ST elevation myocardial infarction (STEMI) patients. @*Materials and Methods@#1537 consecutive STEMI patients were enrolled. HLI in the ER was defined as a ≥2-fold increase in serum aspartate transaminase (AST). HH was defined as a ≥20-fold increase in peak serum transaminase. Patients were divided into four groups according to HLI and HH status (group 1, no HLI or HH; group 2, HLI, but no HH; group 3, no HLI, but HH; group 4, both HLI and HH). @*Results@#The incidences of HLI and HH in the ER were 22% and 2%, respectively. In-hospital mortality rates were 3.1%, 11.8%, 28.6%, and 47.1% for groups 1, 2, 3, and 4, respectively. Patients with HLI and/or HH had worse Killip class, higher cardiac biomarker elevations, and lower left ventricular ejection fraction. Multivariate logistic regression analysis showed that HLI in the ER was an independent predictor of HH [odds ratio 2.572, 95% confidence interval (CI) 1.166–5.675, p=0.019]. The predictive value of HLI in the ER for the development of HH during hospitalization was favorable [area under the curve (AUC) 0.737, 95% CI 0.643–0.830, sensitivity 0.548, specificity 0.805, for cut-off value AST >80]. Furthermore, in terms of in-hospital mortality, predictive values of HLI in the ER and HH during hospitalization were comparable (AUC 0.701 for HLI at ER and AUC 0.674 for HH). @*Conclusion@#Among STEMI patients, HLI in the ER is a significant predictor for the development of HH and mortality during hospitalization (INTERSTELLAR ClinicalTrials.gov number, NCT02800421).

Complete Versus Culprit-Only Revascularization for ST-Segment Elevation Myocardial Infarction and Multivessel Disease in the 2(nd) Generation Drug-Eluting Stent Era: Data from the INTERSTELLAR Registry

BACKGROUND AND OBJECTIVES: We aimed to compare outcomes of complete revascularization (CR) versus culprit-only revascularization for ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) in the 2nd generation drug-eluting stent (DES) era. METHODS: From 2009 to 2014, patients with STEMI and MVD, who underwent primary percutaneous coronary intervention (PCI) using a 2nd generation DES for culprit lesions were enrolled. CR was defined as PCI for a non-infarct-related artery during the index admission. Major adverse cardiovascular event (MACE) was defined as cardiovascular (CV) death, non-fatal myocardial infarction, target lesion revascularization, or heart failure during the follow-up year. RESULTS: In total, 705 MVD patients were suitable for the analysis, of whom 286 (41%) underwent culprit-only PCI and 419 (59%) underwent CR during the index admission. The incidence of MACE was 11.5% in the CR group versus 18.5% in the culprit-only group (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.37–0.86; p<0.01; adjusted HR, 0.64; 95% CI, 0.40–0.99; p=0.04). The CR group revealed a significantly lower incidence of CV death (7.2% vs. 12.9%; HR, 0.51; 95% CI, 0.31–0.86; p=0.01 and adjusted HR, 0.57; 95% CI; 0.32–0.97; p=0.03, respectively). CONCLUSIONS: CR was associated with better outcomes including reductions in MACE and CV death at 1 year of follow-up compared with culprit-only PCI in the 2nd generation DES era.

Complete Versus Culprit-Only Revascularization for ST-Segment Elevation Myocardial Infarction and Multivessel Disease in the 2(nd) Generation Drug-Eluting Stent Era: Data from the INTERSTELLAR Registry

BACKGROUND AND OBJECTIVES@#We aimed to compare outcomes of complete revascularization (CR) versus culprit-only revascularization for ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) in the 2nd generation drug-eluting stent (DES) era.@*METHODS@#From 2009 to 2014, patients with STEMI and MVD, who underwent primary percutaneous coronary intervention (PCI) using a 2nd generation DES for culprit lesions were enrolled. CR was defined as PCI for a non-infarct-related artery during the index admission. Major adverse cardiovascular event (MACE) was defined as cardiovascular (CV) death, non-fatal myocardial infarction, target lesion revascularization, or heart failure during the follow-up year.@*RESULTS@#In total, 705 MVD patients were suitable for the analysis, of whom 286 (41%) underwent culprit-only PCI and 419 (59%) underwent CR during the index admission. The incidence of MACE was 11.5% in the CR group versus 18.5% in the culprit-only group (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.37–0.86; p<0.01; adjusted HR, 0.64; 95% CI, 0.40–0.99; p=0.04). The CR group revealed a significantly lower incidence of CV death (7.2% vs. 12.9%; HR, 0.51; 95% CI, 0.31–0.86; p=0.01 and adjusted HR, 0.57; 95% CI; 0.32–0.97; p=0.03, respectively).@*CONCLUSIONS@#CR was associated with better outcomes including reductions in MACE and CV death at 1 year of follow-up compared with culprit-only PCI in the 2nd generation DES era.

Clinical Outcomes according to the Achievement of Target Low Density Lipoprotein-Cholesterol in Patients with Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: The clinical outcome of patient with an acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI), with or without achievement of target low density lipoprotein-cholesterol (LDL-C), has little known information. This study investigated if target LDL-C level (below 70 mg/dL) achievements in patients with AMI showed better clinical outcomes or not. SUBJECTS AND METHODS: Between May 2008 and September 2012, this study enrolled 13473 AMI patients in a large-scale, prospective, multicenter Korean Myocardial Infarction (KorMI) registry. 12720 patients survived and 6746 patients completed a 1-year clinical follow up. Among them 3315 patients received serial lipid profile follow-ups. Propensity score matching was applied to adjust for differences in clinical baseline and angiographic characteristics, producing a total of 1292 patients (646 target LDL-C achievers vs. 646 non-achievers). The primary end point was the composite of a 1-year major adverse cardiac event (MACE) including cardiac death, recurrent myocardial infarction (MI), target lesion revascularization (TLR) and coronary artery bypass grafting. RESULTS: After propensity score matching, baseline clinical and angiographic characteristics were similar between the two groups. Clinical outcomes of the propensity score matched patients who showed no significant differences in cardiac death (0.5% vs. 0.5%, p=1.000), recurrent MI (1.1% vs. 0.8%, p=0.562), TLR (5.0% vs. 4.5%, p=0.649), MACEs (6.5% vs. 5.9%, p=0.644) and stent thrombosis (2.5% vs. 1.9%, p=0.560). CONCLUSION: In this propensity-matched comparison, AMI patients undergoing PCI with a target LDL-C (below 70 mg/dL) achievement did not show better clinical outcomes.

Coronary Computed Tomographic Angiography Does Not Accurately Predict the Need of Coronary Revascularization in Patients with Stable Angina

PURPOSE: To evaluate the ability of coronary computed tomographic angiography (CCTA) to predict the need of coronary revascularization in symptomatic patients with stable angina who were referred to a cardiac catheterization laboratory for coronary revascularization. MATERIALS AND METHODS: Pre-angiography CCTA findings were analyzed in 1846 consecutive symptomatic patients with stable angina, who were referred to a cardiac catheterization laboratory at six hospitals and were potential candidates for coronary revascularization between July 2011 and December 2013. The number of patients requiring revascularization was determined based on the severity of coronary stenosis as assessed by CCTA. This was compared to the actual number of revascularization procedures performed in the cardiac catheterization laboratory. RESULTS: Based on CCTA findings, coronary revascularization was indicated in 877 (48%) and not indicated in 969 (52%) patients. Of the 877 patients indicated for revascularization by CCTA, only 600 (68%) underwent the procedure, whereas 285 (29%) of the 969 patients not indicated for revascularization, as assessed by CCTA, underwent the procedure. When the coronary arteries were divided into 15 segments using the American Heart Association coronary tree model, the sensitivity, specificity, positive predictive value, and negative predictive value of CCTA for therapeutic decision making on a per-segment analysis were 42%, 96%, 40%, and 96%, respectively. CONCLUSION: CCTA-based assessment of coronary stenosis severity does not sufficiently differentiate between coronary segments requiring revascularization versus those not requiring revascularization. Conventional coronary angiography should be considered to determine the need of revascularization in symptomatic patients with stable angina.

The efficacy and safety of drug-eluting balloons for the treatment of in-stent restenosis as compared with drug-eluting stents and with conventional balloon angioplasty

BACKGROUND/AIMS: Treatment of coronary in-stent restenosis (ISR) is still associated with a high incidence of recurrence. We aimed to compare the efficacy and safety of drug-eluting balloons (DEB) for the treatment of ISR as compared with conventional balloon angioplasty (BA) and drug-eluting stents (DES). METHODS: Between January 2006 and May 2012 a total of 177 patients (188 lesions, 64.1 ± 11.7 years old) who underwent percutaneous coronary intervention for ISR were retrospectively enrolled. Clinical outcomes were compared between patients treated with DEB (n = 58, 32.8%), conventional BA (n = 65, 36.7%), or DES (n = 54, 30.5%). The primary end point was a major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction, and target lesion revascularization(TLR). RESULTS: Baseline characteristics were not different except for a history of previous MI, which was more frequent in patients treated by conventional BA or DES than in patients treated by DEB (40.0% vs. 48.1% vs. 17.2%, respectively, p = 0.002). The total incidences of MACEs were 10.7%, 7.4%, and 15.4% in patients treated by DEB, DES, or conventional BA, respectively (p > 0.05). TLR was more frequent in patients treated by conventional BA than in patients treated by DEB or DES, but this was not statistically significant (10.8% vs. 6.9% vs. 3.7%, p > 0.05 between all group pairs, respectively). CONCLUSIONS: This study showed that percutaneous coronary intervention using DEB might be a feasible alternative to conventional BA or DES implantation for treatment of coronary ISR. Further large-scaled, randomized study assessing long-term clinical and angiographic outcomes will be needed.

Increasing injection frequency enhances the survival of injected bone marrow derived mesenchymal stem cells in a critical limb ischemia animal model

Critical limb ischemia (CLI) is one of the most severe forms of peripheral artery diseases, but current treatment strategies do not guarantee complete recovery of vascular blood flow or reduce the risk of mortality. Recently, human bone marrow derived mesenchymal stem cells (MSCs) have been reported to have a paracrine influence on angiogenesis in several ischemic diseases. However, little evidence is available regarding optimal cell doses and injection frequencies. Thus, the authors undertook this study to investigate the effects of cell dose and injection frequency on cell survival and paracrine effects. MSCs were injected at 10⁶ or 10⁵ per injection (high and low doses) either once (single injection) or once in two consecutive weeks (double injection) into ischemic legs. Mice were sacrificed 4 weeks after first injection. Angiogenic effects were confirmed in vitro and in vivo, and M2 macrophage infiltration into ischemic tissues and rates of limb salvage were documented. MSCs were found to induce angiogenesis through a paracrine effect in vitro, and were found to survive in ischemic muscle for up to 4 weeks dependent on cell dose and injection frequency. In addition, double high dose and low dose of MSC injections increased vessel formation, and decreased fibrosis volumes and apoptotic cell numbers, whereas a single high dose did not. Our results showed MSCs protect against ischemic injury in a paracrine manner, and suggest that increasing injection frequency is more important than MSC dosage for the treatment CLI.

A Randomized, Open-Label, Multicenter Trial for the Safety and Efficacy of Adult Mesenchymal Stem Cells after Acute Myocardial Infarction

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9%+/-8.5% vs 1.6%+/-7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105)

A Comparison of Two Brands of Clopidogrel in Patients With Drug-Eluting Stent Implantation

BACKGROUND AND OBJECTIVES: Although generic clopidogrel is widely used, clinical efficacy and safety between generic and original clopidogrel had not been well evaluated. The aim of this study was to evaluate the clinical outcomes of 2 oral formulations of clopidogrel 75 mg tablets in patients with coronary artery disease (CAD) undergoing drug-eluting stent (DES) implantation. SUBJECTS AND METHODS: Between July 2006 and February 2009, 428 patients that underwent implantation with DES for CAD and completed >1 year of clinical follow-up were enrolled in this study. Patients were divided into the following 2 groups based on treatment formulation, Platless(R) (test formulation, n=211) or Plavix(R) (reference formulation, n=217). The incidence of 1-year major adverse cardiovascular and cerebrovascular event (MACCE) and stent thrombosis (ST) were retrospectively reviewed. RESULTS: The baseline demographic and procedural characteristics were not significantly different between two treatment groups. The incidence of 1-year MACCEs was 8.5% {19/211, 2 deaths, 4 myocardial infarctions (MIs), 2 strokes, and 11 target vessel revascularizations (TVRs)} in Platless(R) group vs. 7.4% (16/217, 4 deaths, 1 MI, 2 strokes, and 9 TVRs) in Plavix(R) group (p=0.66). The incidence of 1-year ST was 0.5% (1 definite and subacute ST) in Platless(R) group vs. 0% in Plavix(R) group (p=0.49). CONCLUSION: In this study, the 2 tablet preparations of clopidogrel showed similar rates of MACCEs, but additional prospective randomized studies with pharmacodynamics and platelet reactivity are needed to conclude whether generic clopidgrel may replace original clopidogrel.

Concerns on Drug Interactions between Proton Pump Inhibitors and Clopidogrel: Unsafe Perspective / 대한내과학회지

Clopidogrel is a prodrug that is converted in the liver to an active thiol metabolite, which irreversibly inhibits the platelet P2Y12 adenosine diphosphate receptor. This mechanism requires cytochrome P450 2C19 (CYP 2C19) enzyme. Proton pump inhibitors (PPIs) competes against CYP 2C19 and inhibits the conversion of clopidogrel into its active metabolite, therefore, clopidogrel-PPIs drugs interaction may exist. These interactions could result in competitive inhibition decreasing the conversion of the clopidogrel pro-drug to the active metabolite and could potentially translate into an increased risk for cardiovascular events by inadequate platelet P2Y12 receptor inhibition. Many studies including retrospective cohort studies and studies using platelet function tests demonstrated the possible interactions between clopidogrel and PPIs leading to a decrease in the antiplatelet efficacy of clopidogrel and worse cardiovascular clinical outcomes than clopidogrel alone. In contrast, few comparative trials using clinical outcomes found no serious drug interactions between them. In this review, we introduce possible harmful effects of combined use of clopidogrel and PPIs on platelet function. In addition, we suggest how to overcome clopidogrel-PPIs interactions.

Acute Severe Symptomatic Hyponatremia Following Coronary Angiography

Hyponatremia is a relatively common electrolyte disorder. Although severe acute hyponatremia following coronary angiography is rare, potentially lethal neurologic manifestations may result. We describe a patient with severe, symptomatic hyponatremia, an unusual complication of coronary angiography. Lack of familiarity with contrast media-related hyponatremia caused a delay in diagnosis and therapy in our case. The diagnosis of acute hyponatremia should be considered in any patient who develops behavioral or neurologic manifestations following coronary angiography. Prompt diagnosis and treatment is essential to avoid permanent neurologic damage or death.

The Effects of Statin and Niacin on Plaque Stability, Plaque Regression, Inflammation and Oxidative Stress in Patients With Mild to Moderate Coronary Artery Stenosis

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the effects of a combination of niacin and simvastatin to simvastatin alone, on plaque regression and inflammatory makers. SUBJECTS AND METHODS: The study had a prospective, randomized design. Subjects were patients with intermediate coronary artery stenosis. A total of 28 patients received a combination of niacin 1,000 mg plus simvastatin 40 mg (N+S group, n=14); the other group received simvastatin 40 mg alone (S group, n=14). All patients had a baseline and a 9-month follow-up coronary angiogram and an intravascular ultrasound procedure. Parameters such as normalized total atheroma volume (nTAV) and percent atheroma volume (PAV) were analyzed before and after treatment as were inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), Matrix me-talloproteinase-9 (MMP-9) and soluble CD40 ligand (sCD40L). RESULTS: There was no difference in baseline characteristics between the two groups. The nTAV and PAV in the N+S group before and after treatment were not different than those in the S group. But the degree of changes (delta) in nTAV in the N+S group was greater than that in the S group (-21.6+/-10.68 vs. 5.25+/-42.19, respectively, p=0.024). Also, the change in PAV in the NS group was higher than that in the S group (-1.2+/-2.5 vs. -0.6+/-5, respectively, p=0.047. Changes in hs-CRP, MMP-9, and sCD40L in the NS group were significantly greater than those of the S group (-0.71+/-1.25, 73.5+/-64.9, -1,970+/-1,925 vs. -0.32+/-0.96, 62.5+/-30.6, -1,673+/-2,628, respectively). CONCLUSION: The combination of niacin plus simvastatin decreases coronary plaque volume and attenuates the inflammatory response in patients with intermediate coronary artery stenosis.

Cardiovascular Parameters Correlated with Metabolic Syndrome in a Rural Community Cohort of Korea: The ARIRANG Study

Although metabolic syndrome (MetS) is associated with increased cardiovascular mortality and the development of atherosclerosis, consensus is still lacking on the status of cardiovascular function and geometry in MetS patients. We investigated the relation between MetS and left ventricle (LV) geometry and function, carotid intima-media thickness (IMT) and arterial stiffness in a community-based cohort of 702 adult subjects. Subjects were categorized into three groups according to the number of MetS components present, as defined by the Adult Treatment Panel III guidelines: 1) Absent (0 criteria), 2) Pre-MetS (1-2 criteria) or 3) MetS (> or =3 criteria). In female subjects, LV mass, LV mass/height(2.7), deceleration time, and aortic pulse wave velocity increased, and E/A ration decreased in a stepwise manner across the three groups. These changes were not observed in male subjects. The mean carotid IMT was higher in the MetS group than in the other two groups. The degree of MetS clustering is found to be strongly correlated with geometric eccentricity of LV hypertrophy, diastolic dysfunction and arterial changes irrespective of age and blood pressure status, particularly in females. Waist circumference is found to have the most powerful effect on cardiovascular parameters.

The Significance of Clopidogrel Low-Responsiveness on Stent Thrombosis and Cardiac Death Assessed by the Verifynow P2Y12 Assay in Patients With Acute Coronary Syndrome Within 6 Months After Drug-Eluting Stent Implantation

BACKGROUND AND OBJECTIVES: Clopidogrel resistance or low-responsiveness may be associated with recurrent atherothrombotic events after drug-eluting stent (DES) implantation. We prospectively evaluated the association between clopidogrel resistance assessed by the Verifynow(TM) P2Y12 assay (Accumetrics, San Diego, CA, USA) and stent thrombosis (ST) or cardiac death (CD) in patients with acute coronary syndrome (ACS) within 6 months after DES implantation. SUBJECTS AND METHODS: We enrolled 237 consecutive patients (160 males, 65.2+/-10.3 years) with ACS who received a DES implantation. The composite endpoint was defined to CD or ST by Academic Research Consortium definitions within 6 months post-implantation. Clopidogrel resistance was defined as <20% inhibition of the P2Y12 receptor. RESULTS: Baseline demographic characteristics were similar between 142 normal individuals and 95 clopidogrel resistant patients. CD occurred in one case (0.7%) in the normal group and two cases (2.13%) in the resistant group (p=0.344). There was no episode of ST in the normal group and four episodes in the resistant group (4.2%, four definite ST) (p=0.035). Univariate logistic regression revealed an adjusted odds ratio (OR) for composite end point of CD or ST of 9.646 {95% confidence interval (CI) 1.139-81.679}, and multivariate logistic regression for composite end point revealed an OR of 12.074 (95% CI 1.205-120.992). CONCLUSION: Clopidogrel low-responsiveness assessed by the Verifynow(TM) P2Y12 assay is an independent predictor of ST and composite end point of ST or CD in patients with ACS within 6 months after DES implantation.