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Item Apamin-Sensitive Calcium-Activated Potassium Currents in Rabbit Ventricles with Chronic Myocardial Infarction(Wiley Online Library, 2013-10-24) Lee, Young Soo; Chang, Po-Cheng; Hsueh, Chia-Hsiang; Maruyama, Mitsunori; Park, Hyung Wook; Rhee, Kyoung-Suk; Hsieh, Yu-Cheng; Shen, Changyu; Weiss, James N.; Chen, Zhenhui; Lin, Shien-Fong; Chen, Peng-Sheng; Department of Medicine, IU School of MedicineIntroduction Apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is increased in heart failure. It is unknown if myocardial infarction (MI) is also associated with an increase of IKAS. Methods and Results We performed Langendorff perfusion and optical mapping in 6 normal hearts and 10 hearts with chronic (5 weeks) MI. An additional 6 normal and 10 MI hearts were used for patch clamp studies. The infarct size was 25% [95% confidence interval, 20 to 31] and the left ventricular ejection fraction was 0.5 [0.46 to 0.54]. The rabbits did not have symptoms of heart failure. The action potential duration measured to 80% repolarization (APD80) in the peri-infarct zone (PZ) was150 [142 to 159] ms, significantly (p=0.01) shorter than in the normal ventricles (158 to 177] ms). The intracellular Ca transient duration was also shorter in the PZ (148 [139 to 157] ms) than in normal ventricles (168 [157 to 180] ms; P=0.017). Apamin prolonged the APD80 in PZ by 9.8 [5.5 to 14.1] %, which is greater than in normal ventricles (2.8 [1.3 to 4.3] %, p=0.006). Significant shortening of APD80 was observed at the cessation of rapid pacing in MI but not in normal ventricles. Apamin prevented postpacing APD80 shortening. Patch clamp studies showed that IKAS was significantly higher in the PZ cells (2.51 [1.55 to 3.47] pA/pF, N=17) than in the normal cells (1.08 [0.36 to 1.80] pA/pF, N=15, p=0.019). Conclusion We conclude that IKAS is increased in MI ventricles and contributes significantly to ventricular repolarization especially during tachycardia.Item The Availability of Prior ECGs Improves Paramedic Accuracy in Recognizing ST-Segment Elevation Myocardial Infarction(Elsevier, 2015-01) O'Donnell, Daniel; Mancera, Mike; Savory, Eric; Christopher, Shawn; Schaffer, Jason; Roumpf, Steve; Department of Emergency Medicine, IU School of MedicineIntroduction Early and accurate identification of ST-elevation myocardial infarction (STEMI) by prehospital providers has been shown to significantly improve door to balloon times and improve patient outcomes. Previous studies have shown that paramedic accuracy in reading 12 lead ECGs can range from 86% to 94%. However, recent studies have demonstrated that accuracy diminishes for the more uncommon STEMI presentations (e.g. lateral). Unlike hospital physicians, paramedics rarely have the ability to review previous ECGs for comparison. Whether or not a prior ECG can improve paramedic accuracy is not known. Study hypothesis The availability of prior ECGs improves paramedic accuracy in ECG interpretation. Methods 130 paramedics were given a single clinical scenario. Then they were randomly assigned 12 computerized prehospital ECGs, 6 with and 6 without an accompanying prior ECG. All ECGs were obtained from a local STEMI registry. For each ECG paramedics were asked to determine whether or not there was a STEMI and to rate their confidence in their interpretation. To determine if the old ECGs improved accuracy we used a mixed effects logistic regression model to calculate p-values between the control and intervention. Results The addition of a previous ECG improved the accuracy of identifying STEMIs from 75.5% to 80.5% (p = 0.015). A previous ECG also increased paramedic confidence in their interpretation (p = 0.011). Conclusions The availability of previous ECGs improves paramedic accuracy and enhances their confidence in interpreting STEMIs. Further studies are needed to evaluate this impact in a clinical setting.Item Blockade of EMAP II protects cardiac function after chronic myocardial infarction by inducing angiogenesis(Elsevier, 2015-02) Yuan, Chujun; Yan, Lin; Solanki, Pallavi; Vatner, Stephen F.; Vatner, Dorothy E.; Schwarz, Margaret A.; Department of Pediatrics, IU School of MedicinePromoting angiogenesis is a key therapeutic target for protection from chronic ischemic cardiac injury. Endothelial-Monocyte-Activating-Polypeptide-II (EMAP II) protein, a tumor-derived cytokine having anti-angiogenic properties in cancer, is markedly elevated following myocardial ischemia. We examined whether neutralization of EMAP II induces angiogenesis and has beneficial effects on myocardial function and structure after chronic myocardial infarction (MI). EMAP II antibody (EMAP II AB), vehicle, or non-specific IgG (IgG) was injected ip at 30 min and 3, 6, and 9 days after permanent coronary artery occlusion in mice. EMAP II AB, compared with vehicle or non-specific antibody, significantly, p<0.05, improved the survival rate after MI, reduced scar size and attenuated the development of heart failure, i.e., left ventricular ejection fraction was significantly higher in EMAP II AB group, fibrosis was reduced by 24%, and importantly, more myocytes were alive in EMAP II AB group in the infarct area. In support of an angiogenic mechanism, capillary density (193/HPF vs. 172/HPF), doubling of the number of proliferating endothelial cells, and angiogenesis related biomarkers were upregulated in mice receiving EMAP II AB treatment as compared to IgG. Furthermore, EMAP II AB prevented EMAP II protein inhibition of in vitro tube formation in HUVECs. We conclude that blockade of EMAP II induces angiogenesis and improves cardiac function following chronic MI, resulting in reduced myocardial fibrosis and scar formation and increased capillary density and preserved viable myocytes in the infarct area.Item Characteristics of ST Elevation Myocardial Infarction Patients Who Do Not Undergo Percutaneous Coronary Intervention After Prehospital Cardiac Catheterization Laboratory Activation(Lippincott, Williams, and Wilkins, 2016-03) Musey, Paul Idun, Jr.; Studnek, Jonathan R.; Garvey, Lee; Department of Emergency Medicine, IU School of MedicineObjectives: To assess the clinical and electrocardiographic characteristics of patients diagnosed with ST elevation myocardial infarction (STEMI) that are associated with an increased likelihood of not undergoing percutaneous coronary intervention (PCI) after prehospital Cardiac Catheterization Laboratory activation in a regional STEMI system. Methods: We performed a retrospective analysis of prehospital Cardiac Catheterization Laboratory activations in Mecklenburg County, North Carolina, between May 2008 and March 2011. Data were extracted from the prehospital patient record, the prehospital electrocardiogram, and the regional STEMI database. The independent variables of interest included objective patient characteristics as well as documented cardiac history and risk factors. Analysis was performed using descriptive statistics and logistic regression. Results: Two hundred thirty-one prehospital activations were included in the analysis. Five independent variables were found to be associated with an increased likelihood of not undergoing PCI: increasing age, bundle branch block, elevated heart rate, left ventricular hypertrophy, and non-white race. The variables with the most significance were any type of bundle branch block [adjusted odds ratios (AOR), 5.66; 95% confidence interval (CI), 1.91–16.76], left ventricular hypertrophy (AOR, 4.63; 95% CI, 2.03–10.53), and non-white race (AOR, 3.53; 95% CI, 1.76–7.08). Conversely, the only variable associated with a higher likelihood of undergoing PCI was the presence of arm pain (AOR, 2.94; 95% CI, 1.36–6.25). Conclusions: Several of the above variables are expected electrocardiogram mimics; however, the decreased rate of PCI in non-white patients highlights an area for investigation and process improvement. This may guide the development of prehospital STEMI protocols, although avoiding false positive and inappropriate activations.Item Comparison of Risk Factor Control in the Year After Discharge for Ischemic Stroke Versus Acute Myocardial Infarction(American Heart Association, 2018-02) Bravata, Dawn M.; Daggy, Joanne; Brosch, Jared; Sico, Jason J.; Baye, Fitsum; Myers, Laura J.; Roumie, Christianne L.; Cheng, Eric; Coffing, Jessica; Arling, Greg; Medicine, School of MedicineBACKGROUND AND PURPOSE: The Veterans Health Administration has engaged in quality improvement to improve vascular risk factor control. We sought to examine blood pressure (<140/90 mm Hg), lipid (LDL [low-density lipoprotein] cholesterol <100 mg/dL), and glycemic control (hemoglobin A1c <9%), in the year post-hospitalization for acute ischemic stroke or acute myocardial infarction (AMI). METHODS: We identified patients who were hospitalized (fiscal year 2011) with ischemic stroke, AMI, congestive heart failure, transient ischemic attack, or pneumonia/chronic obstructive pulmonary disease. The primary analysis compared risk factor control after incident ischemic stroke versus AMI. Facilities were included if they cared for ≥25 ischemic stroke and ≥25 AMI patients. A generalized linear mixed model including patient- and facility-level covariates compared risk factor control across diagnoses. RESULTS: Forty thousand two hundred thirty patients were hospitalized (n=75 facilities): 2127 with incident ischemic stroke and 4169 with incident AMI. Fewer stroke patients achieved blood pressure control than AMI patients (64%; 95% confidence interval, 0.62-0.67 versus 77%; 95% confidence interval, 0.75-0.78; P<0.0001). After adjusting for patient and facility covariates, the odds of blood pressure control were still higher for AMI than ischemic stroke patients (odds ratio, 1.39; 95% confidence interval, 1.21-1.51). There were no statistical differences for AMI versus stroke patients in hyperlipidemia (P=0.534). Among patients with diabetes mellitus, the odds of glycemic control were lower for AMI than ischemic stroke patients (odds ratio, 0.72; 95% confidence interval, 0.54-0.96). CONCLUSIONS: Given that hypertension control is a cornerstone of stroke prevention, interventions to improve poststroke hypertension management are neededItem Optimal Management of Malignant Polyps, From Endoscopic Assessment and Resection to Decisions About Surgery(Elsevier, 2018) Kanuri, Sri H.; Ipe, Joseph; Kassab, Kameel; Gao, Hongyu; Liu, Yunlong; Skaar, Todd C.; Kreutz, Rolf P.; Medicine, School of MedicineBackground: Variation in micro-RNA (miRNA) levels in blood has been associated with alterations of physiological functions of the cardiovascular system. Circulating miRNA have the potential to become reliable biomarkers for risk stratification and early detection of cardiovascular events. Recurrent thrombotic events in patients with established coronary artery disease (CAD) demonstrate the need for personalized approaches to secondary prevention, especially in light of recent novel treatment approaches. Methods: In a single center cohort study, whole blood samples were collected from 437 subjects undergoing cardiac catheterization, who were followed for recurrent cardiovascular events during a mean follow up of 1.5 years. We selected a case cohort (n=22) with recurrent thrombotic events on standard medical therapy (stent thrombosis (n=6) or spontaneous myocardial infarction (MI) (n=16)) and a matched cohort with CAD, but uneventful clinical follow up (n=26), as well as a control group with cardiovascular risk factors, but without angiographic CAD (n=24). We performed complete miRNA next generation sequencing of RNA extracted from whole blood samples (including leukocytes and platelets). Results: Differential pattern of miRNA expression was demonstrated between controls, CAD patients with no events, and CAD patients with recurrent events. MiRNA that have been previously associated with MI, CAD, endothelial function, vascular smooth muscle cells, platelets, angiogenesis, heart failure, cardiac hypertrophy, arrhythmia, and stroke were found variably expressed in our case-control cohorts. Seventy miRNA (FDR <0.05) were linked with risk of recurrent myocardial infarction and future stent thrombosis, as compared to CAD patients with subsequently uneventful follow up. Conclusions: MiRNA next generation sequencing demonstrates altered fingerprint profile of whole blood miRNA expression among subjects with subsequent recurrent thrombotic events on standard medical therapy (‘non-responders’), as compared to subjects with no recurrent cardiovascular events. MiRNA profiling may be useful to identify high risk subjects and provide additional insights into disease mechanisms not currently attenuated with standard medical therapy used in treatment of CAD.Item Simultaneous administration of high-dose atorvastatin and clopidogrel does not interfere with platelet inhibition during percutaneous coronary intervention(Dove Medical Press, 2016) Kreutz, Rolf P.; Breall, Jeffrey A.; Sinha, Anjan; von der Lohe, Elisabeth; Kovacs, Richard J.; Flockhart, David A.; Department of Medicine, IU School of MedicineBACKGROUND: Reloading with high-dose atorvastatin shortly before percutaneous coronary interventions (PCIs) has been proposed as a strategy to reduce periprocedural myonecrosis. There has been a concern that statins that are metabolized by cytochrome P450 3A4 may interfere with clopidogrel metabolism at high doses. The impact of simultaneous administration of high doses of atorvastatin and clopidogrel on the efficacy of platelet inhibition has not been established. METHODS: Subjects (n=60) were randomized to receive atorvastatin 80 mg together with clopidogrel 600 mg loading dose (n=28) versus clopidogrel 600 mg alone (n=32) at the time of PCI. Platelet aggregation was measured at baseline, 4 hours after clopidogrel loading dose, and 16-24 hours after clopidogrel loading dose by light transmittance aggregometry using adenosine diphosphate as agonist. RESULTS: Platelet aggregation was similar at baseline in both the atorvastatin and the control groups (adenosine diphosphate 10 µM: 57%±19% vs 61%±21%; P=0.52). There was no significant difference in platelet aggregation between the atorvastatin and the control groups at 4 hours (37%±18% vs 39%±21%; P=0.72) and 16-24 hours post-clopidogrel loading dose (35%±17% vs 37%±18%; P=0.75). No significant difference in incidence of periprocedural myonecrosis was observed between the atorvastatin and control groups (odds ratio: 1.02; 95% confidence interval 0.37-2.8). CONCLUSION: High-dose atorvastatin given simultaneously with clopidogrel loading dose at the time of PCI does not significantly alter platelet inhibition by clopidogrel. Statin reloading with high doses of atorvastatin at the time of PCI appears to be safe without adverse effects on platelet inhibition by clopidogrel (ClinicalTrials.gov: NCT00979940).Item Slow Conduction through an Arc of Block: A Basis for Arrhythmia Formation Post-Myocardial Infarction(Wiley, 2017) Patterson, Eugene; Scherlag, Benjamin J.; Berbari, Edward J.; Lazzara, Ralph; Department of Engineering Technology, School of Engineering and TechnologyIntroduction The electrophysiologic basis for characteristic rate-dependent, constant-late-coupled (390 + 54 milliseconds) premature ventricular beats (PVBs) present 4–5 days following coronary artery occlusion were examined in 108 anesthetized dogs. Methods and results Fractionated/double potentials were observed in injured zone bipolar and composite electrograms at prolonged sinus cycle lengths (1,296 ± 396 milliseconds). At shorter cycle lengths, conduction of the delayed potential decremented, separating from the initial electrogram by a progressively prolonged isoelectric interval. With sufficient delay of the second potential following an isoelectric interval, a PVB was initiated. Both metastable and stable constant-coupled PVBs were associated with Wenckebach-like patterns of delayed activation following an isoelectric interval. Signal-averaging from the infarct border confirmed the presence of an isoelectric interval preceding the PVBs (N = 15). Pacing from the site of double potential formation accurately reproduced the surface ECG morphology (N = 15) of spontaneous PVBs. Closely-spaced epicardial mapping demonstrated delayed activation across an isoelectric interval representing “an arc of conduction block.” Rate-dependent very slow antegrade conduction through a zone of apparent conduction block (N = 8) produced decremental activation delays until the delay was sufficient to excite epicardium distal to the original “arc of conduction block,” resulting in PVB formation. Conclusion The present experiments demonstrate double potential formation and rate-dependent constant-coupled late PVB formation in infarcted dog hearts. Electrode recordings demonstrate a prolonged isoelectric period preceding PVB formation consistent with very slow conduction (<70 mm/s) across a line of apparent conduction block and may represent a new mechanism of PVB formation following myocardial infarction.Item Stent-Only Versus Adjunctive Balloon Angioplasty Approach for Saphenous Vein Graft Percutaneous Coronary Intervention(American Heart Association, 2020-02-05) Latif, Faisal; Uyeda, Lauren; Edson, Robert; Bhatt, Deepak L.; Goldman, Steven; Holmes, David R.; Rao, Sunil V.; Shunk, Kendrick; Aggarwal, Kul; Uretsky, Barry; Bolad, Islam; Ziada, Khaled; McFalls, Edward; Irimpen, Anand; Truong, Huu Tam; Kinlay, Scott; Papademetriou, Vasilios; Velagaleti, Raghava S.; Rangan, Bavana V.; Mavromatis, Kreton; Shih, Mei-Chiung; Banerjee, Subhash; Brilakis, Emmanouil S.; Medicine, School of MedicineBACKGROUND: Direct stenting without pre-dilation or post-dilation has been advocated for saphenous vein graft percutaneous coronary intervention to decrease the incidence of distal embolization, periprocedural myocardial infarction, and target lesion revascularization. METHODS: We performed a post hoc analysis of patients enrolled in the DIVA (Drug-Eluting Stents Versus Bare Metal Stents in Saphenous Vein Graft Angioplasty; ) prospective, double-blind, randomized controlled trial. Patients were stratified into stent-only and balloon-stent groups. Primary end point was 12-month incidence of target vessel failure (defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization). Secondary end points included all-cause death, stent thrombosis, myocardial infarction, and target lesion revascularization during follow-up. RESULTS: Of the 575 patients included in this substudy, 185 (32%) patients underwent stent-only percutaneous coronary intervention. Patients in the stent-only versus balloon-stent group had similar baseline characteristics and similar incidence of target vessel failure at 12-months (15% versus 19%; hazard ratio, 1.34 [95% CI, 0.86–2.08]; P=0.19). During long-term follow-up (median of 2.7 years), the incidence of definite stent thrombosis (1% versus 5%; hazard ratio, 9.20 [95% CI, 1.23–68.92]; P=0.0085), the composite of definite or probable stent thrombosis (5% versus 11%; hazard ratio, 2.52 [95% CI, 1.23–5.18]; P=0.009), and target vessel myocardial infarction (8% versus 14%; hazard ratio, 1.92 [95% CI, 1.08–3.40]; P=0.023) was lower in the stent-only group. Multivariable analysis showed that a higher number of years since coronary artery bypass grafting and >1 target saphenous vein graft lesions were associated with increased target vessel failure during entire follow-up, while preintervention Thrombolysis in Myocardial Infarction-3 flow was protective. CONCLUSIONS: In patients undergoing percutaneous coronary intervention of de novo saphenous vein graft lesions, there was no difference in target vessel failure at 12 months and long-term follow-up in the stent-only versus the balloon-stent group; however, the incidence of stent thrombosis was lower in the stent-only group, as was target vessel myocardial infarction.Item Subcutaneous nerve activity is more accurate than heart rate variability in estimating cardiac sympathetic tone in ambulatory dogs with myocardial infarction(Elsevier, 2015-07) Chan, Yi-Hsin; Tsai, Wei-Chung; Shen, Changyu; Han, Seongwook; Chen, Lan S.; Lin, Shien-Fong; Chen, Peng-Sheng; Department of Medicine, IU School of MedicineBACKGROUND: We recently reported that subcutaneous nerve activity (SCNA) can be used to estimate sympathetic tone. OBJECTIVE: The purpose of this study was to test the hypothesis that left thoracic SCNA is more accurate than heart rate variability (HRV) in estimating cardiac sympathetic tone in ambulatory dogs with myocardial infarction (MI). METHODS: We used an implanted radiotransmitter to study left stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA), and thoracic SCNA in 9 dogs at baseline and up to 8 weeks after MI. HRV was determined based on time-domain, frequency-domain, and nonlinear analyses. RESULTS: The correlation coefficients between integrated SGNA and SCNA averaged 0.74 (95% confidence interval [CI] 0.41-1.06) at baseline and 0.82 (95% CI, 0.63-1.01) after MI (P <.05 for both). The absolute values of the correlation coefficients were significantly larger than that between SGNA and HRV analysis based on time-domain, frequency-domain, and nonlinear analyses, respectively, at baseline (P <.05 for all) and after MI (P <.05 for all). There was a clear increment of SGNA and SCNA at 2, 4, 6, and 8 weeks after MI, whereas HRV parameters showed no significant changes. Significant circadian variations were noted in SCNA, SGNA, and all HRV parameters at baseline and after MI, respectively. Atrial tachycardia (AT) episodes were invariably preceded by SCNA and SGNA, which were progressively increased from 120th, 90th, 60th, to 30th seconds before AT onset. No such changes of HRV parameters were observed before AT onset. CONCLUSION: SCNA is more accurate than HRV in estimating cardiac sympathetic tone in ambulatory dogs with MI.