Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Reversible versus Persistent Renal Tubular Damage in ST-Segment Myocardial Infarction Patients.

BACKGROUND: Most studies investigated the value of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of renal tubular injury only at a single time point. We investigated the possible utilization of NGAL level dynamics for the identification of different renal injury patterns in ST-elevation myocardial infarction (STEMI) patients. METHODS: Blood samples for plasma NGAL in 132 STEMI patients were drawn immediately before and 24 h following primary coronary intervention. Abnormal elevation of NGAL levels was defined using the cardiac surgery-associated NGAL score with NGAL levels ≥100 ng/mL suggesting renal tubular damage. According to NGAL levels at 0 and 24 h, patients were stratified into 3 groups: no tubular damage (NGAL <100 ng/mL in both exams), reversible tubular damage (NGAL >100 ng/mL at 0 h but <100 ng/mL at 24 h), and persistent tubular damage (NGAL >100 ng/mL at both 0 and 24 h). RESULTS: Mean age was 62 ± 13 years, and 78% were men. Of these patients, 29/132 (22%) demonstrated reversible tubular damage, and 36/132 (27%) persistent tubular damage. Only 13/132 patients (10%) progressed to clinical acute kidney injury during hospitalization, all of whom had persistent tubular injury. In multivariate regression model, symptom duration was independently associated with persistent tubular damage, both as continues variable (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04; p = 0.04) and for symptom duration >360 min (OR 2.66, 95% CI 1.07-6.63; p = 0.03). CONCLUSIONS: Renal tubular damage is common among STEMI patients. Dynamic NGAL measurement may differentiate between reversible and persistent tubular damage. Further trials are needed in order to assess the complex cardiorenal interactions.

Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity after reperfusion therapy in patients with first ST-segment elevation myocardial infarction and normal low-density lipoprotein cholesterol.

BACKGROUND: Statin treatment reduces enhanced cardiac sympathetic nerve activity (CSNA) in patients with heart disease, and reduces adverse cardiac events in patients with coronary artery disease. METHODS: We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients and low-density lipoprotein cholesterol < 120 mg/dL in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Sixty STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients treated with strong statin (n = 30), and those who did not (n = 30). Moreover, echocardiographic left ventricular (LV) parameters were determined, and plasma procollagen type III amino terminal peptide (PIIINP) was also measured before and 3 weeks after treatment. RESULTS: Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the statin group showed significantly lower delayed total defect score and washout rate evaluated by 123I-MIBG scintigraphy (22.4 ± 8.1 vs. 29.6 ± 10.5; P < 0.01, and 30.4 ± 8.9% vs. 40.1 ± 11.4%; P < 0.005, respectively) and higher delayed heart/mediastinum count ratio (2.17 ± 0.38 vs. 1.96 ± 0.30, P < 0.05) compared with the non-statin group. Moreover, the degree of change in LV parameters and PIIINP was more favorable in the statin group than in the non-statin group. CONCLUSIONS: Administration of statin improves CSNA after reperfusion therapy in patients with first STEMI.

Assessment of serum phenylalanine and tyrosine isomers in patients with ST-segment elevation vs non-ST-segment elevation myocardial infarction.

BACKGROUND: Under conditions of oxidative stress, hydroxyl radicals can oxidize phenylalanine (Phe) into various tyrosine (Tyr) isomers (meta-, ortho-, and para-tyrosine; m-, o-, and p-Tyr), depending on the location of the hydroxyl group on the oxidized benzyl ring. This study aimed to compare patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) and the serum levels of Phe and Tyr isomers at the aortic root and distal to the culprit lesion in both groups. METHODS: Forty-four patients participated in the study: 23 with STEMI and 21 with NSTEMI. Arterial blood samples were taken from the aortic root through a guiding catheter and from the culprit vessel segment distal from the primary lesion with an aspiration catheter, during the percutaneous coronary intervention. Serum levels of Phe, p-Tyr, m-Tyr, and o-Tyr were determined using reverse-phase high-performance liquid chromatography. RESULTS: Serum levels of Phe were significantly higher distal to the culprit lesion compared to the aortic root in patients with STEMI. Serum p-Tyr/Phe and m-Tyr/Phe concentration ratios were both lower distal to the culprit lesion than at the aortic root in patients with STEMI. There were no statistically significant differences with respect to changes in serum Phe and Tyr isomers distal to the culprit lesion compared to the aortic root in patients with NSTEMI. CONCLUSION: Our data suggest that changes in serum levels of different Tyr isomers can mediate the effects of oxidative stress during myocardial infarction.

Assessment of Admission Time Cell Blood Count (CBC) Parameters in Predicting Post-primary Percutaneous Coronary Intervention TIMI Frame Count in Patients with ST-segment Elevation Myocardial Infarction.

OBJECTIVES: In this study, we aimed to assess the value of admission time CBC parameters in predicting post-primary PCI corrected TIMI frame count. BACKGROUND: Recent years have witnessed a large series of studies evaluating different laboratory variables to predict no-reflow phenomenon following primary PCI (PPCI) in patients with STEMI. However, a general agreement about the most reliable predictor of the no-reflow phenomenon is challenging and also intriguing. METHODS: The current study concluded 208 consecutive patients who underwent primary PCI for ST-Elevation Myocardial Infarction (STEMI) from January 2014 to February 2016. Blood samples were obtained after taking ECG. Complete blood samples were collected and analyzed within 5 minutes from sampling. Post-PCI corrected Thrombolysis in Myocardial Infarction (TIMI) frame count was determined by one interventional cardiologist blinded to patients' clinical data. The correlation between admission time blood parameters and post-primary PCI corrected TIMI frame count in patients with STEMI were assessed. RESULTS: Corrected TIMI frame count was positively correlated with WBC count (R: 0.18, P-value: <0.01), neutrophil count (R: 0.34, P-value: <0.01), and platelet count (R: 0.23, P-value: <0.01) and negatively correlated with lymphocyte count (R: -0.2, P-value: <0.01). Multiple linear regression results demonstrated that corrected TIMI frame count was positively correlated with neutrophil count (P < 0·001) and platelet count (P < 0·001) and negatively correlated with lymphocyte count (p=0.004). CONCLUSION: High counts of WBC, neutrophil, and platelet and low count of lymphocyte may be predictors of no-reflow in STEMI patients undergoing PPCI. The clinical significance of such predictive parameters becomes clear as we consider the treatment approach in STEMI patients. Appropriate risk stratification leads to better treatment planning and allocation of resources.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(-) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(-) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. RESULTS: Of the study patients, 56 (42%) were NGAL(-)/sCr(-), 58 (44%) NGAL(+)/sCr(-), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(-) patients developed the composite endpoint when compared to NGAL(-)/sCr(-) patients (64 vs. 46%; OR 2.1, [95% CI 1.1-4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. CONCLUSIONS: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

Assessment of the co-relation between 1st set of Troponin I, age, duration of chest pain and LVEF in patients presenting with first stemi and treatment protocol followed.

Coronary heart disease is the cause of 17.1 million deaths per year throughout the world. The rationale of this study was to determine the importance of 1st set of Troponin I in relation to age, duration of chest pain and left ventricular ejection fraction (LVEF) in patients presenting with acute ST elevation myocardial infarction along with the treatment protocol followed in emergency. It was a cross sectional prospective observational study which was conducted at a tertiary care hospital, at the Cardiology department for a period of 12 months. All patients regardless of gender, aged between 30-80 years with co-morbidities were included presenting with acute STEMI. A total of 150 patients were included in this study with a mean age of 61.2±10.3 years out of which males were (71%). Around 61% of the people presented to emergency >12 hours after onset of chest pain. There was non-significant difference in the treatment protocol given to all patients. For statistical analysis SPSS 21 was applied and significant relationship was observed between age, duration of chest pain and LVEF (p value <0.05). It was seen in our population that people older than 50 years tend to present to emergency department late with chest pain symptoms which results in a linear rising relationship with Troponin I and with increasing Troponin I there was significant reduction seen in LVEF.

Pre-hospital risk assessment in suspected non-ST-elevation acute coronary syndrome: A prospective observational study.

BACKGROUND: Pre-hospital risk stratification of non-ST-elevation acute coronary syndrome (NSTE-ACS) by the complete HEART score has not yet been assessed. We investigated whether pre-hospital risk stratification of patients with suspected NSTE-ACS using the HEART score is accurate in predicting major adverse cardiac events (MACE). METHODS: This is a prospective observational study, including 700 patients with suspected NSTE-ACS. Risk stratification was performed by ambulance paramedics, using the HEART score; low risk was defined as HEART score ⩽ 3. Primary endpoint was occurrence of MACE within 45 days after inclusion. Secondary endpoint was myocardial infarction or death. RESULTS: A total of 172 patients (24.6%) were stratified as low risk and 528 patients (75.4%) as intermediate to high risk. Mean age was 53.9 years in the low risk group and 66.7 years in the intermediate to high risk group (p<0.001), 50% were male in the low risk group versus 60% in the intermediate to high risk group (p=0.026). MACE occurred in five patients in the low risk group (2.9%) and in 111 (21.0%) patients at intermediate or high risk (p<0.001). There were no deaths in the low risk group and the occurrence of acute myocardial infarction in this group was 1.2%. In the high risk group six patients died (1.1%) and 76 patients had myocardial infarction (14.4%). CONCLUSIONS: In suspected NSTE-ACS, pre-hospital risk stratification by ambulance paramedics, including troponin measurement, is accurate in differentiating between low and intermediate to high risk. Future studies should investigate whether transportation of low risk patients to a hospital can be avoided, and whether high risk patients benefit from immediate transfer to a hospital with early coronary angiography possibilities.

Complete versus simplified Selvester QRS score for infarct severity assessment in ST-elevation myocardial infarction.

BACKGROUND: Complete and simplified Selvester QRS score have been proposed as valuable clinical tool for estimating myocardial damage in patients with ST-elevation myocardial infarction (STEMI). We sought to comprehensively compare both scoring systems for the prediction of myocardial and microvascular injury assessed by cardiac magnetic resonance (CMR) imaging in patients with acute STEMI. METHODS: In this prospective observational study, 201 revascularized STEMI patients were included. Electrocardiography was conducted at a median of 2 (interquartile range 1-4) days after the index event to evaluate the complete and simplified QRS scores. CMR was performed within 1 week and 4 months thereafter to determine acute and chronic infarct size (IS) as well as microvascular obstruction (MVO). RESULTS: Complete and simplified QRS score showed comparable predictive value for acute (area under the curve (AUC) = 0.64 vs. 0.67) and chronic IS (AUC = 0.63 vs. 0.68) as well as for MVO (AUC = 0.64 vs. 0.66). Peak high sensitivity cardiac troponin T (hs-cTnT) showed an AUC of 0.88 for acute IS and 0.91 for chronic IS, respectively. For the prediction of MVO, peak hs-cTnT represented an AUC of 0.81. CONCLUSIONS: In reperfused STEMI, complete and simplified QRS score displayed comparable value for the prediction of acute and chronic myocardial as well as microvascular damage. However, both QRS scoring systems provided inferior predictive validity, compared to peak hs-cTnT, the clinical reference method for IS estimation.

Assessment of the relationship between preprocedural C-reactive protein/albumin ratio and stent restenosis in patients with ST-segment elevation myocardial infarction.

INTRODUCTION: Stent restenosis remains a clinical challenge for patients with ischemic heart disease, since it is associated with repeated coronary interventions as well as higher hospitalization rates and medical costs. Inflammation plays a significant role. Although an association between stent restenosis, increased C-reactive protein (CRP) and decreased albumin levels has been previously reported, no studies have investigated the ability of the CRP/albumin ratio to predict stent restenosis. METHODS: This retrospective study included 448 patients who had previously undergone primary percutaneous coronary intervention and who were referred for subsequent reintervention due to recurrence of anginal symptoms. The study population was divided into two groups based on whether the patient had developed stent restenosis. They were then stratified into three groups according to their CRP/albumin ratio. RESULTS: Out of 448 patients, stent restenosis was observed in 24.5% (n=110), as determined by coronary angiography. Patients with stent restenosis had a higher CRP/albumin ratio, greater platelet distribution width (PDW), higher CRP levels, and lower levels of both high-density lipoprotein (HDL) cholesterol and serum albumin. The CRP/albumin ratio (OR: 2.289, 95% CI: 1.056-4.959; p=0.036), stent diameter, PDW and HDL cholesterol levels were found to be independent predictors of stent restenosis. A ROC curve comparison demonstrated that the CRP/albumin ratio was a better predictor of restenosis than either albumin and CRP individually, but it was not better than PDW and HDL cholesterol. CONCLUSION: As a novel inflammation-based risk score, the CRP/albumin ratio may be an easily accessible marker for assessment of stent restenosis risk.

Switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction undergoing successful percutaneous coronary intervention in real-world China: Occurrences, reasons, and long-term clinical outcomes.

BACKGROUND: Although switching between ticagrelor and clopidogrel is common in clinical practice, the efficacy and safety of this de-escalation remain controversial. HYPOTHESIS: We assessed the occurrences, reasons, and outcomes of switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing successful primary percutaneous coronary intervention (PCI). METHODS: A total of 653 patients with STEMI were randomly assigned to receive loading dose of ticagrelor or clopidogrel before PCI and then received maintenance dose, respectively, for 12 months follow-up. The primary outcome was major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome included unexpected rehospitalization for angina, coronary revascularization, and stent thrombosis. The safety outcome was bleeding described by the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 602 participants completed the study. The rate of switching from ticagrelor to clopidogrel was 48.6% and the main reason was financial burden. The rate of secondary ischemic events in the de-escalation group was higher than that in the ticagrelor group (15.1% vs 5.6%, P = 0.008), but lower than that in the clopidogrel group (15.1% vs 24.6%, P = 0.03), while there were no significant differences in MACE among the three groups (P = 0.16). De-escalation, ticagrelor, and clopidogrel did not cause significant differences in the rates of major bleeding among the three groups (BARC ≥ 2, P = 0.34). CONCLUSION: Switching from ticagrelor to clopidogrel is very common in patients with STEMI in China. De-escalation might be safe but associated with high risk of ischemic events as compared to ticagrelor.

Antiplatelet Therapy Changes for Patients With Myocardial Infarction With Recurrent Ischemic Events: Insights Into Contemporary Practice From the TRANSLATE-ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) Study.

BACKGROUND: Guidelines recommend P2Y12 inhibitor therapy for 1 year after myocardial infarction (MI), yet little guidance is provided on antiplatelet management for patients with recurrent ischemic events during that year. We describe changes in P2Y12 inhibitor type among patients with recurrent ischemic events in the first year after MI. METHODS AND RESULTS: The TRANSLATE-ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study enrolled 12 365 patients with MI treated with percutaneous coronary intervention. We examined whether P2Y12 inhibitor choice changed among patients with recurrent MI, stent thrombosis, and/or unplanned revascularization during the first year after MI, and modeled factors associated with P2Y12 inhibitor intensification (changing clopidogrel to prasugrel or ticagrelor). In the first year after MI, 1414 patients (11%) had a total of 1740 recurrent ischemic events (771 recurrent MIs, 969 unplanned revascularizations, and 165 stent thromboses). Median time to the first recurrent ischemic event was 154 days (25th-75th percentiles, 55-287 days). Of those with recurrent ischemic events, 101 of 1092 (9.3%) occurring in clopidogrel-treated patients led to P2Y12 inhibitor intensification. Recurrent events involving stent thrombosis or MI were the strongest factors associated with P2Y12 inhibitor intensification, yet only 40% of patients with stent thrombosis and 14% of patients with recurrent MI had P2Y12 inhibitor intensification. Increasing age and longer time from the index MI were associated with lower likelihood for intensification. CONCLUSIONS: Few patients after MI with a recurrent ischemic event who were taking clopidogrel switched to a more potent P2Y12 inhibitor, even after stent thrombosis events. Specific guidance is needed for patients who have recurrent ischemic events, particularly when closely spaced. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503.

Pharmacodynamic Assessment of Platelet Reactivity After a Loading Dose of Prasugrel or Clopidogrel in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Few studies have compared the platelet reactivity of prasugrel and clopidogrel in the acute phase of ST-segment elevation myocardial infarction (STEMI).Methods and Results:Primary percutaneous coronary intervention (PCI) was performed in 78 patients with STEMI within 12 h of onset. Patients were randomly assigned to receive a Japanese standard loading dose of prasugrel 20 mg or clopidogrel 300 mg. Platelet reactivity was serially assessed using the VerifyNow-P2Y12 assay, the results of which were expressed as P2Y12-reaction-units (PRU). PRU values were significantly lower in the prasugrel group (n=38) than in the clopidogrel group (n=40) at 3 h, 24 h, and 14 days after loading (191±101 vs. 271±50, 147±80 vs. 261±57, and 171±67 vs. 221±70, respectively, P<0.05), although the PRU levels at baseline (231±57 vs. 237±58, P=0.65) and 1 h after loading (282±65 vs. 291±62, P=0.54) were similar. As compared with the baseline values, the PRU levels at 1, 3 and 24 h after clopidogrel loading were significantly higher (respectively, P<0.05), whereas only the PRU at 1 h after prasugrel was elevated (P<0.001). CONCLUSIONS: In Japanese patients with STEMI who undergo primary PCI, prasugrel provides stronger platelet inhibition than clopidogrel from 3 h after loading, whereas platelet reactivity remained elevated within 24 h after clopidogrel loading. (Circ J 2016; 80: 2520-2527).

Randomized Comparison of High-Sensitivity Troponin Reporting in Undifferentiated Chest Pain Assessment.

BACKGROUND: High-sensitivity troponin T (hs-TnT) assays promise greater discrimination of evolving myocardial infarction, but the impact of unguided implementation on the effectiveness of care is uncertain. METHODS AND RESULTS: We evaluated the impact of hs-TnT reporting on care and outcome among chest pain patients presenting to 5 emergency departments within a multicenter randomized trial. Patients were allocated to hs-TnT reporting (hs-report) or standard reporting (std-report; Roche Elecys). The primary end point was death and new or recurrent acute coronary syndrome by 12 months. A total of 1937 patients without ST-segment elevation were enrolled between July 2011 and March 2013. The median age was 61 (interquartile range, 48-74) years, and 46.3% were women. During the index hospitalization, 1466 patients (75.7%) had maximal troponin <30 ng/L within 24 hours. Randomization to hs-report format did not alter the admission rate (hs-report: 57.7% versus std-report: 58.0%; P=0.069). There was no difference in angiography (hs-report: 11.9% versus std-report: 10.9%; P=0.479). The hs-reporting did not reduce 12-month death or new/recurrent acute coronary syndrome in the overall population (hs-report: 9.7% versus std-report: 7.2% [hazard ratio, 0.83 (0.57-1.22); P=0.362]). However, among those with troponin levels <30 ng/L, a modest reduction in the primary end point was observed (hs-report: 2.6% versus std-report: 4.4%, [hazard ratio, 0.58; 95% confidence interval, 0.34-0.1.00; P=0.050). CONCLUSIONS: High-sensitivity troponin reporting alone is associated with only modest changes in practice. Clinical effectiveness in the adoption of high-sensitivity troponin may require close coupling with protocols that guide interpretation and care. CLINICAL TRIAL REGISTRATION: URL: http://www.ANZCTR.org.au. Unique identifier: ACTRN12611000879965.

Optimal P2Y12 Inhibitor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Network Meta-Analysis.

OBJECTIVES: The study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI). BACKGROUND: Limited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI. METHODS: Clinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods. RESULTS: A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor. CONCLUSIONS: In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents.