Disruption of Circadian Rhythms by Shift Work Exacerbates Reperfusion Injury in Myocardial Infarction

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

In North America, every 25 seconds someone will have a coronary event and every minute someone will die of one.1 ST elevation myocardial infarction (STEMI) is the most dramatic manifestation of coronary artery disease and remains as one of the most important causes of mortality in the industrialized world. Prompt and successful reperfusion therapy (either pharmacologically with use of fibrinolytic therapy or mechanically with primary percutaneous coronary intervention [PCI]) is currently the cornerstone of acute management of STEMI to salvage ischemic myocardium and limit infarct size. Although undoubtedly beneficial, reperfusion of an occluded artery represents “a double-edge sword,”2 because restoration of epicardial coronary flow initiates a series of complex biochemical and molecular phenomena, which will ultimately mitigate myocardial healing. Thus, with reperfusion comes reperfusion injury.3 Article see p 366 Although the concept of cardioprotection (myocardial salvage) was first suggested by Braunwald,4 it was the seminal works of Reimer et al who crystallized the fact that there exists a window of opportunity to act to limit myocardial injury. They postulated that a “wavefront phenomenon” of cardiac necrosis, if left unchecked, would extend the infarct from the subendocardial region to the subepicardial region by using canine models of transiently or permanently occluded coronary arteries.5 Thereafter, over the course of 3 decades, mixed and disappointing results have plagued both experimental and clinical attempts to limit the deleterious effects of early reperfusion through either pharmacological (adenosine, calcium channel blockers, Na+/H+ exchange inhibitors, KATP channel openers, and glucose-insulin-potassium infusion) or nonpharmacological (therapeutic hypothermia) means.3,6 The reasons for such inconsistent findings in cardioprotection are multifold. First, reperfusion injury encompasses numerous, overlapping mediators of cardiomyocyte death from oxidative stress and Ca2+ overload to alterations in cellular pH, as well as an inflammatory process with a central …

<i>Circulation: Cardiovascular Imaging</i> Editors’ Picks

BackgroundSouth Asians have a higher overall incidence rate and younger age of onset for acute myocardial infarction (AMI) compared to Western populations. However, limited information is available on the association of preventable risk factors and outcomes of AMI among young individuals in Bangladesh. The aim of this study was to determine the risk factors and in-hospital outcome of AMI among young (age ≤40 years) adults in Bangladesh.MethodsWe conducted a prospective observational study among consecutive 50 patients aged ≤40 years and 50 patients aged >40 years with acute ST Segment Elevation Myocardial Infarction (STEMI) and followed-up in-hospital at the National Institute of Cardiovascular Diseases (NICVD). Clinical characteristics, biochemical findings, diet, echocardiography and in-hospital outcomes were compared between the two groups. Multivariate logistic regression was performed to assess the association between risk factors and in-hospital outcome in young patients adjusting for other confounding variables.ResultsThe mean age of the young and older patient groups was 36.5 ± 4.6 years and 57.0 ± 9.1 years respectively. Male sex (OR 3.4, 95 % CI 1.2 − 9.75), smoking (OR 2.4, 95 % CI 1.04 − 5,62), family history of MI (OR 2.4, 95 % CI 1.11 − 5,54), homocysteine (OR 1.2, 95 % CI 1.08 − 1.36), eating rice ≥2 times daily (OR 3.5, 95 % CI 1.15 − 10.6) and eating beef (OR 4.5, 95 % CI 1.83 − 11.3) were significantly associated with the risk of AMI in the young group compared to older group. In multivariate analysis, older patients had significantly greater chance of developing heart failure (OR 7.5, 95 % CI 1.51 to 37.31), re-infarction (OR 7.0, 95 % CI 1.08 − 45.72), arrhythmia (OR 15.3, 95 % CI 2.69 − 87.77) and cardiogenic shock (OR 69.0, 95 % CI 5.81 − 85.52) than the younger group.ConclusionYounger AMI patients have a different risk profile and better in-hospital outcomes compared to the older patients. Control of preventable risk factors such as smoking, unhealthy diet, obesity and dyslipidemia should be reinforced at an early age in Bangladesh.

Ischemia–reperfusion injury is still a big hurdle to overcome for treatment of acute myocardial infarction

A 52-year-old obese male without a prior history of diabetes mellitus (DM) presented with angina and an anterior ST-segment–elevation myocardial infarction (STEMI). Physical examination and chest x-ray were consistent with congestive heart failure. Admission glucose was 230 mg/dL. Coronary angiography revealed an occluded left anterior descending coronary artery, and stenting reestablished TIMI grade 2 flow in that artery within 90 minutes of symptom onset. Left ventricular ejection fraction was 35% with severe anterior hypokinesis. Peak creatine kinase was 600 IU. The next day, fasting glucose was 180 mg/dL. An echocardiogram performed 6 weeks after discharge revealed an ejection fraction of 35% without change in the anterior wall motion. Fasting glucose as an outpatient was 156 mg/dL. The scenario described above is commonly encountered and illustrates how hyperglycemia can affect the outcome of patients with STEMI. Hyperglycemia could have affected the following features of this case: (1) Congestive heart failure was present despite only modest myocardial injury by creatine kinase level; (2) despite successful percutaneous coronary intervention, subnormal coronary perfusion was observed; and (3) left ventricular recovery after STEMI did not occur. Cardiologists need to be cognizant of the hazards associated with hyperglycemia in this setting because these patients will be encountered more frequently as a result of the increasing prevalence of insulin resistance syndromes. Acute hyperglycemia is common in patients with STEMI even in the absence of a history of type 2 DM. Hyperglycemia is encountered in up to 50% of all STEMI patients, whereas previously diagnosed DM is present in only 20% to 25% of STEMI patients.1 The prevalence of type 2 DM or impaired glucose tolerance may be as high as 65% in MI patients without prior DM when oral glucose tolerance testing is performed.2 Elevated …

The mechanisms underlying rupture of a coronary atherosclerotic plaque and development of myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI) remain unresolved. Increased arginase 1 activity leads to reduced nitric oxide (NO) production and increased formation of reactive oxygen species due to uncoupling of the NO-producing enzyme endothelial NO synthase (eNOS). This contributes to endothelial dysfunction, plaque instability and increased susceptibility to ischemia-reperfusion injury in acute myocardial infarction. The purpose of this study was to test the hypothesis that arginase gene and protein expression are upregulated in patients with STEMI. Two cohorts of patients with STEMI were included. In the first cohort (n = 51), expression of arginase and NO-synthases as well as arginase 1 protein levels were determined and compared to a healthy control group (n = 45). In a second cohort (n = 68), plasma arginase 1 levels and infarct size were determined using cardiac magnetic resonance imaging. Expression of the gene encoding arginase 1 was significantly elevated at admission and 24-48 h after STEMI but not 3 months post STEMI, in comparison with the control group. Expression of the genes encoding arginase 2 and endothelial NO synthase (NOS3) were unaltered. Arginase 1 protein levels were elevated at admission, 24 h post STEMI and remained elevated for up to 6 months. No significant correlation between plasma arginase 1 protein levels and infarct size was observed. The markedly increased gene and protein expression of arginase 1 already at admission indicates a role of arginase 1 in the development of STEMI.

BackgroundCurrent cardiovascular magnetic resonance (CMR) methods, such as late gadolinium enhancement (LGE) and oedema imaging (T2W) used to depict myocardial ischemia, have limitations. Novel quantitative T1-mapping techniques have the potential to further characterize the components of ischemic injury. In patients with myocardial infarction (MI) we sought to investigate whether state-of the art pre-contrast T1-mapping (1) detects acute myocardial injury, (2) allows for quantification of the severity of damage when compared to standard techniques such as LGE and T2W, and (3) has the ability to predict long term functional recovery.Methods3T CMR including T2W, T1-mapping and LGE was performed in 41 patients [of these, 78% were ST elevation MI (STEMI)] with acute MI at 12-48 hour after chest pain onset and at 6 months (6M). Patients with STEMI underwent primary PCI prior to CMR. Assessment of acute regional wall motion abnormalities, acute segmental damaged fraction by T2W and LGE and mean segmental T1 values was performed on matching short axis slices. LGE and improvement in regional wall motion at 6M were also obtained.ResultsWe found that the variability of T1 measurements was significantly lower compared to T2W and that, while the diagnostic performance of acute T1-mapping for detecting myocardial injury was at least as good as that of T2W-CMR in STEMI patients, it was superior to T2W imaging in NSTEMI. There was a significant relationship between the segmental damaged fraction assessed by either by LGE or T2W, and mean segmental T1 values (P < 0.01). The index of salvaged myocardium derived by acute T1-mapping and 6M LGE was not different to the one derived from T2W (P = 0.88). Furthermore, the likelihood of improvement of segmental function at 6M decreased progressively as acute T1 values increased (P < 0.0004).ConclusionsIn acute MI, pre-contrast T1-mapping allows assessment of the extent of myocardial damage. T1-mapping might become an important complementary technique to LGE and T2W for identification of reversible myocardial injury and prediction of functional recovery in acute MI.

Background The mechanisms underlying rupture of a coronary atherosclerotic plaque and development of myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI) remain unknown. Increased arginase-1 activity leads to reduced nitric oxide production and increased formation of reactive oxygen species due to uncoupling of the endothelial nitric oxide synthase (eNOS). These events lead to endothelial dysfunction, plaque instability and increased susceptibility to ischemia-reperfusion injury in acute myocardial infarction. Experimental studies have shown that arginase-1 expression and activity are increased in atherosclerosis and during myocardial ischemia-reperfusion. Accordingly, inhibition of arginase-1 reduces atherosclerotic lesion development and limits the extent of infarct size during ischemia-reperfusion via an eNOS-dependent mechanism. Furthermore, arginase-1 inhibition improves endothelial function in patients with coronary artery disease but the potential role of arginase-1 in patients with STEMI is poorly understood. Purpose The purpose of the current study was to test the hypothesis that arginase-1 is upregulated and correlate to infarct size in STEMI patients. Methods and results Two independent cohorts of STEMI patients were included. In cohort 1, plasma and buffy coat leukocytes were collected from 53 STEMI patients at the time of arterial puncture for percutaneous coronary intervention, at 24–48 hours post STEMI and at 3 months post STEMI. Gene expression in leukocytes was determined in 51 patients with Affymetrix Human Transcriptome Array 2.0. In cohort 2, plasma was collected from 82 STEMI patients at admission and at 6 months for determination of plasma arginase-1. These patients underwent cardiac magnetic resonance imaging performed at day 4–7 and at 6 months post STEMI. Plasma arginase-1 levels were quantified with ELISA. Control blood samples were collected from 56 healthy age matched subjects. In cohort 1, ARG1 gene expression was four-fold higher in STEMI patients at admission compared to controls (Figure A). This expression returned to control levels within 3 months. Plasma arginase-1 levels were two times higher in STEMI patients at admission compared to controls, and remained elevated at 24–48 hours and at 3 months post STEMI (Figure B). The increase in plasma arginase-1 in STEMI patients was confirmed in cohort 2 (Figure C). Arginase-1 levels did not correlate with infarct size. Conclusions STEMI patients demonstrate increased gene expression and plasma levels of arginase-1 in the acute setting. In contrast to gene expression plasma arginase-1 levels remain significantly elevated over time. The markedly increased expression of arginase-1 already at admission may suggest a mechanistic role of arginase-1 in the development of STEMI. Further studies are needed to elucidate whether increased expression, induction and activity of arginase-1 are contributing factors for the development of STEMI.

Summary Novel CMR techniques are needed to assess reversible myocardial injury in acute MI. Our results show that pre-contrast T1 mapping CMR could be such a technique: increasingly higher T1 values are associated with larger extent of acute myocardial injury and with reduced functional recovery at 6 months. Background Cardiovascular magnetic resonance (CMR) techniques such as late gadolinium enhancement (LGE) and edema imaging (T2W) are used to delineate acute myocardial infarction (MI). However, the use of LGE and T2W to assess reversible injury acutely is challenged by the dynamic changes occurring in the myocardial tissue. T1mapping is a novel technique that provides voxel-wise quantitative information on the regional tissue state and therefore can characterize in detail the various components of ischemic injury. In acute MI patients, we sought to investigate whether pre-contrast T1-mapping11 (1) detects acute myocardial injury, (2) allows for quantification of the severity of damage when compared to standard techniques such as LGE and T2W, and (3) has the ability to predict long term functional recovery. Methods 3T CMR including T2W, T1 mapping and LGE was performed in patients with acute MI at 12-48 hour after chest pain onset and at 6 months. Patients with ST elevation MI (STEMI) underwent primary PCI prior to CMR. Assessment of acute regional wall motion abnormalities, acute segmental damaged fraction by T2W and LGE and mean segmental T1 values was performed on matching short axis slices. LGE and improvement in regional wall motion at 6M were also obtained.

"Goldilocks" Approach to Deferred Stenting in ST-Segment-Elevation Myocardial Infarction.

Acute myocardial infarction (AMI) is one of the most important perioperative complications of total knee arthroplasty (TKA). Although risk-stratification tools exist for the prediction of cardiac complications including AMI after noncardiac surgery, such stratification does not differentiate the patients with a coronary stent alone, AMI without a stent, or AMI with a stent. The risk of postoperative AMI in these patient groups may vary. Several studies have recommended suitable times for noncardiac surgery in patients with a coronary stent; however, they do not differentiate between the patients with AMI and no AMI. The suitable time of noncardiac surgery for patients with AMI and stent may vary from those with a stent alone. Moreover, a study to evaluate the risk of AMI within 1 year in an Asian population with a history of AMI or coronary stent who underwent TKA has not been reported. (1) What are the risks of AMI within 1 year of TKA in patients who have had a stent alone, AMI without a stent, or AMI with a stent as compared with patients without an AMI/stent? (2) For patients with AMI/stent placement, when can TKA be performed where the risk of subsequent AMI normalizes? (3) What comorbidities are associated with post-TKA AMI? (4) Is the risk of AMI within 1 year after surgery in patients undergoing TKA without a history of AMI/stent higher than that in patients with no surgery? This study is a retrospective study of the medical claim records of 128,216 patients who underwent TKA between 1997 and 2010 in Taiwan. The records were retrieved from the research database of the Bureau of National Health Insurance in Taiwan, which maintains the records of 99.68% of the Taiwan population. The patients who had a history of AMI or coronary stent placement within the year before TKA were compared with the patients who had not experienced AMI or stent placement before TKA. The control subjects were matched according to sex, age, Charlson score, and year of surgery. There were 2413 patients in each group. The patients with a history of AMI or stent placement and the timing of TKA after coronary event were further stratified as with a coronary stent alone, AMI without a stent, and AMI with a stent. The effects of the comorbidities of renal failure, diabetes, liver failure, and hypertension were also analyzed individually. The risk of AMI within 1 year after TKA was investigated using bivariate analysis and the Cox proportional hazard model. To compare the risk of AMI within 1 year of surgery in the patients with a history of TKA and no AMI/stent with the population without a history of surgery, a similar bivariate analysis and the Cox proportional hazard model were applied to their matched case and control groups, each containing 110,980 patients. In the adjusted model, using no AMI/stent before TKA as a reference, patients having undergone AMI + stent had the highest risk (hazard ratio [HR], 5.23; 95% confidence interval [CI], 1.81-15.14; p = 0.002), AMI alone without a stent had less risk (HR, 4.88; 95% CI, 1.49-16.01; p = 0.009), and stent alone with AMI had the lowest risk (HR, 3.16; 95% CI, 1.29-7.71; p = 0.012). In all patients, risk of AMI after TKA was not different than reference values after 1 year of initial AMI or stent (stent: HR, 1.67; 95% CI, 0.71-3.94; p = 0.239; AMI: HR, 1.88; 95% CI, 0.42-8.49; p = 0.412; AMI + stent: HR, 1.91; 95% CI, 0.53-6.89; p = 0.321). The risk of post-TKA AMI was elevated within 1 year of the previous episode of AMI/stent (0-180 days: HR, 8.42; 95% CI, 3.03-23.41; p < 0.001; 181-365 days: HR, 7.52; 95% CI, 2.47-22.88; p < 0.001). Only chronic renal failure under hemodialysis was associated with increased risk of AMI within 1 year of TKA (adjusted HR, 4.34; 95% CI, 1.22-15.43; p = 0.023). Patients undergoing TKA with no history of AMI/stent had a lower risk of AMI within 1 year of TKA compared with the patients with no history of surgery (adjusted HR, 0.92; 95% CI, 0.86-0.99; p = 0.016). This study found the risk of post-TKA AMI remains high within 1 year in patients with a history of AMI/stent. It is recommended that an elective TKA should be performed at least 1 year after an episode of AMI or stent placement. Stents do not provide protection against post-TKA AMI within 6 months of the AMI and patients with AMI + stent have a higher risk of AMI than those with only AMI. Patients of AMI/stent on hemodialysis have a very high risk of post-TKA AMI. However, the risk of AMI is lower in post-TKA patients compared with those with no TKA. Level III, prognostic study.

Cardiovascular magnetic resonance (CMR) imaging uniquely characterizes myocardial and microvascular injury in acute myocardial infarction (AMI), providing powerful surrogate markers of outcomes. The last 10 years have seen an exponential increase in AMI studies utilizing CMR based endpoints. This article provides a contemporary, comprehensive review of the powerful role of CMR imaging in the assessment of outcomes in AMI. The theory, assessment techniques, chronology, importance in predicting left ventricular function and remodelling, and prognostic value of each CMR surrogate marker is described in detail. Major studies illustrating the importance of the markers are summarized, providing an up to date review of the literature base in CMR imaging in AMI.

Objective To explore the relationship between plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and the location and prognosis of acute ST-segment elevation myocardial infarction (STEMI) in elderly people. Methods From May 2012 to April 2014, the 137 elderly patients (aged≥60 years) with acute STEMI within 24 h after symptoms onset admitted in cardiovascular department of Ningbo First Hospital were selected as acute myocardial infarction group (AMI group), and 40 elderly healthy people (age≥60 years) as control group. The plasma NT-proBNP levels were detected by enzyme linked immunosorbent assay(ELISA), and compared between the two groups. The patients in AMI group were classified into four subgroups: anterior AMI group (A group, n=44), anterolateral AMI group (B group, n=21), anterior septal AMI group (C group, n=18) and inferior AMI group (D group, n=54), and the changes of plasma NT-proBNP levels in different infarction location were explored. Meanwhile, all patients were followed up for 30 days and 1 year to observe major adverse cardiac events (MACEs) and mortality rate, then to explore the relationship between plasma NT-proBNP level and prognosis in elderly people with STEMI. Results The plasma NT-proBNP levels were significantly higher in AMI group than in control group 〔(1 406.2±1 322.5)ng/L vs. (63.7±18.5) ng/L, P 0.05), and the plasma NT-proBNP levels were higher in MACE group than in non-MACE group (P<0.05). Conclusions In elderly STEMI patients, there is a correlation between plasma NT-proBNP levels and infarct location, with the highest NT-proBNP level in anterior AMI. The plasma NT-proBNP level could predict MACE. Key words: Acute Myocardial infarction; Natriuretic plasma, brain; Prognosis

Reperfusion injury is an important limiting factor associated with revascularization in acute myocardial infarction (AMI). Various therapies have been tried in an attempt to prevent reperfusion injury, but the search has been elusive. The role of cyclosporine A (CsA) in the prevention of reperfusion injury in AMI is still not clear. The objective of this study was to find out whether CsA is beneficial in reducing reperfusion injury in acute ST elevation myocardial infarction. We performed a systematic search of Pubmed, Scopus, clinicaltrial.gov, and Cochrane Database for randomized control trials (RCT) measuring the effect of CsA in AMI compared to a placebo. The Mantel-Haenszel method and random effect model were used to analyze the data. A total of 1,566 patients (776 in the CsA group and 790 in the placebo group), who participated in 5 RCTs were included in our meta-analysis. We did not find any significant differences between the CsA and placebo groups in terms of all-cause death (odds ratio [OR] 1.21, 95% confidence interval [CI] 0.78-1.87) and cardiovascular death (OR 1.05, 95% CI 0.66-2.49). Similarly, we did not find any significant differences in terms of cardiogenic shock, recurrent ischemia and myocardial infarction, heart failure and echocardiographic outcomes. Cyclosporine A is not helpful in preventing reperfusion injury in AMI.