Altered Gene Expression Pattern in Peripheral Blood Mononuclear Cells in Patients with Acute Myocardial Infarction

Background

Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients.

Methods and Results

Twenty-eight patients with ST-segment elevation myocardial infarction (STEMI) were included. The blood was collected on the 1^st day of myocardial infarction, after 4–6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease, without history of myocardial infarction. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST microarrays and GCS3000 TG system. Lists of genes showing altered expression levels (fold change >1.5, p<0.05) were submitted to Ingenuity Pathway Analysis. Gene lists from each group were examined for canonical pathways and molecular and cellular functions. Comparing acute phase of MI with the same patients after 6 months (stable phase) and with control group we found 24 genes with changed expression. In canonical analysis three pathways were highlighted: signaling of PPAR (peroxisome proliferator-activated receptor), IL-10 and IL-6 (interleukin 10 and 6).

Conclusions

In the acute phase of STEMI, dozens of genes from several pathways linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability show altered expression. Up-regulation of SOCS3 and FAM20 genes in the first days of myocardial infarction is observed in the vast majority of patients.     

Histopathological Features of Aspirated Thrombi after Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction

Background

Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population.

Methodology/Principal Findings

Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (<1 day), lytic (1–5 days), or organized (>5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus.

Conclusions/Significance

Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients.     

Likelihood of Treatment in a Coronary Care Unit for a First-Time Myocardial Infarction in Relation to Sex,Country of Birth and Socioeconomic Position in Sweden

Objective

To examine the relationship between sex, country of birth, level of education as an indicator of socioeconomic position, and the likelihood of treatment in a coronary care unit (CCU) for a first-time myocardial infarction.

Design

Nationwide register based study.

Setting

Sweden.

Patients

199 906 patients (114 387 men and 85,519 women) of all ages who were admitted to hospital for first-time myocardial infarction between 2001 and 2009.

Main outcome measures

Admission to a coronary care unit due to myocardial infarction.

Results

Despite the observed increasing access to coronary care units over time, the proportion of women treated in a coronary care unit was 13% less than for men. As compared with men, the multivariable adjusted odds ratio among women was 0.80 (95% confidence interval 0.77 to 0.82). This lower proportion of women treated in a CCU varied by age and year of diagnosis and country of birth. Overall, there was no evidence of a difference in likelihood of treatment in a coronary care unit between Sweden-born and foreign-born patients. As compared with patients with high education, the adjusted odds ratio among patients with a low level of education was 0.93 (95% confidence interval 0.89 to 0.96).

Conclusions

Foreign-born and Sweden-born first-time myocardial infarction patients had equal opportunity of being treated in a coronary care unit in Sweden; this is in contrast to the situation in many other countries with large immigrant populations. However, the apparent lower rate of coronary care unit admission after first-time myocardial infarction among women and patients with low socioeconomic position warrants further investigation.     

Acute Myocardial Infarction in Sub-Saharan Africa: The Need for Data

Background

Trends in the prevalence of acute myocardial infarction in sub-Saharan Africa have not been well described, despite growing recognition of the increasing burden of cardiovascular disease in low- and middle-income countries. The aim of this systematic review was to describe the prevalence of acute myocardial infarction in sub-Saharan Africa.

Methods

We searched PubMed, EMBASE, Global Health Archive, CINAHL, and Web of Science, and conducted reference and citation analyses. Inclusion criteria were: observational studies, studies that reported incidence or prevalence of acute myocardial infarction, studies conducted in sub-Saharan Africa, and studies that defined acute myocardial infarction by EKG changes or elevation of cardiac biomarkers. Studies conducted prior to 1992 were excluded. Two independent reviewers analyzed titles and abstracts, full-texts, and references and citations. These reviewers also performed quality assessment and data extraction. Quality assessment was conducted with a validated scale for observational studies.

Findings

Of 2292 records retrieved, seven studies met all inclusion criteria. These studies included a total of 92,378 participants from highly heterogeneous study populations in five different countries. Methodological quality assessment demonstrated scores ranging from 3 to 7 points (on an 8-point scale). Prevalence of acute myocardial infarction ranged from 0.1 to 10.4% among the included studies.

Interpretation

There is insufficient population-based data describing the prevalence of acute myocardial infarction in sub-Saharan Africa. Well-designed registries and surveillance studies that capture the broad and diverse population with acute myocardial infarction in sub-Saharan Africa using common diagnostic criteria are critical in order to guide prevention and treatment strategies.

Registration

Registered in International Prospective Register of Systematic Reviews (PROSPERO) Database #CRD42012003161.     

Soluble ST2 and Interleukin-33 Levels in Coronary Artery Disease: Relation to Disease Activity and Adverse Outcome

Objectives

ST2 is a receptor for interleukin (IL)-33. We investigated an association of soluble ST2 (sST2) and IL-33 serum levels with different clinical stages of coronary artery disease. We assessed the predictive value of sST2 and IL-33 in patients with stable angina, non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI).

Methods

We included 373 patients of whom 178 had stable angina, 97 had NSTEMI, and 98 had STEMI. Patients were followed for a mean of 43 months. The control group consisted of 65 individuals without significant stenosis on coronary angiography. Serum levels of sST2 and IL-33 were measured by ELISAs.

Results

sST2 levels were significantly increased in patients with STEMI as compared to patients with NSTEMI and stable angina as well as with controls. IL-33 levels did not differ between the four groups. During follow-up, 37 (10%) patients died and the combined endpoint (all cause death, MI and rehospitalisation for cardiac causes) occurred in 66 (17.6%) patients. sST2 serum levels significantly predicted mortality in the total cohort. When patients were stratified according to their clinical presentation, the highest quintile of sST2 significantly predicted mortality in patients with STEMI, but not with NSTEMI or stable coronary artery disease. sST2 was a significant predictor for the combined endpoint in STEMI patients and in patients with stable angina. Serum levels of IL-33 were not associated with clinical outcome in the total cohort, but the highest quintile of IL-33 predicted mortality in patients with STEMI.

Conclusions

Serum levels of sST2 are increased in patients with acute coronary syndromes as compared to levels in patients with stable coronary artery disease and in individuals without coronary artery disease. sST2 and IL-33 were associated with mortality in patients with STEMI but not in patients with NSTEMI or stable angina.     

Data quality issues impede comparability of hospital treatment delay performance indicators

Aim

To assess the comparability of five performance indicator scores for treatment delay among patients diagnosed with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention in relation to the quality of the underlying data.

Methods

Secondary analyses were performed on data from 1017 patients in seven Dutch hospitals. Data were collected using standardised forms for patients discharged in 2012. Comparability was assessed as the number of occasions the indicator threshold was reached for each hospital.

Results

Hospitals recorded different time points based on different interpretations of the definitions. This led to substantial differences in indicator scores, ranging from 57 to 100 % of the indictor threshold being reached. Some hospitals recorded all the required data elements for calculating the performance indicators but none of the data elements could be retrieved in a fully automated way. Moreover, recording accessibility and completeness of time points varied widely within and between hospitals.

Conclusion

Hospitals use different definitions for treatment delay and vary greatly in the extent to which the necessary data are available, accessible and complete, impeding comparability between hospitals. Indicator developers, users and hospitals providing data should be aware of these issues and aim to improve data quality in order to facilitate comparability of performance indicators.     

Diagnostic and prognostic utility of early measurement with high-sensitivity troponin T assay in patients presenting with chest pain

Background:

High-sensitivity troponin assays are now available for clinical use. We investigated whether early measurement with such an assay is superior to a conventional assay in the evaluation of acute coronary syndromes.

Methods:

Patients presenting to an emergency department with chest pain who did not have ST-segment elevation were prospectively recruited from November 2007 to December 2010. Patients underwent serial testing with a conventional cardiac troponin I assay. Samples were also obtained at presentation and two hours later for measurement of troponin T levels using a high-sensitivity assay. The primary outcome was diagnosis of myocardial infarction on admission; secondary outcomes were death, myocardial infarction and heart failure at one year.

Results:

Of the 939 patients enrolled in the study, 205 (21.8%) had myocardial infarction. By two hours after presentation, the high-sensitivity troponin T assay at the cut-off point of the 99th percentile of the general population (14 ng/L) had a sensitivity of 92.2% (95% confidence interval [CI] 88.1%–95.0%) and a specificity of 79.7% (95% CI 78.6%–80.5%) for the diagnosis of non–ST-segment myocardial infarction. The sensitivity of the assay at presentation was 100% among patients who presented four to six hours after symptom onset. By one year, the high-sensitivity troponin T assay was found to be superior than the conventional assay in predicting death (hazard ratio [HR] 5.4, 95% CI 2.7–10.7) and heart failure (HR 27.8, 95% CI 6.6–116.4), whereas the conventional assay was superior in predicting nonfatal myocardial infarction (HR 4.0, 95% CI 2.4–6.7).

Interpretation:

The high-sensitivity troponin T assay at the cut-off point of the 99th percentile was highly sensitive for the diagnosis of myocardial infarction by two hours after presentation and had prognostic utility beyond that of the conventional assay. To rule out myocardial infarction, the optimal time to test a second sample using the high-sensitivity troponin T level may be four to six hours after symptom onset, but this finding needs verification in future studies before it can become routine practice.For novel cardiac markers to be clinically useful in diagnosing acute coronary syndromes, they need to show their incremental utility beyond that of existing markers, with therapeutic implications designed to improve patient care. Recent improvement in the performance of troponin assays to comply with current guidelines for the diagnosis of acute myocardial infarction¹ has resulted in a new generation of assays with enhanced clinical sensitivity that are now available for use in clinical care. Assays with high sensitivity have been shown to detect myocardial injury earlier^2–8 and identify more patients at risk of future adverse outcomes^8–10 than conventional assays.We conducted a study to assess whether early measurement (at presentation and two hours later) with a high-sensitivity troponin T assay could (a) effectively rule out myocardial infarction without the need for later measurement of troponin levels and (b) identify more patients at risk of adverse cardiac events within one year follow-up compared with a conventional troponin assay.     

Protein Kinase C ε Expression in Platelets from Patients with Acute Myocardial Infarction

Objective

Platelets play crucial roles in the pathophysiology of thrombosis and myocardial infarction. Protein kinase C ε (PKCε) is virtually absent in human platelets and its expression is precisely regulated during human megakaryocytic differentiation. On the basis of what is known on the role of platelet PKCε in other species, we hypothesized that platelets from myocardial infarction patients might ectopically express PKCε with a pathophysiological role in the disease.

Methods and Results

We therefore studied platelet PKCε expression from 24 patients with myocardial infarction, 24 patients with stable coronary artery disease and 24 healthy subjects. Indeed, platelets from myocardial infarction patients expressed PKCε with a significant frequency as compared to both stable coronary artery disease and healthy subjects. PKCε returned negative during patient follow-up. The forced expression of PKCε in normal donor platelets significantly increased their response to adenosine diphosphate-induced activation and adhesion to subendothelial collagen.

Conclusions

Our data suggest that platelet generations produced before the acute event retain PKCε-mRNA that is not down-regulated during terminal megakaryocyte differentiation. Results are discussed in the perspective of peri-infarctual megakaryocytopoiesis as a critical component of myocardial infarction pathophysiology.     

Baseline Q waves as a prognostic modulator in patients with ST-segment elevation: insights from the PLATO trial

Background:

Baseline Q waves may provide additional value compared with time from the onset of symptoms in predicting outcomes for patients with ST-segment elevation. We evaluated whether baseline Q waves superseded time from symptom onset as a prognostic marker of one-year mortality in patients with ST-segment elevation acute coronary syndrome. Our study was derived from data from patients undergoing primary percutaneous coronary intervention within 24 hours in the PLATelet inhibition and patient Outcomes trial

Methods:

Q waves on the baseline electrocardiogram were evaluated by a blinded core laboratory. We assessed the associations between baseline Q waves and time from symptom onset to percutaneous coronary intervention with peak biomarkers, ST-segment resolution on the discharge electrocardiogram, and one-year all-cause and vascular mortality.

Results:

Of 4341 patients with ST-segment elevation, 46% had baseline Q waves. Compared to those without Q waves, those with baseline Q waves were older, more frequently male, had higher heart rates, more advanced Killip class and had a longer time between the onset of symptoms and percutaneous coronary intervention. They also had higher one-year all-cause mortality than patients without baseline Q waves (baseline Q waves: 4.9%; no baseline Q waves: 2.8%; hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.29–2.45, p < 0.001). Complete ST-segment resolution was greatest and all-cause mortality lowest among those with symptom onset three hours or less before percutaneous coronary intervention and no baseline Q waves. After multivariable adjustment, baseline Q waves, but not time from symptom onset, were associated with a significant increase in all-cause mortality (adjusted HR 1.42, 95% CI 1.10–2.01, p = 0.046) and vascular mortality (adjusted HR 1.58, 95% CI 1.09–2.28, p = 0.02).

Interpretation:

The presence of baseline Q waves provides useful additional prognostic insight into the clinical outcome of patients with ST-segment elevation. Clinical Trials.gov registration no. {"type":"clinical-trial","attrs":{"text":"NCT00391872","term_id":"NCT00391872"}}NCT00391872The clinical outcome of patients with ST-segment elevation myocardial infarction (STEMI) is directly related to the extent of myocardial necrosis.¹ Because the extent of necrosis is strongly influenced by the duration of symptoms, time is a key clinical proxy for the stage of evolution of STEMI.² The length of time from the onset of symptoms is important in strategies for triage and management and for gauging prognosis. Although time from the occurrence of epicardial artery occlusion in a laboratory experimental model can be measured precisely, time from the onset of symptoms is often difficult to accurately estimate because of subjectivity and reliance on recall. Thus, establishing a more reliable method for determining the stage of myocardial infarction (MI) evolution in patients with STEMI would be useful for evaluating the potential for myocardial salvage and guiding clinical management.There is evidence that the assessment of Q waves on the baseline electrocardiogram (ECG) in the region of ST-segment elevation may be a useful predictor of left ventricular dysfunction and outcomes in patients with STEMI given streptokinase within four to six hours of the onset of symptoms.^3,4 Because prior studies of the predictive value of baseline Q waves focused on patients receiving fibrinolytic therapy, we extended this question to a large population of patients with STEMI who were at high risk of adverse clinical outcomes (e.g., death, ardiogenic shock and heart failure) and undergoing mechanical reperfusion with percutaneous coronary intervention in the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI)⁵ trial within six hours of symptom onset. A key finding of this study was that Q waves were a key prognostic factor of 90-day mortality and the composite measure of death, cardiogenic shock and heart failure; in addition, Q waves were better than time from symptom onset in predicting these 90-day outcomes.⁶ Whether these findings are applicable to a more general STEMI population studied prospectively is unclear.Given the increasing uptake of therapy for STEMI with primary percutaneous coronary intervention and the continuing challenges in achieving timely reperfusion, we sought to validate these findings in a more contemporary cohort. The PLATelet inhibition and patient Outcomes (PLATO) study not only provided this opportunity in a large population, but it also extended our evaluation to patients with less stringent ST-segment elevation entry criteria (1 mm in two contiguous leads) randomized over a wider entry window (24 h from symptom onset) and followed for a longer period (1 yr).⁷ In the current study, we aimed to prospectively evaluate whether Q waves in the region of qualifying ST-segment elevation on the baseline ECG provided additional value compared with time from symptom onset as a predictor of all-cause mortality in patients with ST-segment elevation undergoing primary percutaneous coronary intervention in the PLATO trial.⁷ We also assessed associations with vascular death, a prespecified component of the primary outcome in the PLATO trial.     

Myocardial Salvage is Reduced in Primary PCI-Treated STEMI Patients with Microvascular Obstruction,Demonstrated by Early and Late CMR

Objectives

This study evaluates the association between microvascular obstruction and myocardial salvage, determined by cardiac magnetic resonance performed both in the acute stage of myocardial infarction and after 4 months.

Methods

In patients with acute ST-elevation myocardial infarction treated by primary percutaneous coronary intervention, myocardial salvage, infarct size, left ventricular volumes, and ejection fraction were assessed by early (1–4 days) and follow-up (4 months) cardiac magnetic resonance. These variables were related to the presence or absence of microvascular obstruction at early investigation. Myocardial salvage was determined by: (1) myocardium at risk and infarct size measured in the acute stage and (2) myocardium at risk, measured acutely, and infarct size measured after 4 months. Multivariate analyses were performed, adjusting for clinical confounders at baseline.

Results

Microvascular obstruction was present in 49 of 94 included patients, (52%). Myocardial salvage was significantly reduced in patients with microvascular obstruction, compared to those without: 23% vs. 38%, measured acutely, and 39.8% vs. 65.4%, after 4 months (p<0.001). The presence of microvascular obstruction was significantly and independently associated with large infarct size, lower left ventricular ejection fraction, and larger left ventricular end-systolic volume.

Conclusion

The presence of microvascular obstruction demonstrated by cardiac magnetic resonance early after infarction was associated with impaired myocardial salvage. This association was more marked when based on measurement of infarct size after 4 months compared to assessment in the acute stage.     

Acute myocardial infarction system of care in the third world

Background

We studied the characteristics of ST-elevation myocardial infarction (STEMI) patients from a local acute coronary syndrome (ACS) registry in order to find and build an appropriate acute myocardial infarction (AMI) system of care in Jakarta, Indonesia.

Methods

Data were collected from the Jakarta Acute Coronary Syndrome (JAC) registry 2008–2009, which contained 2103 ACS patients, including 654 acute STEMI patients admitted to the National Cardiovascular Center Harapan Kita, Jakarta, Indonesia.

Results

The proportion of patients who did not receive reperfusion therapy was 59% in all STEMI patients and the majority of them (52%) came from inter-hospital referral. The time from onset of infarction to hospital admission was more than 12 h in almost 80% cases and 60% had an anterior wall MI. In-hospital mortality was significantly higher in patients who did not receive reperfusion therapy compared with patients receiving acute reperfusion therapy, either with primary percutaneous coronary intervention (PPCI) or fibrinolytic therapy (13.3% vs 5.3% vs 6.2%, p < 0.001).

Conclusion

The Jakarta Cardiovascular Care Unit Network System was built to improve the care of AMI in Jakarta. This network will harmonise the activities of all hospitals in Jakarta and will provide the best cardiovascular services to the community by giving two reperfusion therapy options (PPCI or pharmaco-invasive strategy) depending on the time needed for the patient to reach the cath-lab.     

In-hospital case fatality rates for acute myocardial infarction in Romania

Background

We describe the clinical characteristics, treatments and in-hospital case-fatality rates in an unselected population of patients admitted for acute myocardial infarction.

Methods

From January 2000 to June 2007, we tracked consecutive patients who were admitted to 7 tertiary referral and 21 county hospitals in Romania for medical treatment of ST-segment elevation acute myocardial infarction. These patients were enrolled in the Romanian Registry for ST-segment Elevation Myocardial Infarction. For this prospective study, we collected data on demographic characteristics, cardiovascular risk factors, various aspects of treatment for myocardial infarction, and in-hospital death.

Results

The 9186 patients in the study group had a mean age of 63.8 years. The median time from onset of symptoms to thrombolysis was 230 (interquartile range 120–510) minutes. Of the 9186 patients, 4986 (54.3%) had hypertension, 1974 (21.5%) had diabetes mellitus, 3545 (38.6%) had lipid disorders and 4653 (50.7%) were smokers. The in-hospital mortality rate was 12.7% (1170 deaths). The study group consisted of 2893 women and 6293 men. The women were older than the men and had higher rates of hypertension and diabetes mellitus but were less likely to be smokers. A smaller proportion of women than men presented within 2 hours after onset of symptoms (23.1% v. 34.4%, p < 0.001). Smaller proportions of women received thrombolytics (40.8% v. 53.5%, p < 0.001), anticoagulants (93.4% v. 95.2%; p = 0.001), antiplatelet agents (88.3% v. 91.2%, p < 0.001) and primary percutaneous coronary interventions (1.5% v. 2.2%, p = 0.030). The risk of in-hospital death was greater for women, even after adjustment for confounders (odds ratio 1.33, 95% confidence interval 1.13–1.56; p < 0.001).

Interpretation

The rates of reperfusion therapy for patients with acute myocardial infarction were low, and in-hospital case-fatality rates were high in this study. Excess in-hospital mortality was more pronounced among women.During the past 10 years, the health of people in Eastern Europe and the former Soviet Union has undergone changes very different from the health patterns seen in their Western counterparts. For example, mortality from cardiovascular disease has been decreasing continuously in the United States and many Western European countries, but it has increased or remained unchanged in many of the states of Eastern Europe.¹Analysis of this phenomenon has been hindered by insufficient information. The World Health Organization’s MONICA project for monitoring cardiovascular mortality and risk factors considered only 6 Eastern European countries: Russia, Yugoslavia, Poland, Czechoslovakia, Hungary and the former East Germany.² In geographic terms, Romania is the largest country in southeastern Europe, with a large population and substantial natural resources,³ but in some ways it is a “forgotten country.” Few studies evaluating risks for cardiovascular disease have included Romania. Only 4 trials examining ST-segment elevation myocardial infarction have enrolled patients from Romania,^4–6 and the numbers of patients were too few for reliable subgroup analysis.Our aim was to investigate clinical characteristics, treatments and case fatality rates in an unselected population of patients admitted to hospital in Romania for ST-segment elevation myocardial infarction. In a secondary analysis, we analyzed sex differences in relation to treatment and outcome.     

Time distribution of the onset of chest pain in subjects with acute ST-elevation myocardial infarction: an eight-year, single-center study in China

Objective

The objective of this study was to explore the time distribution patterns of the onset of chest pain in subjects with acute ST-elevation myocardial infarction in a Chinese population.

Methods

A total of 1467 patients with acute ST-elevation myocardial infarction were enrolled from 2003 to 2010. The hourly, daily, monthly, seasonal and day-of-week fluctuations in the prevalence of acute ST-elevation myocardial infarction were analyzed.

Results

A peak was found between the morning hours of 07:31 and 08:30. A second peak was observed between 14:31 and 15:30, and a third peak was found between 23:31 and 00:30 (p<0.001). The monthly maximum was recorded in November and the minimum was in April (p<0.001). The number of daily cases was greatest in autumn and lowest in the spring (p = 0.001). Day-of-the-week variations of ST-elevation acute myocardial infarction were not found, except in patients more than 75-years-old.

Conclusions

Periodic variations in the frequency of ST-elevation acute myocardial infarction in Chinese patients showed significant differences with regard to diurnal, monthly and seasonal patterns. The exact mechanisms underlying these circadian variations require further study.     

C4b-binding protein is present in affected areas of myocardial infarction during the acute inflammatory phase and covers a larger area than C3

Background

During myocardial infarction reduced blood flow in the heart muscle results in cell death. These dying/dead cells have been reported to bind several plasma proteins such as IgM and C-reactive protein (CRP). In the present study we investigated whether fluid-phase complement inhibitor C4b-binding protein (C4BP) would also bind to the infarcted heart tissue.

Methods and Findings

Initial studies using immunohistochemistry on tissue arrays for several cardiovascular disorders indicated that C4BP can be found in heart tissue in several cardiac diseases but that it is most abundantly found in acute myocardial infarction (AMI). This condition was studied in more detail by analyzing the time window and extent of C4BP positivity. The binding of C4BP correlates to the same locations as C3b, a marker known to correlate to the patterns of IgM and CRP staining. Based on criteria that describe the time after infarction we were able to pinpoint that C4BP binding is a relatively early marker of tissue damage in myocardial infarction with a peak of binding between 12 hours and 5 days subsequent to AMI, the phase in which infiltration of neutrophilic granulocytes in the heart is the most extensive.

Conclusions

C4BP, an important fluid-phase inhibitor of the classical and lectin pathway of complement activation binds to jeopardized cardiomyocytes early after AMI and co-localizes to other well known markers such as C3b.     

Changes in clinical profile, treatment, and mortality in patients hospitalised for acute myocardial infarction between 1985 and 2008

Objectives

To quantify the impact of the implementation of treatment modalities into clinical practice since 1985, on outcome of patients with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI).

Methods

All consecutive patients admitted for STEMI or NSTEMI at the Thoraxcenter between 1985 and 2008 were included. Baseline characteristics, pharmacological and invasive treatment modalities, and survival status were collected. The study population was categorised in three groups of patients: those hospitalised between 1985–1990, 1990–2000, and 2000–2008.

Results

We identified 14,434 patients hospitalised for myocardial infarction (MI). Both STEMI and NSTEMI patients were increasingly treated with the current guideline based therapy. In STEMI, at 30 days following admission, cumulative mortality rate decreased from 17% in 1985–1990 to 13% in 1990–2000, and to 6% in 2000–2008. Adjusted 30-day and three-year mortality in the last period was 80% and 68% lower than in 1985, respectively. In NSTEMI, at 30 days following admission, cumulative mortality rate decreased from 6% in 1985–1990 to 4% in 1990–2000, and to 2% in 2000–2008. Adjusted 30-day and three-year mortality in the last period was 78% and 49% lower than in 1985, respectively. For patients admitted between 2000 and 2008, 3 year survival of STEMI and NSTEMI patients was 87% and 88%, respectively.

Conclusions

Our results indicate substantial improvements in acute- and long-term survival in patients hospitalised for MI, related to improved acute- as well as long-term treatment. Early medical evaluation in suspected MI and intensive early hospital treatment both remain warranted in the future.     

Angiographic Lesion Complexity Score and In-Hospital Outcomes after Percutaneous Coronary Intervention

Objective

We devised a percutaneous coronary intervention (PCI) scoring system based on angiographic lesion complexity and assessed its association with in-hospital complications.

Background

Although PCI is finding increasing application in patients with coronary artery disease, lesion complexity can lead to in-hospital complications.

Methods

Data from 3692 PCI patients were scored based on lesion complexity, defined by bifurcation, chronic total occlusion, type C, and left main lesion, along with acute thrombus in the presence of ST-segment elevation myocardial infarction (1 point assigned for each variable).

Results

The patients’ mean age was 67.5 +/- 10.8 years; 79.8% were male. About half of the patients (50.3%) presented with an acute coronary syndrome, and 2218 (60.1%) underwent PCI for at least one complex lesion. The patients in the higher-risk score groups were older (p < 0.001) and had present or previous heart failure (p = 0.02 and p = 0.01, respectively). Higher-risk score groups had significantly higher in-hospital event rates for death, heart failure, and cardiogenic shock (from 0 to 4 risk score; 1.7%, 4.5%, 6.3%, 7.1%, 40%, p < 0.001); bleeding with a hemoglobin decrease of >3.0 g/dL (3.1%, 11.0%, 13.1%, 10.3%, 28.6%, p < 0.001); and postoperative myocardial infarction (1.5%, 3.1%, 3.8%, 3.8%, 10%, p = 0.004), respectively. The association with adverse outcomes persisted after adjustment for known clinical predictors (odds ratio 1.72, p < 0.001).

Conclusion

The complexity score was cumulatively associated with in-hospital mortality and complication rate and could be used for event prediction in PCI patients.     

Association between Exposure to Environmental Tobacco Smoke and Biomarkers of Oxidative Stress Among Patients Hospitalised with Acute Myocardial Infarction

Objective

To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction.

Design

An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction.

Setting

Nine acute hospitals in Scotland.

Participants

Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL) were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL).

Intervention

None.

Main outcome measures

Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA) and oxidised low-density lipoprotein (ox-LDL)) were measured on admission blood samples and adjusted for potential confounders.

Results

After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031) and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001) but not ox-LDL (beta coefficient 2.14, 95% CI −8.94, 13.21, p = 0.703).

Conclusions

Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction.     

Acute Myocardial Infarction and Stress Cardiomyopathy following the Christchurch Earthquakes

Background

Christchurch, New Zealand, was struck by 2 major earthquakes at 4:36am on 4 September 2010, magnitude 7.1 and at 12:51pm on 22 February 2011, magnitude 6.3. Both events caused widespread destruction. Christchurch Hospital was the region''s only acute care hospital. It remained functional following both earthquakes. We were able to examine the effects of the 2 earthquakes on acute cardiac presentations.

Methods

Patients admitted under Cardiology in Christchurch Hospital 3 week prior to and 5 weeks following both earthquakes were analysed, with corresponding control periods in September 2009 and February 2010. Patients were categorised based on diagnosis: ST elevation myocardial infarction, Non ST elevation myocardial infarction, stress cardiomyopathy, unstable angina, stable angina, non cardiac chest pain, arrhythmia and others.

Results

There was a significant increase in overall admissions (p<0.003), ST elevation myocardial infarction (p<0.016), and non cardiac chest pain (p<0.022) in the first 2 weeks following the early morning September earthquake. This pattern was not seen after the early afternoon February earthquake. Instead, there was a very large number of stress cardiomyopathy admissions with 21 cases (95% CI 2.6–6.4) in 4 days. There had been 6 stress cardiomyopathy cases after the first earthquake (95% CI 0.44–2.62). Statistical analysis showed this to be a significant difference between the earthquakes (p<0.05).

Conclusion

The early morning September earthquake triggered a large increase in ST elevation myocardial infarction and a few stress cardiomyopathy cases. The early afternoon February earthquake caused significantly more stress cardiomyopathy. Two major earthquakes occurring at different times of day differed in their effect on acute cardiac events.     

The Impact of SYNTAX Score of Non-Infarct-Related Artery on Long- Term Outcome among Patients with Acute ST Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Objective

We investigated the impact of the severity of stenosis in a non-infarct-related artery (IRA) on the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Methods

Three hundred one consecutive patients (age: 59.7 ± 13.2 years, 85.5% men) underwent primary PCI during 2009–2012. Receiver operating characteristic curve analysis found the optimal cutoff for non-IRA SYNTAX score (SS) to be 2.5. We divided the patients into two groups according to this cutoff value.

Results

By multivariable analysis, non-IRA SS (≥2.5) was an independent predictor of major adverse cardiac events (hazard ratio [HR]: 2.15, 95% confidence interval [CI]: 1.21–3.79, P  =  0.008) and all-cause mortality (HR: 3.49, 95% CI: 1.13–10.8, P  =  0.03). However, the prediction of cardiovascular mortality had only borderline significance (HR: 3.29, 95% CI: 0.90–12.08, P  =  0.07).

Conclusion

STEMI patients treated with primary PCI and moderate to severe non-IRA stenosis (SS ≥2.5) have more subsequent cardiac events. Those populations should be treated with more aggressive preventive and medical management.