Acute Cardiac Ischemia Research Articles

DJ-1 protects against cell death following acute cardiac ischemia–reperfusion injury

Novel therapeutic targets are required to protect the heart against cell death from acute ischemia–reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia–reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1L166P and DJ-1Cys106A mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection.

Angiotensin II receptor antagonists in acute coronary syndromes

It is well known that inappropriate or exaggerated activity of the renin-angiotensin system might contribute to the development of systemic hypertension with consequent organ injury and associated increased risk of acute cardiovascular (CV) diseases. This review will discuss evidence form basic research and clinical studies, investigating the efficacy of angiotensin II receptor blockers (ARBs) in the management of acute coronary syndromes (ACS). This narrative review is based on the material found on MEDLINE and PubMed up to June 2013. We looked for the terms 'angiotensin, AT1 receptor, ACE inhibitors' in combination with 'acute coronary syndromes, acute myocardial infarction, pathophysiology'. Preclinical studies showed relevant protective effects of ARBs to reduce adverse cardiac remodelling in animal models of acute cardiac ischaemia. However, although recommended in Consensus guidelines as a good alternative to angiotensin-converting enzyme inhibitors (ACEIs), clinical studies did not confirm a superior efficacy of the ARBs as compared to ACEIs. As a matter of fact for some authors, these drugs might potentially have deleterious effects increasing the CV risk. Emerging evidence from clinical trials suggests that the use of ARBs in ACS might be controversial, and caution should be used for their clinical use to replace ACEIs in ACS.

An overview on development and application of an experimental platform for quantitative cardiac imaging research in rabbit models of myocardial infarction.

To exploit the advantages of using rabbits for cardiac imaging research and to tackle the technical obstacles, efforts have been made under the framework of a doctoral research program. In this overview article, by cross-referencing the current literature, we summarize how we have developed a preclinical cardiac research platform based on modified models of reperfused myocardial infarction (MI) in rabbits; how the in vivo manifestations of cardiac imaging could be closely matched with those ex vivo macro- and microscopic findings; how these imaging outcomes could be quantitatively analyzed, validated and demonstrated; and how we could apply this cardiac imaging platform to provide possible solutions to certain lingering diagnostic and therapeutic problems in experimental cardiology. In particular, tissue components in acute cardiac ischemia have been stratified and characterized, post-infarct lipomatous metaplasia (LM) as a common but hardly illuminated clinical pathology has been identified in rabbit models, and a necrosis avid tracer as well as an anti-ischemic drug have been successfully assessed for their potential utilities in clinical cardiology. These outcomes may interest the researchers in the related fields and help strengthen translational research in cardiovascular diseases.

Corrected QT Interval During Acute Cardiac Ischemia: A Useful Tool in Future Risk Scores

Corrected QT Interval During Acute Cardiac Ischemia: A Useful Tool in Future Risk Scores

Heat shock 27kDa protein family, member 7 (Hspb7) is implicated in the pathogenesis of cardiomyopathy - emerging evidence for an ischemia-induced Hspb7 gene function

Hspb7 is a member of the small heat shock protein family and is highly expressed in the vertebrate heart. Genome-wide association studies suggest single nucleotide polymorphisms close to the locus of heat shock 27kDa protein family, member 7 (Hspb7) to be involved in the pathogenesis of cardiomyopathy. Furthermore, Hspb7 is suggested as a novel marker of acute cardiac ischemia. Therefore, Hspb7 might have a protective function in cardiovascular disease, especially under hypoxic conditions. Potential mechanisms of action of Hspb7 functions are not sufficiently elucidated to date. To assess the involvement of Hspb7 in the pathogenesis of cardiomyopathy in vivo, we identified the Hspb7 gene in zebrafish and conducted gene-specific knock-down experiments by injecting morpholino (Mo)-modified antisense oligonucleotides into one-cell–stage zebrafish embryos. Mo-splice is designed to block splicing at the exon 2–intron 2 boundary, leading either to inclusion of intron 2 or to skipping of exon 2. Mo-start is directed against the translational start site of Hspb7. Treated embryos develop pericardial edema and 88% of the Mo-splice and 92% of the Mo-start injected zebrafish embryos develop severe heart failure. Contractility and heart rate of Hspb7-Mo-injected embryos are progressively and dose-dependently reduced in contrast to control-injected littermates. Fractional shortening is impaired to 20+4% and heart rate to 52+6 beats per minute (bpm) in treated zebrafish in comparison to 45+3% and 153+2 bpm in control-injected littermates at 72 hours post fertilization, respectively. We found normal development, differentiation and pattering of atrial and ventricular myocytes in Hspb7-injected fish. In addition, transmission electron microscopy of cardiomyocytes revealed a reduced amount of myofibrils, while ultrastructure of the sarcomere is conserved. Interestingly, in contrast to other members of the small heat shock protein family the expression of Hspb7 could not be stimulated by increased temperature suggesting an alternative – for example ischemia-induced – way of induction. To address this question, we exposed zebrafish to cobalt chloride, an established inducer of chemical hypoxia and assessed Hif1 alpha, and Hspb7 mRNA expression by qRT-PCR. Strikingly, while heat shock has no effect, we observe an acute stimulation of Hif1 alpha and Hspb7 mRNA expression by cobalt chloride treatment. Our findings provide evidence for a significant role of Hspb7 gene in the pathogenesis of cardiomyopathy and suggest a novel, ischemia-induced biological function of the Hspb7 gene in vivo.

Taras Shevchenko National University of Kyiv, Ukraine

It was established in experiments on the rats in the acute period of modeling pituitrin-isadrin myocardial infarction the formation of nitrogen monoxide decreases along with its accelerated transformation into peroxynitrite. It was evidenced by more than double inhibition of NO synthase activity in the myocardium and by decreasing the amount of nitrates on the background of the increasing level of peroxynitrites' marker--nitrotyrosine by 246.6% at an average. Experimental therapy of rats by ademol which is a derivate of adamantan (1-adamantiloxy-3-morpholino-2 propanol hydrochloride) better than by corvitin normalizes the processes of synthesis of nitric oxide. At the same time ademol probably exceeded the reference drug in ability to increase NO synthase activity and amount of nitrate, and promoted a decrease of the level of nitrotyrosine in the myocardium on the average by 36.3; 50.6 and 12.7%, respectively. Corrective influence of ademol on indicators of metabolism in NO system under the conditions of acute cardiac ischemia indicates to promicing development of domestic cardioprotector on its base.

Quantitative Video-Oculography to Help Diagnose Stroke in Acute Vertigo and Dizziness

Strokes can be distinguished from benign peripheral causes of acute vestibular syndrome using bedside oculomotor tests (head impulse test, nystagmus, test-of-skew). Using head impulse test, nystagmus, test-of-skew is more sensitive and less costly than early magnetic resonance imaging for stroke diagnosis in acute vestibular syndrome but requires expertise not routinely available in emergency departments. We sought to begin standardizing the head impulse test, nystagmus, test-of-skew diagnostic approach for eventual emergency department use through the novel application of a portable video-oculography device measuring vestibular physiology in real time. This approach is conceptually similar to ECG to diagnose acute cardiac ischemia. Proof-of-concept study (August 2011 to June 2012). We recruited adult emergency department patients with acute vestibular syndrome defined as new, persistent vertigo/dizziness, nystagmus, and (1) nausea/vomiting, (2) head motion intolerance, or (3) new gait unsteadiness. We recorded eye movements, including quantitative horizontal head impulse testing of vestibulo-ocular-reflex function. Two masked vestibular experts rated vestibular findings, which were compared with final radiographic gold-standard diagnoses. Masked neuroimaging raters determined stroke or no stroke using magnetic resonance imaging of the brain with diffusion-weighted imaging obtained 48 hours to 7 days after symptom onset. We enrolled 12 consecutive patients who underwent confirmatory magnetic resonance imaging. Mean age was 61 years (range 30-73), and 10 were men. Expert-rated video-oculography-based head impulse test, nystagmus, test-of-skew examination was 100% accurate (6 strokes, 6 peripheral vestibular). Device-based physiological diagnosis of vertebrobasilar stroke in acute vestibular syndrome should soon be possible. If confirmed in a larger sample, this bedside eye ECG approach could eventually help fulfill a critical need for timely, accurate, efficient diagnosis in emergency department patients with vertigo or dizziness who are at high risk for stroke.

Mechanisms responsible for beneficial and adverse effects of rosiglitazone in a rat model of acute cardiac ischaemia–reperfusion

Despite debate regarding its cardioprotective and pro-arrhythmic effects, the precise mechanisms of action of rosiglitazone on the heart are still unclear. We determined the mechanistic effects of rosiglitazone on cardiac function, arrhythmias and infarct size during cardiac ischaemia-reperfusion. Twenty-six rats were used. In each rat, either rosiglitazone or saline solution was administered intravenously prior to a 30 min left anterior descending coronary artery ligation and a 120 min reperfusion. Cardiac function, infarct size, myocardial levels of connexin43, Bax/Bcl-2, cytochrome c, caspase-3, caspase-8, Akt, tumour necrosis factor-α and interleukin-4 and cardiac mitochondrial function were determined. Isolated cardiomyocytes were used for studying intracellular calcium. Rosiglitazone did not alter cardiac function during the ischaemia-reperfusion periods, but increased the arrhythmia score and mortality rate, decreased the time to onset of ventricular fibrillation and prolonged the Ca2+ decay rate, in comparison to the saline-injected group (P<0.05). However, the infarct size in the rosiglitazone-injected group was reduced (P<0.05). Rosiglitazone decreased the levels of connexin43 phosphorylation, active caspase-8 and tumour necrosis factor-α, but increased the level of procaspase-3. However, levels of Bax/Bcl-2, cytochrome c, Akt and interleukin-4 and the cardiac mitochondrial function were not different between the two groups. Rosiglitazone simultaneously exerted both beneficial and adverse cardiac effects in the heart exposed to ischaemia-reperfusion. Although it decreased the infarct size via the extrinsic anti-apoptotic pathway and anti-inflammatory effects, rosiglitazone facilitated a fatal arrhythmia by decreasing connexin43 phosphorylation and prolonging the Ca2+ decay rate in ischaemia-reperfusion. The higher mortality rate in the rosiglitazone-injected group suggests that its undesirable effect was more pronounced than its benefit on infarct size reduction.

Unstable angina in a young woman with Hodgkin&amp;#8217;s lymphoma

We present the case of a 30 year-old woman - 16 months after successful treatment of Hodgkin's lymphoma (chest location) with chemotherapy (including doxorubicin) and radiotherapy - with recurrent chest pain and dyspnea. In ambulatory event telemetry, she reported nocturnal chest pain with transient ST elevation characteristic for acute cardiac ischemia. Urgent coronary angiography with intravascular ultrasound and virtual histology visualization revealed 70% fibrotic stenosis in the proximal segment of the left anterior descending artery successfully treated with a drug-eluting stent implantation. This case is especially noteworthy because of the short period from initial therapy to the symptomatic coronary artery disease that is entirely unlike the reported mean latency period of several years.

Corrected QT Interval during Acute Cardiac Ischemia: a Useful Tool in Future Risk Scores.

Corrected QT Interval during Acute Cardiac Ischemia: a Useful Tool in Future Risk Scores.

Evolution of Reperfusion Therapies for Acute Brain and Acute Myocardial Ischemia

Early reperfusion is the most effective therapy for both acute brain and cardiac ischemia. However, the cervicocephalic circulatory bed offers more challenges to recanalization interventions. The historical development of reperfusion interventions has not previously been systematically compared. Medline search identified all multi-arm, controlled trials of coronary revascularization for acute myocardial infarction and multicenter trials of cerebral revascularization for acute ischemic stroke reporting angiographic reperfusion rates. Thirty-seven trials of coronary reperfusion enrolled 10 908 patients from 1983 to 2009, and 10 trials of cerebral reperfusion enrolled 1064 patients from 1992 to 2009. Coronary reperfusion trials included 10 of intravenous fibrinolysis alone, 8 combined intravenous fibrinolysis and percutaneous transluminal coronary angioplasty with or without stenting, 3 intra-arterial fibrinolysis, and 16 percutaneous transluminal coronary angioplasty with or without stenting. Cerebral reperfusion trials included 1 of intravenous fibrinolysis alone, 3 intra-arterial fibrinolysis, 3 endovascular device alone, and 3 of endovascular treatment ± intravenous fibrinolysis. In both circulatory beds, endovascular treatments were more efficacious at achieving reperfusion than peripherally administered fibrinolytics. In the coronary bed, rates of achieved reperfusion began at high levels in the 1980s and improved modestly over the subsequent 3 decades. In the cerebral bed, reperfusion rates began at modest levels in the early 1990s and increased more slowly. Most recently, in 2005 to 2009, cardiac reperfusion rates substantially exceeded cerebral, partial reperfusion 86.1% versus 61.1%, complete reperfusion 78.6% versus 23.4%. Reperfusion therapies developed more slowly and remain less effective for cerebral than cardiac ischemia. Further, cerebral circulation-specific technical advances are required for physicians to become as capable at safely restoring blood flow to the ischemic brain as the ischemic heart.

ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation

Treatment of acute cardiac ischemia focuses on reestablishment of blood flow in coronary arteries. However, impaired microvascular perfusion damages peri-infarct tissue, despite arterial patency. Identification of cytokines that induce microvascular dysfunction would provide new targets to limit microvascular damage. Pro-nerve growth factor (NGF), the precursor of NGF, is a well characterized cytokine in the brain induced by injury. ProNGF activates p75 neurotrophin receptor (p75(NTR)) and sortilin receptors to mediate proapoptotic responses. We describe induction of proNGF by cardiomyocytes, and p75(NTR) in human arterioles after fatal myocardial infarction, but not with unrelated pathologies. After mouse cardiac ischemia-reperfusion (I-R) injury, rapid up-regulation of proNGF by cardiomyocytes and p75(NTR) by microvascular pericytes is observed. To identify proNGF actions, we generated a mouse expressing a mutant Ngf allele with impaired processing of proNGF to mature NGF. The proNGF-expressing mouse exhibits cardiac microvascular endothelial activation, a decrease in pericyte process length, and increased vascular permeability, leading to lethal cardiomyopathy in adulthood. Deletion of p75(NTR) in proNGF-expressing mice rescues the phenotype, confirming the importance of p75(NTR)-expressing pericytes in the development of microvascular injury. Furthermore, deficiency in p75(NTR) limits infarct size after I-R. These studies identify novel, nonneuronal actions for proNGF and suggest that proNGF represents a new target to limit microvascular dysfunction.

Abstract 205: The three-throng role of miR-21 in cancer

Abstract MicroRNAs (miRNAs) are short (20-25 nucleotide) RNA molecules, representing one of the largest class of regulatory RNAs. miR-21 is overexpressed in virtually all types of tumor tissues compared to normal noncancerous tissues. Despite the appreciation of miRNA dysregulation, mouse models of cancer have focused on genetic changes in the epithelial tumor cells. Results from several miR-21 transgenic and knockout mouse models show that miR-21-deficiency reduces tumorigenesis and broad miR-21 overexpression leads to pre-B cell lymphoma, yet the underline mechanisms of miR-21 promoting tumorigenesis remain elusive. We used knockout mice to dissect the role of miR-21 in cancer and found three distinct functions for this oncogene. (1) miR-21 is anti-apoptotic; its genetic ablation results in increased apoptotic cell death in a chemical induced skin carcinogenesis model. (2) miR-21 is pro-necrosis; using two pathological necrosis mouse models (acute pancreatitis and cardiac ischemia) and one cell line model, we found loss of miR-21 inhibits necrosis when apoptosis is attenuated naturally or artificially; this suggests that tumor cells with high miR-21 levels would choose necrosis over apoptosis to provoke inflammation, which can provide a fertile environment for tumor growth. (3) We also found a direct role of miR-21 in tumor stroma. During the past decade, epithelial cell-derived solid tumors have increasingly been recognized as organs consisting of parenchyma (tumor cells) and stroma (the surrounding connective, supporting, and inflammatory cells). One such stromal cell is the macrophage and there is a growing body of evidence suggesting that tumor-associated macrophages (TAMs) promote tumor cell proliferation, migration, invasion, angiogenesis, and progression. Plasticity and diversity are hallmarks of macrophages. Two distinct states of polarized activation for macrophages are well-characterized: the classically activated (M1) and the alternatively activated (M2). Differential cytokine production is a key feature of polarized macrophages. The M1 phenotype is typically IL-12high/IL-10low, whereas M2 macrophage is IL-12low/IL-10high. TAMs observed in most human cancers are M2-like. miR-21 upregulates IL-10 through repressing the expression of programmed cell death 4 (PDCD4) that is a negative regulator of IL-10 and down-regulates IL-12 through repressing its α-subunit (IL12A), indicating that its overexpression drives macrophages toward the tumor-promoting M2 phenotype (IL-12low/IL-10high). Our in vitro data suggest that miR-21 deficiency primes macrophages towards the M1 phenotype. Using a syngeneic tumor model, we show that miR-21-null mice bear smaller tumors compared to the wild-type control. Taken together, these data suggest that miR-21's oncogenic role comes from both tumor cells (pro-necrosis and anti-apoptosis) and the stroma, including TAMs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 205. doi:1538-7445.AM2012-205

Study design for the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care (IMMEDIATE) Trial: A double-blind randomized controlled trial of intravenous glucose, insulin, and potassium for acute coronary syndromes in emergency medical services

Experimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris to acute myocardial infarction (AMI), and myocardial infarction size. However, trials of hospital administration of IV GIK to patients with ST-elevation myocardial infarction (STEMI) have generally not shown favorable effects possibly because of the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies. The IMMEDIATE Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK (1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and (2) administered in prehospital emergency medical service settings, rather than later, in hospitals, after emergency department evaluation. The IMMEDIATE Trial was an emergency medical service-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the United States that enrolled 911 participants. Eligible were patients 30 years or older for whom a paramedic performed a 12-lead electrocardiogram to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based acute cardiac ischemia time-insensitive predictive instrument indicated a ≥75% probability of ACS, and/or the thrombolytic predictive instrument indicated the presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately. Prespecified were the primary end point of progression of ACS to infarction and, as major secondary end points, the composite of cardiac arrest or in-hospital mortality, 30-day mortality, and the composite of cardiac arrest, 30-day mortality, or hospitalization for heart failure. Analyses were planned on an intent-to-treat basis, on a modified intent-to-treat group who were confirmed in emergency departments to have ACS, and for participants presenting with STEMI. The IMMEDIATE Trial tested whether GIK, when administered as early as possible in the course of ACS by paramedics using acute cardiac ischemia time-insensitive predictive instrument and thrombolytic predictive instrument decision support, would reduce progression to AMI, mortality, cardiac arrest, and heart failure. It also tested whether it would provide clinical and pathophysiologic information on GIK's biological mechanisms.

Estimating Outcomes of Astronauts with Myocardial Infarction in Exploration Class Space Missions

We estimate likelihood of presenting rhythms and survival to hospital discharge outcome after acute cardiac ischemia with arrhythmia and/or myocardial infarction (AMI) during long-duration space missions (LDSM) using selected terrestrial cohorts in medical literature. Medical scenarios were risk-stratified by coronary artery calcium score (CAC) and Framingham risk factors (FRF). AMI with and without sudden cardiac arrest (SCA) likelihoods and clinically significant rhythm scenarios and associated outcomes in "astronaut-like" cohorts were derived from two prospective trials identified by an evidence-based literature review. Results are presented using an event sequence diagram and event time line. The association of increasing CAC scores and FRF with AMI and SCA outcomes was calculated. Low AMI likelihoods are estimated in individuals with CAC scores of zero or < 100 and a low number of FRF. Survival rate to hospital discharge after out of hospital SCA in a large urban environment study was 5.2%. EMS-witnessed ventricular tachycardia and/or ventricular fibrillation survival rate of 37.5% represents < 1% of all urban out of hospital AMI, and these patients have a high proportion of known ischemic cardiovascular and pulmonary disease "disqualifying for spaceflight." Multiple factors may be expected to delay or defeat rapid access to "chain of survival" resources during LDSM, lowering survival rates below urban levels of 5.2%. Low CAC and FRF reflect lower risk for AMI events. Zero CAC was associated with the lowest risk of AMI after 3.5 yr of follow-up. Quantifiable incidence and outcome characterization suggests AMI in LDSM outcomes will be relatively independent of in-flight medical resources.

An artificial neural network to safely reduce the number of ambulance ECGs transmitted for physician assessment in a system with prehospital detection of ST elevation myocardial infarction

BackgroundPre-hospital electrocardiogram (ECG) transmission to an expert for interpretation and triage reduces time to acute percutaneous coronary intervention (PCI) in patients with ST elevation Myocardial Infarction (STEMI). In order to detect all STEMI patients, the ECG should be transmitted in all cases of suspected acute cardiac ischemia. The aim of this study was to examine the ability of an artificial neural network (ANN) to safely reduce the number of ECGs transmitted by identifying patients without STEMI and patients not needing acute PCI.MethodsFive hundred and sixty ambulance ECGs transmitted to the coronary care unit (CCU) in routine care were prospectively collected. The ECG interpretation by the ANN was compared with the diagnosis (STEMI or not) and the need for an acute PCI (or not) as determined from the Swedish coronary angiography and angioplasty register. The CCU physician's real time ECG interpretation (STEMI or not) and triage decision (acute PCI or not) were registered for comparison.ResultsThe ANN sensitivity, specificity, positive and negative predictive values for STEMI was 95%, 68%, 18% and 99%, respectively, and for a need of acute PCI it was 97%, 68%, 17% and 100%. The area under the ANN's receiver operating characteristics curve for STEMI detection was 0.93 (95% CI 0.89-0.96) and for predicting the need of acute PCI 0.94 (95% CI 0.90-0.97). If ECGs where the ANN did not identify a STEMI or a need of acute PCI were theoretically to be withheld from transmission, the number of ECGs sent to the CCU could have been reduced by 64% without missing any case with STEMI or a need of immediate PCI.ConclusionsOur ANN had an excellent ability to predict STEMI and the need of acute PCI in ambulance ECGs, and has a potential to safely reduce the number of ECG transmitted to the CCU by almost two thirds.

Premature cardiovascular mortality and alcohol consumption before death in Arkhangelsk, Russia: an analysis of a consecutive series of forensic autopsies

High cardiovascular diseases (CVD) mortality among the middle aged is a major cause of reduced life expectancy in Russia, especially among men. Hazardous alcohol consumption is suspected to be a powerful contributing factor. All men (1099) and women (519) aged 30-70 years who died between 1 January 2008 and 31 August 2009 from CVD in the city of Arkhangelsk, north-west Russia, were included. CVD mortality was stratified by age, gender and diagnosis. For the cases diagnosed by forensic pathologists, the blood alcohol concentration (BAC) was determined. The forensic autopsy rate was 72% for men and 62% for women. Age-standardized CVD mortality rate (all age groups) in men was higher than in women. The largest male-female ratio (4.3) was observed in the age group of 50-59 years. Alcoholic and unspecified cardiomyopathies were the most dominant of CVD mortalities in women, and second in men aged <50 years; they accounted for 50 and 25% of deaths, respectively. About one-third of men and women who died from CVD aged <60 years had consumed alcohol shortly before death. This occurred most frequently among the diagnostic groups 'other acute or subacute cardiac ischaemia', 'atherosclerotic heart disease' and 'cardiomyopathies'. Alcohol was more likely to be found at autopsy in men than in women (odds ratio 1.55; 95% confidence interval 1.14-2.10). No difference was found for those who died from myocardial infarction, cerebrovascular diseases and cardiomyopathies. Of the deceased, <1% had a BAC of ≥ 4 g/l. A high proportion of subjects who died from CVD in Arkhangelsk consumed alcohol shortly before death. It was highest among males aged 50-59 years. The largest gender difference in mortality, highest absolute number of premature CVD deaths, and the highest proportion of alcohol-positive autopsies occurred among them. Since associations with alcohol consumption varied considerably between the types of CVD diagnoses, this observation should be taken into account when planning future research. Our study does not provide evidence that cardiovascular deaths are misclassified cases of acute alcohol poisoning.

Prognostic utility of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI)

BackgroundWe sought to evaluate the test characteristics of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) in relation to 30-day major adverse cardiac events (MACE) among patients who presented to the Emergency Department with symptoms suggestive of an acute coronary syndrome. We then examined the test characteristics of various dichotomous ACI-TIPI cut points.MethodsWe prospectively recruited a cohort of Emergency Department (ED) patients with acute chest pain at two urban university hospitals between June and September 2006. Upon enrollment, baseline demographics and cardiac risk factors were collected. An electrocardiogram (ECG) was performed and analyzed with the built-in ACI-TIPI multiple regression model software. An ACI-TIPI probability score was recorded for each patient. Diagnostic test characteristics of ACI-TIPI for MACE (non-ST elevation myocardial infarction (NSTEMI), percutaneous coronary intervention, coronary artery bypass grafting, and all-cause mortality) within 30 days were determined.ResultsOf 144 patients enrolled (mean age 59.1 ± 14.1 years, 59% men), 19 (13%) patients suffered MACE within 30 days. Receiver-operating characteristics (ROC) for ACI-TIPI yielded a c-statistic of 0.69 (95% CI 0.59-0.80, p < 0.01). An ACI-TIPI score of ≥ 20 had 100% sensitivity (95% CI 82-100), 100% negative predictive value (95% CI 86-100), and 21% specificity (14-31%).ConclusionsThese preliminary results suggest that, while ACI-TIPI has limited discriminatory value for MACE overall, a score of < 20 may have 30-day prognostic utility to allow for safe outpatient management in patients with acute chest pain.

In Silico Investigation of Electrically Silent Acute Cardiac Ischemia in the Human Ventricles

Acute cardiac ischemia, which is caused by the occlusion of a coronary artery, often leads to lethal ventricular arrhythmias or heart failure. The early diagnosis of this pathology is based on changes of the electrocardiogram (ECG), i.e., mainly shifts of the ST segment. However, the underlying mechanisms responsible for these shifts are not completely understood. Furthermore, clinical observations indicate that some acute ischemia cases can hardly be detected using standard 12-lead ECG only. Therefore, multiscale computer simulations of cardiac ischemia using realistic models of human ventricles were carried out in this work. For this purpose, the transmembrane voltage distributions in the heart and the corresponding body surface potentials were computed with varying transmural extent of the ischemic region at different ischemia stages. Some of the simulated ischemia cases were " electrically silent," i.e., they could hardly be identified in the 12-lead ECG.

Resolution of an Acute Cardiac Ischemia After the Removal of a Surgical Drain in Mitral and Tricuspid Valve Repair

A 61-year-old woman was admitted to our institution for severe mitral and tricuspid regurgitation. A transesophageal echocardiogram confirmed a posterior (P2) mitral leaflet flail and a severe dilatation of the tricuspid annulus. No coronary artery disease was demonstrated by angiography. She underwent a mitral and tricuspid valve repair, with triangular resection of the mitral posterior leaflet and annuloplasty of the tricuspid valve. As usual we inserted a mediastinal and a retrocardiac drain. The surgical procedure and the first postoperative course were both uneventful. During the morning of the first postoperative day, after the patient’s mobilization in the intensive care unit, the patient was sweating, and nausea, hypotension, electrocardiographic inferior ST elevation and hypokinesia of the inferior wall on echocardiography had developed. The patient was transferred to the catheterization laboratory for an angioFig 1.