Autonomic and cardiovascular effects of acute high altitude exposure after myocardial infarction and in normal volunteers

High sympathetic tone creates a significant risk for ventricular arrhythmias and sudden death, which can especially affect patients after a myocardial infarction (MI) when exercising in a hypoxic environment.

Long-term outcomes of biodegradable versus durable polymer drug-eluting stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of individual patient data from three randomised trials

Aims: Arterial plaque rupture and thrombus characterise ST-elevation myocardial infarction (STEMI) and may aggravate delayed arterial healing following durable polymer drug-eluting stent (DP-DES) implantation. Biodegradable polymer (BP) may improve biocompatibility. We compared long-term outcomes in STEMI patients receiving BP-DES vs. durable polymer sirolimus-eluting stents (DP-SES). Methods and results: We pooled individual patient-level data from three randomised clinical trials (ISAR-TEST-3, ISAR-TEST-4 and LEADERS) comparing outcomes from BP-DES with DP-SES at four years. The primary endpoint (MACE) comprised cardiac death, MI, or target lesion revascularisation (TLR). Secondary endpoints were TLR, cardiac death or MI, and definite or probable stent thrombosis. Of 497 patients with STEMI, 291 received BP-DES and 206 DP-SES. At four years, MACE was significantly reduced following treatment with BP-DES (hazard ratio [HR] 0.59, 95% CI: 0.39-0.90; p=0.01) driven by reduced TLR (HR 0.54, 95% CI: 0.30-0.98; p=0.04). Trends towards reduction were seen for cardiac death or MI (HR 0.63, 95% CI: 0.37-1.05; p=0.07) and definite or probable stent thrombosis (3.6% vs. 7.1%; HR 0.49, 95% CI: 0.22-1.11; p=0.09). Conclusions: In STEMI, BP-DES demonstrated superior clinical outcomes to DP-SES at four years. Trends towards reduced cardiac death or myocardial infarction and reduced stent thrombosis require corroboration in specifically powered trials.

Arterial healing following primary PCI using the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) versus the durable polymer everolimus-eluting metallic stent (XIENCE) in patients with acute ST-elevation myocardial infarction: rationale and design of the randomised TROFI II study

AIMS The Absorb bioresorbable vascular scaffold (Absorb BVS) provides similar clinical outcomes compared with a durable polymer-based everolimus-eluting metallic stent (EES) in stable coronary artery disease patients. ST-elevation myocardial infarction (STEMI) lesions have been associated with delayed arterial healing and impaired stent-related outcomes. The purpose of the present study is to compare directly the arterial healing response, angiographic efficacy and clinical outcomes between the Absorb BVS and metallic EES. METHODS AND RESULTS A total of 191 patients with acute STEMI were randomly allocated to treatment with the Absorb BVS or a metallic EES 1:1. The primary endpoint is the neointimal healing (NIH) score, which is calculated based on a score taking into consideration the presence of uncovered and malapposed stent struts, intraluminal filling defects and excessive neointimal proliferation, as detected by optical frequency domain imaging (OFDI) six months after the index procedure. The study will provide 90% power to show non-inferiority of the Absorb BVS compared with the EES. CONCLUSIONS This will be the first randomised study investigating the arterial healing response following implantation of the Absorb BVS compared with the EES. The healing response assessed by a novel NIH score in conjunction with results on angiographic efficacy parameters and device-oriented events will elucidate disease-specific applications of bioresorbable scaffolds.

Perception of a hectic hospital environment at admission relates to acute stress disorder symptoms in myocardial infarction patients.

OBJECTIVE Hospital crowding is a public health problem that may impact on the quality of medical treatment and increase the risk of developing traumatic stress, e.g., after myocardial infarction (MI). This study examines whether subjective appraisal of crowding at hospital admission due to MI is associated with acute stress disorder (ASD) symptoms. METHOD We investigated 102 consecutive patients with acute MI within 48h after having reached stable circulatory conditions. The appraisal of crowding was measured by the retrospective assessment of the perception of a hectic hospital environment at admission. Furthermore, patients completed the Acute Stress Disorder Scale to rate the psychological stress reaction. RESULTS The perception of a hectic hospital environment was associated with the development of ASD symptoms (r=0.254, P=.013) independently of demographic, peritraumatic and medical factors. Post hoc analysis revealed associations with dissociative (r=0.211, P=.041), reexperiencing (r=0.184, P=.074) and arousal (r=0.179, P=.083) symptoms. CONCLUSION The findings suggest that, besides objective circumstances, the way hospital admission due to MI is perceived by the patient may influence the development of MI-triggered ASD symptoms. The psychological and physiological long-term outcomes of the perception of a hectic hospital environment and the role of preventive interventions need further examination.

Revascularization Treatment of Emergency Patients with Acute ST-Segment Elevation Myocardial Infarction in Switzerland: Results from a Nationwide, Cross-Sectional Study in Switzerland for 2010-2011

BACKGROUND: Cardiovascular diseases are the leading cause of death worldwide and in Switzerland. When applied, treatment guidelines for patients with acute ST-segment elevation myocardial infarction (STEMI) improve the clinical outcome and should eliminate treatment differences by sex and age for patients whose clinical situations are identical. In Switzerland, the rate at which STEMI patients receive revascularization may vary by patient and hospital characteristics. AIMS: To examine all hospitalizations in Switzerland from 2010-2011 to determine if patient or hospital characteristics affected the rate of revascularization (receiving either a percutaneous coronary intervention or a coronary artery bypass grafting) in acute STEMI patients. DATA AND METHODS: We used national data sets on hospital stays, and on hospital infrastructure and operating characteristics, for the years 2010 and 2011, to identify all emergency patients admitted with the main diagnosis of acute STEMI. We then calculated the proportion of patients who were treated with revascularization. We used multivariable multilevel Poisson regression to determine if receipt of revascularization varied by patient and hospital characteristics. RESULTS: Of the 9,696 cases we identified, 71.6% received revascularization. Patients were less likely to receive revascularization if they were female, and 80 years or older. In the multivariable multilevel Poisson regression analysis, there was a trend for small-volume hospitals performing fewer revascularizations but this was not statistically significant while being female (Relative Proportion = 0.91, 95% CI: 0.86 to 0.97) and being older than 80 years was still associated with less frequent revascularization. CONCLUSION: Female and older patients were less likely to receive revascularization. Further research needs to clarify whether this reflects differential application of treatment guidelines or limitations in this kind of routine data.

Cell-specific effects of Nox2 on the acute and chronic response to myocardial infarction

BACKGROUND: Increased reactive oxygen species (ROS) production is involved in the process of adverse cardiac remodeling and development of heart failure after myocardial infarction (MI). NADPH oxidase-2 (Nox2) is a major ROS source within the heart and its activity increases after MI. Furthermore, genetic deletion of Nox2 is protective against post-MI cardiac remodeling. Nox2 levels may increase both in cardiomyocytes and endothelial cells and recent studies indicate cell-specific effects of Nox2, but it is not known which of these cell types is important in post-MI remodeling. METHODS AND RESULTS: We have generated transgenic mouse models in which Nox2 expression is targeted either to cardiomyocytes (cardio-Nox2TG) or endothelial cells (endo-Nox2TG). We here studied the response of cardio-Nox2TG mice, endo-Nox2TG mice and matched wild-type littermates (WT) to MI induced by permanent left coronary artery ligation up to 4weeks. Initial infarct size assessed by magnetic resonance imaging (MRI) and cardiac dysfunction were similar among groups. Cardiomyocyte hypertrophy and interstitial fibrosis were augmented in cardio-Nox2TG compared to WT after MI and post-MI survival tended to be worse whereas endo-Nox2TG mice showed no significant difference compared to WT. CONCLUSIONS: These results indicate that cardiomyocyte rather than endothelial cell Nox2 may have the more important role in post-MI remodeling.

Simultaneous Acute Pulmonary Embolism and Isolated Septal Myocardial Infarction in a Young Patient

We report here the case of a young patient with a simultaneous isolated septal myocardial infarction (MI) and pulmonary embolism (PE). The aim was to describe a rare clinical entity and to explain why these two pathologies were present at the same time in a young patient.
 A review of literature was established. An interventional cardiologist, an interventional radiologist and a lung specialist were consulted. The diagnostic workup revealed only heterozygous Factor Leiden V mutation. This presentation was probably fortuitous, but worth reporting to our opinion.

Clinical effect of intravenous thrombolysis combined with nicorandil therapy in patients with acute ST-segment elevation myocardial infarction

Purpose: To evaluate the effectiveness of intravenous thrombolysis in combination with nicorandil in the treatment of acute ST-segment elevation myocardial infarction (STEMI). Methods: Patients who developed acute STEMI and underwent intravenous thrombolysis in the hospital were selected and divided into observation group (n = 128) and control group (n = 114). Besides thrombolytic therapy, the observation group was also given 20 mg of nicorandil. The control group received conventional thrombolytic therapy only. Clinical effects and rehabilitation of patients were observed. Results: Cardiac troponin I (cTNI) level of the observation group was 4.0 ± 1.5, 8.3 ± 2.8 and 9.8 ± 3.9 after 4, 12 and 24 h, respectively, which is much lower than 5.8 ± 1.4, 11.4 ± 2.7 and 13.2 ± 4.2 in the control group (p < 0.05). ST-segment resolution of observation group was higher (44 ± 14, 52 ± 17, 69 ± 21 and 80 ± 18) % at different time points, compared with the control group (p < 0.05). The proportion of patients with Curtis-Walker score > 3 points, and ventricular wall motion score (4.70 %; 1.38 ± 0.11) in the observation group were both lower than those of the control group (21.00 %; 1.43 ± 0.15) (p < 0.05). The difference in adverse cardiac events between the observation group (N = 6, 4.70 %) and control group (N = 12, 10.50 %) was not statistically significant (p > 0.05) Conclusion: Combining intravenous thrombolysis with nicorandil therapy can enhance myocardial perfusion level, reduce myocardial damage, improve cardiac function and decrease risk of arrhythmia for acute STEMI patients.

Electrocardiographic repolarization variables in detecting myocardial infarction and ischemic injury : From body surface potential mapping to a single lead

The aim of the studies was to improve the diagnostic capability of electrocardiography (ECG) in detecting myocardial ischemic injury with a future goal of an automatic screening and monitoring method for ischemic heart disease. The method of choice was body surface potential mapping (BSPM), containing numerous leads, with intention to find the optimal recording sites and optimal ECG variables for ischemia and myocardial infarction (MI) diagnostics. The studies included 144 patients with prior MI, 79 patients with evolving ischemia, 42 patients with left ventricular hypertrophy (LVH), and 84 healthy controls. Study I examined the depolarization wave in prior MI with respect to MI location. Studies II-V examined the depolarization and repolarization waves in prior MI detection with respect to the Minnesota code, Q-wave status, and study V also with respect to MI location. In study VI the depolarization and repolarization variables were examined in 79 patients in the face of evolving myocardial ischemia and ischemic injury. When analyzed from a single lead at any recording site the results revealed superiority of the repolarization variables over the depolarization variables and over the conventional 12-lead ECG methods, both in the detection of prior MI and evolving ischemic injury. The QT integral, covering both depolarization and repolarization, appeared indifferent to the Q-wave status, the time elapsed from MI, or the MI or ischemia location. In the face of evolving ischemic injury the performance of the QT integral was not hampered even by underlying LVH. The examined depolarization and repolarization variables were effective when recorded in a single site, in contrast to the conventional 12-lead ECG criteria. The inverse spatial correlation of the depolarization and depolarization waves in myocardial ischemia and injury could be reduced into the QT integral variable recorded in a single site on the left flank. In conclusion, the QT integral variable, detectable in a single lead, with optimal recording site on the left flank, was able to detect prior MI and evolving ischemic injury more effectively than the conventional ECG markers. The QT integral, in a single-lead or a small number of leads, offers potential for automated screening of ischemic heart disease, acute ischemia monitoring and therapeutic decision-guiding as well as risk stratification.

Mesenchymal stem cell therapy for the treatment of myocardial infarction

Mesenchymal stem cells (MSCs) are currently under investigation as repair agents in the preservation of cardiac function following myocardial infarction (MI). However concerns have emerged regarding the safety of acute intracoronary (IC) MSC delivery specifically related to mortality, micro-infarction and microvascular flow restriction post cell therapy in animal models. This thesis aimed to firstly identify an optimal dose of MSC that could be tolerated when delivered via the coronary artery in a porcine model of acute MI (AMI). Initial dosing studies identified 25x106 MSC to be a safe MSC cell dose, however, angiographic observations from these studies recognised that on delivery of MSC there was a significant adverse decrease in distal blood flow within the artery. This observation along with additional supportive data in the literature (published during the course of this thesis) suggested MSC may be contributing to such adverse events through the propagation of thrombosis. Therefore further studies aimed to investigate the innate prothrombotic activity of MSC. Expression of the initiator of the coagulation cascade initiator tissue factor (TF) on MSC was detected in high levels on the surface of these cells. MSC-derived TF antigen was catalytically active, capable of supporting thrombin generation in vitro and enhancing platelet-driven thrombus deposition on collagen under flow. Infusion of MSC via IC route was associated with a decreased coronary flow reserve when delivered but not when coadministered with an antithrombin agent heparin. Heparin also reduced MSC-associated in situ thrombosis incorporating platelets and VWF in the microvasculature. Heparin-assisted MSC delivery reduced acute apoptosis and significantly improved infarct size, left ventricular ejection fraction, LV volumes, wall motion and scar formation at 6 weeks post AMI. In addition, this thesis investigated the paracrine factors secreted by MSC, in particular focusing on the effect on cardiac repair of a novel MSC-paracrine factor SPARCL1. In summary this work provides new insight into the mechanism by which MSC may be deleterious when delivered by an IC route and a means of abrogating this effect. Moreover we present new data on the MSC secretome with elucidation of the challenges encountered using a single paracrine factor cardiac repair strategy.

Exendin-4 protects against post-myocardial infarction remodelling via specific actions on inflammation and the extracellular matrix

Glucagon-like peptide-1 (GLP-1) is an insulin-releasing hormone clinically exploited for glycaemic control in diabetes, which also confers acute cardioprotection and benefits in experimental/clinical heart failure. We specifically investigated the role of the GLP-1 mimetic, exendin-4, in post-myocardial infarction (MI) remodelling, which is a key contributor to heart failure. Adult female normoglycaemic mice underwent coronary artery ligation/sham surgery prior to infusion with exendin-4/vehicle for 4 weeks. Metabolic parameters and infarct sizes were comparable between groups. Exendin-4 protected against cardiac dysfunction and chamber dilatation post-MI and improved survival. Furthermore, exendin-4 modestly decreased cardiomyocyte hypertrophy/apoptosis but markedly attenuated interstitial fibrosis and myocardial inflammation post-MI. This was associated with altered extracellular matrix (procollagen IαI/IIIαI, connective tissue growth factor, fibronectin, TGF-β3) and inflammatory (IL-10, IL-1β, IL-6) gene expression in exendin-4-treated mice, together with modulation of both Akt/GSK-3β and Smad2/3 signalling. Exendin-4 also altered macrophage response gene expression in the absence of direct actions on cardiac fibroblast differentiation, suggesting cardioprotective effects occurring secondary to modulation of inflammation. Our findings indicate that exendin-4 protects against post-MI remodelling via preferential actions on inflammation and the extracellular matrix independently of its established actions on glycaemic control, thereby suggesting that selective targeting of GLP-1 signalling may be required to realise its clear therapeutic potential for post-MI heart failure.

Metabolically-inactive glucagon-like peptide-1(9-36)amide confers selective protective actions against post-myocardial infarction remodelling

BACKGROUND: Glucagon-like peptide-1 (GLP-1) therapies are routinely used for glycaemic control in diabetes and their emerging cardiovascular actions have been a major recent research focus. In addition to GLP-1 receptor activation, the metabolically-inactive breakdown product, GLP-1(9-36)amide, also appears to exert notable cardiovascular effects, including protection against acute cardiac ischaemia. Here, we specifically studied the influence of GLP-1(9-36)amide on chronic post-myocardial infarction (MI) remodelling, which is a major driver of heart failure progression.

METHODS: Adult female C57BL/6 J mice were subjected to permanent coronary artery ligation or sham surgery prior to continuous infusion with GLP-1(9-36)amide or vehicle control for 4 weeks.

RESULTS: Infarct size was similar between groups with no effect of GLP-1(9-36)amide on MI-induced cardiac hypertrophy, although modest reduction of in vitro phenylephrine-induced H9c2 cardiomyoblast hypertrophy was observed. Whilst echocardiographic systolic dysfunction post-MI remained unchanged, diastolic dysfunction (decreased mitral valve E/A ratio, increased E wave deceleration rate) was improved by GLP-1(9-36)amide treatment. This was associated with modulation of genes related to extracellular matrix turnover (MMP-2, MMP-9, TIMP-2), although interstitial fibrosis and pro-fibrotic gene expression were unaltered by GLP-1(9-36)amide. Cardiac macrophage infiltration was also reduced by GLP-1(9-36)amide together with pro-inflammatory cytokine expression (IL-1β, IL-6, MCP-1), whilst in vitro studies using RAW264.7 macrophages revealed global potentiation of basal pro-inflammatory and tissue protective cytokines (e.g. IL-1β, TNF-α, IL-10, Fizz1) in the presence of GLP-1(9-36)amide versus exendin-4.

CONCLUSIONS: These data suggest that GLP-1(9-36)amide confers selective protection against post-MI remodelling via preferential preservation of diastolic function, most likely due to modulation of infiltrating macrophages, indicating that this often overlooked GLP-1 breakdown product may exert significant actions in this setting which should be considered in the context of GLP-1 therapy in patients with cardiovascular disease.

Depression as a predictor of work resumption following myocardial infarction (MI): a review of recent research evidence

Background Depression often coexists with myocardial infarction (MI) and has been found to impede recovery through reduced functioning in key areas of life such as work. In an era of improved survival rates and extended working lives, we review whether depression remains a predictor of poorer work outcomes following MI by systematically reviewing literature from the past 15 years.

Methods Articles were identified using medical, health, occupational and social science databases, including PubMed, OVID, Medline, Proquest, CINAHL plus, CCOHS, SCOPUS, Web of Knowledge, and the following pre-determined criteria were applied: (i) collection of depression measures (as distinct from 'psychological distress') and work status at baseline, (ii) examination and statistical analysis of predictors of work outcomes, (iii) inclusion of cohorts with patients exhibiting symptoms consistent with Acute Coronary Syndrome (ACS), (iv) follow-up of work-specific and depression specific outcomes at minimum 6 months, (v) published in English over the past 15 years. Results from included articles were then evaluated for quality and analysed by comparing effect size.

Results Of the 12 articles meeting criteria, depression significantly predicted reduced likelihood of return to work (RTW) in the majority of studies (n = 7). Further, there was a trend suggesting that increased depression severity was associated with poorer RTW outcomes 6 to 12 months after a cardiac event. Other common significant predictors of RTW were age and patient perceptions of their illness and work performance.

Conclusion Depression is a predictor of work resumption post-MI. As work is a major component of Quality of Life (QOL), this finding has clinical, social, public health and economic implications in the modern era. Targeted depression interventions could facilitate RTW post-MI.