Type-II Myocardial Infarction – Patient Characteristics,Management and Outcomes

Background

Type-II MI is defined as myocardial infarction (MI) secondary to ischemia due to either increased oxygen demand or decreased supply. This categorization has been used for the last five years, yet, little is known about patient characteristics and clinical outcomes. In the current work we assessed the epidemiology, causes, management and outcomes of type II MI patients.

Methods

A comparative analysis was performed between patients with type-I and type-II MI who participated in two prospective national Acute Coronary Syndrome Israeli Surveys (ACSIS) performed in 2008 and 2010.

Results

The surveys included 2818 patients with acute MI of whom 127 (4.5%) had type-II MI. The main causes of type-II MI were anemia (31%), sepsis (24%), and arrhythmia (17%). Patients with type-II MI tended to be older (75.6±12 vs. 63.8±13, p<0.0001), female majority (43.3% vs. 22.3%, p<0.0001), had more frequently impaired functional level (45.7% vs. 17%, p<0.0001) and a higher GRACE risk score (150±32 vs. 110±35, p<0.0001). Patients with type-II MI were significantly less often referred for coronary interventions (36% vs. 89%, p<0.0001) and less frequently prescribed guideline-directed medical therapy. Mortality rates were substantially higher among patients with type-II MI both at thirty-day (13.6% vs. 4.9%, p<0.0001) and at one-year (23.9% vs. 8.6%, p<0.0001) follow-ups.

Conclusions

Patients with type-II compared to type-I MI have distinct demographics, increased prevalence of multiple comorbidities, a high-risk cardiovascular profile and an overall worse outcome. The complex medical condition of this cohort imposes a great therapeutic challenge and specific guidelines with recommended medical treatment and invasive strategies are warranted.     

A Detailed Family History of Myocardial Infarction and Risk of Myocardial Infarction – A Nationwide Cohort Study

BackgroundFamily history of myocardial infarction (MI) is an independent risk factor for MI. Several genetic variants are associated with increased risk of MI and family history of MI in a first-degree relative doubles MI risk. However, although family history of MI is not a simple dichotomous risk factor, the impact of specific, detailed family histories has not received much attention, despite its high clinical relevance. We examined risk of MI by MIs in first- and second-degree relatives and by number and age of affected relatives.ConclusionA detailed family history, particularly number of affected first- and second-degree relatives, contributes meaningfully to risk assessment, especially in middle-aged persons. Future studies should test for potential improvement of risk algorithm prediction using detailed family histories.     

Mechanical Complications of Myocardial Infarction—Radiologic Aspects

Left ventricular aneurysm, interventricular septal defect and acute mitral valve incompetence due to papillary muscle damage are three mechanical complications which cause intractable heart failure following myocardial infarction. In each case surgical intervention can result in dramatic improvement of congestive heart failure.A hemodynamically significant left ventricular aneurysm enlarges the cardiac silhouette and frequently causes a localized protrusion as seen radiographically. Cardiac fluoroscopy will disclose an abnormal pulsation of the left ventricular border. The left ventricular angiogram establishes the diagnosis, reveals the extent of the aneurysm and may disclose a filling defect in the aneurysmal sac due to the presence of mural thrombus. Coronary arteriography shows occlusion of a major vessel, most commonly the anterior descending branch of the left coronary artery.Ischemic perforation of the interventricular septum and acute mitral incompetence due to severe papillary muscle damage both cause severe heart failure shortly after myocardial infarction. A similar pansystolic murmur accompanies both conditions, and differentiation between the two is rarely possible on the basis of the electrocardiogram or x-ray film of the chest. Ventricular cardiac catheterization and left ventricular angiocardiography are required for a correct diagnosis.     

Genetic Polymorphisms and the Risk of Myocardial Infarction in Patients Under 45 Years of Age

This study investigates the potential role of 17 chosen polymorphisms in 15 candidate genes and the risk of myocardial infarction in patients under 45 years of age. The study consists of 271 patients with myocardial infarction and 141 controls. The analysis of genetic polymorphisms was performed using the PCR–RFLP method. Of the chosen polymorphisms, two (Leu125Val PECAM1 and A1/A2 FVII) are related to myocardial infarction and two (C677T MTHFR and 5A/6A MMP3) to advanced stenosis in arterial vessels (> 75%). We also found that the frequency of some combinations among the analyzed genes and environmental factors varied between the patient and control groups.     

Association between Ambient Temperature and Acute Myocardial Infarction Hospitalisations in Gothenburg,Sweden: 1985–2010

Cardiovascular disease (CVD) is the number one cause of death globally and evidence is steadily increasing on the role of non-traditional risk factors such as meteorology and air pollution. Nevertheless, many research gaps remain, such as the association between these non-traditional risk factors and subtypes of CVD, such as acute myocardial infarction (AMI). The objective of this study was to investigate the association between daily ambient temperature and AMI hospitalisations using a case-crossover design in Gothenburg, Sweden (1985–2010). A secondary analysis was also performed for out-of-hospital ischemic heart disease (IHD) deaths. Susceptible groups by age and sex were explored. The entire year as well as the warm (April−September) and cold periods (October–March) were considered. In total 28 215 AMI hospitalisations (of 22 475 people) and 21 082 out-of-hospital IHD deaths occurred during the 26-year study period. A linear exposure-response corresponding to a 3% and 7% decrease in AMI hospitalisations was observed for an inter-quartile range (IQR) increase in the 2-day cumulative average of temperature during the entire year (11°C) and the warm period (6°C), respectively, with and without adjustment for PM₁₀, NO₂, NO_x or O₃. No heat waves occurred during the warm period. No evidence of an association in the cold period nor any association between temperature and IHD deaths in the entire year, warm or cold periods - with and without adjusting for PM₁₀, NO₂, NO_x or O₃ was found. No susceptible groups, based on age or sex, were identified either. The inverse association between temperature and AMI hospitalisations (entire year and warm period) in Gothenburg is in accordance with the majority of the few other studies that investigated this subtype of CVD.     

Unrecognized Myocardial Infarction Assessed by Cardiac Magnetic Resonance Imaging – Prognostic Implications

Background

Clinically unrecognized myocardial infarctions (UMI) are not uncommon and may be associated with adverse outcome. The aims of this study were to determine the prognostic implication of UMI in patients with stable suspected coronary artery disease (CAD) and to investigate the associations of UMI with the presence of CAD.

Methods and Findings

In total 235 patients late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging and coronary angiography were performed. For each patient with UMI, the stenosis grade of the coronary branch supplying the infarcted area was determined. UMIs were present in 25% of the patients and 67% of the UMIs were located in an area supplied by a coronary artery with a stenosis grade ≥70%. In an age- and gender-adjusted model, UMI independently predicted the primary endpoint (composite of death, myocardial infarction, resuscitated cardiac arrest, hospitalization for unstable angina pectoris or heart failure within 2 years of follow-up) with an odds ratio of 2.9; 95% confidence interval 1.1–7.9. However, this association was abrogated after adjustment for age and presence of significant coronary disease. There was no difference in the primary endpoint rates between UMI patients with or without a significant stenosis in the corresponding coronary artery.

Conclusions

The presence of UMI was associated with a threefold increased risk of adverse events during follow up. However, the difference was no longer statistically significant after adjustments for age and severity of CAD. Thus, the results do not support that patients with suspicion of CAD should be routinely investigated by LGE-CMR for UMI. However, coronary angiography should be considered in patients with UMI detected by LGE-CMR.

Trial Registration

ClinicalTrials.gov NTC01257282     

β-arrestin2 in Infiltrated Macrophages Inhibits Excessive Inflammation after Myocardial Infarction

Beta-arrestins (β-arrestin1 and β-arrestin2) are known as cytosolic proteins that mediate desensitization and internalization of activated G protein-coupled receptors. In addition to these functions, β-arrestins have been found to work as adaptor proteins for intracellular signaling pathways. β-arrestin1 and β-arrestin2 are expressed in the heart and are reported to participate in normal cardiac function. However, the physiological and pathological roles of β-arrestin1/2 in myocardial infarction (MI) have not been examined. Here, we demonstrate that β-arrestin2 negatively regulates inflammatory responses of macrophages recruited to the infarct area. β-arrestin2 knockout (KO) mice have higher mortality than wild-type (WT) mice after MI. In infarcted hearts, β-arrestin2 was strongly expressed in infiltrated macrophages. The production of inflammatory cytokines was enhanced in β-arrestin2 KO mice. In addition, p65 phosphorylation in the macrophages from the infarcted hearts of β-arrestin2 KO mice was increased in comparison to that of WT mice. These results suggest that the infiltrated macrophages of β-arrestin2 KO mice induce excessive inflammation at the infarct area. Furthermore, the inflammation in WT mice transplanted with bone marrow cells of β-arrestin2 KO mice is enhanced by MI, which is similar to that in β-arrestin2 KO mice. In contrast, the inflammation after MI in β-arrestin2 KO mice transplanted with bone marrow cells of WT mice is comparable to that in WT mice transplanted with bone marrow cells of WT mice. In summary, our present study demonstrates that β-arrestin2 of infiltrated macrophages negatively regulates inflammation in infarcted hearts, thereby enhancing inflammation when the β-arrestin2 gene is knocked out. β-arrestin2 plays a protective role in MI-induced inflammation.     

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.     

Effects of Peroxisome Proliferator-Activated Receptor-δ Agonist on Cardiac Healing after Myocardial Infarction

Peroxisome proliferator-activated receptor-delta (PPAR-δ)-dependent signaling is associated with rapid wound healing in the skin. Here, we investigated the therapeutic effects of PPAR-δ-agonist treatment on cardiac healing in post-myocardial infarction (MI) rats. Animals were assigned to the following groups: sham-operated control group, left anterior descending coronary artery ligation (MI) group, or MI with administration of the PPAR-δ agonist GW610742 group. GW610742 (1 mg/kg) was administrated intraperitoneally after the operation and repeated every 3 days. Echocardiographic data showed no differences between the two groups in terms of cardiac function and remodeling until 4 weeks. However, the degrees of angiogenesis and fibrosis after MI were significantly higher in the GW610742-treated rats than in the untreated MI rats at 1 week following MI, which changes were not different at 2 weeks after MI. Naturally, PPAR-δ expression in infarcted myocardium was highest increased in 3 day after MI and then disappeared in 14 day after MI. GW610742 increased myofibroblast differentiation and transforming growth factor-beta 2 expression in the infarct zone at 7 days after MI. GW610742 also increased bone marrow-derived mesenchymal stem cell (MSC) recruitment in whole myocardium, and increased serum platelet-derived growth factor B, stromal-derived factor-1 alpha, and matrix metallopeptidase 9 levels at day 3 after MI. PPAR-δ agonists treatment have the temporal effect on early fibrosis of infarcted myocardium, which might not sustain the functional and structural beneficial effect.     

Acute Myocardial Infarction in Doncaster. II—Delays in Admission and Survival

The speed of admission of patients with suspected acute myocardial infarction was observed over a period of 12 months during which a “no refusal” coronary care scheme was functioning, with emphasis on minimizing delay. During the same period the duration of survival of cases diagnosed as coronary thrombosis by the coroner''s pathologist was measured. Comparison of the two series shows that 75% to 80% of the coroner''s cases had died before the median time of notification of the general practitioner by those patients referred to hospital.We argue that the provision of mobile coronary care on request from general practitioners is unlikely to have an appreciable effect in preventing deaths from acute myocardial infarction outside hospital.     

Are There Ethnic Inequalities in Revascularisation Procedure Rate after an ST-Elevation Myocardial Infarction?

Background

Previously, ethnic inequalities in prognosis after a first acute myocardial infarction were observed in the Netherlands. This might be due to differences in revascularisation rate between ethnic minority groups and ethnic Dutch. Therefore, we investigated inequalities in revascularisation rate after occurrence of an ST-elevation myocardial infarction (STEMI) between first generation ethnic minority groups (henceforth, migrants) and ethnic Dutch.

Methods

All STEMI events between 2006 and 2011 were identified in a subset of the Achmea Health Database, which records medical care to persons insured at the Achmea health insurance company, a major health insurance company in the central part of the Netherlands. Ethnic Dutch and migrants from Suriname (Hindustani Surinamese and non-Hindustani Surinamese), Morocco, and Turkey were included (n = 1,765). Multivariable Cox proportional hazards regression analyses were used to identify ethnic inequalities in revascularisation rate (percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG)) after a STEMI event.

Results

On average, 73.2% of STEMI events were followed by a revascularisation procedure. After adjustment for confounders (age, sex, degree of urbanization) no significant differences in revascularisation rate were found between the ethnic Dutch population and Hindustani Surinamese (HR: 1.04; 0.85–1.27), non-Hindustani Surinamese (HR: 0.98; 0.63–1.51), Moroccan (HR: 0.94; 0.77–1.14), and Turkish migrants (HR: 1.04; 0.88–1.24). Additional adjustment for comorbidity and neighborhood income did not change our findings.

Conclusion

Our study suggests no ethnic inequalities in revascularisation rate after a STEMI event. This finding is in agreement with the universally accessible health care system in the Netherlands.     

Acute Myocardial Infarction in Doncaster. I—Estimating Size of Coronary Care Unit

A “no refusal” coronary care service (for one year) was offered to a selected sample of 10 general practices (total list 74,657). The patients were admitted to a three-bedded unit in Doncaster Royal Infirmary and data were collected to enable estimation of the size of unit necessary to serve the whole population in the area (census estimate 268,560; total G.P. list 315,811). This estimation was based on:1. The frequency of admission to hospital of suspected acute myocardial infarction in one year, estimated at 978 from the total population.2. The average duration of stay in the unit, which was 2·45 days.3. The distribution of observed occupancy was approximately Poissonian.From these the average expected bed occupancy was calculated as 6·56 and reference to probability tables gave the frequency of overload for different numbers of beds provided. The incidence of acute myocardial infarction in the area is estimated at 275 per 100,000 per annum, on calculations based on the practice list size, and at 323 per 100,000 per annum, on calculations based on census figures.     

Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction

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ELECTROCARDIOGRAMS AND VECTORELECTROCARDIOGRAMS—An Appraisal of Their Value in Subendocardial and in Transmural Myocardial Infarction

By vector methods quantitative differences can be shown to be present between subendocardial and transmural myocardial infarction. In acute transmural infarction the vector shift occurs later, the degree of shift is greater, the return to normal is later in time and an abnormal vector shift remains more frequently than in subendocardial infarction. In acute anteroseptal transmural infarction the degree of vector shift was closely correlated with the severity of the acute illness.     

Protein Kinase G1 α Overexpression Increases Stem Cell Survival and Cardiac Function after Myocardial Infarction

Background

We hypothesized that overexpression of cGMP-dependent protein kinase type 1α (PKG1α) could mimic the effect of tadalafil on the survival of bone marrow derived mesenchymal stem cells (MSCs) contributing to regeneration of the ischemic heart.

Methods and Results

MSCs from male rats were transduced with adenoviral vector encoding for PKG1α (^PKG1αMSCs).Controls included native MSCs (^NatMSCs) and MSCs transduced with an empty vector (^NullMSCs). PKG1α activity was increased approximately 20, 5 and 16 fold respectively in ^PKG1αMSCs. ^PKG1αMSCs showed improved survival under oxygen and glucose deprivation (OGD) which was evidenced by lower LDH release, caspase-3/7 activity and number of positive TUNEL cells. Anti-apoptotic proteins pAkt, pGSK3β, and Bcl-2 were significantly increased in ^PKG1αMSCs compared to ^NatMSCs and ^NullMSCs. Higher release of multiple prosurvival and angiogenic factors such as HGF, bFGF, SDF-1 and Ang-1 was observed in ^PKG1αMSCs before and after OGD. In a female rat model of acute myocardial infarction, ^PKG1αMSCs group showed higher survival compared with ^NullMSCs group at 3 and 7 days after transplantation as determined by TUNEL staining and sry-gene quantitation by real-time PCR. Increased anti-apoptotic proteins and paracrine factors in vitro were also identified. Immunostaining for cardiac troponin I combined with GFP showed increased myogenic differentiation of ^PKG1αMSCs. At 4 weeks after transplantation, compared to DMEM group and ^NullMSCs group, ^PKG1αMSCs group showed increased blood vessel density in infarct and peri-infarct areas (62.5±7.7; 68.8±7.3 per microscopic view, p<0.05) and attenuated infarct size (27.2±2.5%, p<0.01). Heart function indices including ejection fraction (52.1±2.2%, p<0.01) and fractional shortening (24.8%±1.3%, p<0.01) were improved significantly in ^PKG1αMSCs group.

Conclusion

Overexpression of PKG1α transgene could be a powerful approach to improve MSCs survival and their angiomyogenic potential in the infarcted heart.