Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Transmission of external stimuli to intracellular effector proteins via signalling pathways is a ...highly regulated and controlled process that determines muscle mass by balancing protein synthesis and protein degradation. An impaired balance between protein synthesis and breakdown leads to the development of specific myopathies. Sarcopenia and cachexia represent two distinct muscle wasting diseases characterized by inflammation and oxidative stress, where specific regulating molecules associated with wasting are either activated (e.g. members of the ubiquitin‐proteasome system and myostatin) or repressed (e.g. insulin‐like growth factor 1 and PGC‐1α). At present, no therapeutic interventions are established to successfully treat muscle wasting in sarcopenia and cachexia. Exercise training, however, represents an intervention that can attenuate or even reverse the process of muscle wasting, by exerting anti‐inflammatory and anti‐oxidative effects that are able to attenuate signalling pathways associated with protein degradation and activate molecules associated with protein synthesis. This review will therefore discuss the molecular mechanisms associated with the pathology of muscle wasting in both sarcopenia and cachexia, as well as highlighting the intracellular effects of exercise training in attenuating the debilitating loss of muscle mass in these specific conditions.
Objectives The aim of the study was to determine the prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance (CMR) in reperfused ST-segment ...elevation myocardial infarction. Background In acute myocardial infarction, CMR can retrospectively detect the myocardium at risk and the irreversible injury. This allows for quantifying the extent of salvaged myocardium after reperfusion as a potential strong end point for clinical trials and outcome. Methods We analyzed 208 consecutive ST-segment elevation myocardial infarction patients undergoing primary angioplasty <12 h after symptom onset. T2-weighted and contrast-enhanced CMR was used to calculate the myocardial salvage index (MSI). Patients were categorized into 2 groups defined by the median MSI. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and occurrence of new congestive heart failure within 6 months after the index event. Results The median MSI was 48 (interquartile range 27 to 73). Major adverse cardiovascular events were significantly lower in the MSI ≥ median group (2.9% vs. 22.1%, p < 0.001). The stepwise Cox proportional hazards model revealed that the MSI was the strongest predictor of major adverse cardiovascular events at 6-month follow-up (p < 0.001). All prognostic clinical (symptom onset to reperfusion), angiographic (Thrombolysis In Myocardial Infarction flow grade before angioplasty), and electrocardiographic (ST-segment resolution) parameters showed significant correlations with the MSI (p < 0.001 for all). Conclusions This study for the first time demonstrates that the MSI assessed by CMR predicts the outcome in acute reperfused ST-segment elevation myocardial infarction. Therefore, MSI assessment has important implications for patient prognosis as well as for the design of future trials intended to test new reperfusion therapy efficacy. (Myocardial Salvage Assessed by Cardiovascular Magnetic Resonance—Impact on Outcome; NCT00952224 ).
Importantly, there was a clear divergence of mortality curves <=2 months after initial presentation, which implies that arrhythmias are of higher prognostic mortality in the convalescent phase of ...TTC. ...our data illustrate the significance of arrhythmic events as a determinant of outcome and a useful approach to risk stratification in TTC. ...life-threatening arrhythmias are a common finding in patients with TTC and have a major prognostic effect.
Aims
Despite increasing research efforts, the prognostic consequences of takotsubo cardiomyopathy (TTC) remain largely unknown. The aim of this study was therefore to compare the long‐term mortality ...rate of TTC patients with high‐risk patients presenting with ST‐segment elevation myocardial infarction (STEMI).
Methods and results
A total of 286 patients with TTC were matched for age and gender with 286 STEMI patients. Outcome was obtained with a standardized telephone follow‐up. The primary analysis determined long‐term mortality. A secondary analysis was performed evaluating 28‐day and 1‐year mortality. Follow‐up was available for 96% of patients after a mean of 3.8 ± 2.5 years. In TTC patients, long‐term mortality was significantly higher compared with the matched STEMI cohort 24.7% vs. 15.1%, hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.07–2.33; P = 0.02. There was no significant difference in the rates of 28‐day (5.5% vs. 5.7%, HR 0.96, 95% CI 0.47–1.94; P = 0.91) and 1‐year mortality (12.5% vs. 9%, HR 1.42, 95% CI 0.85–2.38; P = 0.18). In multivariable regression analysis, male sex, a high Killip class on admission, and diabetes mellitus were identified as independent predictors of mortality in TTC patients. A risk score consisting of these factors showed a higher mortality with an increasing number of risk factors.
Conclusion
Mortality rates in TTC patients are higher than previously expected and long‐term mortality exceeded that of patients with STEMI. A simple risk score may provide an approach to identify high‐risk patients and predict clinical prognosis.
Abstract Background Although the prognostic value of findings from cardiac magnetic resonance (CMR) imaging has been established in single-center center studies in patients with ST-segment elevation ...myocardial infarction (STEMI), a large multicenter investigation to evaluate the prognostic significance of myocardial damage and reperfusion injury is lacking. Objectives The aim of this study was to assess the prognostic impact of CMR in an adequately powered multicenter study and to evaluate the most potent CMR predictor of hard clinical events in a STEMI population treated by primary percutaneous coronary intervention (PCI). Methods We enrolled 738 STEMI patients in this CMR study at 8 centers. The patients were reperfused by primary PCI <12 h after symptom onset. Central core laboratory–masked analyses for quantified left ventricular (LV) function, infarct size (IS), microvascular obstruction (MO), and myocardial salvage were performed. The primary clinical endpoint of the study was the occurrence of major adverse cardiac events. Results Patients with cardiovascular events had significantly larger infarcts (p < 0.001), less myocardial salvage (p = 0.01), a larger extent of MO (p = 0.009), and more pronounced LV dysfunction (p < 0.001). In a multivariate model that included clinical and other established prognostic parameters, MO remained the only significant predictor in addition to the TIMI (Thrombolysis In Myocardial Infarction) risk score. IS and MO provided an incremental prognostic value above clinical risk assessment and LV ejection fraction (c-index increase from 0.761 to 0.801; p = 0.036). Conclusions In a large, multicenter STEMI population reperfused by primary PCI, CMR markers of myocardial damage (IS and especially MO) provide independent and incremental prognostic information in addition to clinical risk scores and LV ejection fraction. (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction AIDA STEMI; NCT00712101 ).
In this trial, patients with patent foramen ovale and cryptogenic embolism were assigned to undergo closure with the use of a percutaneous device or to receive medical therapy. There was no ...significant difference in the rates of recurrent embolic events or death.
Paradoxical embolism by means of a patent foramen ovale has been blamed as a cause of stroke and other systemic ischemic events since the 19th century.
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The actual passage of a venous clot through a patent foramen ovale has been documented in a few cases and resulted in systemic embolic events such as ischemic stroke, transient ischemic attack (TIA),
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–
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or myocardial infarction.
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Catheter-based closure of patent foramen ovale was introduced in 1992.
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Observational long-term data suggest that closure of patent foramen ovale in patients with a history of ischemic stroke may reduce the risk of recurrent stroke as compared . . .
CONTEXT Stress cardiomyopathy (SC) is a transient form of acute heart failure triggered by stressful events and associated with a distinctive left ventricular (LV) contraction pattern. Various ...aspects of its clinical profile have been described in small single-center populations, but larger, multicenter data sets have been lacking so far. Furthermore, it remains difficult to quickly establish diagnosis on admission. OBJECTIVES To comprehensively define the clinical spectrum and evolution of SC in a large population, including tissue characterization data from cardiovascular magnetic resonance (CMR) imaging; and to establish a set of CMR criteria suitable for diagnostic decision making in patients acutely presenting with suspected SC. DESIGN, SETTING, AND PATIENTS Prospective study conducted at 7 tertiary care centers in Europe and North America between January 2005 and October 2010 among 256 patients with SC assessed at the time of presentation as well as 1 to 6 months after the acute event. MAIN OUTCOME MEASURES Complete recovery of LV dysfunction. RESULTS Eighty-one percent of patients (n = 207) were postmenopausal women, 8% (n = 20) were younger women (aged ≤50 years), and 11% (n = 29) were men. A stressful trigger could be identified in 182 patients (71%). Cardiovascular magnetic resonance imaging data (available for 239 patients 93%) revealed 4 distinct patterns of regional ventricular ballooning: apical (n = 197 82%), biventricular (n = 81 34%), midventricular (n = 40 17%), and basal (n = 2 1%). Left ventricular ejection fraction was reduced (48% SD, 11%; 95% confidence interval CI, 47%-50%) in all patients. Stress cardiomyopathy was accurately identified by CMR using specific criteria: a typical pattern of LV dysfunction, myocardial edema, absence of significant necrosis/fibrosis, and markers for myocardial inflammation. Follow-up CMR imaging showed complete normalization of LV ejection fraction (66% SD, 7%; 95% CI, 64%-68%) and inflammatory markers in the absence of significant fibrosis in all patients. CONCLUSIONS The clinical profile of SC is considerably broader than reported previously. Cardiovascular magnetic resonance imaging at the time of initial clinical presentation may provide relevant functional and tissue information that might aid in the establishment of the diagnosis of SC.
Remote ischaemic conditioning (RIC) and postconditioning (PostC) are both potent activators of innate protection against ischaemia-reperfusion injury and have demonstrated cardioprotection in ...experimental and clinical ST-elevation myocardial infarction (STEMI) trials. However, their combined effects have not been studied in detail. The aim of this study was to evaluate if the co-application of intrahospital RIC and PostC has a more powerful effect on myocardial salvage compared with either PostC alone or control.
This prospective, controlled, single-centre study randomized 696 STEMI patients to one of the following three groups: (i) combined intrahospital RIC + PostC in addition to primary percutaneous coronary intervention (PCI); (ii) PostC in addition to PCI; and (iii) conventional PCI (control). The primary endpoint myocardial salvage index was assessed by cardiac magnetic resonance (CMR) imaging within 3 days after infarction. Secondary endpoints included infarct size and microvascular obstruction (MVO) assessed by CMR. The combined clinical endpoint consisted of death, reinfarction, and new congestive heart failure within 6 months. The primary endpoint myocardial salvage index was significantly greater in the combined RIC + PostC group when compared with the control group (49 interquartile range 30-72 vs. 40 interquartile range 16-68, P = 0.02). Postconditioning alone failed to improve myocardial salvage when compared with conventional PCI (P = 0.39). The secondary endpoints, including infarct size and MVO, showed no significant differences between groups. Clinical follow-up at 6 months revealed no differences in the combined clinical endpoint between groups (P = 0.44).
Combined intrahospital RIC + PostC in conjunction with PCI in STEMI significantly improves myocardial salvage in comparison with control and PostC.
NCT02158468.
MicroRNAs (miRNAs) are small non-coding molecules regulating gene expression. Recently circulating miRNAs could be detected in the plasma, serving as novel biomarkers. Different forms of exercise ...mobilize progenitor cells from the bone marrow, helping in tissue repair. Data of different forms of exercise on endothelial cell damage are lacking. The aim of the study was to evaluate the impact of different exercise modalities on the plasma concentration of miRNA-126, as a marker for endothelial damage.
The plasma concentration of miRNA-126 and miRNA-133 (marker for muscle damage) was assessed by qRT-PCR analysis in plasma samples from healthy individuals performing one of the following exercise tests: (1) maximal symptom-limited exercise test, (2) bicycling for 4 h, (3) running a marathon, and (4) resistance exercise.
A maximal symptom-limited exercise test resulted in a significant increase of circulating miRNA-126 at maximum power (2.1-fold versus begin), whereas the concentration of miRNA-133 remained unchanged. In line, four hours of cycling increased plasma concentration of miRNA-126 with a maximum 30 minutes after begin (4.6-fold versus begin) without an impact on miRNA-133 concentration. Finishing a marathon race resulted in an increase of miRNA-126 and miRNA-133. In contrast, eccentric resistance training led to an isolated increase of miRNA-133 level (2.1-fold versus begin) with unchanged miRNA-126.
Different endurance exercise protocols lead to damage of the endothelial cell layer as evident by an increase in miRNA-126. On the other hand, resistance exercise has no impact on the endothelial cells, but leads to a destruction of muscular cells.
Estrogens play critical roles in embryonic development, gonadal sex differentiation, behavior, and reproduction in vertebrates and in several human cancers. Estrogens are synthesized from ...testosterone and androstenedione by the endoplasmic reticulum membrane-bound P450 aromatase/cytochrome P450 oxidoreductase complex (CYP19/CPR). Here, we report the characterization of novel mammalian CYP19 isoforms encoded by CYP19 gene copies. These CYP19 isoforms are all defined by a combination of mutations in the N-terminal transmembrane helix (E42K, D43N) and in helix C of the catalytic domain (P146T, F147Y). The mutant CYP19 isoforms show increased androgen conversion due to the KN transmembrane helix. In addition, the TY substitutions in helix C result in a substrate preference for androstenedione. Our structural models suggest that CYP19 mutants may interact differently with the membrane (affecting substrate uptake) and with CPR (affecting electron transfer), providing structural clues for the catalytic differences.
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