Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Survival After Out-of-Hospital Cardiac Arrest in Relation to Age and Early Identification of Patients With Minimal Chance of Long-Term Survival
- Population Movement and Sudden Cardiac Arrest Location
- Molecular and Genetic Analyses of Collagen Type IV Mutant Mouse Models of Spontaneous Intracerebral Hemorrhage Identify Mechanisms for Stroke Prevention
- Infective Endocarditis After Transcatheter Aortic Valve Implantation: Results From a Large Multicenter Registry
- MicroRNA-155 Exerts Cell-Specific Antiangiogenic but Proarteriogenic Effects During Adaptive Neovascularization
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Survival After Out-of-Hospital Cardiac Arrest in Relation to Age and Early Identification of Patients With Minimal Chance of Long-Term Survival
Between 2001 and 2011 in Denmark, national initiatives were undertaken to improve cardiac arrest management, including widespread cardiopulmonary resuscitation training of the population, strengthening of the emergency medical service system, and improvements in advanced care. In parallel, bystander cardiopulmonary resuscitation and survival rates have more than doubled, indicating that, although out-of-hospital cardiac arrest is a devastating medical condition associated with a poor prognosis, systematic efforts can result in improvement in overall survival. On the basis of these findings, we assessed how these changes over time were reflected in different adult age groups. The main findings indicate that the national initiatives undertaken to improve cardiac arrest management have had a positive impact in the prehospital setting, regardless of patient age, with a large increase in return of spontaneous circulation on arrival at the hospital. Long-term survival also increased but was numerically negligible in patients >80 years of age. Importantly, rates of anoxic brain damage were low in senior long-term survivors; overall, emphasizing that patient age alone should not be used as a criterion for whether a resuscitation attempt should be terminated. In contrast, with the use of only 2 criteria (no return of spontaneous circulation on hospital arrival and no prehospital shock from a defibrillator), it was possible to identify patients with minimal chance of 30-day survival, regardless of age. Hence, only 3 of 9499 patients achieved 30-day survival if they met these 2 criteria on arrival at the hospital. This information could be helpful in the decision-making process regarding when to terminate a resuscitation attempt. See p 1536.
Population Movement and Sudden Cardiac Arrest Location
Sudden cardiac arrest (SCA) remains a leading cause of death in the industrialized world. Survival remains poor despite decades of research and major financial investments in resuscitation. Because SCA most often presents with initial ventricular fibrillation, external defibrillation has been incorporated as a key factor in the chain of survival since the early 1990s. Public-access defibrillation programs have thus been developed to make automatic external defibrillators (AEDs) more widely available. Although the benefits of AEDs are undeniable, the effectiveness of such programs could be dramatically improved. One of the key issues is the disparity between the locations of AEDs and SCAs. Although preliminary data have identified sites with a higher risk of SCAs, the determinants of those areas have not yet been identified and quantified. In this study, we collected data on SCA locations in Paris over a 10-year period. We emphasized the extent to which, in the setting of a large urban area, the distribution of SCA was clustered in major “hot spots.” We demonstrated that the number of population movements was a major determining factor of SCA location. However, beyond population movements, our results strongly suggest that some areas (especially major train stations) remain at particularly high risk for SCA occurrence (5-fold higher risk compared with tourist areas with similar population movements). This should provide evidence to the medical community and policy makers to guide strategies for optimal AED deployment, especially in concentrating AEDs in high-risk areas for SCA. See p 1546.
Molecular and Genetic Analyses of Collagen Type IV Mutant Mouse Models of Spontaneous Intracerebral Hemorrhage Identify Mechanisms for Stroke Prevention
Despite intracerebral hemorrhage (ICH) being the most fatal form of stroke, there is a lack of effective treatment options, and only a few genetic causes have been identified. Mutations in the collagen type IV alpha1 (COL4A1) and alpha2 (COL4A2) genes cause highly penetrant cerebrovascular disease, including porencephaly, perinatal ICHs, small-vessel disease, and recurrent spontaneous ICHs in adults. Using Col4a1 mutant mice modeling human disease, we showed that the pathogenesis occurs in different phases, with age-related ICHs and macroangiopathy being consequences of abnormal vascular development. Our data suggest that toxic intracellular collagen accumulation in the abnormal vasculature is a key pathogenic event that leads to ICH progression. Using sodium 4-phenylbutyrate, a US Food and Drug Administration–approved drug with chemical chaperone properties, we showed that targeting this event in our mouse model, even after birth, successfully decreases ICH severity in vivo. We also discovered important allelic effects, with mutation class, domain, and position all influencing ICH severity. We recommend considering them when functionally testing putative mutations identified in ICH patients because mutations near the amino terminus may cause only mild intracellular collagen accumulation, resulting in false negatives. Showing that position-matched mutations in Col4a1 and Col4a2 caused similar ICH severity, our results also stress the importance of analyzing both genes when genetically screening patients. Finally, we found that vaginal delivery, intense exercise, and anticoagulant use exacerbate ICH severity. We propose that controlling these modifiable environmental risk factors and targeting intracellular collagen accumulation are viable approaches for stroke prevention in patients with COL4A1 and COL4A2 mutations. See p 1555.
Infective Endocarditis After Transcatheter Aortic Valve Implantation: Results From a Large Multicenter Registry
Data on the predictors, causes, clinical characteristics, treatment, and clinical outcomes of infective endocarditis (IE) after transcatheter aortic valve implantation are scarce. The present multicenter international registry reports 53 cases of IE among 7944 patients who underwent transcatheter aortic valve implantation, representing a 1 year incidence of 0.5% (similar to that reported for surgical prosthetic valves). The 2 factors associated with IE were orotracheal intubation and use of the self-expandable CoreValve system. However, no clear mechanisms linking these factors to IE were found, and further research is needed to confirm these findings. The microbiological profile of IE after transcatheter aortic valve implantation highlighted the important role of healthcare–related infections in such patients (in addition to enterococci), with Staphylococcus aureus and coagulase-negative staphylococci accounting for nearly half of the cases. This finding highlights the importance of reinforcing meticulous aseptic techniques during healthcare procedures. The location of the infection, with more than one third of patients exhibiting vegetations outside the prosthetic valve leaflets (at either the level of the stent frame or the mitral valve), reflects the particularities of this population/procedure, with a significant amount of metal in the ascending aorta and a high proportion of patients with mitral disease left untreated. Although close to 90% of patients developed complications, only 11% of them received surgical treatment, probably reflecting the very high surgical risk profile of this population. However, the prognosis was ominous; close to half of the patients died in hospital, and only one third were still alive at 1 year after the index IE. These results provide important insight into IE after transcatheter aortic valve implantation and should contribute to improving the management of this life-threatening entity. See p 1566.
MicroRNA-155 Exerts Cell-Specific Antiangiogenic but Proarteriogenic Effects During Adaptive Neovascularization
Following the narrowing or occlusion of an arterial vessel during the progression of coronary or peripheral artery disease, the organism can respond with the adaptive growth of new capillaries (angiogenesis) and collateral arteries (arteriogenesis). Although these mechanisms are protective in vascular occlusive disease, they can be harmful in the pathogenesis of other diseases, such as neoplastic tumor growth. In addition, in a clinical setting it can be desirable to selectively stimulate one form of vascular growth, for example, the enlargement of collateral arteries in peripheral artery disease without stimulating angiogenesis-driven processes, such as diabetic retinopathy or intraplaque angiogenesis. In this article we provide evidence that microRNA miR-155 exerts a proarteriogenic but antiangiogenic effect in a mouse model of peripheral artery disease. MiRs are short endogenous RNA molecules with an important regulatory function in many biological processes. The surprising divergent effect of miR-155 on the different forms of vascular growth depends on the cell-specific expression pattern of divergent target genes in endothelial cells and monocytes/macrophages. Our findings also show that blood flow reconstitution in our model of arterial occlusive disease is predominantly dependent on arteriogenesis. Because miRNA expression can be therapeutically targeted by oligonucleotide-based therapies, these regulatory RNAs could be promising targets for the independent therapeutic modulation of the different forms of vascular growth. However, because miR-155 exerts a multifunctional role in basic immunity, future studies will need to explore possible harmful adverse effects and other potential miRNA modulators for clinical application. See p 1575.
- © 2015 American Heart Association, Inc.
- Population Movement and Sudden Cardiac Arrest Location
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