HomeCirculationVol. 130, No. 24Circulation: Clinical Summaries Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCirculation: Clinical SummariesOriginal Research Put Into Perspective for the Practicing Clinician Originally published9 Dec 2014https://doi.org/10.1161/CIR.0000000000000124Circulation. 2014;130:2127–2128Endovascular Treatment of Mycotic Aortic Aneurysms: A European Multicenter StudyPrimary infectious (mycotic) aortic aneurysm is a rare but life-threatening disease. The disease carries a very poor prognosis because mycotic aneurysms have a tendency to grow rapidly and to rupture. Furthermore, patients often have severe comorbidities, are immunosuppressed, and have coexisting sepsis. Conventional surgical treatment with resection of the aneurysm, extensive local debridement, and revascularization by in situ reconstruction or extra-anatomic bypass is the gold standard but carries a high mortality and morbidity. In addition, the anatomic location of the aneurysm sometimes makes surgical repair very demanding, or even impossible. Reports on endovascular treatment for mycotic aneurysm have shown promising results, but only small single-center case series with limited follow-up have been published. The crucial question of durability therefore remains unanswered. The disease is difficult to study because of its rarity, and therefore large-scale multicenter collaborations are necessary. This European multicenter study, the largest ever on mycotic aortic aneurysm, shows that endovascular treatment of mycotic aortic aneurysms is feasible and, for most patients, a durable treatment option. However, late infection–related complications do occur and are often lethal, indicating a need for vigilant antibacterial treatment and follow-up. See p 2136.Body Mass Index and the Risk of All-Cause Mortality Among Patients With Type 2 Diabetes MellitusIn a prospective cohort study of 19 565 black and 15 402 white patients with type 2 diabetes mellitus, we evaluated the association between body mass index (BMI) and death risk. During a mean follow-up of 8.7 years, 4088 deaths were identified. The multivariable-adjusted (age, sex, smoking, income, and type of insurance) hazard ratios of all-cause mortality associated with BMI levels (<23, 23–24.9, 25–29.9, 30–34.9 [reference group], 35–39.9, and ≥40 kg/m2) at baseline were 2.22 (95% confidence interval [CI], 1.90–2.60), 1.74 (95% CI, 1.46–2.07), 1.23 (95% CI, 1.08–1.41), 1.00, 1.19 (95% CI, 1.03–1.39), and 1.23 (95% CI, 1.05–1.43) for blacks and 1.78 (95% CI, 1.50–2.12), 1.51 (95% CI, 1.27–1.80), 1.07 (95% CI, 0.94–1.21), 1.00, 1.07 (95% CI, 0.93–1.23), and 1.20 (95% CI, 1.05–1.38) for whites, respectively. The U-shaped association of BMI with all-cause mortality was confirmed among diabetic patients who were never smokers and current smokers. When we used an updated mean or last-visit value of BMI, the U-shaped association of BMI with all-cause mortality risk did not change. The present study indicated a U-shaped association of BMI with all-cause mortality risk among black and white patients with type 2 diabetes mellitus. A significantly increased risk of all-cause mortality was observed among blacks with BMI <30 and ≥35 kg/m2 and among whites with BMI <25 and ≥40 kg/m2 compared with patients with BMI of 30 to 34.9 kg/m2. Considering the result of Look AHEAD (Action for Health in Diabetes) and our study, we still need to re-evaluate the long-term effects of weight loss on mortality risk among type 2 diabetic patients. See p 2143.Cardiac Remodeling in Response to 1 Year of Intensive Endurance TrainingExercise training is an essential component of the treatment of nearly all cardiovascular diseases, leading to improved functional capacity and reduced cardiovascular morbidity and mortality via multiple mechanisms. Endurance athletes, representing the pinnacle of exercise training, have large, compliant hearts that pump large volumes of blood very quickly to support high rates of oxidative metabolism. Whether such an adaptation is attributable to prolonged and intense exercise training or is an inherited characteristic required to be a successful endurance athlete was hitherto unknown, in part because no one has attempted a long-term training study incorporating training durations and intensities typically practiced by competitive athletes. This study showed that there is quite remarkable plasticity in the heart and circulation: Prolonged and intense training led to increases in cardiac muscle mass equivalent to cross-sectional studies of endurance athletes. Intriguingly, increases in right ventricular mass and volume occur early in an endurance training program and may be permissive of an eventual increase in left ventricular volumes, allowing for the “classic” eccentric hypertrophy of the endurance athlete. However, even a year of training in a previously sedentary, healthy individual cannot generate the same aerobic power (maximum oxygen uptake) and cardiac compliance/enlargement of a successful endurance athlete. The clinician should be aware not only of the extent of cardiac plasticity but the dose–response nature of this adaptation: Lower doses of training lead primarily to increases in left ventricular mass without increases in volume, which only occur after the incorporation of training sessions involving long durations (hours) or high intensities. See p 2152.Transforming Growth Factor β–Activated Kinase 1 Signaling Pathway Critically Regulates Myocardial Survival and RemodelingCumulative loss of functional cardiac myocytes by programmed cell death has been associated with acute myocardial injury, cardiomyopathy, and heart failure. A new form of programmed cell death, called necroptosis or programmed necrosis, has been implicated in a number of pathological conditions such as ischemic injury and neurodegenerative disease. However, how necroptotic cell death is regulated in the heart, and its potential relevance in the pathogenesis of heart disease, remain largely unknown. Here, we identified a novel transforming growth factor β–activated kinase 1 (TAK1) signaling pathway that functions as a nodal regulator of necroptosis in the heart. Cardiac-specific ablation of TAK1 in mice triggered pathological remodeling and heart failure through the induction of necroptotic cell death. Moreover, inhibition of necroptosis prevented adverse remodeling and heart failure progression in the TAK1-deficient mice. Mechanistically, TAK1 critically regulates tumor necrosis factor receptor 1–mediated apoptosis and necroptosis and the formation of 2 critical cell death–inducing complexes, receptor-interacting protein (RIP) 1–FADD–caspase 8 and RIP1-RIP3. These findings suggest that the TAK1 signaling pathway and its effectors may serve as novel therapeutic targets for treating heart failure. Indeed, we showed that activation of TAK1 prevents necroptosis signaling in cardiac myocytes. Importantly, inhibition of the TAK1 interacting protein RIP1 by necrostatin-1 blocked necroptotic myocyte death and rescued pathological remodeling and heart failure in a mouse model of necroptosis. See p 2162.Hydrogen Inhalation During Normoxic Resuscitation Improves Neurological Outcome in a Rat Model of Cardiac Arrest Independently of Targeted Temperature ManagementDespite advances in the management of patients who experience a nontraumatic cardiac arrest (CA), survival rates remain low, and many survivors are left with neurological and cardiac sequelae. Post-CA syndrome, including neurological dysfunction, cardiac damage, and sepsis-like systemic inflammation, is likely to contribute to the multisystem organ dysfunction and ultimate demise of many CA victims. Therapeutic hypothermia is widely accepted as the gold standard method to improve survival and to limit neurological outcomes in patients who achieve return of spontaneous circulation after CA. However, it is still underused, and there is a need for the development of alternative approaches to ameliorate the prognosis of post-CA patients. Hydrogen gas (H2) has antioxidant and anti-inflammatory properties, and its protective effects have been demonstrated in different animal models. For example, H2 limits infarct volume in the brain and heart by reducing ischemia/reperfusion injury without altering hemodynamic parameters. It also provides protection against the multiorgan damage elicited by generalized inflammation. We showed that H2 inhalation, begun after resuscitation with normoxia, improves neurological outcome in a rat model of CA independently of targeted temperature management. Histological studies confirmed that improved neurological outcomes were associated with reduced neuronal degeneration and microglial activation in a selectively vulnerable brain region. It is of particular importance that the combined therapy of targeted temperature management and H2 inhalation produced a better outcome than targeted temperature management alone because a recent randomized controlled trial failed to prove the benefit of therapeutic hypothermia at a targeted temperature of 33°C alone compared with a targeted temperature of 36°C. See p 2173. Previous Back to top Next FiguresReferencesRelatedDetails December 1, 2014Vol 130, Issue 24 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/CIR.0000000000000124 Originally publishedDecember 9, 2014 PDF download Advertisement