Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway
- Continuous Amplitude-Integrated Electroencephalographic Monitoring Is a Useful Prognostic Tool for Hypothermia-Treated Cardiac Arrest Patients
- Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic Stroke: A Pilot Trial
- Improving the Diagnosis of Infective Endocarditis in Prosthetic Valves and Intracardiac Devices With 18F-Fluordeoxyglucose Positron Emission Tomography/Computed Tomography Angiography: Initial Results at an Infective Endocarditis Referral Center
- Impact of Institutional Volume on Outcomes of Catheter Directed Thrombolysis in the Treatment of Acute Proximal Deep Vein Thrombosis: A 6-Year US Experience (2005–2010)
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Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway
The Sir2 family is a NAD+-dependent histone and protein deacetylase, which was originally identified as a regulator of gene silencing in yeast. Sir2 is involved in a wide range of cellular responses, such as stress resistance, senescence, tumorigenesis, and energy metabolism. The Sir2 family of enzymes is well conserved from bacteria to humans and seven different homologs of yeast Sir2, termed sirtuin, exist in mammals. Sirt7 was identified as a seventh member of sirtuin. Cardiac Sirt7 transcript expression is decreased upon aging. On the other hand, Sirt7 expression is increased in malignant tumors, and a recent study showed that Sirt7 promotes the invasion of cancer cells. Because tumor growth and metastasis require fibrotic and angiogenic responses, we hypothesized that Sirt7 plays a role in cardiovascular tissue repair process. In the present study, using homozygous Sirt7-deficient mice, we found that: 1) Sirt7 contributes to scar formation, angiogenesis, and inflammation; 2) loss of Sirt7 attenuates TGF-β signaling, which is associated with reduction in TβRI protein; and 3) Sirt7 maintains TβRI protein by modulating autophagy. To our knowledge, this is the first study that describes the functional role of Sirt7 in tissue repair process in response to acute cardiovascular insults. Since TGF-β modulates a wide variety of cellular responses, Sirt7 seems a potentially attractive therapeutic target to modulate disease progress, not only in cardiovascular disorders, but also in other conditions including fibrotic diseases and malignancies. See p 1081.
Continuous Amplitude-Integrated Electroencephalographic Monitoring Is a Useful Prognostic Tool for Hypothermia-Treated Cardiac Arrest Patients
Continuous electroencephalography can be used to monitor the postischemic brain after cardiac arrest. However, this technique requires experienced specialists for application and interpretation and is often unavailable. Amplitude-integrated electroencephalography provides a simplified and, therefore, more readily available brain function–monitoring tool for not only perinatal hypoxic-ischemic encephalopathy in neonates, but also cardiac arrest in adults. In neonates, the time from birth to a normal amplitude-integrated electroencephalography background was the best predictor of poor neurological outcome. In this study, we found that the time from the return of spontaneous circulation to a normal amplitude-integrated electroencephalography trace within 24 hours was associated with good neurological outcome in patients who survived for 72 hours after successful resuscitation from cardiac arrest. We also show that the lack of normal trace development within 36 hours and the occurrence of burst suppression or status epilepticus contributed to the prediction of poor outcome. Importantly, the combination of these negative predictors reduced the time to prognostication. Based on early amplitude-integrated electroencephalography monitoring, patients could be categorized early according to the degree of brain injury. Thus, future studies should continue to define patient subgroups and should evaluate the benefit of tailored therapies for each patient’s brain injury. See p 1094.
Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic Stroke: A Pilot Trial
Alteplase is the only approved medical treatment for acute ischemic stroke. The extremely narrow time window of indication (4.5 hours after onset) results in only 3% to 10% of patients being eligible for this therapy. Inflammatory and immune responses triggered by brain ischemia worsen clinical outcomes of stroke and contribute to hemorrhagic transformation, massive edema, and reperfusion injury associated with intravenous alteplase. We assessed whether a combination of the immune-modulator fingolimod and alteplase is safe and effective in attenuating reperfusion injury in patients with acute ischemic stroke treated within the first 4.5 hours of symptom onset. In this early-phase clinical trial, the combination of fingolimod with alteplase appeared to be well tolerated, attenuated reperfusion injury with improvement in hemorrhage formation, halted enlargement of lesion volume, and improved the short-term and long-term clinical outcomes in patients with acute ischemic stroke within 4.5 hours of onset. The efficacy of modulating the immune system in conjunction with intravenous thrombolysis in acute ischemic stroke urges further investigation in large late-phase trials. See p 1104.
Improving the Diagnosis of Infective Endocarditis in Prosthetic Valves and Intracardiac Devices With 18F-Fluordeoxyglucose Positron Emission Tomography/Computed Tomography Angiography: Initial Results at an Infective Endocarditis Referral Center
The diagnosis of infective endocarditis in patients with prosthetic valves and devices is difficult because echocardiography has limitations in this field. The prognosis of this very serious disease may improve by earlier diagnosis and management. On the other hand, ruling out the diagnosis in doubtful cases is also important to avoid unnecessary, long, potentially dangerous treatments. In this article, the role of fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and F-FDG PET/CT angiography is analyzed in this clinical setting. The sensitivity and specificity of the conventional Duke criteria for the diagnosis of IE increased significantly with the addition of IE 18F-FDG PET/CT from 52% and 95% to 91% and 89%, respectively, and allowed a reclassification of possible infective endocarditis into a more conclusive (definite/rejected) diagnosis in 95% of cases. The addition of CT angiography improved the results by decreasing the number of doubtful cases. These results are encouraging, and we believe that 18F-FDG PET/CT and, when available, 18F-FDG PET/CT angiography will help clinicians make an earlier definite diagnosis of this very difficult disease and consequently start antibiotic treatment and discuss surgical indications promptly. In addition, this technique will help clinicians reject the diagnosis in doubtful cases. Our study also emphasizes the need for having a multidisciplinary team to diagnose and treat patients with endocarditis. See p 1113.
Impact of Institutional Volume on Outcomes of Catheter Directed Thrombolysis in the Treatment of Acute Proximal Deep Vein Thrombosis: A 6-Year US Experience (2005–2010)
Catheter-directed thrombolysis (CDT) is a minimally invasive therapeutic intervention that has evolved over the past 2 decades to reduce the incidence of postthrombotic syndrome, a very frequent and disabling complication of proximal deep vein thrombosis. CDT has been shown to significantly reduce this lifestyle-limiting complication of deep vein thrombosis, and as a result, we have observed a significant increase in the use rates of CDT. Recent observational data suggest that higher adverse events such as intracranial hemorrhage rates and need for blood transfusions are seen with CDT use, but specific reasons for these findings have not been explored before our study. This study shows a significant inverse relationship between the institutional CDT volumes and safety outcomes such as death and intracranial hemorrhage. These findings highlight the importance of standardization of CDT practice and bring into focus the factors that may decrease adverse bleeding complications. Our observation that the major safety outcomes (death and intracranial hemorrhage) were not significantly different between patients undergoing CDT and patients undergoing anticoagulation therapy alone at high-volume centers suggests that these complications can be minimized. As use of CDT continues to increase, we propose that institutions follow standardized CDT protocols that include careful patient selection and patient monitoring. In addition, establishing centers of excellence in treating venous thromboembolic disease may provide the necessary framework within which bleeding risk to the patient can be minimized. See p 1127.
- © 2015 American Heart Association, Inc.
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