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Normoxic reperfusion may improve cardiac arrest outcomes
Genome-wide search identifies genes that may predict cardiovascular risk
Atrial electrograms improve nurses’ diagnosis of postoperative cardiac arrhythmias
Cardiac arrest survival may improve with resuscitation care at critical care centers
PCI approaches successful in revascularizing patients with chronic CTO
Normoxic reperfusion may improve cardiac arrest outcomes
Minimizing the use of hyperoxic reperfusion during resuscitation after cardiac arrest might minimize oxidative stress and improve neurologic outcomes, an anesthesiology researcher said Saturday.Gary Fiskum, Ph.D., presented his conclusions at the Resuscitation Science Symposium titled “Molecular Insights For and Against Hyperoxygenation After Cardiac Arrest.”
Reperfusion is associated with a surge in reactive oxygen species (ROS), which leads to the induction of apoptotic gene expression and enzyme activity, said Dr. Fiskum, professor in the Departments of Anesthesiology, Biochemistry & Molecular Biology, and Pharmacology & Experimental Therapeutics at the University of Maryland School of Medicine in Baltimore. “It is well known that oxidative stress can contribute to the induction of that gene expression,” he said.
In vitro data indicate that very low or very high brain tissue oxygen tension (PtO2) are associated with higher rates of free radical production. Dr. Fiskum said that increasing the PtO2 — for example, from 30 to 70 mm Hg — may further stimulate ROS production without necessarily stimulating energy metabolism.
These observations led Dr. Fiskum and colleagues to ask whether using lower oxygen concentrations during resuscitation after cardiac arrest could improve neurologic outcomes.
In a canine model of cardiac arrest, Dr. Fiskum and colleagues have found that oximetry-guided normoxic resuscitation that rapidly adjusts the fraction of inspired oxygen is associated with lower rates of cerebral hyperoxia, improved neurologic outcomes, and less neuronal cell death compared with continued ventilation with 100 percent oxygen.
Normoxic resuscitation also appears to have early effects detectable at the molecular level that improve cell function and survival, including reductions in oxidative lipid and protein modifications, metabolic enzyme inactivation, brain lactate accumulation, and improvements in aerobic energy metabolism. Early normoxic reperfusion is also associated with reductions in delayed microglial activation, delayed macrophage infiltration, and delayed DNA oxidation.
Based on these findings, Dr. Fiskum concluded that clinical trials are needed to compare hyperoxic resuscitation to safe, normoxic resuscitation.
Echoing this sentiment, a recent International Liaison Committee on Resuscitation (ILCOR) Consensus Statement recommends, on the basis of preclinical evidence alone, that clinicians avoid unnecessary arterial hyperoxia in post-cardiac arrest syndrome by adjusting the fraction of inspired oxygen (FiO2). However, this approach has not been evaluated in randomized, prospective, controlled trials.
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Genome-wide search identifies genes that may predict cardiovascular risk
At least 20 different DNA variants at different sites in the genome put patients at risk for elevated levels of low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI), a Harvard cardiologist said Saturday.Sekar Kathiresan, M.D., director of preventive cardiology, Massachusetts General Hospital, and assistant professor of medicine, Harvard Medical School, presented his research on “Genes for Prognosis: Integrating Genetic Determinants into Risk Scores” during the Third Annual Cardiovascular Nursing Symposium.
To improve the ability to predict risk beyond traditional risk factors for MI, Dr. Kathiresan and his collaborators sought to determine DNA sequence variants that may predict patients at increased risk for elevated LDL-C and MI.
He and his collaborators first determined how nine specific DNA sequence variants called single nucleotide polymorphisms or SNPs that affect lipid levels contributed to the risk of CV events. Based on whether individuals had 0, 1 or 2 copies of the unfavorable allele, a genotype score that ranged from 0 to 18 was generated. Researchers showed that genotype scores, independent of traditional risk factors, could correctly estimate the risk of CV events in 5,414 subjects from the cardiovascular cohort of the Malmö Diet and Cancer Study.
“Genotype score adds information above and beyond measured plasma lipids,” Dr. Kathiresan said. “It is an index of the lifelong change in LDL-C and a more precise measure of exposure than single time point plasma LDL-C.”
Having shown that SNPs could provide a genotype score, Dr. Kathiresan and colleagues surveyed 19,840 genomes and about 2.4 million DNA variants and determined that 30 genetic loci affected blood lipid levels, of which 11 affected LDL-C. Using the genotype scoring system on these, the researchers found that those with the highest genotype scores were one and a half times more likely to have higher LDL-C levels compared with the lowest genotype scores.
They next determined if, independent of LDL-C, there were separate loci that were directly associated with risk for MI. The Myocardial Infarction Genetics Consortium, which included centers in the United States and Europe, provided their initial insights into this analysis. Six centers provided 2,967 cases and 3,075 controls. Surveying 6,042 genomes and about 2.5 million variants, Dr. Kathiresan and colleagues found six common variants at different genetic loci that independently predicted risk for CV events. They determined that the individuals with the highest genotype scores had twice the risk of MI compared with individuals who had the lowest scores. The question remains whether this set of genes can be used as a diagnostic test to treat individuals pharmacologically, which would decrease CV risk. “Not yet,” said Dr. Kathiresan. “Additional studies need to be done. The greatest value of these studies is that new clues can be obtained about the causal genes that may be associated in human subjects for elevated LDL-C and MI.”
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Atrial electrograms improve nurses’ diagnosis of postoperative cardiac arrhythmias
Using atrial electrograms (AEGs) may significantly improve nurses’ ability to accurately diagnose cardiac arrhythmias in postoperative cardiac surgery patients, according to a study presented Saturday during the Third Annual Cardiovascular Nursing Symposium.“Diagnosing cardiac rhythms correctly is key to ensuring patients receive appropriate treatment for rhythm abnormalities, and the responsibility for detecting cardiac arrhythmias falls largely to nurses,” said Marion McRae, R.N., B.C., M.Sc.N., CCRN-CSC-CMC, CCN(C), APRN, a nurse practitioner in cardiovascular surgery at the Toronto General Hospital, University Health Network, and a clinical associate on the nursing faculty at the University of Toronto.
Atrial activity is difficult to discern using surface electrocardiograms. However, in postoperative cardiac surgery patients, it can be magnified using atrial electrograms recorded from temporary atrial epicardial pacemaker wires.
The 2004 AHA Practice Standards for ECG Monitoring in Hospital Settings recommend using an AEG to improve the diagnostic accuracy of postoperative tachyarrhythmias. Continuous monitoring of atrial electrograms on a bedside monitor can increase the detection of atrial arrhythmias.
Many nurses do not regularly use AEGs, despite their value. However, in a study involving 261 nurses at three teaching hospitals, McRae and associates demonstrated that nurses could easily learn to record and interpret an AEG, resulting in improvements in diagnosing cardiac arrhythmias compared with surface ECG alone.
In the study, nurses first interpreted surface ECG rhythms that might benefit from AEG use. After completing a standardized 30-minute educational session regarding AEG interpretation and an eight-week practice period, they reanalyzed the same ECG rhythms in the context of AEG findings. The nurses’ diagnostic accuracy significantly improved by using AEG (P < .001), in particular for discerning sinus vs. junctional rhythms and for differentiating between junctional rhythms and atrial fibrillation and flutter.
Nurses in the study generally found AEGs easy to record and moderately easy to interpret, but only 43 percent reported using AEGs at least monthly, and only 3 percent used them daily. Nurses cited a need for more education and practice on the technology.
Many bedside cardiac monitors and telemetry systems can’t be properly set to appropriate AEG alarm levels, resulting in more false alarms, McRae said.
“Monitoring systems that enable AEGs to be separately labeled with separate alarm parameters may help prevent unnecessary alarms,” McRae said.
Despite these challenges, she said the success of their training program supports the expense of including content on AEG monitoring in cardiac surgical educational and orientation programs.
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Cardiac arrest survival may improve with resuscitation care at critical care centers
Survival from out-of-hospital cardiac arrest may improve when initial resuscitation and post-arrest care is provided at a hospital designated as a critical care center, noted an emergency medicine and critical care investigator from Japan.Kentaro Kajino, M.D., Ph.D., presented his study findings at the Resuscitation Science Symposium titled “Impact of Transport to Critical Care Centers vs. Non-Critical Care Hospitals on Outcomes from Out-of-Hospital Cardiac Arrest in Osaka, Japan.” The study examined whether treatment in a specialized critical care hospital results in better outcomes for patients who have had cardiac arrest out of hospital.
“It has been reported that in-hospital post-resuscitation care, including the use of hypothermia and early PCI, improves out-of-hospital cardiac arrest survival,” Dr. Kajino said. “Others have reported that hospital differences in survival from all out-of-hospital cardiac arrests are primarily related to pre-hospital factors rather than in-hospital factors or patient characteristics.”
Dr. Kajino and his colleagues compared survival outcomes among cardiac arrest patients transported to critical care centers vs. non-critical care hospitals in Osaka. One-month neurologically favorable survival was the primary outcome of the study. Over the three years of the study, emergency medical technicians (EMTs) transported more than 2,800 cardiac arrest patients to hospitals designated as critical care centers and more than 7,500 cardiac arrest patients to non-critical care centers. In some cases, cardiac arrest patients had a return of spontaneous circulation (ROSC) prior to transport to either a critical care center or non-critical care center. Other patients were transported without ROSC.
The investigators found that neurologically favorable survival at one month was greater among the patients transported to a critical care center and resuscitated in hospital than among those taken to a non-critical care center, after adjusting for confounding variables, such as the patient’s age, gender, transport time and initial rhythm.
“For patients without field ROSC, in-hospital resuscitation and post-resuscitation care in a critical care center was an independent predictor of outcome,” Dr. Kajino concluded.
However, among patients who had ROSC in the field, there was no significant difference in neurologically favorable one-month survival outcomes regardless of transport destination.
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PCI approaches successful in revascularizing patients with chronic CTO
Percutaneous coronary intervention (PCI) for the treatment of chronic coronary total occlusion (CTOs) has introduced new benefits and new dilemmas as presented in the Saturday daytime seminar focusing on “Chronic CTOs: State of the Art.” Presenter David E. Kandzari, M.D., FACC, FSCAI, director of Interventional Cardiology Research at Scripps Clinic, Mayo Clinic in Rochester, Minn., described the rationale for CTO PCI. “CTO is the main reason for incomplete revascularization,” Dr. Kandzari said. “Yet, from observational registries, there is a striking consistency that procedural success in opening CTOs is associated with a survival benefit over one to 10 years.”
For instance, Valenti et al. (2008) recently showed in a study of 527 CTOs that successful revascularization was possible in 68 percent of CTO lesions, which led to higher cardiac survival (94 percent), compared to incomplete revascularization (84 percent). The benefit was mainly driven by the differences in outcome among patients with multivessel disease who achieved complete revascularization.
New approaches, such as the retrograde technique, have greatly increased procedural attempts and success rates. But new complications come with new techniques, Dr. Kandzari said. “We need CTO-specific clinical trials that better inform procedural outcomes.”
The rationale for the “late open artery hypothesis” is found to avoid future ischemic or arrhythmic events, improve left ventricular function and enhance survival, Dr. Kandzari said.
Within the context of the late open artery hypothesis, “Many patients who might benefit from CTO revascularization may be dismissed in clinical practice on the basis of age or length of the occlusion, prior history of MI, or left ventricular dysfunction,” Dr. Kandzari said. “However, our ability to determine lesion age is not exact and patients with abnormal left ventricular function and healthy myocardium downstream may be considered for revascularization and their prognosis improved.”Dr. Kandzari recommends clinicians consider key questions in selecting patients for PCI revascularization:
• Is the patient symptomatic?
• What are the chances of procedural success, and will this improve symptoms and prognosis?
• What are the risks of attempted recanalization in this patient?
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