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NHLBI Working Group: Pulseless Electrical Activity (PEA) – Definition, Causes, Mechanisms, Management, and Research Priorities for the Next DecadeExecutive SummaryOn June 6, 2012, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group (WG) in Bethesda, MD to discuss current knowledge and future directions for research in prediction, prevention, and management of pulseless electrical activity (PEA), as well as to explore probable causal pathways. During the past decade, PEA has emerged as one of the dominant mechanisms associated with sudden cardiac arrest (SCA), frequently resulting in sudden cardiac death. WG participants had expertise in basic, clinical, and epidemiologic aspects of SCA, including PEA in particular. WG participants focused on identification of current scientific gaps and areas that require NHLBI leadership, facilitation, and support for scientific and clinical progress. DiscussionAs a greater proportion of out-of-hospital SCAs and resulting deaths have been associated with PEA, as opposed to ventricular tachycardia (VT) and ventricular fibrillation (VF), PEA is recognized as an increasingly important public health burden. In general, SCA is a leading cause of death in adults in the U.S., resulting in an estimated >200,000 to 450,000 deaths each year, and accounts for 50% of all cardiovascular deaths. This wide range is a result of reporting differences for SCA and a lack of consistent definitions and epidemiologic methods. WG participants explored whether the emergence of PEA as a major contributor to SCA results from an absolute increase in its incidence, or if the apparent increase results from past progress in the recognition, prevention, and treatment of VT/VF, resulting in reduced contributions of these rhythm disturbances. WG participants also discussed difficulties in diagnosing PEA in- and out-of-hospital resulting from the inability to detect a pulse, especially in differing clinical environments. Additionally, the absence of common definitions between scientific fields of expertise was noted. Based on limited existing data from clinical observations and experimental models, it is reasonable to assume that PEA may result from multiple and differing mechanisms, each with specific implications for prediction and prevention. With respect to the fundamental causes of PEA, WG participants noted that this phenomenon is difficult to study experimentally due to the limited range of mechanisms that have been explored using existing animal models of PEA. As with VT and VF, WG participants indicated that understanding of PEA could be improved by using approaches that explore genetic factors that might predispose certain individuals to its occurrence. Similarly, WG participants explored whether current approaches employing proteomic techniques might also aid in identifying both risk factors and biomarkers that would better identify patients most likely to experience PEA. Because of the apparent diversity of clinical associations with different mechanisms of PEA, and the previous concentrated focus on VT/VF, strategies are lacking to define risk prediction in small subgroups or individuals. Potential therapeutic interventions to improve survival from PEA were also explored. Considerations included strategies targeting ischemic injury cascade, such as early application of hypothermia, improved reperfusion strategies, and possible novel pharmacological interventions aimed at mitigating ischemia/reperfusion injury and increased blood flow to at-risk myocardium, brain, and other vital organs. It was specifically noted that improved methods are needed to appropriately monitor hemodynamics and the metabolic state during resuscitation and recovery. Thus, WG discussions centered on four major areas: a) epidemiology and the prediction patients at risk for developing PEA, b) causes and pathophysiology, c) clinical profiling, and d) development of effective therapeutic interventions. WG Recommendations:The working group made the following specific recommendations: I. EPIDEMIOLOGYDesign surveillance studies, with both clinical and electrocardiographic documentation, that identify and risk-stratify specific subgroups of PEA according to population burden, predictability, mechanisms, and survivability. Refine current definitions as they apply to multiple medical and scientific specialties that establish commonalities and differences between terms applicable to subgroups of PEA. II. MECHANISMS AND PATHOPHYSIOLOGYDefine subgroups amenable to specific and potentially-effective preventive strategies and interventional therapies. This will require development of new experimental models that replicate specific clinical circumstances. Models should be developed in conjunction with studies of potential pathophysiological pathways suggested by biomarkers identified before or during PEA, potential genetic determinants, and proteomic insights, to guide the development of practical clinical and therapeutic strategies. The interactions of specific medications in the pathophysiology of PEA should be defined. III. CLINICAL PROFILINGDesign studies targeted to the development of systems for monitoring transient risk for PEA in specific subgroups, including small clinical trials designed to justify large intervention studies. These studies should be carried out in specific subgroups, based upon hypotheses derived from pathophysiologic mechanisms and justified by existing and newly emerging data on the etiologic bases of PEA. IV. INTERVENTIONSDesign interventional studies with specific targets, including: a) development and testing of methods to improve blood flow during resuscitation, including the use of compressions synchronized to residual cardiac activity, when present; b) testing the value of induction of mild hypothermia during resuscitation; and c) development of methods for controlled reperfusion during resuscitation. In addition, develop new drug strategies to favorably alter the metabolic milieu during resuscitation, as well as improved techniques to monitoring hemodynamics and metabolic state during resuscitation. Publication PlansA report is planned for publication in a peer-reviewed journal. Participating DivisionDivision of Cardiovascular Sciences Staff Contact
Debra Egan, MSc, MPH Working Group MembersChairs
Participants
NHLBI StaffRobin Boineau, MD Last Updated July 2012 |