The Real Time Monitoring of Ventricular Fibrillation Dynamics from Human Langendorff Model for Optimizing Resuscitation Outcomes

Principal Investigator: Nanthakumar, Kumaraswamy (Toronto General Hospital).

A.  Statement of the health problem

When a patient has gone into cardiac arrest and the heart has been shocked to restart it, return of blood flow to the heart is not always spontaneous. Clinical research has established that after three minutes of abnormal blood flow (known as ventricular fibrillation due to rapid, unsynchronized pumping of the heart), it may be appropriate to perform cardiopulmonary resuscitation (CPR) before shocking the heart (known as defibrillation) in order to achieve spontaneous circulation. 
The current theory holds that if we shock the heart before the flow of blood is even and regular, the heart will stop beating (asystole) or there will be disease in the cardiac muscle (EMD). However, if we shock the heart after first forcing adequate blood flow with CPR, it increased the “readiness” of the heart and thus the probability of good blood flow rhythm post-shock. Some studies suggest that delaying defibrillation until after some amount of CPR is important and has been the main change to CPR guidelines 2006. However, what is unclear is how long we should perform CPR, how we know that CPR is being performed adequately, and when to stop CPR and defibrillate in order to have the best chance of return of spontaneous circulation.

B.  Objective

Our goal is to evaluate the usefulness of real time monitoring of cardiac electrical activity during ventricular fibrillation as a measure of the effectiveness of CPR, in order to optimize the outcomes following CPR.
The specific objectives are to:
  • study the relationship between ECG showing ventricular fibrillation and coronary perfusion.
  • assess integrated coronary flow (indicating chest compression efficacy) using this metric during ventricular fibrillation.
  • determine the relation between cardiac electrical state (rhythm of blood flow through the heart) at the moment of defibrillation and the resulting rhythm and cardiac contractile function (contracting of the heart as it beats).

C.  Approach

The Langendorff model refers to a beating heart outside the body maintained on a perfusion system. This is a novel model for studying human ventricular fibrillation in which we harvest hearts from patients who are undergoing cardiac transplant. This will allow us to study the dynamics while controlling time in ventricular fibrillation and coronary perfusion (blood flow). 
We are the only center in the world performing this work. Our approach allows for the study of human ventricular fibrillation without the limitations of studying it inside people or extrapolation from simulation and animal studies. The strength of our approach involves diseased hearts that are prone to ventricular fibrillation. We performed 21 human Langendorff experiments at the Toronto General Hospital last year and have been able to maintain a human Langendorff blood perfused heart for almost four hours without any degradation of the specimen. We plan to use ten hearts per year for this project. Thus, over the next three years, we hope to study 30 diseased human hearts. 

D. Unique / Innovative aspect

Our primary objective is to develop and use a metric which will allow us to monitor CPR performance and indicate when defibrillation should be performed to improve outcomes. Current CPR techniques define the rate and depth of compression. The recoil of the chest is variable and the amount of perfusion achieved by CPR is unknown. The novelty of our proposal relates to identifying a surrogate for the amount of coronary flow, using a novel metric based on the information content in the ECG, and correlating it with return of spontaneous circulation. 
We propose to use advanced analysis of electrograms of human ventricular fibrillation from epicardial, endocardial and volume averaged surface ECG of  perfused myopathic human hearts, the relate them to surface electrocardiograms using Wavelet decomposition. The novelty of our approach is the use of a metric in a novel way, to inform the CPR performer on the efficacy of coronary perfusion.

E. Relevance to the objectives of Monitoring and Optimizing CPR initiative

Our study will optimize the integrated effectiveness of CPR by providing real time feedback on its effect on the heart and calculating a moment when a defibrillation shock will be most likely to produce survival. Our results will provide:
  • evidence and rationale for how long one should perform CPR for a ventricular fibrillation arrest prior to shock and the appropriate time to stop chest compression, informing specific recommendations to CPR guidelines in 2010.
  • a tool to be incorporated in resuscitation equipment to objectively quantify the effectiveness of a coronary perfusion.
  • further development of local expertise in resuscitation research in the laboratory of a young investigator.