Review of NASA s Evidence Report on Arrhythmic Risk During Spaceflight David Spragg, MD FHRS Johns Hopkins Hospital Washington DC, July 27 th, 2017
Objectives Review of arrhythmia mechanisms Distinguishing relevant versus insignificant arrhythmias Addressing specific questions about the Report How well is the risk understood? What, if any, are the major sources of disagreement in the literature pertaining to this risk? Does the evidence report provide sufficient evidence, as well as sufficient risk context, that the risk is of concern for long-term space missions? Does the evidence report provide evidence that the named gaps are the most critical presented? Are there any additional gaps or aspects of existing gaps that are not addressed for this specific risk? Does the evidence report address relevant interactions among risks? Is the breadth of the cited literature sufficient?
AUTOMATICITY phase 4
TRIGGERING
60 40 20 -dofetilide 0-20 -40-60 -80 Voltage (mv) -100 60 40 20 0-20 -40-60 1s + dofetilide EAD reactivation of DHP-sensitive Ca current -80-100 1s
REENTRY
Risk of Hemodynamic Compromise Lowest Risk PACs PVCs Limited SVT Limited NSVT Moderate Risk PSVT AF Bradycardia (sinus node dysfunction) Highest Risk VT VF PEA Asystole Bradycardia (AV block)
SUDDEN DEATH
SUDDEN DEATH 1435 Competitive Athletes Who Died Suddenly Circulation 2007;115:1643-1655
ATRIAL FIBRILLATION
ATRIAL FIBRILLATION ATRIAL FIBRILLATION RISK FACTORS Age HTN DM Sleep apnea Obesity Calkins H, et al. HeartRhythm 2012; 9: 632-96.
ATRIAL FIBRILLATION Miyasaka Y, et al. Circulation 2006; 114: 119-25.
Thought Experiment: Maximal Arrhythmia Screening Components History and physical ECG Cardiac imaging Contrast-enhanced MRI CT and calcium scoring Echo 2 week Holter/Zio patch Exercise stress testing
Thought Experiment II: Effect of Prolonged Spaceflight Tabulation of observed events Large-animal experimental data
General Reaction to Risk Report Anecdotal nature of the data Relatively minor clinical importance of observed phenomena Clear appreciation of pre-existing disease progression versus spaceflight-induced acceleration/causation of disease Broad gaps in knowledge Cumulative effects versus new steady state Results of years-long exposure Lack of large-animal data
Specific Questions 1. How well is the risk understood? What, if any, are the major sources of disagreement in the literature pertaining to this risk? 2. Does the evidence report provide sufficient evidence, as well as sufficient risk context, that the risk is of concern for long-term space missions? 3. Does the evidence report provide evidence that the named gaps are the most critical presented? Are there any additional gaps or aspects of existing gaps that are not addressed for this specific risk? 4. Does the evidence report address relevant interactions among risks? 5. Is the breadth of the cited literature sufficient?
Specific Questions 1. How well is the risk understood? What, if any, are the major sources of disagreement in the literature pertaining to this risk? 2. Does the evidence report provide sufficient evidence, as well as sufficient risk context, that the risk is of concern for long-term space missions? 3. Does the evidence report provide evidence that the named gaps are the most critical presented? Are there any additional gaps or aspects of existing gaps that are not addressed for this specific risk? 4. Does the evidence report address relevant interactions among risks? 5. Is the breadth of the cited literature sufficient?
Reasonable data about the nature and frequency of benign events seen during short-term spaceflight PACs, PVCs, NSVT Reasonable data (some mixed) about the post-spaceflight, long term outcomes in astronauts Acknowledgement of limits, including small, voluntary group of subjects Very little about risk of clinically meaningful arrhythmias during longterm spaceflight Low incidence of events Limited data to analyze
Specific Questions 1. How well is the risk understood? What, if any, are the major sources of disagreement in the literature pertaining to this risk? 2. Does the evidence report provide sufficient evidence, as well as sufficient risk context, that the risk is of concern for long-term space missions? 3. Does the evidence report provide evidence that the named gaps are the most critical presented? Are there any additional gaps or aspects of existing gaps that are not addressed for this specific risk? 4. Does the evidence report address relevant interactions among risks? 5. Is the breadth of the cited literature sufficient?
There appears to be very limited data about long-term spaceflight Risk contextualization is in the report, though disproportionate weight is given (understandably) to clinically minor observations
Specific Questions 1. How well is the risk understood? What, if any, are the major sources of disagreement in the literature pertaining to this risk? 2. Does the evidence report provide sufficient evidence, as well as sufficient risk context, that the risk is of concern for long-term space missions? 3. Does the evidence report provide evidence that the named gaps are the most critical presented? Are there any additional gaps or aspects of existing gaps that are not addressed for this specific risk? 4. Does the evidence report address relevant interactions among risks? 5. Is the breadth of the cited literature sufficient?
Named gaps appear to be critical Long-term weightlessness Radiation exposure Consequences of physiological changes Unnamed gaps Tissue fibrosis with spaceflight Common thread for several clinically meaningful arrhythmias (AF, heart block, VT) Assessment possible with cardiac MRI Consideration of pre- and post-flight assessment
Specific Questions 1. How well is the risk understood? What, if any, are the major sources of disagreement in the literature pertaining to this risk? 2. Does the evidence report provide sufficient evidence, as well as sufficient risk context, that the risk is of concern for long-term space missions? 3. Does the evidence report provide evidence that the named gaps are the most critical presented? Are there any additional gaps or aspects of existing gaps that are not addressed for this specific risk? 4. Does the evidence report address relevant interactions among risks? 5. Is the breadth of the cited literature sufficient?
I don t know
Specific Questions 1. How well is the risk understood? What, if any, are the major sources of disagreement in the literature pertaining to this risk? 2. Does the evidence report provide sufficient evidence, as well as sufficient risk context, that the risk is of concern for long-term space missions? 3. Does the evidence report provide evidence that the named gaps are the most critical presented? Are there any additional gaps or aspects of existing gaps that are not addressed for this specific risk? 4. Does the evidence report address relevant interactions among risks? 5. Is the breadth of the cited literature sufficient?
Yes
Summary No clinically threatening arrhythmias have been documented Importance of prescreening Consideration of cumulative (e.g. fibrosis) versus dynamic (autonomic tone) processes seems important Inherent paucity of data Consideration of fibrosis as an important contributor to risk THANK YOU