Early Repolarization: Difference between revisions

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[[File:Semantic_confusion_early_repolarization.svg|thumb|400px|right]]
[[File:Semantic_confusion_early_repolarization.svg|thumb|400px|right]]
'''[[Early Repolarization]]''' is a term used classically for ST segment elevation without underlying disease. It probably has nothing to do with actual early repolarization. It is commonly seen in young men. It is important to discern early repolarization from ST segment elevation from other causes such as [[ischemia]]. Characteristics of early repolarization are:<cite>Kambara</cite>
'''[[Early Repolarization]]''' is a term used classically for ST segment elevation without underlying disease. It probably has nothing to do with actual early repolarization. It is commonly seen in young men. It is important to discern early repolarization from ST segment elevation from other causes such as [[ischemia]]. Characteristics of early repolarization are:<cite>2</cite>
* an upward concave elevation of the RS-T segment with distinct or "embryonic" J waves
* an upward concave elevation of the RS-T segment with distinct or "embryonic" J waves
* slurred downstroke of R waves or distinct J points or both
* slurred downstroke of R waves or distinct J points or both
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Prior to 2009, ECG waveform definitions and measurement were based on inclusion of the R wave downslope phenomena in the QRS complex per the CSE Measurement Statement but recent studies have not done so.
Prior to 2009, ECG waveform definitions and measurement were based on inclusion of the R wave downslope phenomena in the QRS complex per the CSE Measurement Statement but recent studies have not done so.


These stable 12 lead ECG measurment issues have to be resolved if appropriate population studies can be performed to demonstrate that R wave downslope phenomena (Haïssaguerre ECG patterns) can be used to predict individuals at risk of sudden cardiac death due to this genetic mutation.
These stable 12 lead ECG measurment issues have to be resolved if appropriate population studies can be performed to demonstrate that R wave downslope phenomena (Haïssaguerre ECG patterns<cite>24</cite><cite>25</cite>) can be used to predict individuals at risk of sudden cardiac death due to this genetic mutation.
 
==Early Repolarization==
==Early Repolarization==
Characterization of standard 12 lead ECG abnormalities can be facilitated by considering the portion of the cardiac ventricular myocytes action potential which influences them. This is only helpful for action potential phenomena originating with the initial wave of activation. Their temporal timing is influenced mainly by transmural dispersion from endo to epicardium. This contrasts with late potentials which are due to phase 0 of the action potentials (depolarization) originating from myocardium isolated by fatty tissue (epsilon waves of ARVD) or by fibrosis (cardiomyopathy) experiencing major delays. These can be arrhythmogenic because they compete with the normal pacemakers.  
Characterization of standard 12 lead ECG abnormalities can be facilitated by considering the portion of the cardiac ventricular myocytes action potential which influences them. This is only helpful for action potential phenomena originating with the initial wave of activation. Their temporal timing is influenced mainly by transmural dispersion from endo to epicardium. This contrasts with late potentials which are due to phase 0 of the action potentials (depolarization) originating from myocardium isolated by fatty tissue (epsilon waves of ARVD) or by fibrosis (cardiomyopathy) experiencing major delays. These can be arrhythmogenic because they compete with the normal pacemakers.  
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Phase 3 (late-repolarization) abnormalities can result in T wave abnormalities with similar causes as ST depression as well as abnormalities of QT length caused by medications, electrolyte disturbances and specific genetic conditions (LQTS, SQTS).
Phase 3 (late-repolarization) abnormalities can result in T wave abnormalities with similar causes as ST depression as well as abnormalities of QT length caused by medications, electrolyte disturbances and specific genetic conditions (LQTS, SQTS).


Less understood but recently highlighted are abnormalities of phase 1 (Early Repolarization). These include abnormal action potentials originating in the right ventricle outflow tract (Brugada syndrome) and those originating in the left ventricle (J wave syndromes).  
Less understood but recently highlighted are abnormalities of phase 1 (Early Repolarization). These include abnormal action potentials originating in the right ventricle outflow tract ([[Brugada syndrome]]) and those originating in the left ventricle (J wave syndromes).  


The exciting feature of these abnormalities is their specific genetic associations. Similar to the QT syndromes, relatively few genes appear to be involved contrasting with the genetic complexity of more common conditions such as cardiomyopathies, atherosclerosis and diabetes.
The exciting feature of these abnormalities is their specific genetic associations. Similar to the QT syndromes, relatively few genes appear to be involved contrasting with the genetic complexity of more common conditions such as cardiomyopathies, atherosclerosis and diabetes.


Introduced in the NEJM in 2009 as ''Early Repolarization'', this new ECG pattern and syndrome is more appropriately named after Michel Haïssaguerre who first reported it (as suggested by Viskin JACC, 2009). The ECG pattern consists of J waves, slurs or notches particularly in the inferior leads and the syndrome requires sudden cardiac death (SCD) without cardiac abnormalities, family history and genetic markers.
Introduced in the NEJM in 2009 as ''Early Repolarization'', this new ECG pattern and syndrome is more appropriately named after Michel Haïssaguerre<cite>3</cite> who first reported it (as suggested by Viskin JACC, 2009<cite>1</cite>). The ECG pattern consists of J waves, slurs or notches particularly in the inferior leads and the syndrome requires sudden cardiac death (SCD) without cardiac abnormalities, family history and genetic markers.


However, Early repolarization (ER) was already defined for two areas:
However, Early repolarization (ER) was already defined for two areas:
#In cellular physiology, ER is defined as Phase 1 of the action potential.
#In cellular physiology, ER is defined as Phase 1 of the action potential.
#In clinical medicine, ER is defined as a resting ECG pattern of ST elevation in the lateral>Inferior leads sometimes accompanied by J waves or slurs on the R wave downslope, occurring particularly in athletic, young male African Americans.  
#In clinical medicine, ER is defined as a resting ECG pattern of ST elevation in the lateral>Inferior leads sometimes accompanied by J waves or slurs on the R wave downslope, occurring particularly in athletic, young male African Americans<cite>25</cite>.  


The main concern with this pattern was distinguishing it from ischemia and pericarditis.
The main concern with this pattern was distinguishing it from ischemia and pericarditis.
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===Prognostic Implications of the Haïssaguerre ECG Patterns===
===Prognostic Implications of the Haïssaguerre ECG Patterns===
Hopefully, there are markers on the stable, surface ECG of the Haïssaguerre Pattern (ST elevation and end QRS notching and slurring) that occur in community populations and athletes that can predict risk of cardiovascular death and/or the Haïssaguerre Syndrome.  
Hopefully, there are markers on the stable, surface ECG of the Haïssaguerre Pattern (ST elevation and end QRS notching and slurring) that occur in community populations and athletes that can predict risk of cardiovascular death and/or the Haïssaguerre Syndrome.  


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Clearly the best follow up study and one unlikely to be duplicated is that by Tikkannen et al. This classic study was only ''limited'' by non-computerized ECG acquisition; the paper ECG recordings from over 30 years ago (requiring using the ''adjacent lead'' criteria for accuracy unlike modern ECG analyses that rely on waveforms averaged over 10 seconds).  
Clearly the best follow up study and one unlikely to be duplicated is that by Tikkannen et al<cite>4</cite>. This classic study was only ''limited'' by non-computerized ECG acquisition; the paper ECG recordings from over 30 years ago (requiring using the ''adjacent lead'' criteria for accuracy unlike modern ECG analyses that rely on waveforms averaged over 10 seconds).  


Sinner et al. documented an increased hazard ratio of mortality associated with ER, especially in the inferior leads. However, they used a case-cohort design which only considered a subset of their community based population ''enriched by all those who died'' resulting in a ''limited challenge'' due to the older age of those who died.
Sinner et al. documented an increased hazard ratio of mortality associated with ER, especially in the inferior leads. However, they used a case-cohort design which only considered a subset of their community based population ''enriched by all those who died'' resulting in a ''limited challenge'' due to the older age of those who died.
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A third outcome study, by Haruta et al. concluded that ER was only predictive of ''unexplained death''. Although ''unexplained death'' was intended to be a surrogate for cardiac arrest, the main category coded was unexplained accidental death.
A third outcome study, by Haruta et al. concluded that ER was only predictive of ''unexplained death''. Although ''unexplained death'' was intended to be a surrogate for cardiac arrest, the main category coded was unexplained accidental death.


A fourth study by Stavrakis et al considered 852 consecutive patients with ST elevation ≥0.1 mV in inferior or lateral leads from the VA ECG system, similar to what we have used, and randomly selected 257 age-matched patients with normal ECGs as controls.<cite>17</cite>  
A fourth study by Stavrakis et al<cite>17</cite> considered 852 consecutive patients with ST elevation ≥0.1 mV in inferior or lateral leads from the VA ECG system, similar to what we have used, and randomly selected 257 age-matched patients with normal ECGs as controls.<cite>17</cite>  


Early repolarization was associated with a modest increased mortality compared to controls (hazard ratio of 1.49), but comparison to controls rather than the total population from the sampling period of those with ER violates the assumptions of the Cox model.  
Early repolarization was associated with a modest increased mortality compared to controls (hazard ratio of 1.49), but comparison to controls rather than the total population from the sampling period of those with ER violates the assumptions of the Cox model.  


A 5th study was that of Rollins et al with the French participants in the Monica Study. It was a retrospective study of 1,161 southwestern French subjects 35 to 64 years old. This relatively small study without isolating risk to the inferior leads is hard to reconcile with the larger Finnish study. Some of the examples they provide of high risk ECGs puts their conclusions in doubt.  
A 5th study was that of Rollins et al<cite>19</cite> with the French participants in the Monica Study. It was a retrospective study of 1,161 southwestern French subjects 35 to 64 years old. This relatively small study without isolating risk to the inferior leads is hard to reconcile with the larger Finnish study. Some of the examples they provide of high risk ECGs puts their conclusions in doubt.  


[[Image:projects_repolarization_2.svg|300px|right|thumbnail|The figure shows where the CSE experts indicated that these measurements be made.]]
[[Image:projects_repolarization_2.svg|300px|right|thumbnail|The figure shows where the CSE experts indicated that these measurements be made.]]


A sixth and seventh studies by Olson et al and Hisamatsu et al were excellent population studies but did not consider R wave downslope phenomena (Haïssaguerre Pattern) but only ST elevation and included the anterior leads. Uberoi et al from the Veterans Affairs was one of the largest multi-ethnic population studies and considered R wave downslope phenomena (Haïssaguerre Pattern) as well as ST elevation.
A sixth and seventh studies by Olson et al and Hisamatsu et al<cite>23</cite> were excellent population studies but did not consider R wave downslope phenomena (Haïssaguerre Pattern) but only ST elevation and included the anterior leads. Uberoi et al<cite>6</cite><cite>20</cite> from the Veterans Affairs was one of the largest multi-ethnic population studies and considered R wave downslope phenomena (Haïssaguerre Pattern) as well as ST elevation.
   
   
Studies that have used the same population as a study summarized but considered confounders are not listed but worthy of mention is the study of Perez which found a risk in non-African Americans as opposed to African Americans and a Finnish sub-study which found risk isolated to those with downsloping ST depression. Also of mention, is the study of Uberoi demonstrating any risk of R wave downslope phenomena to be dependent on accompanying Q waves and/or T wave inversion.
Studies that have used the same population as a study summarized but considered confounders are not listed but worthy of mention is the study of Perez<cite>22</cite> which found a risk in non-African Americans as opposed to African Americans and a Finnish sub-study which found risk isolated to those with downsloping ST depression. Also of mention, is the study of Uberoi demonstrating any risk of R wave downslope phenomena to be dependent on accompanying Q waves and/or T wave inversion.


===ECG Measuement Issues===
===ECG Measuement Issues===