Sudden cardiac death accounts for an estimated fifteen percent of total mortality in the United States each year. (Photo provided by Ray Fowler, MD)

A New Way to Predict the Risk for Sudden Cardiac Death  

Routine screening of electrocardiograms in patients has revealed that patients with T-waves that vary in direction — especially in the lateral leads — have an increased incidence of sudden death later in life.

Ray Fowler, MD

Abstract

Sudden cardiac death (SCD) is a leading cause of death worldwide. Efforts are consistently underway to identify people at risk of life-threatening arrhythmias that may result in cardiac arrest.

Recent work in Finland has revealed a strong association between decreased T-wave area dispersion (one measure of T-wave repolarization heterogeneity) and risk of SCD.

Recent work in Finland has revealed a strong association between decreased T-wave area dispersion (one measure of T-wave repolarization heterogeneity) and risk of SCD.

This study aimed to assess the awareness of a large international cohort of emergency medical services (EMS) medical directors of the association between T-wave repolarization heterogeneity and SCD, and whether electrocardiography (ECG) machines used under their direction are equipped with repolarization heterogeneity interpretive algorithms.

Study authors found that this association had not yet been identified by the majority of the medical directors surveyed as a screening tool for SCD, though most medical directors favor the incorporation of such software into ECG machines. The authors propose further study to improve identification of patients at risk for sudden arrhythmic death.

Related

Introduction

Sudden cardiac death (SCD) accounts for an estimated fifteen percent of total mortality in the United States, causing 300,000 to 400,000 deaths annually.1,2 In the majority of adult cases of SCD, the patient has a structural heart defect.

A recent prospective autopsy study completed in San Francisco County identified 98% of sudden arrhythmic deaths as having structural heart disease at autopsy.3 The most common structural heart disease resulting in SCD has been shown to be coronary artery disease (CAD), accounting for an estimated 80% of cases.4 In fact, SCD is often the initial clinical manifestation of CAD, that is, the majority of patients who experience SCD have previously unrecognized coronary artery disease.3

That is not to say that persons who will eventually experience SCD are not without warning symptoms such as chest pain and dyspnea. In fact, an ongoing prospective population study has shown that in the four weeks preceding SCD, the majority (51%) of patients have warning symptoms, and these same warning symptoms often recur in the 24 hours preceding the SCD event.5

An ongoing prospective population study has shown that in the four weeks preceding SCD, the majority (51%) of patients have warning symptoms, and these same warning symptoms often recur in the 24 hours preceding the SCD event.

However, in most cases, warning symptoms do not convince patients to present for medical evaluation – such as by contacting emergency medical services (EMS) – and only a minority of symptomatic patients (19%) contact EMS prior to experiencing SCD.5

The mortality burden of SCD in the United States, the nonspecific and often unrecognized nature of warning symptoms, and the fact that most individuals who experience SCD are not aware of their coronary heart disease at the time of death all contribute to the need for EMS and emergency department staff to be able to identify members of the general adult population who are at risk of SCD in order to target interventions and decrease incidence.

In the general population, primary SCD prevention currently entails managing those risks that underlie coronary artery disease, often reserving screening tests (e.g. 12-lead ECG, stress tests) for those individuals who are considered high risk for cardiovascular diseases based on standardized guidelines.6

However, this algorithm for screening fails to capture asymptomatic, undiagnosed patients, which make up the majority of instances of SCD.3

A relatively new area of research has shown that in healthy, asymptomatic individuals, ECG-based changes can be coupled with other metrics to quantify an individual’s risk of an impending ventricular arrhythmia and possible SCD.

A relatively new area of research has shown that in healthy, asymptomatic individuals, ECG-based changes can be coupled with other metrics to quantify an individual’s risk of an impending ventricular arrhythmia and possible SCD.

These studies all build on electrophysiological studies from the late twentieth and early twenty-first centuries that demonstrated that susceptibility to ventricular arrhythmias (and thus SCD) can be characterized by “heterogeneity in myocardial activation … recovery times … and action potential morphology,” 7and that QRST integral maps from ECGs may detect these heterogeneities.7-13

In one such prospective study (“Global Electric Heterogeneity Risk Score” [GEHRS]) analyzing a low-risk, community-based, biracial, general adult population, a risk score incorporating five ECG markers representing myocardial global electric heterogeneity was shown to be independently (after multivariable adjustment for known SCD risk factors) and specifically (versus non-sudden death due to CAD) associated with SCD.7

The GEHRS study also demonstrated that the addition of selected ECG parameters into a risk score based on clinical and demographic parameters (age, gender, race, hypertension, diabetes, stroke, coronary heart disease) improved the prediction for SCD risk compared to risk calculated on clinical data alone.7

The GEHRS study demonstrated that the addition of selected ECG parameters into a risk score based on clinical and demographic parameters (age, gender, race, hypertension, diabetes, stroke, coronary heart disease) improved the prediction for SCD risk compared to risk calculated on clinical data alone.

Still other studies evaluating electrical heterogeneity of the heart have demonstrated that ECG markers alone are able to represent increased risk of SCD. In one such study conducted using epidemiological data representative of the adult population of Finland, an increased heterogeneity of repolarization in a standard 12-lead EKG during a single cardiac cycle was shown to be an independent predictor of SCD in the adult population.14 In particular, study authors showed that a low T-wave dispersion area, representing increased repolarization heterogeneity, was associated with a 4.6 x adjusted risk for SCD.14

In one study, authors showed that a low T-wave dispersion area, representing increased repolarization heterogeneity, was associated with a 4.6 x adjusted risk for SCD.14

Studies have clearly demonstrated the relationship between electrical heterogeneity measured with 12-lead ECG and risk of SCD.

This study by the authors therefore aimed to determine whether EMS medical directors – who are responsible for the medical care provided by EMS systems around the world – are aware of the utility of repolarization heterogeneity as a predictor of SCD in the general adult population and whether the ECG machines used under their direction are currently equipped with such predictive algorithms.

Our study went further to also determine whether manufacturers of ECG equipment for EMS systems in the United States are consideringor have already incorporated these screening metrics into ECG machines for the purpose of screening populations served by EMS systems for SCD.

We hypothesized that EMS medical directors would not be aware of repolarization heterogeneity’s utility as a predictor of SCD in the general adult population and that ECG manufacturers in the United States would not be planning on incorporating these screening metrics into machines.

Methods

The participants in our study were drawn from two cohorts of individuals, and data was obtained via survey. The first survey was administered to members of the Metropolitan Urban EMS Medical Directors Coalition (“EMS Medical Directors”), an international group of EMS medical directors representing a potential clinical service volume of over 120 million lives.

The cardiac evaluation equipment utilized in the field by first responders, paramedics, EMTs, and others, under the direction of these medical directors represents the typical equipment employed for prehospital electrocardiographic evaluation in patients. The second survey was administered to medical directors for prehospital ECG equipment manufacturers.

The surveys were administered via email. The questions administered via survey are found below in Figure 1. Survey respondents were also provided with a free text box to provide plain text comments.

Figure 1. Questions administered via survey.

All members of the Metropolitan Urban EMS Medical Directors Coalition were invited to voluntarily participate in the study, as were medical directors for prehospital ECG equipment manufacturers.

To protect privacy, data was de-identified by the project authors via the assignment of a number in sequential order (001, 002, etc.). No identification of survey participants was or is available outside of the project’s author group.

Data was collected from individual surveys and entered into an Excel spreadsheet for summary analysis and evaluation.

Results

EMS Medical Directors

Thirty-two EMS Medical Directors responded to the survey, representing a potential clinical service volume of approximately 43 million people in 21 states and geographic areas. The response rate for the survey administered to EMS Medical Directors was 32/100.

Consistent with the hypothesis of study authors, the majority of EMS Medical Directors (72%) were not aware of the association between T-wave repolarization heterogeneity and risk of SCD.

Further, the majority (78%) of EMS Medical Directors were “not sure” that T-wave repolarization heterogeneity is a valid concern based on their clinical and scientific experience.

Contrary to expectations of study authors, the majority (59%) of EMS Medical Directors did believe that analysis software of prehospital 12-lead ECGs should be updated for the purpose of predicting risk for SCD.

Finally, when asked whether current ECG machines used under their care are equipped with software for analysis of spatial dispersion of repolarization, the majority of EMS Medical Directors were “not sure” whether machines were currently equipped with such software (53%), followed closely by medical directors who stated that their machines are not equipped with such software (44%).

Full survey results are available in Figures 2-5.

Figure 2: Q1, EMS Medical Directors (n=32)
Figure 3: Q2, EMS Medical Directors (n=32)
Figure 4: Q3, EMS Medical Directors (n=32)
Figure 5: Q4, EMS Medical Directors (n=32)

The results from this study are likely generalizable to represent the view of most EMS medical directors in the United States, and the EMS systems and patients under their care, given the breadth of medical directors participating in the survey representing 21 states and the District of Columbia.

Medical Directors for Prehospital ECG Equipment Manufacturers

Two medical directors for prehospital ECG equipment manufacturers responded to the survey.  Neither EMS ECG manufacturer medical director was specifically aware of the association between T-wave repolarization heterogeneity and risk of SCD. One reply indicated that the medical director was “not sure” that T-wave repolarization heterogeneity is a valid concern based on clinical and scientific experience, and there was an indication that this finding may not be a valid concern for prehospital services in general at this time.

Another consideration raised was that, in the future, advancing science may allow 12-lead ECGs in the field to be updated for the purpose of predicting SCD. However, at the present, it was observed that commercial ECG machines for EMS systems are not currently equipped with software for analysis and quantification of spatial dispersion of repolarization.

In terms of future plans to incorporate SCD predictive software into prehospital ECG machines, those surveyed indicated that “predictive analysis” software would eventually be a part of EMS ECG machines.

Discussion

Analysis of this large cohort of EMS Medical Directors and medical directors for prehospital ECG equipment manufacturers revealed several important findings.

First, we demonstrated a current lack of awareness of research regarding associations between T-wave repolarization heterogeneity and risk of SCD.  Second, we demonstrated that more than fifty percent of EMS Medical Directors are in favor of updating prehospital 12-lead ECGs for the purpose of predicting SCD.

We demonstrated that more than fifty percent of EMS Medical Directors are in favor of updating prehospital 12-lead ECGs for the purpose of predicting SCD.

This sentiment mirrors recommendations made in recent studies of SCD screening metrics and also from observations made during the survey of EMS ECG manufacturer medical directors. Authors of the GEHRS argue that while there are no currently “accepted interventions specifically for the primary prevention of SCD in the general population,” “prediction and prevention of SCD” are “interconnected in that the development of effective SCD prevention requires the availability of effective SCD risk prediction tools,” and that “existing 12-lead ECG systems could easily report their values with minimal additional software modification.”7

One of the EMS ECG manufacturer medical directors stated that their company is considering T-wave area dispersion and other predictive algorithms alongside additional data points (bundle branch block, axis, left ventricular hypertrophy) for both 12-leads and also ECG monitors, observing that while such algorithms are not yet ready for commercial use, they are currently in development.

On the other hand, one concern raised by EMS ECG manufacturer medical directors was that updates in the ECG software to include these capabilities would provide medical information that would require action, with a comparison made to discharging a patient with elevated blood pressure but not providing follow-up. 

This sentiment was also echoed by the majority of those EMS Medical Directors who were not in favor of such prehospital software updates, with comments made on the EMS system structural changes that would be necessary to accommodate such updates in prehospital 12-lead ECGs. Specifically, some EMS Medical Directors responded that new EMS prehospital protocols would be required if such software were to be integrated into prehospital ECG machines, as decisions would have to be made regarding, for example, whether to transport all patients shown to have SCD risk to hospital or whether such patients could be advised to follow up with their primary care physicians or cardiologists at a later date.

Another common sentiment expressed by the surveyed EMS Medical Directors not in favor of such software updates for prehospital ECG machines was that this technology would instead be more appropriate and useful for ECG machines utilized in hospitals.

Finally, some EMS Medical Directors not in favor of software updates believed that further research was still needed to prove clinical utility in terms of sensitivity and specificity.

Finally, we demonstrated that the machines currently being employed in prehospital EMS care are not currently equipped with capabilities to measure spatial analysis of repolarization. It was noted that data may be downloaded from certain ECG machines for analysis with predictive algorithms, but this analysis capability is not readily available on commercial ECG machines at this time.

A common question posed by the surveyed EMS Medical Directors was how long electrical changes such as T-wave repolarization heterogeneity are typically seen before the SCD event.

Indeed, the importance of a long time frame when examining ECG changes is demonstrated by a retrospective study that examined the long-term outcome of early repolarization, showing that early repolarization identified in middle-aged patients was associated with an increased risk of death from cardiac causes in follow-up – with a mean follow-up time of 30 years.15,16 

As discussed by the GEHRS authors, abnormal electrical heterogeneity alone serves as an electrical milieu that is favorable for ventricular arrhythmias, but which still requires a triggering event.7 Thus, abnormal heterogeneity measurements provide impetus for evaluation and potential corrective actions.7

A limitation for this study is the fact that this study was administered as a voluntary survey and as such could suffer from a degree of nonresponse bias. Despite this limitation, this study provides helpful information on the current awareness and mindset of EMS medical directors toward potential future ECG software upgrades to detect risk of SCD.

Conclusions

Sudden cardiac death is often the first manifestation of coronary artery disease and continues to exact a significant toll on worldwide morbidity and mortality. Recent studies have shown that ECG-based SCD risk scores are successful in predicting which asymptomatic individuals are at risk of SCD.

This study shows that while the majority of EMS Medical Directors are not aware of these findings of T-wave repolarization heterogeneity research, they do favor incorporation of algorithms predictive of SCD into prehospital ECG machines.

A large international cohort of emergency medical services (EMS) medical directors they do favors incorporation of algorithms predictive of sudden cardiac death into prehospital ECG machines.

Further, this study shows that prehospital medical direction for major ECG manufacturers are not in full agreement at this time on whether or not future prehospital ECG machines should be equipped with such capabilities. Future studies should strive to validate in additional populations ECG-based SCD risk scores and to determine the EMS system structural changes that would be required to accommodate such prehospital machine upgrades.

Acknowledgements

Study authors would like to thank Dr. Tuomas Kenttä (University of Oulu) for his kind assistance in this study regarding ECG-based risk scores in the identification of risk for SCD.

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