Sudden Cardiac Death Risk Assessment Research Articles

Prediction of sudden cardiac death: next steps in pursuit of effective methodology

The recognition that severe left ventricular dysfunction is a predictor of sudden cardiac death (SCD) risk enabled widespread utilization of the implantable cardioverter defibrillator (ICD) for SCD prevention. Use of the ICD prior to any signs or symptoms of ventricular arrhythmias (“primary prevention”) is particularly important for SCD because case fatality for patients with sustained ventricular tachyarrhythmias is among the highest of any disease process. At the same time, primary prevention of SCD presents a unique epidemiologic challenge for many reasons [1, 2]: (1) high-risk subgroups constitute only a small proportion of all patients at risk for SCD, (2) the pathophysiologic etiologies of SCD are complex and infrequently recognized prior to arrest, (3) ventricular arrhythmia substrate often evolves over time and may require repeated risk stratification, (4) classification of arrhythmic death is particularly imprecise, (5) triggers for SCD may be transient, and (6) patients at high risk for SCD have many competing risks that are not ameliorated by ICDs. This review will address the limitations of risk stratification based on left ventricular ejection fraction (LVEF), summarize new developments in the field that extend beyond LVEF, and suggest new investigative approaches for refinement of SCD risk assessment.

T wave alternans evaluation using adaptive time–frequency signal analysis and non-negative matrix factorization

Each year 400,000 North Americans die from sudden cardiac death (SCD). Identifying those patients at risk of SCD remains a formidable challenge. T wave alternans (TWA) evaluation is emerging as an important tool to risk stratify patients with heart diseases. TWA is a heart rate dependent phenomenon that manifests on the surface electrocardiogram (ECG) as a change in the shape or amplitude of the T wave every second heart beat. The presence of large magnitude TWA often presages lethal ventricular arrhythmias. Because the TWA signal is typically in the microvolt range, accurate detection algorithms are required to control for confounding noise and changing physiological conditions (i.e. data nonstationarity). In this study, we address the limitations of two common TWA estimation methods, spectral method (SM) and modified moving average (MMA). To overcome their limitations, we propose a modified TWA quantification framework, called Adaptive SM, that uses non-linear time–frequency distribution (TFD). In order to increase the robustness of TWA detection in ambulatory ECGs, we also propose a new technique, called non-negative matrix factorization (NMF)-Adaptive SM. We present the analytical background of these methods, and evaluate their accuracy in detecting synthetic TWA signal in simulated and real-world ambulatory ECG recordings under conditions of noise and data non-stationarity. The results of the numerical simulations support the effectiveness of the proposed approaches for TWA analysis, which may ultimately improve SCD risk assessment.

What is the role of risk stratification for sudden death in the defibrillator era?

Accurate and timely prediction of sudden cardiac death (SCD) is a necessary prerequisite for effective prevention and therapy. Although the largest numbers of SCD events occur in patients without overt heart disease, there are currently no tests that are of proven predictive value in this population. Efforts in risk stratification for SCD have focused primarily on predicting SCD in patients with known structural heart disease. Despite the ubiquity of tests that have been purported to predict SCD vulnerability in such patients, there is little consensus on which test, in addition to the left ventricular ejection fraction, should be used to select patients for implantable cardioverter defibrillators (ICDs). Effective therapy exists for SCD but it is costly and is associated with potential complications. Currently used strategies for selection of the best candidates for ICDs are imperfect and leave many high-risk patients unprotected. At the same time, some patients who receive ICDs will never develop ventricular tachyarrhythmia requiring ICD intervention. This article summarizes the current status and applicability of the non-invasive and invasive tests used for SCD risk assessment.

Preventing tomorrow's sudden cardiac death today: Part II: Translating sudden cardiac death risk assessment strategies into practice and policy

Although current evidence supporting a more precise strategy for identifying patients at highest risk for sudden cardiac death (SCD) is sparse, strategies for translating existing and future evidence into clinical practice and policy are needed today. A great many unanswered questions exist. Examples include the following: At what level of risk for SCD should we pursue further testing or therapy? How should clinical strategies ethically and economically balance alternative outcomes? How can we best translate optimal strategies into clinical practice so as to prevent tomorrow's SCDs? On July 20 and 21, 2006, a group of individuals with expertise in clinical cardiovascular medicine, biostatistics, economics, and health policy was joined by government (Food and Drug Administration; Centers for Medicare and Medicaid Services; National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality), professional societies (Heart Rhythm Society), and industry to discuss strategies for risk assessment and prevention of SCD. The meeting was organized by the Duke Center for the Prevention of Sudden Cardiac Death and the Duke Clinical Research Institute. This article, the second of 2 documents, summarizes the policy discussions of that meeting, discusses an analytic framework for evaluating the risks and benefits associated with SCD prevention and risk stratification, and addresses the translation of SCD risk assessment strategies into practice and policy.

Sudden cardiac death: The role of risk stratification

Sudden cardiac death syndrome remains a major health problem responsible for approximately 400,000 deaths annually in the US. Effective therapies exist but are costly and are associated with potential complications. Currently used strategies for selection of the best candidates for implantable cardioverter defibrillator (ICD) therapy are imperfect and leave a large number of high-risk patients unprotected. At the same time, many patients who received ICDs will never develop tachyarrhythmia and require ICD intervention. The article summarizes the current status and applicability of the noninvasive and invasive tests used for sudden cardiac death risk assessment with the emphasis on the increasingly recognized value of microvolt T wave alternans.

Lessons From the Failure and Recall of an Implantable Cardioverter-Defibrillator

Multiple clinical trials have shown that a properly functioning implantable cardioverter-defibrillator (ICD) is capable of interrupting sudden death caused by ventricular tachyarrhythmias. Unfortunately, ICDs are complex medical devices, and they do not always perform as expected. For example, only 5% of ICD batteries last >7 years, and most dual-chamber ICD models must be replaced for battery depletion every 3 to 5 years.1 Normal battery depletion, however, is reliably predicted by routine follow-up methods before an ICD fails. In contrast, electronic malfunctions are unpredictable and may not be detected by standard follow-up techniques before an ICD is unable to deliver effective therapy. Thus, sudden cardiac arrest or death may be the first and only sign that an ICD has failed.2 Recently, we reported the death of a 21-year-old patient who received a Prizm 2 DR model 1861 ICD pulse generator (Guidant, Inc) in 2001 to prevent sudden cardiac death resulting from hypertrophic cardiomyopathy.3 In March 2005, this young man experienced a witnessed arrest and could not be resuscitated. His ICD was returned to Guidant, which found that the device had failed during the delivery of a shock. The cause of failure was massive electronic damage caused by electrical overstress that occurred when a short circuit developed between a high-voltage wire and a tube used to test the housing during manufacturing (see the Figure). At the time of our patient’s death, Guidant had knowledge of 25 similar Prizm 2 DR model 1861 failures in patients, 3 of whom had required rescue defibrillation. Indeed, Guidant had first observed this mode of failure 3 years earlier, in February 2002, when 2 returned Prizm 2 DR pulse generators exhibited the same short circuiting that caused our patient’s device to fail. Guidant was sufficiently concerned about these failures that manufacturing changes were made …

Levels of oxidative stress are associated with C-reactive protein levels in patients with stable and unstable angina

In cohort studies, elevated levels of plasma nonesterified free fatty acids (NEFAs) have been associated with increased risk of sudden cardiac death (SCD) in men, but blood samples were drawn several years before SCD.To confirm this relationship by evaluating levels of plasma NEFAs at the time of the SCD event in a group of both men and women.From the ongoing Oregon Sudden Unexpected Death Study, we compared levels of plasma NEFAs in 149 SCD cases presenting with ventricular fibrillation (mean age 64 ± 12 years; 73% men) and 149 age- and sex-matched controls with coronary artery disease. Plasma was processed from blood drawn at the time of arrest (cases) and at a routine visit (controls). The levels of plasma NEFAs were compared after categorizing into quartiles on the basis of control values. Conditional logistic regression was used to predict adjusted odds ratio for SCD associated with plasma NEFA levels per increased quartile.The plasma NEFA levels were significantly higher in SCD cases than in controls (median 0.39 mmol/L [interquartile range 0.28–0.60 mmol/L] vs 0.32 mmol/L [interquartile range 0.20–0.49 mmol/L]; P = .002). There were no significant differences in body mass index, smoking, and diabetes. The odds ratio for SCD was 1.42 (95% confidence interval 1.14–1.78) per quartile increase in the plasma NEFA level (P = .002). Individuals with plasma NEFA levels above the prespecified cutoff point of 0.32 mmol/L were at increased risk of SCD (odds ratio 2.00; 95% confidence interval 1.20–3.34; P = .008).These findings strengthen the role of plasma NEFA as a potential biomarker for the assessment of SCD risk.