Non-invasive sudden death risk stratification.

Most sudden cardiac deaths are caused by fatal ventricular arrhythmias (ventricular tachycardia [VT] and fibrillation) in patients with and without known structural heart diseases. Given the large number of patients potentially at risk for developing ventricular arrhythmias, any strategy for treating them prophylactically requires efficient and effective risk stratification. Both non-invasive and invasive testing may be used for prognostic evaluation of patients with heart diseases. The optimal way to use them in the risk stratification for sudden cardiac death will depend in part on the goals of screening. At present risk markers perform better at identifying low-risk patients who may not need an implantable cardioverter-defibrillator (ICD), because all tests have a high negative predictive accuracy. In our opinion an electrophysiological test should not be performed and an ICD should not be implanted in post-myocardial infarction patients with moderate left ventricular dysfunction (left ventricular ejection fraction 30-40%) with a preserved autonomic balance and without non-sustained VT. In MADIT II-like patients electrophysiological testing does not seem necessary and an ICD could not be implanted only in patients with a negative T-wave alternans test. Most of the data available refer to patients with ischemic cardiomyopathy but the preliminary data on T-wave alternans suggest its usefulness in patients with non-ischemic cardiomyopathy too, although a large definitive study has not yet been completed in this important population.     

T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation

In a trial of prophylactic implantation of a defibrillator, a mortality benefit was seen among patients with previous myocardial infarction and a left-ventricular ejection fraction of 0.30 or less. We identified 129 similar patients from two previously published clinical trials in which microvolt T-wave alternans testing was prospectively assessed. At 24 months of follow-up, no sudden cardiac death or cardiac arrest was seen among patients who tested T-wave alternans negative, compared with an event rate of 15.6% among the remaining patients. Testing of T-wave alternans seems to identify patients who are at low risk of ventricular tachyarrhythmic event and who may not benefit from defibrillator therapy.     

Electrophysiologic testing guided risk stratification approach for sudden cardiac death beyond the left ventricular ejection fraction

Sudden cardiac death threats ischaemic and dilated cardiomyopathy patients. Anti- arrhythmic protection may be provided to these patients with implanted cardiac defibrillators(ICD), after an efficient risk stratification approach. The proposed risk stratifier of an impaired left ventricular ejection fraction has limited sensitivity meaning that a significant number of victims will remain undetectable by this risk stratification approach because they have a preserved left ventricular systolic function. Current risk stratification strategies focus on combinations of non invasive methods like T wave alternans, late potentials, heart rate turbulence, deceleration capacity and others, with invasive methods like the electrophysiologic study. In the presence of an electrically impaired substrate with formed post myocardial infarction fibrotic zones, programmed ventricular stimulation provides important prognostic information for the selection of the patients expected to benefit from an ICD implantation, while due to its high negative predictive value, patients at low risk level may also be detected. Clustering evidence from different research groups and electrophysiologic labs support an electrophysiologic testing guided risk stratification approach for sudden cardiac death.     

ICD-Therapie zur Primärprävention des plötzlichen Herztods

ICD therapy represents a major advance in the treatment of patients with severely impaired left ventricular function after myocardial infarction. While an ICD implantation also remains a valuable option late (>5 years) after myocardial infarction, patients early after this event are at a competitive risk of arrhythmogenic and nonarrhythmogenic cardiac death. Prevention of sudden cardiac death in patients early after myocardial infarction, therefore, just converts the mode of death in a significant number of patients from sudden to nonsudden cardiac death (conversion theory). In patients with a left ventricular ejection fraction (LVEF) of ≤30% after myocardial infarction, implantation of the ICD should, therefore, be postponed to at least 30–40 days after the event. It is, however, not clear how the risk of sudden cardiac death should be approached during this post infarction phase. Similarly, it is not clear if patients with a reduced LVEF post infarction and additional specific risks (nonsustained ventricular tachycardia, atrial fibrillation, bundle branch block, etc.) beyond this single criterion may also benefit from ICD implantation and which risk factors may be relevant. In any case, ICD therapy should avoid right ventricular pacing and shock discharges whenever possible.     

Risk of sudden death in heart failure patients

Sudden death is one of the more important cause of mortality in patients with chronic heart failure. The highest risk occurs among patients with less severe functional impairment, whereas patients in NYHA class IV usually die of progression of heart failure. Predictors of sudden death have been evaluated. Nevertheless, current methods of risk stratification for sudden death are still inadequate, especially in patients with advanced heart failure. Low left ventricular ejection fraction is widely used for the risk stratification, but it lacks of sensitivity and specificity in distinguishing patients with an increased arrhythmic mortality from those with an increased mortality due to pump failure. Unsustained ventricular tachycardia and inducibility at electrophysiological study may help identifying high-risk patients, requiring more aggressive therapy, as the ICD implantation. Heart rate variability and baroreflex sensitivity analysis have been utilized to obtain information on autonomic modulation, but with uncertain conclusion on the identification of high-risk patients. Increased QT dispersion, the presence of T-wave alternans and abnormal signal-averaged electrocardiography have also been proposed, but, up-to-now, any of these parameters showed a strong predictor power. In conclusion, our capability to identifying heart failure patients at risk for arrhythmic death is still far from being satisfactory.     

Ventrikuläre Tachykardien bei Postinfarktpatienten und koronarer Herzkrankheit

Patients with coronary heart disease are subject to an increased risk for sudden cardiac death (SCD). Within the first 30–90 days after the myocardial infarct the risk is particularly high. In times of implantable cardioverter-defibrillator (ICD) on the one hand and the ability to bridge high-risk periods with e. g. wearable defibrillator vests on the other, adequate risk stratification is essential. Currently, the main parameter for this is the left ventricular ejection fraction (LVEF). However, risk stratification by measurement of the LVEF has severe limitations, especially since the majority of patients suffering from SCD have a normal LVEF. Various other methods like ventricular ectopy, signal-averaged ECG, QRS width, microvolt T-wave alternans and programmed ventricular stimulation have been previously evaluated. None of these methods alone or in combination with a left ventricular function assessment was capable of improving the predictability of arrhythmic events significantly. Considering the multiple mechanisms that can lead to SCD, a single risk stratifier seems unrealistic. However, patients with chronic total occlusion of a coronary artery and residual or provocable ischemia have an increased risk for SCD. Therefore a combination of clinical and angiographic parameters seems reasonable. Advanced echocardiographic parameters e.g. mechanical dispersion could be used on a complementary role.     

Prognostic value of T-wave alternans in patients with heart failure due to nonischemic cardiomyopathy: results of the ALPHA Study.

OBJECTIVES: The aim of this study was to assess the prognostic value of T-wave alternans (TWA) in New York Heart Association (NYHA) functional class II/III patients with nonischemic cardiomyopathy and left ventricular ejection fraction (LVEF) < or =40%. BACKGROUND: There is a strong need to identify reliable risk stratifiers among heart failure candidates for implantable cardioverter-defibrillator (ICD) prophylaxis. T-wave alternans may identify low-risk subjects among post-myocardial infarction patients with depressed LVEF, but its predictive role in nonischemic cardiomyopathy is unclear. METHODS: Four hundred forty-six patients were enrolled and followed up for 18 to 24 months. The primary end point was the combination of cardiac death + life-threatening arrhythmias; secondary end points were total mortality and the combination of arrhythmic death + life-threatening arrhythmias. RESULTS: Patients with abnormal TWA (65%) compared with normal TWA (35%) tests were older (60 +/- 13 years vs. 57 +/- 12 years), were more frequently in NYHA functional class III (22% vs. 19%), and had a modestly lower LVEF (29 +/- 7% vs. 31 +/- 7%). Primary end point rates in patients with abnormal and normal TWA tests were 6.5% (95% confidence interval [CI] 4.5% to 9.4%) and 1.6% (95% CI 0.6% to 4.4%), respectively. Unadjusted and adjusted hazard ratios were 4.0 (95% CI 1.4% to 11.4%; p = 0.002) and 3.2 (95% CI 1.1% to 9.2%; p = 0.013), respectively. Hazard ratios for total mortality and for arrhythmic death + life-threatening arrhythmias were 4.6 (p = 0.002) and 5.5 (p = 0.004), respectively; 18-month negative predictive values for the 3 end points ranged between 97.3% and 98.6%. CONCLUSIONS: Among NYHA functional class II/III nonischemic cardiomyopathy patients, an abnormal TWA test is associated with a 4-fold higher risk of cardiac death and life-threatening arrhythmias. Patients with normal TWA tests have a very good prognosis and are likely to benefit little from ICD therapy.     

Role of the Automatic Implantable Cardioverter Defibrillator in the Post-myocardial Infarction Patient

Patients with a myocardial infarction are at an increased risk of sudden cardiac death largely due to ventricular arrhythmias associated with myocardial scarring. Implantable cardioverter defibrillators (ICDs) have been established as the best available treatment for the secondary prevention of an arrhythmic death in patients at high risk. This includes patients who have survived sudden cardiac death, have had sustained ventricular tachycardia or fibrillation, or have had syncope assumed to be due to a ventricular arrhythmia. High-risk features of patients with infarction without a previous arrhythmic event who qualify for a primary prevention ICD are an ejection fraction (EF) <30% or symptoms of Class II or III heart failure with an EF ≤ 35%. In addition, patients with nonsustained ventricular tachycardia, a positive electrophysiology study, and EF ≤ 40% are candidates under the current primary prevention guidelines. The current guidelines have specified the timing for ICD implantation as >40 days following the acute myocardial infarction. Despite the establishment of the guidelines, current clinical practice has revealed that ICDs are underutilized in patients who qualify. This article reviews the ICD implantation guidelines to encourage the appropriate use of the device.     

Risk stratification and prevention of sudden death in patients with heart failure

Patients with heart failure can die of progressive refractory heart failure or sudden cardiac death. This article reviews the major clinical predictors of sudden death in patients with heart failure due to left ventricular systolic dysfunction. Although earlier studies have identified many independent univariate predictors of reduced survival in these patients, the positive predictive value of most of them is low. Cardioverter defibrillator implantation has been shown to be the most effective therapy in patients resuscitated after cardiac arrest caused by ventricular fibrillation or poorly tolerated ventricular tachycardia. Low left ventricular ejection fraction, low New York Heart Association functional class, unsustained ventricular tachycardia and inducibility of ventricular arrhythmia in electrophysiological studies may also identify high-risk patients who are candidates for cardioverter defibrillator implantation. The role of amiodarone in preventing sudden death in high-risk patients with heart failure seems to be small. Further studies are needed to improve risk stratification criteria to select patients with heart failure who are candidates for cardioverter defibrillator implantation.     

Should Primary Prevention ICDs Still Be Placed in Patients with Non-ischemic Cardiomyopathy? A Review of the Evidence

Purpose of Review

Recent evidence has suggested that implantable defibrillator (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit in the presence of guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT).

Recent Findings

Despite significant benefits of GDMT and CRT, current evidence is derived from ICD trials that rely predominantly on reduced left ventricular ejection fraction alone (LVEF). The majority of patients with sudden cardiac death (SCD) have LVEF >?30% indicating that LVEF by itself is an inadequate predictor of SCD. The Danish study to assess the efficacy of ICD in patients with non-ischemic systolic heart failure on mortality (DANISH) highlights the importance of better risk stratifying NICM patients for ICD implantation.

Summary

Assessment of life expectancy, comorbidities, presence of advanced heart failure, etiology of NICM, and the presence of myocardial fibrosis can help risk stratify ICD beyond LVEF. Genetics and biomarkers can be of further assistance in risk stratification.

     

Added Value of 3- Versus 2-Dimensional Echocardiography Left Ventricular Ejection Fraction to Predict Arrhythmic Risk in Patients With Left Ventricular Dysfunction

ObjectivesThis study sought to evaluate the potential clinical impact of using 3-dimensional echocardiography (3DE) to measure left ventricular ejection fraction (LVEF) in patients considered for implantable cardioverter-defibrillator (ICD) implantation and to assess the predictive value of 3DE LVEF for arrhythmic events.BackgroundICD therapy is currently recommended to prevent sudden cardiac death in patients with symptomatic heart failure and LVEF ≤35%, and in asymptomatic patients with ischemic heart disease and LVEF ≤30%. Two-dimensional echocardiography (2DE) is currently used to calculate LVEF. However, 3DE has been reported to be more reproducible and accurate than 2DE to measure LVEF.MethodsThe study prospectively enrolled 172 patients with LV dysfunction (71% ischemic). Both 2DE and 3DE LVEF were obtained during the same study. The outcome was the occurrence of major arrhythmic events (sudden cardiac death, aborted cardiac arrest, appropriate ICD therapy).ResultsAfter a median follow up of 56 (range 18 to 65) months, major arrhythmic events occurred in 30% of the patients. Compared with 2DE, 3DE changed the assignment above or below the LVEF thresholds for ICD implantation in 20% of patients, most of them having 2DE LVEFs within ± 10% from threshold. By cause-specific hazard model, 3DE LVEF was the only independent predictor of the occurrence of major arrhythmic events.ConclusionsLVEF by 3DE was an independent predictor of major arrhythmic events and improved arrhythmic risk prediction in patients with LV dysfunction. When compared with 2DE LVEF, 3DE measurement of LVEF may change the decision to implant an ICD in a sizable number of patients.     

How to evaluate sudden cardiac death risk after myocardial infarction?

Sudden cardiac death is the mode of death of more than half of coronary heart disease patients. Preventing sudden cardiac death involves prevention of ventricular arrhythmias occurrence as well as the treatment by an implantable cardioverter defibrillator. The evaluation of sudden cardiac death risk should consider the underlying cardiopathy, the associated coronary risk factors and all pharmacological treatment efficient to reduce ventricular remodeling and myocardial ischemia. Only significant low ejection fraction and positive ventricular testing in some cases are now considered are now considered by the current French recommendations for cardioverter defibrillator implantation in primary prevention. However, other noninvasive markers such as heart rate variability and T wave alternans are of interest in sudden cardiac death risk stratification after myocardial infarction.     

Prophylactic Implantation of Cardioverter Defibrillators in Idiopathic Nonischemic Cardiomyopathy for the Primary Prevention of Death: A Narrative Review

Implantable cardioverter defibrillator (ICD) therapy reduces sudden cardiac death rates and reduces mortality in patients with ischemic heart disease and low ejection fractions. One‐third of the deaths in patients with nonischemic cardiomyopathy are sudden. However, the efficacy of ICDs in the primary prevention of death in these patients is less clear. The most common cause of mortality in patients treated with ICDs is heart failure progression. ICD shocks can cause direct myocardial injury, fibrosis, inflammation, and adverse psychological outcomes, and these changes may contribute to the ventricular dysfunction in patients who already have a significantly depressed ejection fraction. We have reviewed the published randomized controlled trials and meta‐analysis of prophylactic ICD therapy in the primary prevention of death in patients with nonischemic cardiomyopathy. The individual randomized controlled trials do not report a statistically significant reduction of mortality unless the ICD treatment is added to cardiac resynchronization therapy, but the meta‐analysis did show a significant mortality reduction and favored ICD therapy in these patients. Medical management of many study participants was suboptimal, at least based on current guidelines. The patients with non‐ischemic cardiomyopathy have good outcomes with medical therapy, and ICD therapy in this relatively low‐risk population needs better selection criteria. Copyright © 2010 Wiley Periodicals, Inc.     

Sudden cardiac death in Chagas' heart disease in the contemporary era

This article reviews epidemiology, clinical-morphological aspects, and primary and secondary prevention of sudden cardiac death in patients with chronic Chagas' heart disease in the current era. Chagas' disease patients with life-threatening ventricular tachyarrhythmias are at risk of sudden cardiac death. No evidence-based support is available for guiding prophylaxis of sudden cardiac death in patients with this condition. Therefore, measurements for sudden cardiac death prevention in Chagas' disease patients have been derived from data obtained in non-Chagas' disease patients as well as on expertise of physicians dealing with this disorder in areas where Chagas' disease is endemic. For primary prevention, therefore, we suggest that patients with non-sustained VT be referred to programmed ventricular stimulation. Patients with inducible VT will be better treated with Implantable Cardioverter-Defibrillator (ICD) than with amiodarone therapy. For secondary prevention, we suggest that patients with malignant ventricular tachyarrhythmias with hemodynamic instability receive ICD therapy. For patients with life-threatening ventricular arrhythmias and no hemodynamic instability, however, secondary prevention can be accomplished with ICD therapy or catheter ablation in those with a left ventricular ejection fraction (LVEF) of 30% or less, and with electrophysiologic testing-guided drug therapy or empiric treatment with amiodarone in those with a LVEF of 30% or high.     

Sudden cardiac death

Opinion statement Sudden cardiac death is often due to a ventricular arrhythmia. When a patient presents with a malignant arrhythmia unrelated to a transient reversible cause, there is a high probability of recurrent arrhythmia and sudden death. Clinical trials have shown a uniform survival benefit from implantable cardioverter-defibrillator (ICD) therapy in survivors of a malignant arrhythmia when compared with drug therapy. However, only 1% to 5% of patients survive an out-of-hospital cardiac arrest, emphasizing the need for primary prevention of sudden death. Clinical trial data available in this regard are largely limited to patients with coronary artery disease (CAD). Mortality can be reduced by the ICD in patients with CAD and depressed left ventricular ejection fraction (LVEF) less than 30%. If left ventricular function is only moderately depressed (LVEF between 30% and 40%), the presence of nonsustained ventricular tachycardia with inducible ventricular arrhythmia at electrophysiologic testing identifies patients who benefit from an ICD. The role of the ICD in primary prevention of sudden death in patients with nonischemic dilated cardiomyopathy is less clear at this time. Preliminary data indicate that the presence of heart failure symptoms in this population increases risk of sudden death that can be prevented by an ICD. Antiarrhythmic drugs have little role in prevention of sudden death; however, drugs that block the effects of β-adrenergic stimulation, angiotensin, and aldosterone reduce mortality partly through their salutary effects on sudden death. Finally, a number of inherited defects of genes coding for ion channels, contractile sarcomeric proteins, and cell-to-cell junction proteins can result in primary electrical abnormalities and sudden death. The ICD is effective for secondary prevention, but its role in primary prevention is controversial and should be based on individual risk factors.     

Implantable cardioverter-defibrillators: a new preventive medical option

Implantable cardioverter-defibrillator (ICD or defibrillator) therapy has revolutionized the fields of cardiology and electrophysiology. Hundreds of thousands of patients at risk for sudden cardiac death receive them each year. The devices are not much larger than a pacemaker, and they have full pacemaker capabilities in addition to being able to shock patients out of life-threatening ventricular arrhythmias. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) in 1996 was a landmark trial that showed for the first time a mortality benefit of ICD therapy over medications in patients at high risk for sudden death. Multicenter Automatic Defibrillator Implantation Trial II, published in 2002, extended these results to all patients with ischemic heart failure with depressed heart function. Candidates for ICD implantation include most patients with an ejection fraction of <30%, especially those with coronary artery disease. More work needs to be done to define those patients with nonischemic cardiomyopathies who will benefit from ICDs and biventricular pacing for heart failure.     

Sudden death prophylaxis in heart failure

Sudden cardiac death (SCD) is the leading cause of mortality in heart failure (HF). Today the implantable cardioverter-defibrillator (ICD) has become a commonplace therapy around the world for patients with both ischemic and non-ischemic cardiomyopathy and an ejection fraction (EF) < or = 35%. However, EF alone does not discriminate between the modes of death from HF (sudden arrhythmic death vs. non-sudden death). Other risk statifiers, such as electrophysiologic study and microvolt T-wave alternans testing, should therefore be used in the appropriate settings to minimize the number of unnecessary device implants. In addition, left ventricular mechanical dyssynchrony has now become recognized as an additional major marker of cardiac mortality. Its assessment should entail echocardiography rather than measurement of the QRS duration. This will allow us to better integrate the ability of cardiac resynchronization therapy (CRT) in enhancing cardiac function with the ability of an ICD in preventing SCD. This review aims to: 1) give a synthesis of the published evidence regarding the value of implantable ICDs and CRT in the primary prophylaxis of SCD in HF; 2) discuss controversial clinical issues in this area; and 3) recommend practical device-based management strategies.     

Cardiac magnetic resonance for risk stratification: the sudden death risk portrayed

Risk stratification of patients with structural heart disease remains problematic. While patients with low ejection fractions have been shown to be at significant risk for sudden cardiac death, a risk that can be decreased by ICD implantation, the sensitivity and specificity of ejection fraction for predicting sudden death are sub-optimal. Contrast enhanced magnetic resonance imaging (CMRI) has been shown to carefully delineate the extent and morphology of myocardial scar. Recent studies have suggested that the extent of myocardial scar and potentially its heterogeneity can help risk stratify patient with coronary artery disease. Ongoing clinical studies will help determine the utility of incorporating CMRI into a risk prediction algorithm.     

Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study

OBJECTIVES: This study was designed to evaluate the ability of microvolt-level T-wave alternans (MTWA) to identify prospectively patients with idiopathic dilated cardiomyopathy (DCM) at risk of ventricular tachyarrhythmic events and to compare its predictive accuracy with that of conventional risk stratifiers. BACKGROUND: Patients with DCM are at increased risk of sudden death from ventricular tachyarrhythmias. At present, there are no established methods of assessing this risk. METHODS: A total of 137 patients with DCM underwent risk stratification through assessment of MTWA, left ventricular ejection fraction, baroreflex sensitivity (BRS), heart rate variability, presence of nonsustained ventricular tachycardia (VT), signal-averaged electrocardiogram, and presence of intraventricular conduction defect. The study end point was either sudden death, resuscitated ventricular fibrillation, or documented hemodynamically unstable VT. RESULTS: During an average follow-up of 14 +/- 6 months, MTWA and BRS were significant univariate predictors of ventricular tachyarrhythmic events (p < 0.035 and p < 0.015, respectively). Multivariate Cox regression analysis revealed that only MTWA was a significant predictor. CONCLUSIONS: Microvolt-level T-wave alternans is a powerful independent predictor of ventricular tachyarrhythmic events in patients with DCM.     

Improved survival in patients with nonischemic advanced heart failure and syncope treated with an implantable cardioverter-defibrillator

The purpose of this study was to assess whether in patients with syncope and heart failure due to nonischemic cardiomyopathy, treatment with an implantable cardioverter-defibrillator (ICD) compared with conventional medical therapy is associated with a reduction in sudden death and total mortality. Patients with advanced heart failure who have syncope have been shown to be at high risk for sudden death. Further risk stratification has been difficult in patients with nonischemic cardiomyopathy in whom inducibility on electrophysiologic study is not predictive of future risk. Of 639 consecutive patients with nonischemic cardiomyopathy referred for heart transplantation, 147 patients with history of syncope and no prior history of sustained ventricular tachycardia or cardiac arrest were identified. Outcomes were compared for the 25 patients managed with an ICD and 122 patients managed with conventional medical therapy. There were no differences in the baseline variables in the 2 groups of patients, including age, ejection fraction, and medical treatments for heart failure, but patients receiving an ICD were more likely to have had nonsustained ventricular tachycardia (56% vs. 15%, p = 0.001). During a mean follow-up of 22 months, there were 31 deaths, 18 sudden, in patients treated with conventional therapy, whereas there were 2 deaths, none sudden, in patients treated with an ICD. An appropriate shock occurred in 40% of the ICD patients. Actuarial survival at 2 years was 84.9% with ICD therapy and 66.9% with conventional therapy (p = 0.04). Thus, in patients with nonischemic cardiomyopathy and syncope, therapy with an ICD is associated with a reduction in sudden death and an improvement in overall survival.