Risk Stratification For Sudden Cardiac Death Research Articles

Utility of electrophysiological studies to predict arrhythmic events.

To evaluate the prognostic value of electrophysiological stimulation (EPS) in the risk stratification for tachyarrhythmic events and sudden cardiac death (SCD). We conducted a prospective cohort study and analyzed the long-term follow-up of 265 consecutive patients who underwent programmed ventricular stimulation at the Luzerner Kantonsspital (Lucerne, Switzerland) between October 2003 and April 2012. Patients underwent EPS for SCD risk evaluation because of structural or functional heart disease and/or electrical conduction abnormality and/or after syncope/cardiac arrest. EPS was considered abnormal, if a sustained ventricular tachycardia (VT) was inducible. The primary endpoint of the study was SCD or, in implanted patients, adequate ICD-activation. During EPS, sustained VT was induced in 125 patients (47.2%) and non-sustained VT in 60 patients (22.6%); in 80 patients (30.2%) no arrhythmia could be induced. In our cohort, 153 patients (57.7%) underwent ICD implantation after the EPS. During follow-up (mean duration 4.8 ± 2.3 years), a primary endpoint event occurred in 49 patients (18.5%). The area under the receiver operating characteristic curve (AUROC) was 0.593 (95%CI: 0.515-0.670) for a left ventricular ejection fraction (LVEF) < 35% and 0.636 (95%CI: 0.563-0.709) for inducible sustained VT during EPS. The AUROC of EPS was higher in the subgroup of patients with LVEF ≥ 35% (0.681, 95%CI: 0.578-0.785). Cox regression analysis showed that both, sustained VT during EPS (HR: 2.26, 95%CI: 1.22-4.19, P = 0.009) and LVEF < 35% (HR: 2.00, 95%CI: 1.13-3.54, P = 0.018) were independent predictors of primary endpoint events. EPS provides a benefit in risk stratification for future tachyarrhythmic events and SCD and should especially be considered in patients with LVEF ≥ 35%.

Sudden Cardiac Death Risk Stratification - An Update.

Sudden cardiac death (SCD) remains a major public health problem worldwide, yet current methods to identify those at greatest risk are inadequate. High-risk individuals may benefit from potentially life-saving treatment, such as insertion of an implantable-cardioverter defibrillator (ICD). However, such treatments are expensive and have their own associated risks. Furthermore, most cases of SCD occur in the general adult population who may be relatively asymptomatic but yet have an underlying predisposition to SCD. Hence, there is great interest and clinical need in improving methods for risk stratification of SCD to identify those at greatest risk and implement the most appropriate treatment. This review provides an update on current risk-stratification methods for SCD in high-risk groups, in particular patients with reduced left ventricular function following acute myocardial infarction and those with non-ischaemic dilated cardiomyopathy, and highlights some novel methods that may have a role to play in future risk-stratification schemes. Approaches and challenges for SCD risk stratification among the general public are also discussed.

Microvolt T-wave alternans in adult patients with repaired tetralogy of Fallot.

Indications for sudden cardiac death (SCD) primary prevention are unknown in patients with repaired tetralogy of Fallot (ToF). The role of microvolt T-wave alternans (MTWA) in SCD risk stratification was documented. However, the prevalence of spectral MTWA and its association with ventricular arrhythmia (VA) in adults after ToF repair were not elucidated. Microvolt T-wave alternans, electrocardiogram (ECG), ambulatory ECG monitoring, echocardiography, and spiroergometry were evaluated in 102 adults after ToF repair. Microvolt T-wave alternans results were classified as normal: negative(-), abnormal: positive(+), and indeterminate(ind). Owing to similar prognostic significance, MTWA(+) and MTWA(ind) due to patient factors were combined into nonnegative group: MTWA(abnormal). Microvolt T-wave alternans(abnormal) was more frequent in the studied group as compared with controls (P = .0005). The MTWA(abnormal) group had greater right ventricular end-diastolic diameter (P = .005), higher incidence of pulmonary regurgitation (P = .015), lower peak oxygen consumption (P = .01), and higher VE/VCO2 slope (P = .04) in comparison with MTWA(normal). Univariate logistic regression proved pulmonary regurgitation (OR = 3.57, 95% CI 1.27-10.04), VA (OR = 3.26, 95% CI 1.06-10.05), right ventricular end-diastolic enlargement (OR = 1.11, 95% CI 1.03-1.2), increase in VE/VCO2 slope (OR = 1.08, 95% CI 1.01-1.17), and decrease in peak oxygen uptake (OR = .91, 95% CI 0.83-0.99) to increase MTWA(abnormal) prevalence. In adults after ToF repair, abnormal MTWA occurred more often than in controls. Probability of abnormal MTWA did not rise with prevalence of malignant VA; however, presence of abnormal MTWA was associated with VA risk factors: pulmonary regurgitation, right ventricular enlargement, and consequent heart failure. The role of MTWA in selecting patients late after ToF repair at risk of SCD needs further observation.

Abstract 13286: Non-Specific Intraventricular Conduction Delay and Risk of Sudden Death

Introduction: We and others have reported an independent association between prolonged QRS duration and risk of sudden cardiac death (SCD) in the general population. Left and right bundle branch block have been studied previously, but there is little information regarding non-specific intraventricular conduction delay and risk of SCD. Hypothesis: Completed conduction defects, including non-specific IVCD, are associated with increased SCD risk. Methods: Sudden cardiac death cases and controls from an ongoing large population based study in the Northwestern US (2002 to 2010) were included if age ≥ 35 years with a non-paced 12-lead ECG (recorded prior and unrelated to SCD in cases). QRS morphology was subcategorized as normal, intermediate [left anterior fascicular block (LAFB), left posterior fascicular block (LPFB), and incomplete right or left bundle branch block (IRBBB/ILBBB)] or completed conduction defects [left bundle branch block (LBBB), right bundle branch block (RBBB), or nonspecific intraventricular conduction delay (IVCD)]. Comparisons were conducted using chi-square tests for categorical variables and independent samples t-tests for continuous variables. Logistic regression was used to evaluate the association of QRS morphology with SCD. Results: We evaluated 761 SCD cases (64% male) and 539 controls (65% male). Cases were significantly older (69.7 vs 66.3 years, p&lt;0.0001) with greater QRS duration (102 vs. 98 ms, p=0.001). For conduction categories, intermediate or completed conduction defects were significantly more common in cases whereas normal QRS morphology was more common among controls (p=0.01). And for specific morphology overall, QRS morphology patterns differed between cases and controls (p=0.03); abnormal QRS morphologies were more frequent in cases than controls except for LAFB. After adjustment for age and gender, however, only a finding of LBBB or non-specific IVCD remained a significant predictor of SCD [OR 1.34 (95% CI 1.03-1.75)]. Conclusions: LBBB and non-specific IVCD, but not RBBB, are significant predictors of SCD in the general population. These findings contribute to the utility of the 12-lead EKG for SCD risk stratification.

5Improving sudden cardiac death risk stratification in patients with ischaemic cardiomyopathy: a combined electrocardiogram and plasma biomarker approach

Introduction: Sudden cardiac death (SCD) risk prediction has substantial limitations. The Regional Restitution Instability Index (R2I2) is a promising new ECG-based biomarker of SCD. R2I2 uses the surface 12-lead ECG to quantify regional heterogeneity of electrical restitution, a property of ventricular myocardium implicated in arrhythmogenesis. We investigated the potential of a combined R2I2 and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) SCD risk marker in an ischaemic cardiomyopathy cohort. Methods: Blinded, prospective, observational study of 55 ischaemic cardiomyopathy patients (age: 67±9years, ejection fraction: 31±10%) undergoing risk stratification for an implantable cardioverter defibrillator (ICD). R2I2 was calculated using a pre-defined technique: an electrophysiology study is performed and ECG surrogates for action potential duration (QRS-onset to T-peak) and diastolic interval (T-peak to QRS-onset) are used to measure heterogeneity of electrical restitution. Plasma samples obtained on the day of the ICD procedure were assayed for NT-proBNP. A pre-defined R2I2 cut-off (1.03) was combined with an optimal log NT-proBNP cut-off (2.65) to investigate the potential of a combined risk marker. Results: During median follow up of 22 months, 15 patients experienced ventricular arrhythmia (VA)/SCD. R2I2 was significantly higher in patients experiencing VA/SCD than those not (mean±SEM:1.12±0.05 vs 0.84±0.09, p=0.004). R2I2 was independent of age, gender, left ventricular ejection fraction, QRS duration and log NT-proBNP in prediction of endpoint (Cox model, p=0.002). Partitioning patients using a log NT-proBNP ≥ 2.65 gave a significantly higher rate of VA/SCD in those with high versus low log NT-proBNP (38% vs. 6%, p=0.01). Patients with R2I2 ≥ 1.03 and log NT-proBNP ≥ 2.65 had a hazard ratio for VA/SCD 17.2 times that of patients negative for both (Cox model, p=0.007). Kaplan Meier analysis (Figure 1) showed significant separation in rates of VA/SCD in patients stratified by R2I2 ≥ 1.03 and log NT-proBNP ≥ 2.65 (log-rank, p<0.0001). Conclusion: A combined R2I2 + NT-proBNP risk marker identifies patients at particularly high risk of ventricular arrhythmia/SCD. These patients might benefit from careful treatment optimisation. R2I2 + NT-proBNP might retain sufficient positive predictive value for application to lower risk cohorts. ![Graphic][1] Figure 1 Kaplan-Meier curves illustrating rates of VA/SCD in patients stratified using R212 and NT-proBNP [1]: /embed/inline-graphic-1.gif

22Combining a novel electrical restitution based biomarker with heart rate variability analysis improves prediction of sudden cardiac death risk

Introduction: Sudden cardiac death (SCD) remains a significant cause of mortality worldwide. Current SCD risk markers have substantial limitations. Peak Electrical Restitution Slope (PERS) is a promising new SCD risk marker. PERS uses the surface 12-lead ECG to measure peak restitution gradient, a property of myocardium known to play a role in ventricular arrhythmogenesis. By combining PERS with heart rate variability (HRV) analysis, we sought to improve SCD risk prediction in patients with ischaemic cardiomyopathy (ICM). Methods: Blinded, prospective, observational study of 44 ICM patients (>18 years of age) undergoing risk stratification for an implantable cardioverter defibrillator. Patients underwent programmed ventricular stimulation for determination of PERS. Surface ECG surrogates for action potential duration (QRS-onset to T-peak) and diastolic interval (T-peak to QRS-onset) were used to measure peak restitution gradient. Patients underwent 24-hour ambulatory ECG monitoring to determine time-domain HRV (standard deviation of normal to normal RR intervals [SDNN]). A pre-defined SDNN cut off (100ms) was combined with an optimal PERS cut-off (1.21) to determine if combining these risk markers could improve SCD risk stratification. Results: During median follow up of 22 months, 11 patients experienced ventricular arrhythmia (VA)/SCD. PERS was significantly higher in patients experiencing VA/SCD than those not (mean±SEM:1.73±0.27 vs 1.07±0.08, p=0.002). PERS was independent of age, gender, left ventricular ejection fraction, QRS duration and SDNN in prediction of endpoint (Cox model, p=0.002). Patients with low SDNN (<100ms) experienced a non-significantly higher rate of VA/SCD than those with high SDNN (33% vs 19%, p=0.24). Patients with PERS ≥ 1.21 and SDNN<100ms had a hazard ratio for VA/SCD 17.4 times that of patients negative for both (Cox model, p=0.01). Kaplan Meier analysis (Figure 1) showed significant separation in rates of VA/SCD in patients stratified by PERS and SDNN (log-rank, p=0.002). Conclusions: Combining PERS with SDNN identifies patients at particularly high risk of ventricular arrhythmia/SCD. A combined PERS + SDNN risk marker may improve SCD risk stratification in patients with ischaemic cardiomyopathy. ![Graphic][1] Figure 1 Kaplan-Meier curves illustrating rates of VA/SCD in patients stratified using PERS and SDNN. [1]: /embed/inline-graphic-1.gif

Implantable cardiac defibrillator among adults with transposition of the great arteries and atrial switch operation: Case series and review of literature

BackgroundThe experience with the implantable cardiac defibrillator (ICD) in patients with transposition of the great arteries (TGA) and history of atrial switch surgery remains limited. MethodsRetrospective evaluation aiming to assess characteristics and outcomes of consecutive TGA patients with history of atrial switch surgery implanted with an ICD between January 2005 and June 2012 in four French centers. ResultsOf the 12 patients (median 34years [28, 40]; 67% male), 4 patients (33%) were implanted for secondary prevention after symptomatic documented sustained ventricular tachycardia or sudden cardiac arrest. ICDs were implanted for primary prevention in 8 patients (67%), including cardiac resynchronization in 3 patients; severe systemic ventricle dysfunction was present in all cases (median ejection fraction 27% [20, 40]). Overall, one patient died during the ICD implantation secondary to refractory cardiac arrest after defibrillation testing. Over a median follow-up of 19months [10, 106], 6 patients out of 11 (54%) experienced worsening of congestive heart failure, including 5 who were eventually transplanted. Overall, 3 patients (27%) experienced significant ICD-related complications, whereas only one patient (primary prevention indication) developed appropriate ICD therapy (successful anti-tachycardia pacing without shock). Half of the patients presented with at least one episode of sustained (≥5min) atrial arrhythmia during follow-up. ConclusionsOur findings underline the key role of progressive heart failure in dictating outcomes among TGA patients with prior atrial switch repair. Our results also underline the need of better risk-stratification for sudden cardiac death in those patients.

Utility of the exercise electrocardiogram testing in sudden cardiac death risk stratification.

Sudden cardiac death (SCD) remains a major public health problem. Current established criteria identifying those at risk of sudden arrhythmic death, and likely to benefit from implantable cardioverter defibrillators (ICDs), are neither sensitive nor specific. Exercise electrocardiogram (ECG) testing was traditionally used for information concerning patients' symptoms, exercise capacity, cardiovascular function, myocardial ischemia detection, and hemodynamic responses during activity in patients with hypertrophic cardiomyopathy. We conducted a systematic review of MEDLINE on the utility of exercise ECG testing in SCD risk stratification. Exercise testing can unmask suspected primary electrical diseases in certain patients (catecholaminergic polymorphic ventricular tachycardia or concealed long QT syndrome) and can be effectively utilized to risk stratify patients at an increased (such as early repolarization syndrome and Brugada syndrome) or decreased risk of SCD, such as the loss of preexcitation on exercise testing in asymptomatic Wolff-Parkinson-White syndrome. Exercise ECG testing helps in SCD risk stratification in patients with and without arrhythmogenic hereditary syndromes.

Abstract 351: Optimizing the Frequency of Surveillance Echocardiography in Clinically Stable Patients With Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) affects 0.2% of the population and is an important cause of sudden cardiac death, heart failure and stroke. However, most patients with HCM experience normal longevity. Optimal longitudinal management of stable HCM patients is poorly defined, although consensus guidelines advise annual echocardiography (echo). We report the clinical impact of surveillance echo and a protocol to improve the efficiency of repeat testing in a cohort of HCM patients followed at one center. Methods and Results: A Standardized Clinical Assessment and Management Plan (SCAMP) was developed by clinicians, supported by a quality improvement (QI) team, to maximize the utility of cardiac imaging in patients with HCM. SCAMPs are an established approach to QI that aim to optimize outcomes and resource utilization through standardization of care. The HCM SCAMP was designed to achieve these goals through implementation of a practice algorithm, data capture at the time of outpatient encounters, and iterative analysis. This SCAMP recommended decreased frequency of surveillance echo in stable patients, from every 12 to every 24 months. Stability was defined as &gt;3 years since diagnosis, stable symptoms for ≥2 years, &gt;2 unchanged echos, and no family history of end stage HCM. All patients with HCM followed longitudinally in one HCM clinic from 7/17/13 to 12/15/13 (n=127) were enrolled. After excluding patients with a new diagnosis (n=16), no recent echo (n=15), or incomplete SCAMP documentation (n=1), 92 were included in this analysis. At enrollment, baseline echo (mean interval from prior echo: 15.8±5.8 months) identified clinically significant changes in 13 (14%) patients; including new pulmonary hypertension (n=6), and significant change (≥Δ50mmHg) or interval appearance of severe left ventricular outflow tract obstruction (LVOTO) (n=6). Clinical management was impacted by echo findings in 8/92 (9%); including medication adjustment (n=6), referral for exercise testing (n=2) and refined sudden cardiac death risk stratification (n=1). In the 79 patients with stable echo findings (86%), 25 (32%) were qualified by the SCAMP as clinically stable and were advised to undergo repeat echo in 24 (instead of 12) months. Providers adhered to this recommendation in 19 patients (76%). Reasons for deviating from recommendations and continuing annual echo in SCAMP defined stable patients included patient preference, atrial fibrillation, severe LVOTO, and pulmonary hypertension. Conclusions: In select clinically stable patients with HCM, repeat echo may be unlikely to identify significant changes or impact practice. In these patients, a decreased frequency of echocardiography could decrease resource utilization without compromising care. Ongoing data collection and better risk stratification tools may allow more targeted surveillance strategies in the future.

Microvolt T-wave alternans in adults with complex congenital heart diseases

Sudden cardiac death (SCD) mostly resulting from ventricular arrhythmia remains a cause of mortality in 19-30% of adults with congenital heart defects. Indications for implantable cardioverter-defibrillators in primary prophylaxis are still under research. MicrovoltT wave alternans (MTWA) is one of the SCD risk stratification methods. We determined the incidence of MTWA in these patients and its coincidence with ventricular arrhythmia, as well as risk factors of ventricular arrhythmia/SCD. 204 patients with complex congenital heart anomalies and 45 healthy volunteers underwent ambulatory ECG monitoring, a cardiopulmonary test, B-type natriuretic peptide assessment, echocardiography and an MTWA test. After excluding technically inadequate traces, the remaining 179 patients and 43 controls were classified into MTWA positive (+), negative (-) and indeterminate (ind) subgroups. Additionally, MTWA (+) and MTWA (ind) formed an 'abnormal' group, labeled MTWA (non-). Abnormal MTWA was observed more frequently in the study group compared to controls (59 [33.0%] vs. 1 [2.3%], p = 0.000001). The MTWA (non-) group compared to MTWA (-) presented a higher number of males (61.0% vs. 37.5%, p = 0.005), predominance of patients with NYHA > I (44.1% vs. 25.0%, p = 0.007), pulmonary hypertension (16.9% vs. 0.8%, p = 0.00007), lower blood saturation (97% [73-100] vs. 99% [69-100], p = 0.0003), higher incidence of malignant arrhythmia (9 [15.2%] vs. 3 [2.5%], p = 0.003), lower peak oxygen consumption VO2 [mL/kg/min] (23.1 ± 5.9 vs. 26.3 ± 6.7, p = 0.002), higher VE//VCO2 slope (36.0 [25-74] vs. 31.0 [21-58], p = 0.01). Multivariate logistic regression analysis proved that pulmonary hypertension (OR = 13.7, p = 0.03), male gender (OR = 10.4,p = 0.00002), VE/VCO2 slope (OR = 1.07, p = 0.045) and VO2 (OR = 0.89, p = 0.04) increase the probability of MTWA (non-). Abnormal MTWA is more frequent in adults with congenital heart diseases than in the healthy population. Its probability increases in patients demonstrating clinical findings conducive to lethal arrhythmia like heart failure and pulmonary hypertension.

Hypertrophic cardiomyopathy in 2013: Current speculations and future perspectives

Hypertrophic cardiomyopathy (HCM), the most variable cardiac disease in terms of phenotypic presentation and clinical outcome, represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance. To date, more than 1400 mutations of myofilament proteins associated with the disease have been identified, most of them "private" ones. This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations. Additionally, topics pertaining to patients' everyday lives, such as sudden cardiac death (SCD) risk stratification and prevention, along with disease prognosis, are grossly related to the genetic variation of HCM. This review incorporates contemporary research findings and addresses major aspects of HCM, including preclinical diagnosis, genetic analysis, left ventricular outflow tract obstruction and SCD. More specifically, the spectrum of genetic analysis, the selection of the best method for obstruction alleviation and the need for a unique and accurate factor for SCD risk stratification are only some of the controversial HCM issues discussed. Additionally, future perspectives concerning HCM and myocardial ischemia, as well as atrial fibrillation, are discussed. Rather than enumerating clinical studies and guidelines, challenging problems concerning the disease are critically appraised by this review, highlighting current speculations and recommending future directions.

Sudden Cardiac Death: A Review Focused on Cardiovascular Imaging.

Sudden cardiac death (SCD) is defined as natural death due to cardiac causes, heralded by abrupt loss of consciousness within 1 h of the onset of acute symptoms; pre-existing heart disease may have been known to be present but the time and mode of death are unexpected. Prediction and prevention of SCD is an area of active investigation, but considerable challenges persist that limit the efficacy and cost-effectiveness of available methodologies. It was well-recognized that optimization of SCD risk stratification would require integration of multi-disciplinary efforts at the bench and bedside, with studies in the general population. This integration has yet to be effectively accomplished. There is also increasing awareness that more investigation needs to be directed toward the identification of early predictors of SCD. Significant advancements have recently occurred for risk prediction in the inherited channelopathies and other inherited conditions that predispose to SCD, but there is much to be accomplished in this regard for the more common complex phenotypes, such as SCD among patients with coronary artery disease. A multimodality imaging approach is actually the most important tool to provide comprehensive information on different pathophysiological mechanisms related to SCD.

Tools for risk stratification of sudden cardiac death: A review of the literature in different patient populations

While various modalities to determine risk of sudden cardiac death (SCD) have been reported in clinical studies, currently reduced left ventricular ejection fraction remains the cornerstone of SCD risk stratification. However, the absolute burden of SCD is greatest amongst populations without known cardiac disease. In this review, we summarize the evidence behind current guidelines for implantable cardioverter defibrillator (ICD) use for the prevention of SCD in patients with ischemic heart disease (IHD). We also evaluate the evidence for risk stratification tools beyond clinical guidelines in the general population, patients with IHD, and patients with other known or suspected medical conditions.

A combined anatomic and electrophysiologic substrate based approach for sudden cardiac death risk stratification

Although left ventricular ejection fraction (LVEF) is the primary determinant for sudden cardiac death (SCD) risk stratification, in isolation, LVEF is a sub-optimal risk stratifier. We assessed whether a multi-marker strategy would provide more robust SCD risk stratification than LVEF alone. We collected patient-level data (n = 3355) from 6 studies assessing the prognostic utility of microvolt T-wave alternans (MTWA) testing. Two thirds of the group was used for derivation (n = 2242) and one-third for validation (n = 1113). The discriminative capacity of the multivariable model was assessed using the area under the receiver-operating characteristic curve (c-index). The primary endpoint was SCD at 24 months. In the derivation cohort, 59 patients experienced SCD by 24 months. Stepwise selection suggested that a model based on 3 parameters (LVEF, coronary artery disease and MTWA status) provided optimal SCD risk prediction. In the derivation cohort, the c-index of the model was 0.817, which was significantly better than LVEF used as a single variable (0.637, P < .001). In the validation cohort, 36 patients experienced SCD by 24 months. The c-index of the model for predicting the primary endpoint was again significantly better than LVEF alone (0.774 vs 0.671, P = .020). A multivariable model based on presence of coronary artery disease, LVEF and MTWA status provides significantly more robust SCD risk prediction than LVEF as a single risk marker. These findings suggest that multi-marker strategies based on different aspects of the electro-anatomic substrate may be capable of improving primary prevention implantable cardioverter-defibrillator treatment algorithms.

Ambulatory ECG-Based T-Wave Alternans Monitoring for Risk Assessment and Guiding Medical Therapy: Mechanisms and Clinical Applications

Identification of individuals at risk for sudden cardiac death (SCD), the main cause of adult mortality in developed countries, remains a major challenge. The main contemporary noninvasive marker, left ventricular ejection fraction (LVEF), has not proved adequately reliable, as the majority of individuals who die suddenly have relatively preserved cardiac mechanical function. Monitoring of T-wave alternans (TWA), a beat-to-beat fluctuation in ST-segment or T-wave morphology, on ambulatory electrocardiogram (AECG) is an attractive approach on both scientific and clinical grounds. Specifically, TWA's capacity to assess risk for malignant arrhythmias has been shown to rest on sound electrophysiologic principles and AECG-based TWA monitoring can be performed in the flow of routine clinical evaluation. This review addresses: (1) electrophysiologic and ionic mechanisms underlying TWA's predictivity, (2) principles and practical aspects of AECG-based TWA monitoring, (3) clinical evidence supporting this approach to SCD risk stratification, and (4) current and potential applications in guiding medical therapy.

Late gadolinium enhancement cardiac magnetic resonance imaging for the prediction of ventricular tachyarrhythmic events: a meta‐analysis

Approaches to the risk stratification for sudden cardiac death (SCD) remain unsatisfactory. Although late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) for SCD risk stratification has been evaluated in several studies, small sample size has limited their clinical validity. We performed this meta-analysis to better gauge the predictive accuracy of LGE-CMR for SCD risk stratification. Electronic databases and published bibliographies were systematically searched to identify studies evaluating the association between the extent of LV scar on LGE-CMR and ventricular arrhythmic events [SCD, resuscitated cardiac arrest, the occurrence of ventricular arrhythmias, or appropriate implantable cardioverter defibrillator (ICD) therapy]. Only studies enrolling patients with CAD or non-ischaemic cardiomyopathy were included. Summary estimates of the relative risk (RR) and likelihood ratios (LRs) were calculated using random effects models. Eleven studies comprising 1105 patients were identified. During a mean/median follow-up of 8.5-41 months 207 patients had ventricular arrhythmic events. Ventricular arrhythmic events were more common in patients with a greater extent of LV scar: RR 4.33 [95% confidence interval (CI) 2.98-6.29], positive LR 1.98 (95% CI 1.66-2.37), and negative LR 0.33 (95% CI 0.24-0.46). The extent of LGE on CMR is strongly associated with the occurrence of ventricular arrhythmias in patients with reduced LVEF and may be a valuable risk stratification tool for identifying patients who will benefit from ICD therapy. However, uncertainties regarding clinical application persist and need to be addressed prior to introduction into broad clinical practice.

Electrocardiogram as a screening tool in the general population: A strategic review

Sudden cardiac death (SCD) is a major public health concern, accounting for 400,000 deaths in the US each year. Clinical and autopsy studies have consistently demonstrated a predominant, common pathophysiology in Western populations, showing that the most common electrophysiological mechanism of SCD is ventricular fibrillation, and the most common pathologic substrate is coronary heart disease (CHD). In about half of SCD cases, death is the first clinical manifestation of CHD. Yet risk factors of SCD early in the natural history of conditions predisposing SCD have not been fully identified, and SCD risk stratification strategy in the general population has not been developed. ECG is an easily available, non-expensive and non-invasive tool, which carries valuable information on electrophysiological properties of the heart. However, traditional analysis of ECG includes very limited assessment of the arrhythmogenic substrate. In this review rationale for development of ECG SCD risk score for screening in the general population is discussed.

Microvolt T-wave alternans in adults with congenital heart diseases

Purpose: Sudden cardiac death (SCD) in adults with congenital heart diseases (CHD) is usually caused by ventricular arrhythmia (VA). Microvolt T-wave alternans (MTWA) proved its role in SCD risk stratification. Aim of study: Evaluation of spectral MTWA incidence in patients (P) with CHD and determination its association with VA and potential risk factors of SCD. Methods: Study group: 204P (93men), aged 33,8±11,4years with CHD (TGA, UVH, Ebstein's anomaly, ccTGA, Eisenmenger syndrome, DORV, CAT, unoperated and operated ToF) underwent MTWA, ECG, 24h Holter ECG, BNP assessment and cardiopulmonary exercise test. Control group: 45 adults age- and sex-matched. MTWA classification: normal: negative (-) and abnormal: positive (+) and indeterminate (ind). Due to similar prognostic significance tests classified as MTWA(+) and MTWA(ind) were combined into non-negative(non-) group. VA classification: malignant- sustained ventricular tachycardia (sVT), potentially malignant- non-sustained ventricular tachycardia (nsVT) and >10 premature ventricular complexes per hour (PVC/h). Results: 31P were MTWA(+), 53P MTWA(ind) and 120P MTWA(-). Due to excessive noise 25P were excluded. MTWA(non-) was more frequent in study group vs. controls (p=0,000001). The highest ratio of MTWA(non-) was in Eisenmenger syndrome (87,5%). Among patients with MTWA(non-) malignant and potentially malignant VA was more frequent compared to MTWA(-) (p=0,003; p=0,016, respectively). Male gender and pulmonary hypertension (PH) were more often in MTWA(non-) vs. MTWA(-) (p=0,0049; p=0,00007, respectively). MTWA(non-) compared to MTWA(-) had lower: blood saturation (p=0,000295), maximal oxygen consumption (peakVO2) (p=0,002) and VE/VCO2slope (p=0,012). MTWA(non-) vs. MTWA(-) had higher: BNP values (p=0,0306) and NYHA class (p=0,007). Factors increasing MTWA(non-) incidence are: in univariate logistic regression: PH (OR=24,29), sVT (OR=7,31), VA (OR=3,01), male gender (OR=2,61), NYHA>I (OR=2,06), worse VE/VCO2slope (OR=1,07) and peakVO2 fall (OR=0,92); in multivariate logistic regression: PH (OR=14,16), male gender (OR=10,2), worse VE/VCO2slope (OR=1,06) and peakVO2 fall (OR=0,89). Conclusions: In adults with CHD abnormal MTWA occurs more often than in healthy population. Probability of this phenomenon increases in patients with malignant ventricular arrhythmia and clinical findings possibly related to lethal arrhythmia including advanced heart failure and pulmonary hypertension. Incidence of abnormal MTWA is higher in men. MTWA might be of potential role in SCD risk stratification in adults with congenital heart diseases.

Left ventricular hypertrophy is associated with the risk of sudden cardiac death

Aims: The echocardiographic identification of risk markers may enhance risk stratification for the development of sudden cardiac death (SCD). However, the value of left ventricular (LV) hypertrophy in the prediction for the risk for SCD is not well known. Methods and results: Echocardiography with the assessment of LV mass was defined in a representative population-based sample of 906 men (age 42-61 years). During an average follow-up period of 20.2 years (interquartile range 18.8-21.3 years), 66 SCDs occurred. The hazard ratio (HR) for SCD was 1.10 (95% confidence interval, CI 1.06-1.15, p<0.001) for each 10 g increment in LV mass, after adjustment for age, alcohol consumption, cigarette smoking, serum low and high density lipoprotein cholesterol, systolic blood pressure, type 2 diabetes, body mass index, high sensitivity C-reactive protein, previous myocardial infarction and cardiorespiratory fitness. Men with elevated LV mass of over 253 grams (highest quartile) had a 3.24-fold (95% CI 1.52 to 6.91, p=0.002) adjusted HR for an SCD as compared to those with LV mass of less than 186 grams (lowest quartile). After additional adjustment for LV function, the relation between LV mass and SCD remained statistically significant in the highest quartile of LV mass (HR 2.72, 95% CI 1.25 to 5.96, p=0.012). The risk for SCD was increased in 175 men with an indexed LV mass of over 125 g/m2 (3.25-fold, 95% CI 1.94 to 5.43, p<0.001). The integrated discrimination index was 0.094 (p=0.0002) indicating the significant level of discrimination improvement with LV mass. Conclusion: LV mass provides an incremental predictive value for SCD beyond that of other well-known risk factors. This study provides evidence that LV hypertrophy improves risk stratification for SCD in the general male population.

Obstructive Sleep Apnea and the Risk of Sudden Cardiac Death: A Longitudinal Study of 10,701 Adults

This study sought to identify the risk of sudden cardiac death (SCD) associated with obstructive sleep apnea (OSA). Risk stratification for SCD, a major cause of mortality, is difficult. OSA is linked to cardiovascular disease and arrhythmias and has been shown to increase the risk of nocturnal SCD. It is unknown if OSA independently increases the risk of SCD. We included 10,701 consecutive adults undergoing their first diagnostic polysomnogram between July 1987 and July 2003. During follow-up up to 15 years, we assessed incident resuscitated or fatal SCD in relation to the presence of OSA, physiological data including the apnea-hypopnea index (AHI), and nocturnal oxygen saturation (O 2 sat) parameters, and relevant comorbidities. During an average follow-up of 5.3 years, 142 patients had resuscitated or fatal SCD (annual rate 0.27%). In multivariate analysis, independent risk factors for SCD were age, hypertension, coronary artery disease, cardiomyopathy or heart failure, ventricular ectopy or nonsustained ventricular tachycardia, and lowest nocturnal O 2 sat (per 10% decrease, hazard ratio [HR]: 1.14; p = 0.029). SCD was best predicted by age >60 years (HR: 5.53), apnea-hypopnea index >20 (HR: 1.60), mean nocturnal O 2 sat <93% (HR: 2.93), and lowest nocturnal O 2 sat <78% (HR: 2.60; all p < 0.0001). In a population of 10,701 adults referred for polysomnography, OSA predicted incident SCD, and the magnitude of risk was predicted by multiple parameters characterizing OSA severity. Nocturnal hypoxemia, an important pathophysiological feature of OSA, strongly predicted SCD independently of well-established risk factors. These findings implicate OSA, a prevalent condition, as a novel risk factor for SCD.