Aapo L. Aro

Electrical risk score beyond the left ventricular ejection fraction: prediction of sudden cardiac death in the Oregon Sudden Unexpected Death Study and the Atherosclerosis Risk in Communities Study

AimsnThere is an urgent need to extend sudden cardiac death (SCD) risk stratification beyond the left ventricular ejection fraction (LVEF). We evaluated whether a cumulative electrocardiogram (ECG) risk score would improve identification of individuals at high risk of SCD.nnnMethods and resultsnIn the community-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), 522 SCD cases with archived 12-lead ECG available (65.3u2009±u200914.5 years, 66% male) were compared with 736 geographical controls to assess the incremental value of multiple ECG parameters in SCD prediction. Heart rate, LV hypertrophy, QRS transition zone, QRS-T angle, QTc, and Tpeak-to-Tend interval remained significant in the final model, which was externally validated in the Atherosclerosis Risk in Communities (ARIC) Study. Sixteen percent of cases and 3% of controls had ≥4 abnormal ECG markers. After adjusting for clinical factors and LVEF, increasing ECG risk score was associated with progressively greater odds of SCD. Overall, subjects with ≥4 ECG abnormalities had an odds ratio (OR) of 21.2 for SCD [95% confidence interval (CI) 9.4-47.7; Pu2009<u20090.001]. In the LVEF >35% subgroup, the OR was 26.1 (95% CI 9.9-68.5; Pu2009<u20090.001). The ECG risk score increased the C-statistic from 0.625 to 0.753 (Pu2009<u20090.001), with net reclassification improvement of 0.319 (Pu2009<u20090.001). In the ARIC cohort validation, risk of SCD associated with ≥4 ECG abnormalities remained significant after multivariable adjustment (hazard ratio 4.84; 95% CI 2.34-9.99; Pu2009<u20090.001; C-statistic improvement 0.759-0.774; Pu2009=u20090.019).nnnConclusionnThis novel cumulative ECG risk score was independently associated with SCD and was particularly effective for LVEF >35% where risk stratification is currently unavailable. These findings warrant further evaluation in prospective clinical investigations.

Clinical Diagnosis of Electrical Versus Anatomic Left Ventricular Hypertrophy Prognostic and Therapeutic Implications

Left ventricular hypertrophy (LVH) can develop in association with chronic arterial hypertension and other cardiovascular disorders and is a well-established risk factor for cardiac arrhythmias, cardiovascular events, and mortality.1 Over 4 decades ago the Framingham Heart Study reported that electrocardiographic evidence of LVH (ECG LVH) was associated with 3- to 4-fold increase in cardiovascular and all-cause mortality, with a disproportionately high risk of sudden cardiac death (SCD).2,3 Subsequently, multiple studies in different population samples have confirmed these associations.4,5nnIn early studies, the 12-lead ECG was the only available method to diagnose LVH in living subjects. In subsequent years, anatomic LVH diagnosed by echocardiography (echo LVH) became the gold standard.6,7 Despite the development of fairly detailed diagnostic ECG criteria for LVH,8 echocardiographic measurements have virtually replaced the ECG diagnosis of LVH. This shift in clinical practice was driven by the low reported sensitivity (usually <25%), albeit high specificity (up to 95%) of ECG criteria for diagnosis of LVH with echocardiography, magnetic resonance imaging (MRI), or during autopsy.9,10nnMore recently, however, we are learning that ECG LVH and echo LVH may be clinically distinct entities. In fact, there are now data to suggest that although these 2 entities can often overlap, each may provide distinct prognostic and potentially, mechanistic information, especially in the context of cardiac arrhythmias. This review will attempt to put these findings into perspective for the clinical electrophysiologist, by discussing the significance of electrical versus anatomic LVH for occurrence of atrial fibrillation (AF) and SCD.nnTo diagnose increased left ventricular (LV) mass from the 12-lead ECG, over 30 different ECG criteria have been developed. Most of the commonly used LVH criteria, such as Sokolow and Lyon, and Cornell voltage, rely solely on measuring QRS voltage. …

Delayed intrinsicoid deflection of the QRS complex is associated with sudden cardiac arrest

BACKGROUNDnProlongation of initial ventricular depolarization on the 12-lead electrocardiogram (ECG), or delayed intrinsicoid deflection (DID), can indicate left ventricular hypertrophy (LVH). The possibility that this marker could convey distinct risk of sudden cardiac arrest (SCA) has not been evaluated.nnnOBJECTIVEnTo evaluate the association of DID and SCA in the community.nnnMETHODSnIn the ongoing prospective, population-based Oregon Sudden Unexpected Death Study (Oregon SUDS; catchment area approximately 1 million), SCA cases were compared to geographic controls with no SCA. Archived ECGs (closest and unrelated to SCA event for cases) were evaluated for the presence of DID, defined as ≥0.05 second in leads V5 or V6. Left ventricular (LV) mass and function were evaluated from archived echocardiograms.nnnRESULTSnSCA cases (n = 272, 68.7 ± 14.6 years, 63.6% male) as compared to controls (n = 351, 67.6 ± 11.4 years, 63.3% male) were more likely to have DID on ECG (28.3% vs. 17.1%, P = .001). DID was associated with increased SCA odds (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.31-2.81; P = .001), but showed poor correlation with LV mass and echocardiographic LVH (kappa 0.13). In multivariate analysis adjusted for clinical and ECG markers, reduced LV ejection fraction, and echocardiographic LVH, DID remained an independent predictor of SCA (OR 1.82; 95% CI 1.12-2.97; P = .016). Additionally, in a sensitivity analysis restricted to narrow QRS, DID and ECG LVH by voltage were each independently associated with SCA risk.nnnCONCLUSIONnDID was associated with increased SCA risk independent of echocardiographic LVH, ECG LVH, and reduced LV ejection fraction, potentially reflecting unique electrical remodeling that warrants further investigation.

Left-ventricular geometry and risk of sudden cardiac arrest in patients with preserved or moderately reduced left-ventricular ejection fraction

AimsnThe majority of sudden cardiac arrests (SCAs) occur in patients with left-ventricular (LV) ejection fraction (LVEF) >35%, yet there are no methods for effective risk stratification in this sub-group. Since abnormalities of LV geometry can be identified even with preserved LVEF, we investigated the potential impact of LV geometry as a novel risk marker for this patient population.nnnMethods and resultsnIn the ongoing Oregon Sudden Unexpected Death Study, SCA cases with archived echocardiographic data available were prospectively identified during 2002-15, and compared with geographical controls. Analysis was restricted to subjects with LVEF >35%. Based on established measures of LV mass and relative wall thickness (ratio of wall thickness to cavity diameter), four different LV geometric patterns were identified: normal geometry, concentric remodelling, concentric hypertrophy, and eccentric hypertrophy. Sudden cardiac arrest cases (n = 307) and controls (n = 280) did not differ in age, sex, or LVEF, but increased LV mass was more common in cases. Twenty-nine percent of SCA cases presented with normal LV geometry, 35% had concentric remodelling, 25% concentric hypertrophy, and 11% eccentric hypertrophy. In multivariate model, concentric remodelling (OR 1.76; 95%CI 1.18-2.63; P = 0.005), concentric hypertrophy (OR 3.20; 95%CI 1.90-5.39; P < 0.001), and eccentric hypertrophy (OR 2.47; 95%CI 1.30-4.66; P = 0.006) were associated with increased risk of SCA.nnnConclusionnConcentric and eccentric LV hypertrophy, but also concentric remodelling without hypertrophy, are associated with increased risk of SCA. These novel findings suggest the potential utility of evaluating LV geometry as a potential risk stratification tool in patients with preserved or moderately reduced LVEF.

Wide QRS-T Angle on the 12-Lead ECG as a Predictor of Sudden Death Beyond the LV Ejection Fraction

Improvements in risk stratification for sudden cardiac arrest (SCA) will require discovery of markers that extend beyond the LV ejection fraction (LVEF). The frontal QRS‐T angle has been shown to predict risk of SCA but the value of this marker independent of the LVEF has not been investigated.

Cardiac structural and functional profile of patients with delayed QRS transition zone and sudden cardiac death

AIMSnDelayed QRS transition zone in the precordial leads of the 12-lead electrocardiogram (ECG) has been recently associated with increased risk of sudden cardiac death (SCD), but the underlying mechanisms are unknown. We correlated echocardiographic findings with ECG and clinical characteristics to investigate how alterations in cardiac structure and function contribute to this risk marker.nnnMETHODS AND RESULTSnFrom the ongoing population-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), SCD cases with prior ECG available (n = 627) were compared with controls (n = 801). Subjects with delayed transition at V5 or later were identified, and clinical and echocardiographic patterns associated with delayed transition were analysed. Delayed transition was present in 31% of the SCD cases and 17% of the controls. These subjects were older and more likely to have cardiovascular risk factors and history of myocardial infarction. Delayed transition was associated with increased left ventricular (LV) mass (122.7 ± 40.2 vs. 102.9 ± 33.7 g/m(2); P < 0.001), larger LV diameter (53.3 ± 10.4 vs. 49.2 ± 8.0 mm; P < 0.001), and lower LV ejection fraction (LVEF) (46.4 ± 15.7 vs. 55.6 ± 12.5%; P < 0.001). In multivariate analysis, delayed transition was independently associated with myocardial infarction, reduced LVEF, and LV hypertrophy. The association between delayed transition and SCD was independent of the LVEF (OR 1.57; 95% CI 1.04-2.38; P = 0.032).nnnCONCLUSIONnThe underpinnings of delayed QRS transition zone extend beyond previous myocardial infarction and reduced LVEF. Since the association with sudden death is independent of these factors, this novel marker of myocardial electrical remodelling should be explored as a potential risk predictor of SCD.AimsnDelayed QRS transition zone in the precordial leads of the 12-lead electrocardiogram (ECG) has been recently associated with increased risk of sudden cardiac death (SCD), but the underlying mechanisms are unknown. We correlated echocardiographic findings with ECG and clinical characteristics to investigate how alterations in cardiac structure and function contribute to this risk marker.nnnMethods and ResultsnFrom the ongoing population-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), SCD cases with prior ECG available (n = 627) were compared with controls (n = 801). Subjects with delayed transition at V5 or later were identified, and clinical and echocardiographic patterns associated with delayed transition were analysed. Delayed transition was present in 31% of the SCD cases and 17% of the controls. These subjects were older and more likely to have cardiovascular risk factors and history of myocardial infarction. Delayed transition was associated with increased left ventricular (LV) mass (122.7 ± 40.2 vs. 102.9 ± 33.7 g/m2; P < 0.001), larger LV diameter (53.3 ± 10.4 vs. 49.2 ± 8.0 mm; P < 0.001), and lower LV ejection fraction (LVEF) (46.4 ± 15.7 vs. 55.6 ± 12.5%; P < 0.001). In multivariate analysis, delayed transition was independently associated with myocardial infarction, reduced LVEF, and LV hypertrophy. The association between delayed transition and SCD was independent of the LVEF (OR 1.57; 95% CI 1.04-2.38; P = 0.032).nnnConclusionnThe underpinnings of delayed QRS transition zone extend beyond previous myocardial infarction and reduced LVEF. Since the association with sudden death is independent of these factors, this novel marker of myocardial electrical remodelling should be explored as a potential risk predictor of SCD.

Syncope and risk of sudden cardiac arrest in coronary artery disease

BACKGROUNDnSyncope has been associated with increased risk of sudden cardiac arrest (SCA) in specific patient populations, such as hypertrophic cardiomyopathy, heart failure, and long QT syndrome, but data are lacking on the risk of SCA associated with syncope among patients with coronary artery disease (CAD), the most common cause of SCA. We investigated this association among CAD patients in the community.nnnMETHODSnAll cases of SCA due to CAD were prospectively identified in Portland, Oregon (population approximately 1 million) as part of the Oregon Sudden Unexpected Death Study 2002-2015, and compared to geographical controls. Detailed clinical information including history of syncope and cardiac investigations was obtained from medical records.nnnRESULTSn2119 SCA cases (68.4±13.8years, 66.9% male) and 746 controls (66.7±11.7years, 67.0% male) were included in the analysis. 143 (6.8%) of cases had documented syncope prior to the SCA. SCA cases with syncope were >5years older and had more comorbidities than other SCA cases. After adjusting for clinical factors and left ventricular ejection fraction (LVEF), syncope was associated with increased risk of SCA (OR 2.8; 95%CI 1.68-4.85). When analysis was restricted to subjects with LVEF ≥50%, the risk of SCA associated with syncope remained significantly elevated (adjusted OR 3.1; 95%CI 1.68-5.79).nnnCONCLUSIONSnSyncope was associated with increased risk of SCA in CAD patients even with preserved LV function. These findings suggest a role for this clinical marker among patients with CAD and normal LVEF, a large sub-group without any current means of SCA risk stratification.

Left Ventricular Geometry and Risk of Sudden Cardiac Arrest in Patients With Severely Reduced Ejection Fraction

Background Recent reports indicate that specific left ventricular (LV) geometric patterns predict recurrent ventricular arrhythmias in patients with implantable cardioverter‐defibrillators and reduced left ventricular ejection fraction (LVEF). However, this relationship has not been evaluated among patients at risk of sudden cardiac arrest (SCA) in the general population. Methods and Results Adult SCA cases from the Oregon Sudden Unexpected Death Study were compared with geographic controls with no prior history of SCA. Archived echocardiograms performed closest and prior to the SCA event were reviewed. LV geometry was defined as normal (normal LV mass index [LVMI] and relative wall thickness [RWT]), concentric remodeling (normal LVMI and increased RWT), concentric hypertrophy (increased LVMI and RWT), or eccentric hypertrophy (increased LVMI and normal RWT). Analysis was restricted to those with LVEF ≤40%. A total of 246 subjects were included in the analysis. SCA cases (n=172, 68.6±13.3 years, 78% male), compared to controls (n=74, 66.8±12.1 years, 73% male), had lower LVEF (29.4±7.9% vs 30.8±6.3%, P=0.021). Fewer cases presented with normal LV geometry (30.2% vs 43.2%, P=0.048) and more with eccentric hypertrophy (40.7% vs 25.7%, P=0.025). In a multivariate model, eccentric hypertrophy was independently predictive of SCA (OR 2.15, 95% CI 1.08–4.29, P=0.03). Conclusions Eccentric LV hypertrophy was independently associated with increased risk of SCA in subjects with EF ≤40%. These findings, now consistent between device‐implanted and non‐implanted populations, indicate the potential of improving SCA risk stratification from the same noninvasive echocardiogram at no additional cost.

The Romhilt-Estes electrocardiographic score predicts sudden cardiac arrest independent of left ventricular mass and ejection fraction

The Romhilt‐Estes point score system (RE) is an established ECG criterion for diagnosing left ventricular hypertrophy (LVH). In this study, we assessed for the first time, whether RE and its components are predictive of sudden cardiac arrest (SCA) independent of left ventricular (LV) mass.

Prevention of sudden cardiac death in children and young adults

In the present review, we summarize current approaches to the prevention of sudden cardiac death (SCD) in children and young adults, focusing on age less than 35 years. SCD in the young is rare, but devastating from the societal perspective. While coronary artery disease is the main etiology of SCD in the older age groups, conditions such as cardiomyopathies and electrical channelopathies are more likely to be found in the young. In the majority of younger cases, cardiac arrest can be the first recognized manifestation of the underlying cardiac pathology, although some have experienced cardiovascular symptoms prior to the SCD. Since identification of a cardiac disease is pivotal for implementation of appropriate preventive measures, measures such as electrocardiographic screening in subpopulations such as athletes have been proposed. However, these efforts are impeded by the large number of individuals needed to test in order to find one with cardiac disease, leading to significant rates of false positive findings and high costs. When a high-risk cardiac condition is identified in a young person, measures of lifestyle modification, appropriate medical treatment and ICD implantation in selected individuals based on risk stratification are warranted. Nevertheless, the benefits of lifelong ICD therapy need to be balanced with long-term complications and quality of life.