Nonsudden Cardiac Death Research Articles

Dynamic predictive accuracy of electrocardiographic biomarkers of sudden cardiac death within a survival framework: the Atherosclerosis Risk in Communities (ARIC) study

BackgroundThe risk of sudden cardiac death (SCD) is known to be dynamic. However, the accuracy of a dynamic SCD prediction is unknown. We aimed to measure the dynamic predictive accuracy of ECG biomarkers of SCD and competing non-sudden cardiac death (non-SCD).MethodsAtherosclerosis Risk In Community study participants with analyzable ECGs in sinus rhythm were included (n = 15,716; 55% female, 73% white, age 54.2 ± 5.8 y). ECGs of 5 follow-up visits were analyzed. Global electrical heterogeneity and traditional ECG metrics (heart rate, QRS, QTc) were measured. Adjudicated SCD was the primary outcome; non-SCD was the competing outcome. Time-dependent area under the receiver operating characteristic curve (ROC(t) AUC) analysis was performed to assess the prediction accuracy of a continuous biomarker in a period of 3,6,9 months, and 1,2,3,5,10, and 15 years using a survival analysis framework. Reclassification improvement as compared to clinical risk factors (age, sex, race, diabetes, hypertension, coronary heart disease, stroke) was measured.ResultsOver a median 24.4 y follow-up, there were 577 SCDs (incidence 1.76 (95%CI 1.63–1.91)/1000 person-years), and 829 non-SCDs [2.55 (95%CI 2.37–2.71)]. No ECG biomarkers predicted SCD within 3 months after ECG recording. Within 6 months, spatial ventricular gradient (SVG) elevation predicted SCD (AUC 0.706; 95%CI 0.526–0.886), but not a non-SCD (AUC 0.527; 95%CI 0.303–0.75). SVG elevation more accurately predicted SCD if the ECG was recorded 6 months before SCD (AUC 0.706; 95%CI 0.526–0.886) than 2 years before SCD (AUC 0.608; 95%CI 0.515–0.701). Within the first 3 months after ECG recording, only SVG azimuth improved reclassification of the risk beyond clinical risk factors: 18% of SCD events were reclassified from low or intermediate risk to a high-risk category. QRS-T angle was the strongest long-term predictor of SCD (AUC 0.710; 95%CI 0.668–0.753 for ECG recorded within 10 years before SCD).ConclusionShort-term and long-term predictive accuracy of ECG biomarkers of SCD differed, reflecting differences in transient vs. persistent SCD substrates. The dynamic predictive accuracy of ECG biomarkers should be considered for competing SCD risk scores. The distinction between markers predicting short-term and long-term events may represent the difference between markers heralding SCD (triggers or transient substrates) versus markers identifying persistent substrate.

Death with an implantable cardioverter-defibrillator: a MADIT-II substudy.

There are limited data regarding factors that identify implantable cardioverter-defibrillator (ICD) patients who will experience either ventricular tachyarrhythmic (VTA) or non-arrhythmic (NA) mortality, and the commonly used clinical classification of sudden cardiac death (SCD) vs. non-sudden cardiac death (NSCD) may not be accurate enough. We aimed to correlate clinical adjudication of mortality events to device interrogation data and to identify risk factors for VTA mortality in Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). Of the 746 patients who received an ICD in MADIT-II, 44 died from cardiac causes and had available interrogation data at the time of death. Sudden cardiac death vs. NSCD was defined by an adjudication committee. Ventricular tachyarrhythmic and NA arrhythmic deaths were categorized by the presence or absence of ventricular tachycardia or fibrillation (VT/VF) during the terminal event. Mode of death was found to be inaccurate when validated by device interrogation for VTA events: 50% patients adjudicated as SCD did not have a VTA event at the time of death; and 25% of adjudicated NSCD were found to have VT/VF during the mortality event. Multivariate analysis showed that factors independently associated with VTA mortality included: VT/VF >72 h prior to the mortality event [hazard ratio (HR) 8.0; P < 0.001], hospitalization for heart failure (HR 6.7; P = 0.001), and a history of hypertension (HR 4; P = 0.04). Current classification of SCD vs. NSCD fails to identify VTA events at the time of death in a significant proportion of patients, and simple clinical parameters can be used to identify ICD recipients with increased risk for VTA mortality.

P5647Temporal variability of T-wave morphology and risk of sudden cardiac death in patients with coronary artery disease

Abstract Background The possible relationship between temporal variability of electrocardiographic spatial heterogeneity of repolarisation and the risk of sudden cardiac death (SCD) in patients with coronary artery disease (CAD) is not completely understood. Purpose To investigate the prognostic value of temporal variability of T-wave spatial heterogeneity in SCD in patients with CAD. Methods The Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study population consisted of 1,946 patients with angiographically verified CAD. T-wave morphology dispersion (TMD), which estimates the average angle between all reconstruction vector pairs in T-wave loop based on leads I-II and V2-V6, was analysed on beat-to-beat basis from 10 minutes period of the baseline electrocardiographic recording in 1,678 study subjects. The temporal variability of TMD was evaluated by standard deviation of TMD (TMD-SD). Results After on average of 7.4±2.0 years of follow-up, a total of 47 of the 1,678 study subjects (2.8%) had experienced SCD or were resuscitated from sudden cardiac arrest (SCA). TMD-SD was significantly higher in patients who had experienced SCD/SCA compared with those who remained alive (3.64±2.57 vs. 2.65±2.54, p&lt;0.01, respectively), but did not differ significantly between the patients who had experienced non-sudden cardiac death (n=40, 2.4%) and those who remained alive (2.98±2.43 vs. 2.67±2.55, p=0.45, respectively) or between the patients who succumbed to non-cardiac death (n=88, 5,2%) and those who stayed alive (2.74±2.44 vs. 2.67±2.55, p=0.81). After adjustments with relevant clinical risk indicators of SCD/SCA, such as left ventricular ejection fraction, diabetes, left bundle branch block and Canadian Cardiac Society class, TMD-SD still predicted SCD/SCA (HR 1.113, 95% CIs 1.028–1.206, p&lt;0.01). The discrimination and reclassification accuracy increased significantly (p=0.02, p=0.033) and the C-index increased from 0.733 to 0.741 when TMD-SD was added to the clinical risk model of SCD/SCA. The Kaplan-Meier survival curves show proportional probabilities of event-free survival for different modes of death for patients classified according to the optimised TMD-SD cut-off point (Figure). Figure 1 Conclusions Temporal variability of electrocardiographic spatial heterogeneity of repolarisation represented by TMD-SD independently predicts long-term risk of SCD/SCA in patients with CAD. Acknowledgement/Funding Sigrid Juselius Foundation and Finnish Foundation for Cardiovascular Research

The role of heart rate variability, heart rate turbulence, and deceleration capacity in predicting cause-specific mortality in chronic heart failure

BackgroundThe volume of regional denervated myocardium (D-M) on positron emission tomography has been recently suggested as a strong independent predictor of cause-specific mortality from sudden cardiac arrest (SCA) in chronic heart failure. We sought to evaluate whether ECG indices of global autonomic function predict risk of SCA to a similar degree as regional D-M. MethodsSubjects enrolled in the Prediction of Arrhythmic Events using Positron Emission Tomography (PAREPET) study were included in this study. Patients completed a 24-hour Holter ECG at enrollment and were followed up at 3-month intervals. SCA events were adjudicated by two board-certified cardiologists. Other cardiovascular death events were classified as nonsudden cardiac death (NSCD). Eight measures of heart rate variability were analyzed: SDNN, RMSSD, low-frequency (LF) and high-frequency (HF) power, heart rate turbulence onset and slope, and acceleration and deceleration capacity. We used competing risk regression to delineate cause-specific mortality from SCA versus NSCD. ResultsOur sample included 127 patients (age 67 ± 12, 92% male). After a median follow-up of 4.1 years, there were 22 (17%) adjudicated SCA and 18 (14%) adjudicated NSCD events. In multivariate Cox-regression, LF power was the only HRV parameter to predict time-to-SCA. However, in competing risk analysis, reduced LF power was preferentially associated with NSCD rather than SCA (HR = 0.92 [0.85–0.98], p = 0.019). ConclusionDepressed LF power might indicate impaired vagal reflex, which suggests that increasing vagal tone in these patients would have a protective effect against NSCD beyond that achieved by the mere slowing of heart rate using β-blockers.

Abstract P018: Poincare Plot Asymmetry is Associated With Sudden Cardiac Death in the Community: The Atherosclerosis Risk in Community Study

Introduction: Poincare plot asymmetry has been associated with sustained ventricular tachyarrhythmias, implicating involvement of the autonomic nervous system. An association between sudden cardiac death (SCD) and Poincare plot asymmetry has not previously been studied in a general population cohort. Porta index measures time asymmetry in heart rate variability (HRV), corresponding to disproportionate relative tachycardic predominance. Hypothesis: We hypothesized that increasing tachycardic asymmetry as measured by Porta Index is associated with SCD. Methods: We analyzed 10-second ECG in 14,247 participants across 5 visits in the Atherosclerosis Risk in Communities (ARIC) cohort (mean age 54.1±5.87y; 6,380 [45%] men; 10,569 [74%] white, 1,582 [11%] with prevalent cardiovascular disease (CVD)). Participants with atrial fibrillation, premature contractions, sinoatrial (SA) or atrioventricular (AV) blocks II-III were excluded. Only normal sinus beats were included in the semi-automated analysis. Accuracy of automated R-peak detection was manually validated. SCD, non-SCD, and non-cardiac death served as competing outcomes in a Fine and Gray competing risk model. Results: Overall, there was larger variability in Porta index within the same participant from visit to visit (50.0±12.1) than between different participants (50.0±8.4). Over median follow-up of 24.4 years, there were 497 SCDs (incidence 1.66 [95% CI 1.52-1.82], 742 non-SCD (incidence 2.48 [95%CI 2.31-2.67], and 3,753 non-cardiac deaths (incidence 12.6 [95% CI 12.1-13.0]) per 1,000 person-years. In time-updated analysis, Porta index was independently associated with increased risk of SCD (HR 1.13 [1.04-1.23]). Neither non-sudden cardiac death nor non-cardiac death are associated with Porta ndex. Conclusion: Time-updated Poincare Plot asymmetry as measured by Porta index, reflecting tachycardic runs longer than bradycardic runs, is independently associated with SCD in the community. Poincare plot asymmetry requires further study.

Abstract P027: Time-updated Premature Ventricular Contractions on 12-lead ECG Are Associated With the Risk of Sudden Cardiac Death: Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

Introduction: The association between premature ventricular contractions (PVCs) and Sudden Cardiac Death (SCD) remains controversial. Hypothesis: We hypothesized that PVCs are associated with SCD. Methods: Presence of PVCs was detected on 12-lead ECG recorded at baseline or any of 4 follow-up visits in 15,667 participants (pts) (mean age: 54.2 + 5.8 Yrs; 55% female; 73% Whites) of the Atherosclerosis Risk in Communities (ARIC) study. For validation cohort, we included baseline and 9 follow-up visits ECG data in 5,846 pts (mean age: 72.8+ 5.6 yrs; 57.7% female, 84.2% whites) from Cardiovascular Health Study (CHS). Competing risk analyses models were constructed to test the association between time-updated PVCs and SCD risk. Model 1 was adjusted for age, sex, race and study center. Model 2 in addition was adjusted for time-updated coronary heart disease, heart failure, atrial fibrillation, stroke, and hypertension. Results: In ARIC pts, across all study visits, PVCs were observed in 2.6% of the ECGs; 99.7% of pts were PVC-free at least once; 8.8% of pts had PVC at least once. 97.7% of pts without PVCs remained PVC-free at the next visit; 19.1% of pts with detected PVC had PVC at the next visit; 2.4% of pts who were PVC-free on previous ECG, transitioned to having PVC on subsequent visit ECG. In CHS, across all 10 yearly study visits, on average, PVC was observed on 4.85% of ECG recordings; 99.4% of participants were PVC-free at least once; 21.9% of pts had PVC at least once. 96.4% of PVC-free pts remained free from PVC at the next visit. 30.6% of pts with detected PVC on a given ECG had PVC at the next visit. 3.6% of pts who did not have PVC on previous ECG, transitioned to having PVC at the next visit. 69.4% of pts with PVC on a given ECG transitioned to being PVC-free next year. In adjusted competing risk analysis PVC was associated with SCD, but not with non-sudden cardiac death or non-cardiac death (Table). Conclusions: Time-updated presence of PVC on a short 10-sec resting 12-lead ECG is associated with SCD.

Prognostic value of T-wave morphology parameters in coronary artery disease in current treatment era.

The prognostic value of T-wave morphology parameters in coronary artery disease in the current treatment era is not well established. The Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included 1,946 patients with angiographically verified coronary artery disease (CAD). The study patients underwent thorough examinations including 12-lead digital electrocardiogram (ECG) at baseline. During a follow-up period of 73±22months, a total of 201 (10.3%) patients died. Of the study patients, 95 (4.9%) experienced cardiac death (CD) consisting of 44 (2.3%) sudden cardiac deaths (SCD) and 51 (2.6%) nonsudden cardiac deaths (NSCD), and 106 (5.4%) patients experienced noncardiac death (NCD). T-wave morphology dispersion (TMD), T-wave area dispersion (TWAD), and total cosine R-to-T (TCRT) had a significant association with CD even after adjustment with relevant clinical risk markers in the Cox regression analysis (multivariate HRs: 1.015, 95% CI 1.007-1.023, p=.0003; 0.474, 95% CI 0.305-0.737, p=.0009; 0.598, 95% CI 0.412-0.866, p=.006, respectively). When including these parameters to the clinical risk model for CD, the C-index increased from 0.810 to 0.823 improving the discrimination significantly (integrated discrimination index [IDI]=0.0118, 95% CI 0.0028-0.0208, p=.01). These parameters were more closely associated with NSCD (multivariate p-values from .016 to .001) than with SCD (univariate/multivariate p-values for TMD .015/.197 and for TCRT .012/.43). T-wave morphology parameters describing repolarization heterogeneity improve the predictive power of the clinical risk model for CD in patients with CAD in the current treatment era.

Analysis and strategy of related factors in patients with sudden cardiac death in Department of Cardiology

The clinical data of 196 cases of sudden death in hospital were randomly selected, which were divided into two groups: patients with sudden cardiac death (SCD) (n = 138) and non-sudden cardiac death (NSCD) (n = 58), of which 123 were male and 73 females; and according to their age, they were divided into three groups: age 60 group. The general situation, previous medical history (coronary heart disease, hypertension, diabetes mellitus), sudden death precipitating factors, aura and the results of laboratory-assisted examination of patients with SCD and SNCD were analyzed retrospectively to select the related risk factors of SCD.

Heart rate variability: implications for perioperative anesthesia care.

Heart rate variability (HRV) is a measure of the balance between both the parasympathetic and sympathetic nervous system and may provide useful information for anesthesia care providers. HRV may offer predictive information about critically ill and operative patients. Further, HRV collection provides real-time information of patient autonomic nervous system status and may allow tailoring of the analgesia for patients in the ICU and operating room. Reduced and abnormal resting HRV predict sudden and nonsudden cardiac death. Recent evidence shows that decreased HRV correlates with worsened outcomes in both trauma patients and patients with sepsis, as well as the risk of developing hypotension after induction of general anesthesia and placement of intrathecal local anesthesia. In addition, HRV appears to provide an accurate assessment of the nociception-analgesia balance in deeply sedated ICU patients and those under general anesthesia. No study has assessed the prognostic value of preoperative HRV in patients presenting for surgery. Use of HRV for patient risk stratification and intraoperative analgesia management may allow tailored perioperative care and improved outcomes. If intraoperative HRV data leads to decreased perioperative opioid use, opioid-related adverse events, a serious perioperative issue, may be decreased. Not applicable.

Highlights From the Circulation Family of Journals.

Highlights From the Circulation Family of Journals.

Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality.

Previous studies have identified multiple risk factors that are associated with total cardiac mortality. Nevertheless, identifying specific factors that distinguish patients at risk of arrhythmic death versus heart failure could better target patients likely to benefit from implantable cardiac defibrillators, which have no impact on nonsudden cardiac death. We performed a pilot competing risks analysis of the National Institutes of Health-sponsored PAREPET trial (Prediction of Arrhythmic Events with Positron Emission Tomography). Death from cardiac causes was ascertained in subjects with ischemic cardiomyopathy (n=204) eligible for an implantable cardiac defibrillator for the primary prevention of sudden cardiac arrest after baseline clinical evaluation and imaging at enrollment (positron emission tomography and 2-dimensional echo). Mean age was 67±11 years with an ejection fraction of 27±9%, and 90% were men. During 4.1 years of follow-up, there were 33 sudden cardiac arrests (arrhythmic death or implantable cardiac defibrillator discharge for ventricular fibrillation or ventricular tachycardia >240 bpm) and 36 nonsudden cardiac deaths. Sudden cardiac arrest was correlated with a greater volume of denervated myocardium (defect of the positron emission tomography norepinephrine analog 11C-hydroxyephedrine), lack of angiotensin inhibition therapy, elevated B-type natriuretic peptide, and larger left ventricular end-diastolic volume index. In contrast, nonsudden cardiac death was associated with a higher resting heart rate, older age, elevated creatinine, larger left atrial volume index, and larger left ventricular end-diastolic volume index. Distinct clinical, laboratory, and imaging variables are associated with cause-specific cardiac mortality in primary-prevention candidates with ischemic cardiomyopathy. If prospectively validated, these multivariable associations may help target specific therapies to those at the greatest risk of sudden and nonsudden cardiac death. URL: https://clinicaltrials.gov. Unique identifier: NCT01400334.

52 Suitability for subcutaneous implantable cardioverter-defibrillator therapy – the impact of different selection policies

BackgroundWith subcutaneous ICDs (S-ICD) not offering the same range of pacing therapies as transvenous systems (T-ICD), it is unclear how many ICD recipients may be suitable for a S-ICD. In...

Prediction of sudden and non-sudden cardiac death in post-infarction patients with reduced left ventricular ejection fraction by periodic repolarization dynamics: MADIT-II substudy.

AimsTo test the value of Periodic Repolarization Dynamics (PRD), a recently validated electrocardiographic marker of sympathetic activity, as a novel approach to predict sudden cardiac death (SCD) and non-sudden cardiac death (N-SCD) and to improve identification of patients that profit from ICD-implantation.Methods and resultsWe included 856 post-infarction patients with left-ventricular ejection fraction (LVEF) ≤30% of the MADIT-II trial in sinus rhythm. Of these, 507 and 348 patients were randomized to ICD or conventional treatment. PRD was assessed from multipolar 10-min baseline ECGs. Primary and secondary endpoints were total mortality, SCD and N-SCD. Multivariable analyses included treatment group, QRS-duration, New York Heart Association classification, blood-urea nitrogen, diabetes mellitus, beta-blocker therapy and LVEF. During follow-up of 20.4 months, 119 patients died (53 SCD and 36 N-SCD). On multivariable analyses, increased PRD was a significant predictor of mortality (standardized coefficient 1.37[1.19–1.59]; P < 0.001) and SCD (1.40 [1.13–1.75]; P = 0.003) but also predicted N-SCD (1.41[1.10–1.81]; P = 0.006). While increased PRD predicted SCD in conventionally treated patients (1.61[1.23–2.11]; P < 0.001), it was predictive of N-SCD (1.63[1.28–2.09]; P < 0.001) and adequate ICD-therapies (1.20[1.03–1.39]; P = 0.017) in ICD-treated patients. ICD-treatment substantially reduced mortality in the lowest three PRD-quartiles by 53% (P = 0.001). However, there was no effect in the highest PRD-quartile (mortality increase by 29%; P = 0.412; P < 0.001 for difference) as the reduction of SCD was compensated by an increase of N-SCD.ConclusionIn post-infarction patients with impaired LVEF, PRD is a significant predictor of SCD and N-SCD. Assessment of PRD is a promising tool to identify post-MI patients with reduced LVEF who might benefit from intensified treatment.

Identifying patients with less potential to benefit from implantable cardioverter-defibrillator therapy: comparison of the performance of four risk scoring systems

PurposePatients at high non-sudden cardiac death risk may gain no significant benefit from implantable cardioverter-defibrillator (ICD) therapy. A number of approaches have been proposed to identify these patients, including single clinical markers and more complex scoring systems. The aims of this study were to use the proposed scoring systems to (1) establish how many current ICD recipients may be too high risk to derive significant benefit from ICD therapy and (2) evaluate how well the scoring systems predict short-term mortality in an unselected ICD cohort.MethodsWe performed a single-centre retrospective observational study of all new ICD implants over 5 years (2009–2013). We used four published scoring systems (Bilchick, Goldenberg, Kramer and Parkash) and serum urea to identify new ICD recipients whose short-term predicted mortality risk was high. We evaluated how well the scoring systems predicted death.ResultsOver 5 years, there were 406 new implants (79% male, mean age 70 (60–76), 58% primary prevention). During a follow-up of 936 ± 560 days, 96 patients died. Using the scoring systems, the proportion of ICD recipients predicted to be at high short-term mortality risk were 5.9% (Bilchick), 34.7% (Goldenberg), 7.4% (Kramer), 21.4% (Parkash) and 25% (urea, cut-off of >9.28 mM). All four risk scores predicted mortality (P < 0.0001); however, none outperformed urea for the prediction of 1- or 3-year mortality.ConclusionsUsing published scoring systems, a significant proportion of current ICD recipients are at high short-term mortality risk. Although all four scoring systems predicted mortality during follow-up, none significantly outperformed serum urea.

Abstract MP083: Autonomic Imbalance at the Level of Atrioventricular Node, but Not at the Level of Sinus Node, is Associated With Sudden Cardiac Death: The Atherosclerosis Risk in Community Study

Introduction: Autonomic imbalance, quantified by decreased heart rate variability (HRV), is associated with increased cardiovascular mortality. It is unknown if autonomic influences on sinus and atrioventricular (AV) nodes are equally important for the risk of sudden cardiac death (SCD). Hypothesis: Autonomic influences on sinus and AV node are equally strongly associated with increased SCD, non-sudden cardiac death (non-SCD), and non-cardiac death. Methods: Baseline visit 10-second ECGs (n=14,250) of the Atherosclerosis Risk in Communities (ARIC) cohort were analyzed. Normalized variance of P-onset to P-onset intervals (PPVN) and QRS-onset to QRS-onset intervals (QQVN) was calculated to assess autonomic influence on sinus and AV node respectively. Normalized variance of Rpeak - Rpeak intervals was determined as HRV measure. Values were log-transformed to normalize distribution. SCD served as primary outcome. Secondary outcomes were non-SCD and non-cardiac death. Three Cox regression models were constructed for dichotomized at 20 th percentile predictor variables. Results: Over median follow-up of 24.4 years, there were 497 SCDs (incidence 1.66 [95%CI 1.52-1.82], 742 non-SCDs (incidence 2.48 [95%CI 2.31-2.67], and 3,753 non-cardiac deaths (incidence 12.6 [95%CI 12.1-13.0]) per 1,000 person-years. In paired analysis, LogPPVN was significantly larger than LogQQVN (-7.28±1.06 vs. -7.72±1.24; P&lt;0.0001). There was no difference between LogQQVN and Log RRVN (-7.72±1.24 vs -7.72±1.23; P=0.364). After full adjustment, LogRRVN and LogQQVN were significantly associated with non-SCD and SCD. Association with non-SCD was stronger. LogPPVN was independently associated with non-SCD but not SCD. No value was associated with non-cardiac death. Conclusion: Autonomic imbalance at the AV node, with likely summary effect at the bundle of His, is associated with SCD and non-SCD. Autonomic imbalance at the SA node is associated with non-SCD only. Autonomic input to SA and AV node should be further studied.

Abstract MP081: Short-long-short Sequence of RR Intervals is Associated With Increased Risk of Sudden Cardiac Death: the Atherosclerosis Risk in Community Study

Introduction: A Short-long-short sequence of RR’ intervals frequently precedes ventricular tachyarrhythmia. However, an association of RR’ alternans with sudden cardiac death (SCD) in the general population has not been previously studied. Hypothesis: We hypothesized that RR’ alternans is associated with SCD. Methods: We analyzed baseline visit 10-second ECG in 14,250 participants of the Atherosclerosis Risk in Communities (ARIC) cohort (mean age 54.1±5.87y; 45% men; 74% white). Only normal sinus beats were included in the semi-automated analysis. Digital 12-lead ECG was transformed into orthogonal ECG, from which respiratory signal was derived. Joint symbolic analysis was used to assess increase or decrease in successive RR’ intervals and R-instant respiratory phases calculated using the Hilbert transform. Short-long-short or long-short-long RR’ sequence was defined as RR’ alternans. RR’ alternans occurring during respiratory phase transitions were not considered. SCD, non-SCD, and non-cardiac death served as competing outcomes. Three competing risks models were constructed. Model 1 was adjusted for age, sex, race, and study center. Model 2 was in addition adjusted for prevalent CVD. Model 3 was further adjusted for subclinical CVD, its risk factors, including traditional ECG predictors, and medications affecting SA or AV nodes. Results: Over median follow-up of 24.4 years, there were 497 SCDs (incidence 1.66 [95%CI 1.52-1.82], 742 non-sudden cardiac deaths (incidence 2.48 [95%CI 2.31-2.67], and 3,753 non-cardiac deaths (incidence 12.6 [95%CI 12.1-13.0]) per 1,000 person-years. RR alternans was present in 1,679(11.8%) participants. In competing risks analysis (Table) the presence of RR’ alternans, excluding those occurring due to respiratory phase changes, was independently associated with increased risk of SCD. Conclusion: In competing risks analysis the presence of RR’ alternans that are not due to respiratory phase transition is associated with SCD. Further study of RR’ alternans is warranted.

Elevated fibroblast growth factor-23 and risk of cardiovascular disease or mortality in the general population: A meta-analysis

Elevated fibroblast growth factor-23 and risk of cardiovascular disease or mortality in the general population: A meta-analysis

Diabetes, glucose tolerance, and the risk of sudden cardiac death.

BackgroundDiabetes predisposes to sudden cardiac death (SCD). However, it is uncertain whether greater proportion of cardiac deaths are sudden among diabetes patients than other subjects. It is also unclear whether the risk of SCD is pronounced already early in the course of the disease. The relationship of impaired glucose tolerance (IGT) and SCD is scarcely documented.MethodsA general population cohort of 10594 middle-aged subjects (mean age 44 years, 52.6 % male, follow-up duration 35–41 years) was divided into diabetes patients (n = 82), subjects with IGT (n = 3806, plasma glucose ≥9.58 mmol/l in one-hour glucose tolerance test), and controls (n = 6706).ResultsDiabetes patients had an increased risk of SCD after adjustment confounders (hazard ratio 2.62, 95 % confidence interval 1.46–4.70, p = 0.001) but risk for non-sudden cardiac death was similarly increased and the proportion of SCD of cardiac deaths was not increased. The SCD risk persisted after exclusion of subjects with baseline cardiac disease or non-fatal cardiac events during the follow-up. Subjects with IGT were at increased risk for SCD (univariate hazard ratio 1.51; 95 % confidence interval 1.31–1.74; p < 0.001) and also for non-sudden cardiac deaths and non-fatal cardiac events but adjustments for other risk factors attenuated these effects.ConclusionsDiabetes was associated with increased risk of SCD but also the risk of non-sudden cardiac death was similarly increased. The proportion of cardiac deaths being sudden in subjects with diabetes was not increased. The higher SCD risk in diabetes patients was independent of known cardiac disease at baseline or occurrence of non-fatal cardiac event during the follow-up.

Abstract 13695: Global Electrical Heterogeneity Risk Score Predicts Sudden Cardiac Death in the General Population

Background: The majority of sudden cardiac deaths (SCDs) in the general population occur in asymptomatic individuals. Our goal was to develop and validate a SCD risk score for use in the general population. Methods: The prospective Atherosclerosis Risk in Communities (ARIC) study [n=15,366; age 45-64 yr; 45% male; 73% white; 5% prevalent coronary heart disease (CHD), median 14 yrs of follow-up] was used for risk score development. ECG markers of global electrical heterogeneity (GEH) [sum absolute QRST integral (SAI QRST), spatial ventricular gradient (SVG), and spatial QRS-T angle] were measured on standard 12-lead ECGs and abnormal values were derived using the Youden index. Competing risk models were evaluated using C-statistics, integrated discrimination improvement, net reclassification improvement (NRI), and Akaike Information Criterion. Internal cross-validation was performed in 5 partitions. Adjudicated SCD was the primary outcome. Results: Overall SCD incidence was 1.51 (95% CI 1.35-1.69) per 1,000 person-yrs. The most accurate risk model included gender-, race-, and CHD-specific GEH ECG parameters [SAI QRST, spatial QRS-T angle, and SVG direction (azimuth and elevation)], demographics (sex, race, age≥55 y), clinical characteristics (CHD, diabetes, hypertension, stroke), QTc interval, and 1 interaction term (abnormal SVG azimuth in age≥55 yrs). C-statistic was 0.842 (95% CI 0.814-0.859) in the whole cohort and ranged 0.782-0.866 in 5 cross-validation partitions. The risk score classified 10-yr SCD risk as low (0 to &lt;1%), intermediate (1-10%), and high (&gt;10%) in 65.5%, 32.3%, and 2.2% of participants, respectively. With addition of GEH ECG markers to clinical/demographic factors C-statistic increased from 0.813 to 0.837 (p=0.004), 28/311 (9%) of participants were appropriately reclassified from intermediate to high risk, and only 4/311 (1.3%) were inappropriately reclassified from high to intermediate risk. NRI was 13.3% (P&lt;0.001). The score was highly specific (98.2%) for SCD, and predicted SCD better than non-sudden cardiac death. Negative predictive value for SCD was up to 99.5%. Conclusion A risk score using basic clinical characteristics and novel GEH ECG parameters accurately predicted SCD in the general population.

Abstract 15631: The Hemodynamic Determinants and Physiologic Correlates of QTc Interval Using Impedance Cardiography in Heart Failure

Background: Prolonged QTc interval is a known risk factor for adverse cardiac events, including sudden and non-sudden cardiac death. Understanding the determinants and physiologic correlates of QTc can guide the proper strategy for the primary prevention of sudden death in high risk patients. Methods &amp; Results: This was an observational study that recruited ambulatory heart failure patients (NYHA I-III) from an outpatient clinic in NL, Canada. In supine resting position, consented participants underwent non-invasive 12-lead ECG and hemodynamic monitoring using BioZ Dx Impedance Cardiography (Sonosite Inc., WA, USA). ECGs were evaluated by a reviewer blinded to clinical data. Participants with pacing (n=12) or left bundle branch block (n=9) were excluded. Three measures of interest were automatically computed: (1) QTc interval (i.e., from QRS onset to T offset), (2) QRS duration (i.e., from QRS onset to QRS offset), and (3) JTc (i.e., QTc interval minus QRS duration). Effect sizes were computed using Pearson’s r coefficients. The final sample (n=23) was 62±13 years of age and 70% male with LVEF of 34±10%. The mean QTc was 441±39 milliseconds, and 10 patients (43%) had prolonged QTc (≥450 milliseconds). QTc interval negatively correlated with cardiac output (r= -0.57), and positively correlated with systemic vascular resistance (r= +0.57), as well as thoracic fluid content (r= +0.43). QRS duration alone was not specifically associated with any hemodynamic parameter, but JTc interval positively correlated with total arterial compliance (r=+0.42). Conclusions: In heart failure patients, we interestingly found that increased systemic vascular resistance results in QTc interval prolongation, where repolarization time is specifically influenced by arterial compliance. This suggests potential benefit from antihypertensive therapy targeted at lowering systemic vascular resistance in those with prolonged QTc/JTc. Nevertheless, these intervals need to be interpreted with caution in patients with thoracic fluid overload (e.g., pulmonary edema).