Impact of untreated chronic obstructive coronary artery disease on outcomes after transcatheter aortic valve replacement.

BACKGROUND AND AIMS: In transcatheter aortic valve replacement (TAVR) recipients, the optimal management of concomitant chronic obstructive coronary artery disease (CAD) remains unknown. Some advocate for pre-TAVR percutaneous coronary intervention, while others manage it expectantly. The aim of this study was to assess the impact of varying degrees and extent of untreated chronic obstructive CAD on TAVR and longer-term outcomes. METHODS: The authors conducted a retrospective cohort study of TAVR recipients from January 2015 to November 2021, separating patients into stable non-obstructive or varying degrees of obstructive CAD. The major outcomes of interest were procedural all-cause mortality and complications, major adverse cardiovascular events, and post-TAVR unplanned coronary revascularization. RESULTS: Of the 1911 patients meeting inclusion, 75%, 6%, 10%, and 9% had non-obstructive, intermediate-risk, high-risk, and extreme-risk CAD, respectively. Procedural complication rates overall were low (death 0.4%, shock 0.1%, extracorporeal membrane oxygenation 0.1%), with no difference across groups. At a median follow-up of 21 months, rates of acute coronary syndrome and unplanned coronary revascularization were 0.7% and 0.5%, respectively, in the non-obstructive population, rising in incidence with increasing severity of CAD (P < .001 for acute coronary syndrome/unplanned coronary revascularization). Multivariable analysis did not yield a significantly greater risk of all-cause mortality or major adverse cardiovascular events across groups. One-year acute coronary syndrome and unplanned coronary revascularization rates in time-to-event analyses were significantly greater in the non-obstructive (98%) vs. obstructive (94%) subsets (Plog-rank< .001). CONCLUSIONS: Transcatheter aortic valve replacement can be performed safely in patients with untreated chronic obstructive CAD, without portending higher procedural complication rates and with relatively low rates of unplanned coronary revascularization and acute coronary syndrome at 1 year.

Clinician use of the Statin Choice Shared Decision-making Encounter Tool in a Major Health System.

BACKGROUND: Effective shared decision-making (SDM) tools for use during clinical encounters are available, but, outside of study settings, little is known about clinician use of these tools in practice. OBJECTIVE: To describe real-world use of an SDM encounter tool for statin prescribing, Statin Choice, embedded into the workflow of an electronic health record. DESIGN: Cross-sectional study. PARTICIPANTS: Clinicians and their statin-eligible patients who had outpatient encounters between January 2020 and June 2021 in Cleveland Clinic Health System. MAIN MEASURES: Clinician use of Statin Choice was recorded within the Epic record system. We categorized each patient's 10-year atherosclerotic cardiovascular disease risk into low (< 5%), borderline (5-7.5%), intermediate (7.5-20%), and high (≥ 20%). Other patient factors included age, sex, insurance, and race. We used mixed effects logistic regression to assess the odds of using Statin Choice for statin-eligible patients, accounting for clustering by clinician and site. We generated a residual intraclass correlation coefficient (ICC) to characterize the impact of the clinician on Statin Choice use. KEY RESULTS: Statin Choice was used in 7% of 68,505 eligible patients. Of 1047 clinicians, 48% used Statin Choice with ≥ 1 patient, and these clinicians used it with a median 9% of their patients (interquartile range: 3-22%). In the mixed effects logistic regression model, patient age (adjusted OR per year: 1.04; 95%CI 1.03-1.04) and 10-year ASVCD risk (aOR for 5-7.5% versus < 5% risk: 1.28; 95%CI: 1.14-1.44) were associated with use of Statin Choice. Black versus White race was associated with a lower odds of Statin Choice use (aOR: 0.83; 95%CI: 0.73-0.95), as was female versus male sex (aOR: 0.83; 95%CI: 0.76-0.90). The model ICC demonstrated that 53% of the variation in use of Statin Choice was clinician-driven. CONCLUSIONS: Patient factors, including race and sex, were associated with clinician use of Statin Choice; half the variation in use was attributable to individual clinicians.

Competing risks of monomorphic vs. non-monomorphic ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study.

AIMS: Ablation of monomorphic ventricular tachycardia (MMVT) has been shown to reduce shock frequency and improve survival. We aimed to compare cause-specific risk factors for MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models. METHODS AND RESULTS: The multicentre retrospective cohort study included 2668 patients (age 63.1 ± 13.0 years; 23% female; 78% white; 43% non-ischaemic cardiomyopathy; left ventricular ejection fraction 28.2 ± 11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and electrocardiogram metrics. Global electrical heterogeneity was measured by spatial QRS-T angle (QRSTa), spatial ventricular gradient elevation (SVGel), azimuth, magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). We compared the out-of-sample performance of the lasso and elastic net for Cox proportional hazards and the Fine-Gray competing risk model. During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate implantable cardioverter-defibrillator (ICD) therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.01-1.34], larger SVGel (HR 1.17; 95% CI 1.05-1.30), and smaller SVGmag (HR 0.74; 95% CI 0.63-0.86) and SAIQRST (HR 0.84; 95% CI 0.71-0.99). The best-performing 3-year competing risk Fine-Gray model for MMVT [time-dependent area under the receiver operating characteristic curve (ROC(t)AUC) 0.728; 95% CI 0.668-0.788] identified high-risk (> 50%) patients with 75% sensitivity and 65% specificity, and PVT/VF prediction model had ROC(t)AUC 0.915 (95% CI 0.868-0.962), both satisfactory calibration. CONCLUSION: We developed and validated models to predict the competing risks of MMVT or PVT/VF that could inform procedural planning and future randomized controlled trials of prophylactic ventricular tachycardia ablation. CLINICAL TRIAL REGISTRATION: URL:www.clinicaltrials.gov Unique identifier:NCT03210883.

Management of patients with an electrical storm or clustered ventricular arrhythmias: a clinical consensus statement of the European Heart Rhythm Association of the ESC-endorsed by the Asia-Pacific Heart Rhythm Society, Heart Rhythm Society, and Latin-American Heart Rhythm Society.

Electrical storm (ES) is a state of electrical instability, manifesting as recurrent ventricular arrhythmias (VAs) over a short period of time (three or more episodes of sustained VA within 24 h, separated by at least 5 min, requiring termination by an intervention). The clinical presentation can vary, but ES is usually a cardiac emergency. Electrical storm mainly affects patients with structural or primary electrical heart disease, often with an implantable cardioverter-defibrillator (ICD). Management of ES requires a multi-faceted approach and the involvement of multi-disciplinary teams, but despite advanced treatment and often invasive procedures, it is associated with high morbidity and mortality. With an ageing population, longer survival of heart failure patients, and an increasing number of patients with ICD, the incidence of ES is expected to increase. This European Heart Rhythm Association clinical consensus statement focuses on pathophysiology, clinical presentation, diagnostic evaluation, and acute and long-term management of patients presenting with ES or clustered VA.

ISE/ISHNE expert consensus statement on the ECG diagnosis of left ventricular hypertrophy: The change of the paradigm.

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria. The classical paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces, reflected in the augmented QRS amplitude. However, the low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm. The theoretical background for voltage measured at the body surface is defined by the solid angle theorem, which relates the measured voltage to spatial and non-spatial determinants. The spatial determinants are represented by the extent of the activation front and the distance of the recording electrodes. The non-spatial determinants comprise electrical characteristics of the myocardium, which are comparatively neglected in the interpretation of the QRS patterns. Various clinical conditions are associated with LVH. These conditions produce considerable diversity of electrical properties alterations thereby modifying the resultant QRS patterns. The spectrum of QRS patterns observed in LVH patients is quite broad, including also left axis deviation, left anterior fascicular block, incomplete and complete left bundle branch blocks, Q waves, and fragmented QRS. Importantly, the QRS complex can be within normal limits. The new paradigm stresses the electrophysiological background in interpreting QRS changes, i.e., the effect of the non-spatial determinants. This postulates that the role of ECG is not to estimate LV size in LVH, but to understand and decode the underlying electrical processes, which are crucial in relation to cardiovascular risk assessment.

Protection Conferred by Delta and BA.1/BA.2 Infection Against BA.4/BA.5 Infection and Hospitalization: A Retrospective Cohort Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 immunity has declined with subsequent waves and accrual of viral mutations. In vitro studies raise concern for immune escape by BA.4/BA.5, and a study in Qatar showed moderate protection, but these findings have yet to be reproduced. METHODS: This retrospective cohort study included individuals tested for coronavirus disease 2019 by polymerase chain reaction during Delta or BA.1/BA.2 and retested during BA.4/BA.5. The preventable fraction (PF) was calculated as ratio of the infection to the hospitalization rate for initially positive patients divided by the ratio for initially negative patients, stratified by age and adjusted for age, sex, comorbid conditions, and vaccination using logistic regression. RESULTS: A total of 20 987 patients met inclusion criteria. Prior Delta infection provided no protection against BA.4/BA.5 infection (adjusted PF, 11.9% [95% confidence interval, .8%-21.8%]); P = .04) and minimal protection against hospitalization (10.7% [4.9%-21.7%]; P = .003). In adjusted models, prior BA.1/BA.2 infection provided 45.9% (95% confidence interval, 36.2%-54.1%; P < .001) protection against BA.4/BA.5 reinfection and 18.8% (10.3%-28.3%; (P < .001) protection against hospitalization. Up-to-date vaccination provided modest protection against reinfection with BA.4/BA.5 and hospitalization. CONCLUSIONS: Prior infection with BA.1/BA.2 and up-to-date vaccination provided modest protection against infection with BA.4/BA.5 and hospitalization, while prior Delta infection provided minimal protection against hospitalization and none against infection.

Protection Against the Omicron Variant Offered by Previous Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Retrospective Cohort Study.

BACKGROUND: Previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides strong protection against future infection. There is limited evidence on whether such protection extends to the Omicron variant. METHODS: This retrospective cohort study included 635 341 patients tested for SARS-CoV-2 via polymerase chain reaction from 9 March 2020 to 1 March 2022. Patients were analyzed according to the wave in which they were initially infected. The primary outcome was reinfection during the Omicron period (20 December 2021-1 March 2022). We used a multivariable model to assess the effects of prior infection and vaccination on hospitalization. RESULTS: Among the patients tested during the Omicron wave, 30.6% tested positive. Protection of prior infection against reinfection with Omicron ranged from 18.0% (95% confidence interval [CI], 13.0-22.7) for patients infected in wave 1 to 69.2% (95% CI, 63.4-74.1) for those infected in the Delta wave. In adjusted models, previous infection reduced hospitalization by 28.5% (95% CI, 19.1-36.7), whereas full vaccination plus a booster reduced it by 59.2% (95% CI, 54.8-63.1). CONCLUSIONS: Previous infection offered less protection against Omicron than was observed in past waves. Immunity against future waves will likely depend on the degree of similarity between variants.

An electrophysiological substrate of COVID-19.

SARS-CoV-2 infection is associated with an increased risk of late cardiovascular (CV) outcomes. However, more data is needed to describe the electrophysiologic (EP) manifestation of post-acute CV sequelae of COVID-19. We compared two cohorts of adult patients with SARS-CoV-2 polymerase chain reaction (PCR) test and an electrocardiogram (ECG) performed between March 1, 2020, and September 13, 2020, in a retrospective double-cohort study, "Cardiovascular Risk Stratification in Covid-19" (CaVaR-Co19; NCT04555187). Patients with positive PCR comprised a COVID-19(+) cohort (n = 41; 61% women; 80% symptomatic), whereas patients with negative tests formed the COVID-19(-) cohort (n = 155; 56% women). In longitudinal analysis, comparing 3 ECGs recorded before, during, and on average 40 days after index COVID-19 episode, after adjustment for demographic and socioeconomic characteristics, baseline CV risk factors and comorbidities, use of prescription medications (including QT-prolonging drugs) before and during index COVID-19 episode, and the longitudinal changes in RR' intervals, heart rhythm, and ventricular conduction type, only in the COVID-19(+) cohort QTc increased by +30.2(95% confidence interval [CI] 0.1-60.3) ms and the spatial ventricular gradient (SVG) elevation increased by +13.5(95%CI 1.2-25.9)°. In contrast, much smaller, statistically nonsignificant changes were observed in the COVID-19(-) cohort. In conclusion, post-acute CV sequelae of SARS-CoV-2 infection manifested on ECG by QTc prolongation and rotation of the SVG vector upward.

ISE/ISHNE Expert Consensus Statement on ECG Diagnosis of Left Ventricular Hypertrophy: The Change of the Paradigm. The joint paper of the International Society of Electrocardiology and the International Society for Holter Monitoring and Noninvasive Electrocardiology.

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria, i.e. the increased QRS complex amplitude in defined leads. The classical ECG diagnostic paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces. These increased forces are reflected in the augmented QRS amplitude in the corresponding leads. However, the clinical observations document increased QRS amplitude only in the minority of patients with LVH. The low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm.

Association of abnormal electrocardiograph metrics with prolonged recovery time in incident hemodialysis patients.

BACKGROUND: Patients receiving intermittent hemodialysis have variable times of recovery to feeling better after dialysis. QT prolongation, a precursor to clinical and subclinical cardiovascular events, may contribute to delayed recovery time. We hypothesized that abnormal electrocardiographic parameters indicating perturbations in ventricular action are associated with longer recovery times thus impacting a patient-centered quality of life. METHODS: Among 242 incident in-center hemodialysis participants from the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, corrected QT interval (QTc), QRST angle and heart rate variance were measured on non-dialysis days using a standard 5-min electrocardiograph recording. Left ventricular hypertrophy (LVH) was defined using the Cornell voltage product. Recovery time was ascertained during a phone interview with a standardized validated questionnaire. Associations between QTc, QRST angle, heart rate variance, and LVH and natural log-transformed recovery time were examined using linear regression adjusted for participant characteristics and electrolytes. RESULTS: Mean age was 55 (standard deviation 13) years, 55% were male, 72% were African American. Longer QTc interval was associated with increased recovery time (per 10 ms increase in QTc, recovery time increased by 6.2%; 95% confidence interval: 0.0-10.5). QRST angle, heart rate, heart rate variability and LVH were not significantly associated with recovery time. CONCLUSION: Longer QTc intervals are associated with longer recovery time independent of serum electrolytes. This supports a relationship between a patient's underlying arrhythmic status and time to recovery after hemodialysis. Future studies will determine if maneuvers to reduce QTc improves recovery time and quality of life of patients on hemodialysis.

Emerging Frontline Leaders' Voices in Response to COVID-19 Crisis.

BACKGROUND: The COVID-19 pandemic has significantly affected healthcare institutions, introducing new challenges for nurse leaders and their colleagues. However, little is known about how the pandemic has specifically affected the lives of these leaders and what methods and strategies they are using to overcome pandemic-related challenges. OBJECTIVES: The aim of this study was to examine the effect of the 2019 pandemic on emerging healthcare leaders and highlight methods and strategies they used to overcome pandemic-related challenges. METHODS: The participants in this study represent a diverse group of interprofessional healthcare faculty enrolled in a transformational leadership course (Paths to Leadership) when the pandemic first appeared. Three months into the pandemic, the leadership cohort was invited to participate in this qualitative study, exploring four questions: Q1: How have you transformed your working styles in response to the pandemic? Q2: How have you adjusted your personal life in response to the pandemic? Q3: How have you used leadership skills learned from Paths to Leadership during the pandemic? Q4: What lessons have you learned from the pandemic? Participant narratives were analyzed by a team of nurse researchers using conventional qualitative content analysis. RESULTS: Themes for Q1 (working styles) included shifted from face-to-face to telework, faced novel disease and decisions, worked more from home, and challenged to maintain contact with professional peers and team. Themes for Q2 (personal life) included accommodate adults working and children learning from home, looked for and found the positive, and continue to struggle. Themes for Q3 (leadership skills) included reflective practice, listening, holding, and reframing. Finally, themes for Q4 (pandemic lessons) included leadership, human connection, be prepared, taking care of ourselves, and connecting with nature. DISCUSSION: The 2019 pandemic brought hardships and opportunities to faculty members enrolled in an interprofessional transformational leadership course. In conjunction with this course, the pandemic provided a unique opportunity for participants to apply newly acquired relationship building, positive organizational psychology, and reframing skills during a time of crisis. Nursing leaders, whose educational offerings may be immediately "put to the test," may find our lessons learned helpful as they develop strategies to cope with unanticipated future challenges.

Ventricular Arrhythmias in Patients with Implanted Cardiac Devices at High Risk of Obstructive Sleep Apnea.

Background and Objectives: Patients with pre-existing cardiac disease have a higher prevalence of Obstructive Sleep Apnea (OSA). OSA has been associated with an increased risk of supraventricular and ventricular arrhythmia. We screened subjects with implanted pacemakers and automated implantable cardioverter defibrillators (AICD) for OSA with the Berlin Questionnaire and compared the incidence of ventricular arrhythmias and automated implantable cardioverter defibrillator (AICD) firing between high and low OSA risk groups. Materials and Methods: We contacted 648 consecutive patients from our arrhythmia clinic to participate in the study and performed final analyses on 171 subjects who consented and had follow-up data. Data were abstracted from the electronic health record for the incidence of non-sustained ventricular tachycardia (NSVT), ventricular tachycardia (VT), ventricular fibrillation (VF) and AICD firing and then compared between those at high versus low risk of OSA using the Berlin Questionnaire and multivariate negative binomial regression. Results: The average follow-up period was 24.2 ± 4.4 months. After adjusting for age, gender and history of heart failure, those subjects at high risk of OSA had a higher burden of NSVT vs. those with a low risk of OSA (33.4 ± 96.2 vs. 5.82 ± 17.1 episodes, p = 0.003). A predetermined subgroup analysis of AICD recipients also demonstrated a significantly higher burden of NSVT in the high vs. low OSA risk groups (66.2 ± 128.6 vs. 18.9 ± 36.7 episodes, p = 0.033). There were significant differences in the rates of VT, VF or AICD shock burden between the high and low OSA risk groups and in the AICD subgroup analysis. Conclusions: There was increased ventricular ectopy among pacemaker and AICD recipients at high risk of OSA, but the prevalence of VT, VF or AICD shocks was similar to those with low risk of OSA.

Reproducibility of global electrical heterogeneity measurements on 12-lead ECG: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Vectorcardiographic (VCG) global electrical heterogeneity (GEH) metrics showed clinical usefulness. We aimed to assess the reproducibility of GEH metrics. METHODS: GEH was measured on two 10-s 12­lead ECGs recorded on the same day in 4316 participants of the Multi-Ethnic Study of Atherosclerosis (age 69.4 ± 9.4 y; 2317(54%) female, 1728 (40%) white, 1138(26%) African-American, 519(12%) Asian-American, 931(22%) Hispanic-American). GEH was measured on a median beat, comprised of the normal sinus (N), atrial fibrillation/flutter (S), and ventricular-paced (VP) beats. Spatial ventricular gradient's (SVG's) scalar was measured as sum absolute QRST integral (SAIQRST) and vector magnitude QT integral (VMQTi). RESULTS: Two N ECGs with heart rate (HR) bias of -0.64 (95% limits of agreement [LOA] -5.68 to 5.21) showed spatial area QRS-T angle (aQRST) bias of -0.12 (95%LOA -14.8 to 14.5). Two S ECGs with HR bias of 0.20 (95%LOA -15.8 to 16.2) showed aQRST bias of 1.37 (95%LOA -33.2 to 35.9). Two VP ECGs with HR bias of 0.25 (95%LOA -3.0 to 3.5) showed aQRST bias of -1.03 (95%LOA -11.9 to 9.9). After excluding premature atrial or ventricular beat and two additional beats (before and after extrasystole), the number of cardiac beats included in a median beat did not affect the GEH reproducibility. Mean-centered log-transformed values of SAIQRST and VMQTi demonstrated perfect agreement (Bias 0; 95%LOA -0.092 to 0.092). CONCLUSION: GEH measurements on N, S, and VP median beats are reproducible. SVG's scalar can be measured as either SAIQRST or VMQTi. SIGNIFICANCE: Satisfactory reproducibility of GEH metrics supports their implementation.

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

BACKGROUND: The 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). METHODS: Atherosclerosis 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. RESULTS: Over 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). CONCLUSION: Short-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.

Early Heart Rate Variability and Electroencephalographic Abnormalities in Acutely Brain-Injured Children Who Progress to Brain Death.

OBJECTIVES: Heart rate variability is controlled by the autonomic nervous system. After brain death, this autonomic control stops, and heart rate variability is significantly decreased. However, it is unknown if early changes in heart rate variability are predictive of progression to brain death. We hypothesized that in brain-injured children, lower heart rate variability is an early indicator of autonomic system failure, and it predicts progression to brain death. We additionally explored the association between heart rate variability and markers of brain dysfunction such as electroencephalogram and neurologic examination between brain-injured children who progressed to brain death and those who survived. DESIGN: Retrospective case-control study. SETTING: PICU, single institution. PATIENTS: Children up to 18 years with a Glasgow Coma Scale score of less than 8 admitted between August of 2016 and December of 2017, who had electrocardiographic data available for heart rate variability analysis, were included. EXCLUSION CRITERIA: patients who died of causes other than brain death. Twenty-three patients met inclusion criteria: six progressed to brain death (cases), and 17 survived (controls). Five-minute electrocardiogram segments were used to estimate heart rate variability in the time domain (SD of normal-normal intervals, root mean square successive differences), frequency domain (low frequency, high frequency, low frequency/high frequency ratio), Poincaré plots, and approximate entropy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients who progressed to brain death exhibited significantly lower heart rate variability in the time domain, frequency domain, and Poincaré plots (p < 0.01). The odds of death increased with decreasing low frequency (odds ratio, 4.0; 95% CI, 1.2-13.6) and high frequency (odds ratio, 2.5; 95% CI, 1.2-5.4) heart rate variability power (p < 0.03). Heart rate variability was significantly lower in those with discontinuous or attenuated/featureless electroencephalogram versus those with slow/disorganized background (p < 0.03). CONCLUSIONS: These results support the concept of autonomic system failure as an early indicator of impending brain death in brain-injured children. Furthermore, decreased heart rate variability is associated with markers of CNS dysfunction such as electroencephalogram abnormalities.

Vectorcardiogram in athletes: The Sun Valley Ski Study.

BACKGROUND: Global electrical heterogeneity (GEH) is associated with sudden cardiac death (SCD) in adults of 45 years and above. However, GEH has not been previously measured in young athletes. The goal of this study was to establish a reference for vectorcardiograpic (VCG) metrics in male and female athletes. METHODS: Skiers (n = 140; mean age 19.2 ± 3.5 years; 66% male, 94% white; 53% professional athletes) were enrolled in a prospective cohort. Resting 12-lead ECGs were interpreted per the International ECG criteria. Associations of age, sex, and athletic performance with GEH were studied. RESULTS: In age and training level-adjusted analyses, male sex was associated with a larger T vector [T peak magnitude +186 (95% CI 106-266) µV] and a wider spatial QRS-T angle [+28.2 (17.3-39.2)°] as compared to women. Spatial QRS-T angle in the ECG left ventricular hypertrophy (LVH) voltage group (n = 21; 15%) and normal ECG group did not differ (67.7 ± 25.0 vs. 66.8 ± 28.2; p = 0.914), suggesting that ECG LVH voltage in athletes reflects physiological remodeling. In contrast, skiers with right ventricular hypertrophy (RVH) voltage (n = 26, 18.6%) had wider QRS-T angle (92.7 ± 29.6 vs. 66.8 ± 28.2°; p = 0.001), larger SAI QRST (194.9 ± 30.2 vs. 157.8 ± 42.6 mV × ms; p < 0.0001), but similar peak SVG vector magnitude (1976 ± 548 vs. 1939 ± 395 µV; p = 0.775) as compared to the normal ECG group. Better athletic performance was associated with the narrower QRS-T angle. Each 10% worsening in an athlete's Federation Internationale de' Ski downhill ranking percentile was associated with an increase in spatial QRS-T angle by 2.1 (95% CI 0.3-3.9) degrees (p = 0.013). CONCLUSION: Vectorcardiograpic adds nuances to ECG phenomena in athletes.

Associations of serum and dialysate electrolytes with QT interval and prolongation in incident hemodialysis: the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) study.

BACKGROUND: Prolonged QT interval in hemodialysis patients may be associated with sudden cardiac death, however, few studies examined the longitudinal associations of modifiable factors such as serum and dialysate concentrations of calcium, potassium, and magnesium with corrected QT (QTc) prolongation in incident hemodialysis patients. METHODS: In 330 in-center hemodialysis participants from the PACE study who were followed up for one year, we examined the associations of predialysis serum electrolytes (total calcium [Ca], corrected Ca [cCa], ionized Ca [iCa], potassium [K], magnesium [Mg]), dialysate (dCa and dK), and serum-to-dialysate gradient measures with QTc interval and prolongation (≥460 ms in women and ≥ 450 ms in men). RESULTS: At the first study visit, 47% had QTc prolongation. Lower iCa and K were associated with longer QTc interval independent of potential confounders (QTc difference = 8.55[95% CI: 2.13, 14.97] ms for iCa; QTc difference = 9.89[1.58, 18.20] ms for K). Lower iCa was also associated with a higher risk of QTc prolongation. At 1 year of follow-up, 31% had persistent QTc prolongation. In longitudinal analyses, the associations of iCa and K with QTc interval remained significant, and lower K was associated with a higher risk of QTc prolongation while the association of iCa with QTc prolongation was borderline statistically significant. Serum Mg, dCa or dK, and respective gradients were not associated with QTc interval or prolongation. CONCLUSION: Prolonged QTc is very common in incident hemodialysis participants and persists over follow-up. Ionized Ca and K are consistently inversely associated with QTc prolongation, which suggests closer monitoring for a low calcium or potassium level to mitigate risk.

Association of Abdominal Adiposity with Cardiovascular Mortality in Incident Hemodialysis.

BACKGROUND: The risk of cardiovascular mortality is high among adults with end-stage renal disease (ESRD) undergoing hemodialysis. Waist-to-hip ratio (WHR), a metric of abdominal adiposity, is a predictor of cardiovascular disease (CVD) and mortality in the general population; however, no studies have examined the association with CVD mortality, particularly sudden cardiac death (SCD), in incident hemodialysis. METHODS: Among 379 participants incident (< 6 months) to hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in ESRD study, we evaluated associations between WHR and risk of CVD mortality, SCD, and non-CVD mortality in Cox proportional hazards regression models. RESULTS: At study enrollment, mean age was 55 years with 41% females, 73% African Americans, and 57% diabetics. Mean body mass index was 29.3 kg/m2, and mean WHR was 0.95. During a median follow-up time of 2.5 years, there were 35 CVD deaths, 15 SCDs, and 48 non-CVD deaths. Every 0.1 increase in WHR was associated with higher risk (hazard ratio [95% CI]) of CVD mortality (1.75 [1.06-2.86]) and SCD (2.45 [1.20-5.02]), but not non-CVD mortality (0.93 [0.59-1.45]), independently of demographics, body mass index, comorbidities, inflammation, and traditional CVD risk factors. CONCLUSIONS: WHR is significantly associated with CVD mortality including SCD, independently of other CVD risk factors in incident hemodialysis. This simple, easily obtained bedside metric may be useful in dialysis patients for CVD risk stratification.

Torso geometry reconstruction and body surface electrode localization using three-dimensional photography.

We conducted a prospective clinical study (n=14; 29% female) to assess the accuracy of a three-dimensional (3D) photography-based method of torso geometry reconstruction and body surface electrodes localization. The position of 74 body surface electrocardiographic (ECG) electrodes (diameter 5mm) was defined by two methods: 3D photography, and CT (marker diameter 2mm) or MRI (marker size 10×20mm) imaging. Bland-Altman analysis showed good agreement in X (bias -2.5 [95% limits of agreement (LoA) -19.5 to 14.3] mm), Y (bias -0.1 [95% LoA -14.1 to 13.9] mm), and Z coordinates (bias -0.8 [95% LoA -15.6 to 14.2] mm), as defined by the CT/MRI imaging, and 3D photography. The average Hausdorff distance between the two torso geometry reconstructions was 11.17±3.05mm. Thus, accurate torso geometry reconstruction using 3D photography is feasible. Body surface ECG electrodes coordinates as defined by the CT/MRI imaging, and 3D photography, are in good agreement.

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.

AIMS: There 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. METHODS AND RESULTS: In the community-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), 522 SCD cases with archived 12-lead ECG available (65.3 ± 14.5 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; P < 0.001]. In the LVEF >35% subgroup, the OR was 26.1 (95% CI 9.9-68.5; P < 0.001). The ECG risk score increased the C-statistic from 0.625 to 0.753 (P < 0.001), with net reclassification improvement of 0.319 (P < 0.001). 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; P < 0.001; C-statistic improvement 0.759-0.774; P = 0.019). CONCLUSION: This 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.