Publications by authors named "Christine M Albert"

218 Publications

Risk of sudden cardiac death associated with QRS, QTc, and JTc intervals in the general population.

Heart Rhythm 2022 Apr 25. Epub 2022 Apr 25.

Research Unit of Internal Medicine, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland. Electronic address:

Background: QRS duration and corrected QT (QTc) interval have been associated with sudden cardiac death (SCD), but no data are available on the significance of repolarization component (JTc interval) of the QTc interval as an independent risk marker in the general population.

Objective: In this study, we sought to quantify the risk of SCD associated with QRS, QTc, and JTc intervals.

Methods: This study was conducted using data from 3 population cohorts from different eras, comprising a total of 20,058 individuals. The follow-up period was limited to 10 years and age at baseline to 30-61 years. QRS duration and QT interval (Bazett's) were measured from standard 12-lead electrocardiograms at baseline. JTc interval was defined as QTc interval - QRS duration. Cox proportional hazards models that controlled for confounding clinical factors identified at baseline were used to estimate the relative risk of SCD.

Results: During a mean period of 9.7 years, 207 SCDs occurred (1.1 per 1000 person-years). QRS duration was associated with a significantly increased risk of SCD in each cohort (pooled hazard ratio [HR] 1.030 per 1-ms increase; 95% confidence interval [CI] 1.017-1.043). The QTc interval had borderline to significant associations with SCD and varied among cohorts (pooled HR 1.007; 95% CI 1.001-1.012). JTc interval as a continuous variable was not associated with SCD (pooled HR 1.001; 95% CI 0.996-1.007).

Conclusion: Prolonged QRS durations and QTc intervals are associated with an increased risk of SCD. However, when the QTc interval is deconstructed into QRS and JTc intervals, the repolarization component (JTc) appears to have no independent prognostic value.
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http://dx.doi.org/10.1016/j.hrthm.2022.04.016DOI Listing
April 2022

Arrhythmic sudden death survival prediction using deep learning analysis of scarring in the heart.

Nat Cardiovasc Res 2022 Apr 7;1(4):334-343. Epub 2022 Apr 7.

Alliance for Cardiovascular Diagnostic and Treatment Innovation (ADVANCE), Johns Hopkins University, Baltimore, 21224, USA.

Sudden cardiac death from arrhythmia is a major cause of mortality worldwide. Here, we develop a novel deep learning (DL) approach that blends neural networks and survival analysis to predict patient-specific survival curves from contrast-enhanced cardiac magnetic resonance images and clinical covariates for patients with ischemic heart disease. The DL-predicted survival curves offer accurate predictions at times up to 10 years and allow for estimation of uncertainty in predictions. The performance of this learning architecture was evaluated on multi-center internal validation data and tested on an independent test set, achieving concordance index of 0.83 and 0.74, and 10-year integrated Brier score of 0.12 and 0.14. We demonstrate that our DL approach with only raw cardiac images as input outperforms standard survival models constructed using clinical covariates. This technology has the potential to transform clinical decision-making by offering accurate and generalizable predictions of patient-specific survival probabilities of arrhythmic death over time.
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http://dx.doi.org/10.1038/s44161-022-00041-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022904PMC
April 2022

Diabetes Mellitus, Race, and Effects of Omega-3 Fatty Acids on Incidence of Heart Failure Hospitalization.

JACC Heart Fail 2022 Apr 9;10(4):227-234. Epub 2022 Mar 9.

Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Objectives: The primary aim was to evaluate whether prevalent type 2 diabetes (T2D) modifies the effects of omega-3 supplementation on heart failure (HF) hospitalization. The secondary aim was to examine if race modifies the effects of omega-3 supplements on HF risk.

Background: It is unclear whether race and T2D modify the effects of omega-3 supplementation on the incidence of HF.

Methods: In this ancillary study of the parent VITAL (Vitamin D and Omega-3 Trial)-a completed randomized trial testing the efficacy of vitamin D and omega-3 fatty acids on cardiovascular diseases and cancer, we assessed the role of T2D and race on the effects of omega-3 supplements on the incidence of HF hospitalization (adjudicated by a review of medical records and supplemented with a query of Centers for Medicare and Medicaid Services data).

Results: When omega-3 supplements were compared with placebo, the HR for first HF hospitalization was 0.69 (95% CI: 0.50-0.95) in participants with prevalent T2D and 1.09 (95% CI: 0.88-1.34) in those without T2D (P for interaction = 0.019). Furthermore, prevalent T2D modified the effects of omega-3 fatty acids on the incidence of recurrent HF hospitalization (HR: 0.53; 95% CI: 0.41-0.69 in participants with prevalent T2D vs HR: 1.07; 95% CI: 0.89-1.28 in those without T2D; P interaction <0.0001). In our secondary analysis, omega-3 supplementation reduced recurrent HF hospitalization only in Black participants (P interaction race × omega-3 = 0.0497).

Conclusions: Our data show beneficial effects of omega-3 fatty acid supplements on incidence of HF hospitalization in participants with T2D but not in those without T2D, and such benefit appeared to be stronger in Black participants with T2D. (Intervention With Vitamin D and Omega-3 Supplements and Incident Heart Failure; NCT02271230; Vitamin D and Omega-3 Trial [VITAL]; NCT01169259 [parent study]).
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http://dx.doi.org/10.1016/j.jchf.2021.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986092PMC
April 2022

Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data.

Nat Genet 2022 03 7;54(3):263-273. Epub 2022 Mar 7.

Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular whether the causal variants are rare, or whether it is overestimated due to bias in inference from pedigree data. Here we estimated heritability for height and body mass index (BMI) from whole-genome sequence data on 25,465 unrelated individuals of European ancestry. The estimated heritability was 0.68 (standard error 0.10) for height and 0.30 (standard error 0.10) for body mass index. Low minor allele frequency variants in low linkage disequilibrium (LD) with neighboring variants were enriched for heritability, to a greater extent for protein-altering variants, consistent with negative selection. Our results imply that rare variants, in particular those in regions of low linkage disequilibrium, are a major source of the still missing heritability of complex traits and disease.
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http://dx.doi.org/10.1038/s41588-021-00997-7DOI Listing
March 2022

Arrhythmias in Female Patients: Incidence, Presentation and Management.

Circ Res 2022 02 17;130(4):474-495. Epub 2022 Feb 17.

Division of Cardiology, Cooper Medical School of Rowan University, Camden, NJ (F.S., A.M.R.).

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.319893DOI Listing
February 2022

The year in cardiovascular medicine 2021: arrhythmias.

Eur Heart J 2022 03;43(12):1191-1197

Department of Cardiology, University College London and Barts Heart Centre, London, UK.

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http://dx.doi.org/10.1093/eurheartj/ehac007DOI Listing
March 2022

Sex-Specific Temporal Trends in Hypertensive Crisis Hospitalizations in the United States.

J Am Heart Assoc 2022 02 27;11(4):e021244. Epub 2022 Jan 27.

Department of Cardiology Smidt Heart InstituteCedars-Sinai Medical Center Los Angeles CA.

Background Despite recent improvements in hypertension control overall, the extent to which these trends apply to the most extreme forms of elevated blood pressure-hypertensive crises requiring hospitalization-in both women and men at risk remains unknown. Methods and Results Using data from the National Inpatient Sample, we estimated sex-pooled and sex-specific temporal trends in hypertensive crisis hospitalization and case fatality rates over serial time periods: years 2002 to 2006, 2007 to 2011, and 2012 to 2014. Over the entire study period (years 2002-2014), there were an estimated 918 392±9331 hypertensive crisis hospitalizations and 4377±157 in-hospital deaths. Hypertensive crisis represented 0.23%±0.002% of all hospitalizations during the entire study period: 0.24%±0.002% for men and 0.22%±0.002% for women. In multivariable analyses adjusting for age, race or ethnicity, and cardiovascular conditions, the odds of experiencing a hospitalization primarily for hypertensive crisis increased annually for both men (odds ratio [OR], 1.083 per year; 95% CI, 1.08-1.09) and women (OR, 1.07 per year, 95% CI, 1.07-1.08) with a higher rate of increase observed in men compared with women (<0.001). The multivariable-adjusted odds of death during hypertensive crisis hospitalization decreased annually and similarly for men (OR, 0.89 per year; 95% CI, 0.86-0.92) and for women (0.92 per year; 95% CI, 0.90-0.94). Conclusions Hypertensive crisis hospitalizations have steadily increased, slightly more among men than women, along with an observed increase in the burden of cardiovascular conditions. These trends, observed despite contemporaneous improvements in hypertension prevention and control nationwide, warrant further investigations to identify contributing factors that could be amenable to targeted interventions.
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http://dx.doi.org/10.1161/JAHA.121.021244DOI Listing
February 2022

Harmonization of the definition of sudden cardiac death in longitudinal cohorts of the European Sudden Cardiac Arrest network - towards Prevention, Education, and New Effective Treatments (ESCAPE-NET) consortium.

Am Heart J 2022 03 20;245:117-125. Epub 2021 Dec 20.

Department of Cardiology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark; Department of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: The burden of sudden cardiac death (SCD) in the general population is substantial and SCD frequently occurs among people with few or no known risk factors for cardiac disease. Reported incidences of SCD vary due to differences in definitions and methodology between cohorts. This study aimed to develop a method for adjudicating SCD cases in research settings and to describe uniform case definitions of SCD in an international consortium harmonizing multiple longitudinal study cohorts.

Methods: The harmonized SCD definitions include both case definitions using data from multiple sources (eg, autopsy reports, medical history, eyewitnesses) as well as a method using only information from registers (eg, cause of death registers, ICD-10 codes). Validation of the register-based method was done within the consortium using the multiple sources definition as gold standard and presenting sensitivity, specificity, accuracy and positive predictive value.

Results: Consensus definitions of "definite," "possible" and "probable" SCD for longitudinal study cohorts were reached. The definitions are based on a stratified approach to reflect the level of certainty of diagnosis and degree of information. The definitions can be applied to both multisource and register-based methods. Validation of the method using register-information in a cohort comprising 1335 cases yielded a sensitivity of 74%, specificity of 88%, accuracy of 86%, and positive predictive value of 54%.

Conclusions: This study demonstrated that a harmonization of SCD classification across different methodological approaches is feasible. The developed classification can be used to study SCD in longitudinal cohorts and to merge cohorts with different levels of information.
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http://dx.doi.org/10.1016/j.ahj.2021.12.008DOI Listing
March 2022

Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Circulation 2021 12 6;144(25):1981-1990. Epub 2021 Oct 6.

Department of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA (C.M.A.).

Background: Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine ɷ-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose-related.

Methods: The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012, and December 31, 2020, in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine ɷ-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year were included. RCTs specifically examining shorter-term effects of ɷ-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was meta-analyzed using random effects model with Knapp-Hartung adjustment and evaluated a dose-response relationship with a meta-regression model.

Results: Of 4049 screened records, 7 studies were included in the meta-analysis. Of those, 5 were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81 210 patients from 7 trials, 58 939 (72.6%) were enrolled in trials testing ≤1 g/d and 22 271 (27.4%) in trials testing >1 g/d of ɷ-3 fatty acids. The mean age was 65 years, and 31 842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine ɷ-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07-1.46]; =0.013). In analyses stratified by dose, the HR was greater in the trials testing >1 g/d (HR, 1.49 [95% CI, 1.04-2.15]; =0.042) compared with those testing ≤1 g/d (HR, 1.12 [95% CI, 1.03-1.22]; =0.024; for interaction <0.001). In meta-regression, the HR for AF increased per 1 g higher dosage of ɷ-3 fatty acids dosage (HR, 1.11 [95% CI, 1.06-1.15]; =0.001).

Conclusions: In RCTs examining cardiovascular outcomes, marine ɷ-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1 g/d.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109217PMC
December 2021

Leveraging Large Clinical Data Sets for Artificial Intelligence in Medicine.

JAMA Cardiol 2021 11;6(11):1296-1297

Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California.

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http://dx.doi.org/10.1001/jamacardio.2021.2878DOI Listing
November 2021

Diabetes and Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction.

JACC Clin Electrophysiol 2021 12 28;7(12):1604-1614. Epub 2021 Jul 28.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. Electronic address:

Objectives: This study sought to determine the absolute and relative associations of diabetes mellitus (DM) and hemoglobin A (HbA) with sudden and/or arrhythmic death (SAD) versus other modes of death in patients with coronary artery disease (CAD) who do not qualify for implantable cardioverter-defibrillators.

Background: Patients with CAD and DM are at elevated risk for SAD; however, it is unclear whether these patients would benefit from implantable cardioverter-defibrillators given competing causes of death and/or whether HbA might augment SAD risk stratification.

Methods: In the PRE-DETERMINE study of 5,764 patients with CAD with left ventricular ejection fraction (LVEF) of >30% to 35%, competing risk analyses were used to compare the absolute and relative risks of SAD versus non-SAD by DM status and HbA level and to identify risk factors for SAD among 1,782 patients with DM.

Results: Over a median follow-up of 6.8 years, DM and HbA were significantly associated with SAD and non-SAD (P < 0.05 for all comparisons); however, the cumulative incidence of non-SAD (19.2%; 95% CI: 17.3%-21.2%) was almost 4 times higher than SAD (4.8%; 95% CI: 3.8%-5.9%) in DM patients. A similar pattern of absolute risk was observed across categories of HbA. In analyses limited to patients with DM, HbA was not associated with SAD, whereas low LVEF, atrial fibrillation, and electrocardiogram measurements were associated with higher SAD risk.

Conclusions: In patients with CAD and LVEF of >30% to 35%, patients with DM and/or elevated HbA are at much higher absolute risk of dying from non-SAD than SAD. Clinical risk markers, and not HbA, were associated with SAD risk in patients with DM. (PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study; NCT01114269).
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http://dx.doi.org/10.1016/j.jacep.2021.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788939PMC
December 2021

Improving Efficiency of the Barbershop Model of Hypertension Care for Black Men With Virtual Visits.

J Am Heart Assoc 2021 07 22;10(13):e020796. Epub 2021 Jun 22.

Department of Cardiology Smidt Heart InstituteCedars-Sinai Medical Center Los Angeles CA.

Background The LABBPS (Los Angeles Barbershop Blood Pressure Study) developed a new model of hypertension care for non-Hispanic Black men that links health promotion by barbers to medication management by pharmacists. Barriers to scaling the model include inefficiencies that contribute to the cost of the intervention, most notably, pharmacist travel time. To address this, we tested whether virtual visits could be substituted for in-person visits after blood pressure (BP) control was achieved. Methods and Results We enrolled 10 Black male patrons with systolic BP ≥140 mm Hg into a proof-of-concept study in which barbers promoted follow-up with pharmacists who initially met each patron in the barbershop, where they prescribed BP medication under a collaborative practice agreement with the patrons' physician. Medications were titrated during bimonthly in-person visits to achieve a BP goal of ≤130/80 mm Hg. Once BP goal was reached, visits were done by videoconference. Final BP and safety outcomes were assessed at 12 months. Nine patients completed the intervention. Baseline BP of 155±14/83.9±11 mm Hg decreased by -28.7±13/-8.9±15 mm Hg (<0.0001). These data are statistically indistinguishable from prior LABBPS data (=0.8 for change in systolic BP and diastolic BP). Hypertension control (≤130/80 mm Hg) was 67% (6 of 9), numerically greater than the 63% observed in LABBPS (=not significant). As intended, the mean number of in-person visits decreased from 11 in LABBPS to 6.6 visits over 12 months. No treatment-related serious adverse events occurred. Conclusions Virtual visits represent a viable substitute for in-person visits, both improving pharmacist efficiency and reducing cost while preserving intervention potency. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03726710.
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http://dx.doi.org/10.1161/JAHA.120.020796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403295PMC
July 2021

2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families.

J Arrhythm 2021 Jun 8;37(3):481-534. Epub 2021 Apr 8.

The First Affiliated Hospital of Nanjing Medical University Nanjing China.

This international multidisciplinary document intends to provide clinicians with evidence-based practical patient-centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.
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http://dx.doi.org/10.1002/joa3.12449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207384PMC
June 2021

Nationwide burden of sudden cardiac death: A study of 54,028 deaths in Denmark.

Heart Rhythm 2021 10 7;18(10):1657-1665. Epub 2021 May 7.

Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark; Section of Forensic Pathology, Copenhagen University, Copenhagen, Denmark.

Background: A large proportion of all deaths are sudden cardiac deaths (SCDs). Reliable estimates of nationwide incidence of SCD, however, are missing.

Objectives: The goals of this study were to estimate SCD burden across all age groups in Denmark and to compare it with the estimates of other common causes of death.

Methods: All deaths in Denmark (population of 5.5 million) in 2010 were manually reviewed case by case. Autopsy reports, death certificates, and information from nationwide health registries were systematically examined to identify all SCD cases in 2010. According to the level of detail of the available information, all deaths were categorized as either non-SCD, definite SCD, probable SCD, or possible SCD.

Results: There were 54,028 deaths in Denmark in 2010, of which 6867 (13%) were categorized as SCD (591 (9%) definite SCD, 1568 (23%) probable SCD, and 4708 (68%) possible SCD). The incidence rate of definite SCD was 11 (95% confidence interval 10-12) per 100,000 person-years. Including definite, probable, and possible SCD cases, the highest possible overall SCD incidence rate was 124 (95% confidence interval 121-127) per 100,000 person-years. Estimated SCD burden was similar to or greater than the estimates of all other common causes of death. Of all SCD cases, 49% were not diagnosed with cardiovascular disease before death.

Conclusion: SCD accounted for up to 13% of all deaths. Almost half of all SCD cases occurred in persons without a history of cardiovascular disease. Consequently, the optimization of risk stratification and prevention of SCD in the general population should be given high priority.
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http://dx.doi.org/10.1016/j.hrthm.2021.05.005DOI Listing
October 2021

Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial.

JAMA 2021 03;325(11):1061-1073

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: Atrial fibrillation (AF) is the most common heart rhythm disturbance, continues to increase in incidence, and results in significant morbidity and mortality. The marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D have been reported to have both benefits and risks with respect to incident AF, but large-scale, long-term randomized trial data are lacking.

Objective: To test the effects of long-term administration of marine omega-3 fatty acids and vitamin D on incident AF.

Design, Setting, And Participants: An ancillary study of a 2 × 2 factorial randomized clinical trial involving 25 119 women and men aged 50 years or older without prior cardiovascular disease, cancer, or AF. Participants were recruited directly by mail between November 2011 and March 2014 from all 50 US states and were followed up until December 31, 2017.

Interventions: Participants were randomized to receive EPA-DHA (460 mg/d of EPA and 380 mg/d of DHA) and vitamin D3 (2000 IU/d) (n = 6272 analyzed); EPA-DHA and placebo (n = 6270 analyzed); vitamin D3 and placebo (n = 6281 analyzed); or 2 placebos (n = 6296 analyzed).

Main Outcomes And Measures: The primary outcome was incident AF confirmed by medical record review.

Results: Among the 25 119 participants who were randomized and included in the analysis (mean age, 66.7 years; 50.8% women), 24 127 (96.1%) completed the trial. Over a median 5.3 years of treatment and follow-up, the primary end point of incident AF occurred in 900 participants (3.6% of study population). For the EPA-DHA vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19). For the vitamin D3 vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.25; P = .19). There was no evidence for interaction between the 2 study agents (P = .39).

Conclusions And Relevance: Among adults aged 50 years or older, treatment with EPA-DHA or vitamin D3, compared with placebo, resulted in no significant difference in the risk of incident AF over a median follow-up of more than 5 years. The findings do not support the use of either agent for the primary prevention of incident AF.

Trial Registration: ClinicalTrials.gov Identifiers: NCT02178410; NCT01169259.
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http://dx.doi.org/10.1001/jama.2021.1489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967086PMC
March 2021

Seroprevalence of antibodies to SARS-CoV-2 in healthcare workers: a cross-sectional study.

BMJ Open 2021 02 12;11(2):e043584. Epub 2021 Feb 12.

Center for Neural Science and Medicine, Department of Biomedical Sciences, Board of Governors Regenerative Medicine Institute, Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Objective: We sought to determine the extent of SARS-CoV-2 seroprevalence and the factors associated with seroprevalence across a diverse cohort of healthcare workers.

Design: Observational cohort study of healthcare workers, including SARS-CoV-2 serology testing and participant questionnaires.

Settings: A multisite healthcare delivery system located in Los Angeles County.

Participants: A diverse and unselected population of adults (n=6062) employed in a multisite healthcare delivery system located in Los Angeles County, including individuals with direct patient contact and others with non-patient-oriented work functions.

Main Outcomes: Using Bayesian and multivariate analyses, we estimated seroprevalence and factors associated with seropositivity and antibody levels, including pre-existing demographic and clinical characteristics; potential COVID-19 illness-related exposures; and symptoms consistent with COVID-19 infection.

Results: We observed a seroprevalence rate of 4.1%, with anosmia as the most prominently associated self-reported symptom (OR 11.04, p<0.001) in addition to fever (OR 2.02, p=0.002) and myalgias (OR 1.65, p=0.035). After adjusting for potential confounders, seroprevalence was also associated with Hispanic ethnicity (OR 1.98, p=0.001) and African-American race (OR 2.02, p=0.027) as well as contact with a COVID-19-diagnosed individual in the household (OR 5.73, p<0.001) or clinical work setting (OR 1.76, p=0.002). Importantly, African-American race and Hispanic ethnicity were associated with antibody positivity even after adjusting for personal COVID-19 diagnosis status, suggesting the contribution of unmeasured structural or societal factors.

Conclusion And Relevance: The demographic factors associated with SARS-CoV-2 seroprevalence among our healthcare workers underscore the importance of exposure sources beyond the workplace. The size and diversity of our study population, combined with robust survey and modelling techniques, provide a vibrant picture of the demographic factors, exposures and symptoms that can identify individuals with susceptibility as well as potential to mount an immune response to COVID-19.
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http://dx.doi.org/10.1136/bmjopen-2020-043584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883610PMC
February 2021

Changes in the digital health landscape in cardiac electrophysiology: A pre-and peri-pandemic COVID-19 era survey.

Cardiovasc Digit Health J 2021 Feb 25;2(1):55-62. Epub 2020 Dec 25.

Department of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, California.

Background: Digital health is transforming healthcare delivery.

Objective: To compare the current digital health landscape in select groups of cardiac electrophysiology (EP) professionals prior to and during the COVID-19 era.

Methods: Two online surveys were emailed to 4 Heart Rhythm Society communities and tweeted out to Twitter EP, 1 before and 1 during the pandemic. Categorical variables were analyzed using the test and reported as absolute numbers and percentages.

Results: There were 253 pre-pandemic (S1) and 273 follow-up surveys (S2) completed. The majority of respondents to both surveys were male, aged <55 years (70.6% vs 75.1%), university-affiliated (52.6% vs 55%), and physicians (83.3% vs 87.9%). Between S1 and S2, routine use of video-telehealth increased (5.9% vs 58.6%; < .001) for all types of consultations ( < .001 for all). Wireless electrocardiogram prescribing was prevalent and similar (80.2% vs 81.0%), whereas wireless blood pressure monitoring (9.9% vs 18.3%) and wireless oximetry (1.6% vs 8.1%; = .006 for both) prescribing both increased. For smartphone mobile applications (mApps), prescriptions for heart rate mApps decreased (50.6% vs 40.7%; = .022), while vital sign (28.9% vs 37%; = .04) and symptom trackers (15.8% vs 24.9%; = .01) prescribing increased. A majority in both surveys (84.6% vs 75.5%) reported no workplace infrastructure or support for digital health with concerns for lack of parity in reimbursement.

Conclusion: Our results show an increase in adoption of digital health by EP during the COVID-19 pandemic. Concerns regarding a lack of supportive infrastructure persisted. Development of professional society guidelines on optimal clinical workflow, infrastructure, and reimbursement may help advance and sustain digital health integration in EP.
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http://dx.doi.org/10.1016/j.cvdhj.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890346PMC
February 2021

Validation of electrocardiographic criteria for identifying left ventricular dysfunction in patients with previous myocardial infarction.

Ann Noninvasive Electrocardiol 2021 03 30;26(2):e12812. Epub 2020 Oct 30.

Cardiac Safety Services, IQVIA, Mumbai, India.

Background: Eleven criteria correlating electrocardiogram (ECG) findings with reduced left ventricular ejection fraction (LVEF) have been previously published. These have not been compared head-to-head in a single study. We studied their value as a screening test to identify patients with reduced LVEF estimated by cardiac magnetic resonance (CMR) imaging.

Methods: ECGs and CMR from 548 patients (age 61 + 11 years, 79% male) with previous myocardial infarction (MI), from the DETERMINE and PRE-DETERMINE studies, were analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each criterion for identifying patients with LVEF ≤ 30% and ≤ 40% were studied. A useful screening test should have high sensitivity and NPV.

Results: Mean LVEF was 40% (SD = 11%); 264 patients (48.2%) had LVEF ≤ 40%, and 96 patients (17.5%) had LVEF ≤ 30%. Six of 11 criteria were associated with a significant lower LVEF, but had poor sensitivity to identify LVEF ≤ 30% (range 2.1%-55.2%) or LVEF ≤ 40% (1.1%-51.1%); NPVs were good for LVEF ≤ 30% (range 82.8%-85.9%) but not for LVEF ≤ 40% (range 52.1%-60.6%). Goldberger's third criterion (RV4/SV4 < 1) and combinations of maximal QRS duration > 124 ms + either Goldberger's third criterion or Goldberger's first criterion (SV1 or SV2 + RV5 or RV6 ≥ 3.5 mV) had high specificity (95.4%-100%) for LVEF ≤ 40%, although seen in only 48 (8.8%) patients; predictive values were similar on subgroup analysis.

Conclusions: None of the ECG criteria qualified as a good screening test. Three criteria had high specificity for LVEF ≤ 40%, although seen in < 9% of patients. Whether other ECG criteria can better identify LV dysfunction remains to be determined.
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http://dx.doi.org/10.1111/anec.12812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935098PMC
March 2021

2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families.

Heart Rhythm 2021 01 19;18(1):e1-e50. Epub 2020 Oct 19.

The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

This international multidisciplinary document intends to provide clinicians with evidence-based practical patient-centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.
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http://dx.doi.org/10.1016/j.hrthm.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194370PMC
January 2021

Celebrating Frank Marcus.

Heart Rhythm 2020 10;17(10):1637

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http://dx.doi.org/10.1016/j.hrthm.2020.07.007DOI Listing
October 2020

HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic.

J Arrhythm 2020 Jun 25. Epub 2020 Jun 25.

Society Washington US.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in the city of Wuhan late in 2019. Within a few months, the disease spread toward all parts of the world and was declared a pandemic on March 11, 2020. The current health care dilemma worldwide is how to sustain the capacity for quality services not only for those suffering from COVID-19 but also for non-COVID-19 patients, all while protecting physicians, nurses, and other allied health care workers.
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http://dx.doi.org/10.1002/joa3.12389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361598PMC
June 2020

Association Between Atrial Fibrillation and Sudden Cardiac Death: Pathophysiological and Epidemiological Insights.

Circ Res 2020 07 2;127(2):301-309. Epub 2020 Jul 2.

From the European Georges Pompidou Hospital, Cardiology Department, Paris, France (V.W., X.J., E.M.).

Emerging evidence suggests that atrial fibrillation (AF) may be associated with an increased risk of sudden cardiac death (SCD). However, AF shares risk factors with numerous cardiac conditions, including coronary heart disease and heart failure-the 2 most common substrates for SCD-making the AF-SCD relationship particularly challenging to address. A careful consideration of confounding factors is essential, since interventions for AF will be effective in reducing SCD only if there is a causal association between these 2 conditions. In this translational review, we detail the plausible underlying pathophysiological mechanisms through which AF may promote or lead to SCD, as well as the existing epidemiological evidence supporting an association between AF and SCD. While the role of AF in predicting SCD in the general population appears limited and not established, AF might be integrated to improve risk stratification in some specific phenotypes. Optimal AF management, including that of its associated conditions, appears to be of interest to prevent AF-related SCD, especially because the AF-SCD relationship is in part driven by heart failure.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.316756DOI Listing
July 2020

Guidance for Rebooting Electrophysiology Through the COVID-19 Pandemic From the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology: Endorsed by the American College of Cardiology.

JACC Clin Electrophysiol 2020 08 12;6(8):1053-1066. Epub 2020 Jun 12.

Cooper Medical School of Rowan University, Camden, New Jersey, USA.

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.
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http://dx.doi.org/10.1016/j.jacep.2020.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291987PMC
August 2020

Pre-existing traits associated with Covid-19 illness severity.

PLoS One 2020 23;15(7):e0236240. Epub 2020 Jul 23.

Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.

Importance: Certain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear.

Objective: To determine the demographic and clinical characteristics associated with increased severity of Covid-19 infection.

Design: Retrospective observational study. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation.

Setting: A large, multihospital healthcare system in Southern California.

Participants: All patients with confirmed Covid-19 infection (N = 442).

Results: Of all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P = 0.001), African American (OR 2.1, P = 0.011), obese (OR 2.0, P = 0.021), with diabetes mellitus (OR 1.8, P = 0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (Pinteraction<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P = 0.003) irrespective of age, race, or morbidity profile.

Conclusions And Relevance: In our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236240PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377468PMC
August 2020

Markers of Myocardial Stress, Myocardial Injury, and Subclinical Inflammation and the Risk of Sudden Death.

Circulation 2020 09 23;142(12):1148-1158. Epub 2020 Jul 23.

Divisions of Preventive Medicine (B.M.E., M.V.M., J.T.T., N.R.C., C.M.A.), Department of Medicine, Brigham and Women's Hospital, Boston, MA.

Background: The majority of sudden cardiac deaths (SCDs) occur in low-risk populations often as the first manifestation of cardiovascular disease (CVD). Biomarkers are screening tools that may identify subclinical cardiovascular disease and those at elevated risk for SCD. We aimed to determine whether the total to high-density lipoprotein cholesterol ratio, high-sensitivity cardiac troponin I, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity C-reactive protein individually or in combination could identify individuals at higher SCD risk in large, free-living populations with and without cardiovascular disease.

Methods: We performed a nested case-control study within 6 prospective cohort studies using 565 SCD cases matched to 1090 controls (1:2) by age, sex, ethnicity, smoking status, and presence of cardiovascular disease.

Results: The median study follow-up time until SCD was 11.3 years. When examined as quartiles or continuous variables in conditional logistic regression models, each of the biomarkers was significantly and independently associated with SCD risk after mutually controlling for cardiac risk factors and other biomarkers. The mutually adjusted odds ratios for the top compared with the bottom quartile were 1.90 (95% CI, 1.30-2.76) for total to high-density lipoprotein cholesterol ratio, 2.59 (95% CI, 1.76-3.83) for high-sensitivity cardiac troponin I, 1.65 (95% CI, 1.12-2.44) for NT-proBNP, and 1.65 (95% CI, 1.13-2.41) for high-sensitivity C-reactive protein. A biomarker score that awarded 1 point when the concentration of any of those 4 biomarkers was in the top quartile (score range, 0-4) was strongly associated with SCD, with an adjusted odds ratio of 1.56 (95% CI, 1.37-1.77) per 1-unit increase in the score.

Conclusions: Widely available measures of lipids, subclinical myocardial injury, myocardial strain, and vascular inflammation show significant independent associations with SCD risk in apparently low-risk populations. In combination, these measures may have utility to identify individuals at risk for SCD.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995996PMC
September 2020

The electrocardiogram and sudden death: capturing electrical physiology and arrhythmic substrate.

Eur Heart J 2020 08;41(30):2911-2912

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1093/eurheartj/ehaa472DOI Listing
August 2020

Guidance for rebooting electrophysiology through the COVID-19 pandemic from the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology: Endorsed by the American College of Cardiology.

Heart Rhythm 2020 Sep 12;17(9):e242-e254. Epub 2020 Jun 12.

Cooper Medical School of Rowan University, Camden, New Jersey.

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.
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http://dx.doi.org/10.1016/j.hrthm.2020.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291964PMC
September 2020

Canakinumab After Electrical Cardioversion in Patients With Persistent Atrial Fibrillation: A Pilot Randomized Trial.

Circ Arrhythm Electrophysiol 2020 07 14;13(7):e008197. Epub 2020 Jun 14.

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Canada (D.C.).

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http://dx.doi.org/10.1161/CIRCEP.119.008197DOI Listing
July 2020
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