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Article ; Online: Detection of Previously Unrecognized (Subclinical) Atrial Fibrillation.

Kochav, Stephanie M / Reiffel, James A

2020 Volume 127, Page(s) 169–175

Abstract: Atrial fibrillation (AF) has been associated with increased morbidity and mortality, even when symptoms are absent and the arrhythmia is unrecognized (e.g., subclinical AF [SCAF]). Despite substantial evidence demonstrating an association between AF and ... ...

Abstract	Atrial fibrillation (AF) has been associated with increased morbidity and mortality, even when symptoms are absent and the arrhythmia is unrecognized (e.g., subclinical AF [SCAF]). Despite substantial evidence demonstrating an association between AF and adverse outcomes, the role of mass screening for previously unrecognized SCAF, such that its individual and population risks may be reduced by prophylactic therapy, remains uncertain. Many AF screening strategies exist, from pulse palpation and single-use devices to implanted cardiac monitors; however, existing guidelines are insufficient in specifying who to screen and for how long. In general, higher age, more (and more severe) comorbidities, and longer monitoring periods are associated with greater detection of SCAF. Herein we review the significance of previously unrecognized SCAF and current status of SCAF detection methods. We then propose a clinical approach to help clinicians incorporate AF screening into their practice. In conclusion, we report that SCAF may not be rare, that inserted cardiac monitors have the highest yield of SCAF detection, that clinical concern regarding SCAF is appropriate, but that evidence for therapy mandates is still being collected.
MeSH term(s)	Asymptomatic Diseases/epidemiology ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/epidemiology ; Electrocardiography/methods ; Humans ; Mass Screening/methods ; Risk Factors
Language	English
Publishing date	2020-04-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2020.04.013
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Article ; Online: A Peak into the Pace of Cardiac Amyloidosis.

Kochav, Stephanie M / Dizon, Jose' / Maurer, Mathew S

JACC. Clinical electrophysiology

2020 Volume 6, Issue 9, Page(s) 1155–1157

MeSH term(s)	Amyloidosis ; Cardiac Pacing, Artificial ; Electronics ; Humans
Language	English
Publishing date	2020-09-22
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2846739-5
ISSN	2405-5018 ; 2405-500X ; 2405-500X
ISSN (online)	2405-5018 ; 2405-500X
ISSN	2405-500X
DOI	10.1016/j.jacep.2020.05.027
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Article ; Online: Cardiac Sympathetic Denervation for the Management of Ventricular Arrhythmias.

Kochav, Stephanie M / Garan, Hasan / Gorenstein, Lyall A / Wan, Elaine Y / Yarmohammadi, Hirad

Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing

2022 Volume 65, Issue 3, Page(s) 813–826

Abstract: Background: The autonomic nervous system contributes to the pathogenesis of ventricular arrhythmias (VA). Though anti-arrhythmic drug therapy and catheter ablation are the mainstay of management of VAs, success may be limited in patients with more ... ...

Abstract	Background: The autonomic nervous system contributes to the pathogenesis of ventricular arrhythmias (VA). Though anti-arrhythmic drug therapy and catheter ablation are the mainstay of management of VAs, success may be limited in patients with more refractory arrhythmias. Sympathetic modulation is increasingly recognized as a valuable adjunct tool for managing VAs in patients with structural heart disease and inherited arrhythmias. Results: In this review, we explore the role of the sympathetic nervous system and rationale for cardiac sympathetic denervation (CSD) in VAs and provide a disease-focused review of the utility of CSD for patients both with and without structural heart disease. Conclusions: We conclude that CSD is a reasonable therapeutic option for patients with VA, both with and without structural heart disease. Though not curative, many studies have demonstrated a significant reduction in the burden of VAs for the majority of patients undergoing the procedure. However, in patients with unilateral CSD and subsequent VA recurrence, complete bilateral CSD may provide long-lasting reprieve from VA.
MeSH term(s)	Humans ; Heart Diseases ; Arrhythmias, Cardiac ; Denervation
Language	English
Publishing date	2022-04-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1329179-8
ISSN	1572-8595 ; 1383-875X
ISSN (online)	1572-8595
ISSN	1383-875X
DOI	10.1007/s10840-022-01211-2
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Zs.A 5214: Show issues

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Article ; Online: Tafamidis and Incidence of Atrial Fibrillation in Transthyretin Amyloid Cardiomyopathy.

Girvin, Zachary P / Sweat, Austin O / Kochav, Stephanie M / Maurer, Mathew S / Dizon, Jose / Wan, Elaine Y / Biviano, Angelo / Garan, Hasan / Yarmohammadi, Hirad

JACC. Clinical electrophysiology

2023 Volume 9, Issue 4, Page(s) 586–587

MeSH term(s)	Humans ; Prealbumin/genetics ; Atrial Fibrillation/drug therapy ; Atrial Fibrillation/epidemiology ; Incidence ; Cardiomyopathies/epidemiology
Chemical Substances	tafamidis (8FG9H9D31J) ; Prealbumin
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural
ZDB-ID	2846739-5
ISSN	2405-5018 ; 2405-500X ; 2405-500X
ISSN (online)	2405-5018 ; 2405-500X
ISSN	2405-500X
DOI	10.1016/j.jacep.2022.11.005
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Article ; Online: Effect of Ventricular Pacing on Morbidity in Adults After Fontan Repair.

Kochav, Jonathan D / Rosenbaum, Marlon / Kochav, Stephanie M / Slater, Emily / Wassercug-Zemer, Noa / Lewis, Matthew J

The American journal of cardiology

2020 Volume 125, Issue 8, Page(s) 1263–1269

Abstract: Implantation of a permanent pacemaker is a negative prognostic marker in patients with Fontan palliation; however, data delineating outcomes in adult patients with pacemaker requirements are lacking. We hypothesize that high ventricular pacing burden is ... ...

Abstract	Implantation of a permanent pacemaker is a negative prognostic marker in patients with Fontan palliation; however, data delineating outcomes in adult patients with pacemaker requirements are lacking. We hypothesize that high ventricular pacing burden is associated with adverse outcomes in adult Fontan patients. We performed a retrospective review comprising adult patients with history of Fontan repair. A high burden of ventricular pacing was defined as ≥40% pacing. Major adverse clinical events (MACE) were defined as all-cause mortality or need for advanced cardiac therapies (ventricular assist device or heart transplant). A total of 145 adult patients with Fontan were studied for a median of 3.1 years. Twenty (14%) patients had implanted pacemakers with ≥40% ventricular pacing. Twelve events occurred in those with ≥40% ventricular pacing (incidence 60.0%) versus 11 in those without (incidence 8.8%). In multivariable analysis, ≥40% ventricular-pacing (odds ratio 12.51, confidence interval [CI] 3.56 to 43.83, p <0.001) was associated with MACE independent of initial Fontan type, New York Heart Association functional class at baseline, or history of atrial tachyarrythmia. In survival analysis, patients with ≥40% ventricular pacing had nearly 8 times the risk of MACE compared with those with a lower ventricular pacing burden (hazard ratio 7.79, 95% CI 2.56 to 23.66, p <0.001), whereas patients with atrial-only or <40% ventricular pacing burden had a trend toward higher hazard of MACE compared with those without permanent pacemaker (hazard ratio 3.38, 95% CI 0.92 to 12.47, p = 0.07) that did not meet statistical significance. These findings suggest that high ventricular pacing burden contributes to poor outcomes in the adult Fontan patients and bear consideration when determining optimal treatment of tachyarrhythmias in this population.
MeSH term(s)	Adult ; Cardiac Pacing, Artificial/statistics & numerical data ; Female ; Fontan Procedure ; Heart Block/physiopathology ; Heart Block/therapy ; Heart Defects, Congenital/surgery ; Heart Septal Defects/surgery ; Heart Transplantation/statistics & numerical data ; Heart-Assist Devices/statistics & numerical data ; Humans ; Hypoplastic Left Heart Syndrome/surgery ; Male ; Mortality ; Odds Ratio ; Pacemaker, Artificial ; Postoperative Complications/physiopathology ; Postoperative Complications/therapy ; Proportional Hazards Models ; Retrospective Studies ; Sick Sinus Syndrome/physiopathology ; Sick Sinus Syndrome/therapy ; Tricuspid Atresia/surgery ; Young Adult
Language	English
Publishing date	2020-02-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2020.01.026
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Article ; Online: Application of Proteomics Profiling for Biomarker Discovery in Hypertrophic Cardiomyopathy.

Shimada, Yuichi J / Hasegawa, Kohei / Kochav, Stephanie M / Mohajer, Pouya / Jung, Jeeyoun / Maurer, Mathew S / Reilly, Muredach P / Fifer, Michael A

Journal of cardiovascular translational research

2019 Volume 12, Issue 6, Page(s) 569–579

Abstract: High-throughput proteomics profiling has never been applied to discover biomarkers in patients with hypertrophic cardiomyopathy (HCM). The objective was to identify plasma protein biomarkers that can distinguish HCM from controls. We performed a case- ... ...

Abstract	High-throughput proteomics profiling has never been applied to discover biomarkers in patients with hypertrophic cardiomyopathy (HCM). The objective was to identify plasma protein biomarkers that can distinguish HCM from controls. We performed a case-control study of patients with HCM (n = 15) and controls (n = 22). We carried out plasma proteomics profiling of 1129 proteins using the SOMAscan assay. We used the sparse partial least squares discriminant analysis to identify 50 most discriminant proteins. We also determined the area under the curve (AUC) of the receiver operating characteristic curve using the Monte Carlo cross validation with balanced subsampling. The average AUC was 0.94 (95% confidence interval, 0.82-1.00) and the discriminative accuracy was 89%. In HCM, 13 out of the 50 proteins correlated with troponin I and 12 with New York Heart Association class. Proteomics profiling can be used to elucidate protein biomarkers that distinguish HCM from controls.
MeSH term(s)	Aged ; Biomarkers/blood ; Blood Proteins/analysis ; Cardiomyopathy, Hypertrophic/blood ; Cardiomyopathy, Hypertrophic/diagnosis ; Case-Control Studies ; Female ; High-Throughput Screening Assays ; Humans ; Least-Squares Analysis ; Male ; Middle Aged ; Predictive Value of Tests ; Protein Interaction Maps ; Proteomics
Chemical Substances	Biomarkers ; Blood Proteins
Language	English
Publishing date	2019-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2422411-X
ISSN	1937-5395 ; 1937-5387
ISSN (online)	1937-5395
ISSN	1937-5387
DOI	10.1007/s12265-019-09896-z
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Article ; Online: Cardiac Arrhythmias in COVID-19 Infection.

Kochav, Stephanie M / Coromilas, Ellie / Nalbandian, Ani / Ranard, Lauren S / Gupta, Aakriti / Chung, Mina K / Gopinathannair, Rakesh / Biviano, Angelo B / Garan, Hasan / Wan, Elaine Y

Circulation. Arrhythmia and electrophysiology

2020 Volume 13, Issue 6, Page(s) e008719

MeSH term(s)	Aged ; Arrhythmias, Cardiac/diagnosis ; Arrhythmias, Cardiac/etiology ; Arrhythmias, Cardiac/physiopathology ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/diagnosis ; Electrocardiography ; Fatal Outcome ; Female ; Follow-Up Studies ; Heart Rate/physiology ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnosis ; Radiography, Thoracic ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2426129-4
ISSN	1941-3084 ; 1941-3149
ISSN (online)	1941-3084
ISSN	1941-3149
DOI	10.1161/CIRCEP.120.008719
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Article ; Online: Predicting the development of adverse cardiac events in patients with hypertrophic cardiomyopathy using machine learning.

Kochav, Stephanie M / Raita, Yoshihiko / Fifer, Michael A / Takayama, Hiroo / Ginns, Jonathan / Maurer, Mathew S / Reilly, Muredach P / Hasegawa, Kohei / Shimada, Yuichi J

International journal of cardiology

2020 Volume 327, Page(s) 117–124

Abstract: Background: Only a subset of patients with hypertrophic cardiomyopathy (HCM) develop adverse cardiac events - e.g., end-stage heart failure, cardiovascular death. Current risk stratification methods are imperfect, limiting identification of high-risk ... ...

Abstract	Background: Only a subset of patients with hypertrophic cardiomyopathy (HCM) develop adverse cardiac events - e.g., end-stage heart failure, cardiovascular death. Current risk stratification methods are imperfect, limiting identification of high-risk patients with HCM. Our aim was to improve the prediction of adverse cardiac events in patients with HCM using machine learning methods. Methods: We applied modern machine learning methods to a prospective cohort of adults with HCM. The outcome was a composite of death due to heart failure, heart transplant, and sudden death. As the reference model, we constructed logistic regression model using known predictors. We determined 20 predictive characteristics based on random forest classification and a priori knowledge, and developed 4 machine learning models. Results Of 183 patients in the cohort, the mean age was 53 (SD = 17) years and 45% were female. During the median follow-up of 2.2 years (interquartile range, 0.6-3.8), 33 subjects (18%) developed an outcome event, the majority of which (85%) was heart transplant. The predictive accuracy of the reference model was 73% (sensitivity 76%, specificity 72%) while that of the machine learning model was 85% (e.g., sensitivity 88%, specificity 84% with elastic net regression). All 4 machine learning models significantly outperformed the reference model - e.g., area under the receiver-operating-characteristic curve 0.79 with the reference model vs. 0.93 with elastic net regression (p < 0.001). Conclusions: Compared with conventional risk stratification, the machine learning models demonstrated a superior ability to predict adverse cardiac events. These modern machine learning methods may enhance identification of high-risk HCM subpopulations.
MeSH term(s)	Adult ; Cardiomyopathy, Hypertrophic/diagnosis ; Cardiomyopathy, Hypertrophic/epidemiology ; Female ; Heart Failure ; Humans ; Machine Learning ; Male ; Middle Aged ; Prospective Studies ; Risk Factors
Language	English
Publishing date	2020-11-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2020.11.003
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Article ; Online: Difference in Metabolomic Response to Exercise between Patients with and without Hypertrophic Cardiomyopathy.

Shimada, Yuichi J / Batra, Jaya / Kochav, Stephanie M / Patel, Parth / Jung, Jeeyoun / Maurer, Mathew S / Hasegawa, Kohei / Reilly, Muredach P / Fifer, Michael A

Journal of cardiovascular translational research

2020 Volume 14, Issue 2, Page(s) 246–255

Abstract: It is unclear how hypertrophic cardiomyopathy (HCM) affects cardiac metabolic pathways at rest and with exercise. This case-control study compared 15 cases with HCM to 2 control groups without HCM. Metabolomic profiling of 210 metabolites was carried out ...

Abstract	It is unclear how hypertrophic cardiomyopathy (HCM) affects cardiac metabolic pathways at rest and with exercise. This case-control study compared 15 cases with HCM to 2 control groups without HCM. Metabolomic profiling of 210 metabolites was carried out at rest and at peak exercise. The 50 most discriminant metabolites differentially regulated during exercise were selected using partial least squares discriminant analysis. Pathway enrichment analysis was also performed. At rest, no significant difference was observed in metabolomic profiling of HCM cases as compared to controls. By contrast, there were significant differences in metabolomic profiling in response to exercise (p < 0.05) in the following metabolic pathways: the aminoacyl-tRNA biosynthesis pathway; the nitrogen metabolism pathway; the glycine, serine, and threonine metabolism pathway; and the arginine and proline metabolism pathway. The present study demonstrates differential regulation of several metabolic pathways in patients with HCM in the setting of exercise stress.
MeSH term(s)	Adult ; Aged ; Biomarkers/blood ; Cardiomyopathy, Hypertrophic/blood ; Cardiomyopathy, Hypertrophic/diagnosis ; Cardiomyopathy, Hypertrophic/physiopathology ; Case-Control Studies ; Exercise ; Exercise Test ; Female ; Humans ; Male ; Metabolome ; Metabolomics ; Middle Aged ; Predictive Value of Tests
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-06-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2422411-X
ISSN	1937-5395 ; 1937-5387
ISSN (online)	1937-5395
ISSN	1937-5387
DOI	10.1007/s12265-020-10051-2
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Article ; Online: Evidence-Based Assessment of Congenital Heart Disease Genes to Enable Returning Results in a Genomic Study.

Griffin, Emily L / Nees, Shannon N / Morton, Sarah U / Wynn, Julia / Patel, Nihir / Jobanputra, Vaidehi / Robinson, Scott / Kochav, Stephanie M / Tao, Alice / Andrews, Carli / Cross, Nancy / Geva, Judith / Lanzilotta, Kristen / Ritter, Alyssa / Taillie, Eileen / Thompson, Alexandra / Meyer, Chris / Akers, Rachel / King, Eileen C /

Cnota, James F / Kim, Richard W / Porter, George A / Brueckner, Martina / Seidman, Christine E / Shen, Yufeng / Gelb, Bruce D / Goldmuntz, Elizabeth / Newburger, Jane W / Roberts, Amy E / Chung, Wendy K

Circulation. Genomic and precision medicine

2023 Volume 16, Issue 2, Page(s) e003791

Abstract: Background: Congenital heart disease (CHD) is the most common major congenital anomaly and causes significant morbidity and mortality. Epidemiologic evidence supports a role of genetics in the development of CHD. Genetic diagnoses can inform prognosis ... ...

Abstract	Background: Congenital heart disease (CHD) is the most common major congenital anomaly and causes significant morbidity and mortality. Epidemiologic evidence supports a role of genetics in the development of CHD. Genetic diagnoses can inform prognosis and clinical management. However, genetic testing is not standardized among individuals with CHD. We sought to develop a list of validated CHD genes using established methods and to evaluate the process of returning genetic results to research participants in a large genomic study. Methods: Two-hundred ninety-five candidate CHD genes were evaluated using a ClinGen framework. Sequence and copy number variants involving genes in the CHD gene list were analyzed in Pediatric Cardiac Genomics Consortium participants. Pathogenic/likely pathogenic results were confirmed on a new sample in a clinical laboratory improvement amendments-certified laboratory and disclosed to eligible participants. Adult probands and parents of probands who received results were asked to complete a post-disclosure survey. Results: A total of 99 genes had a strong or definitive clinical validity classification. Diagnostic yields for copy number variants and exome sequencing were 1.8% and 3.8%, respectively. Thirty-one probands completed clinical laboratory improvement amendments-confirmation and received results. Participants who completed postdisclosure surveys reported high personal utility and no decision regret after receiving genetic results. Conclusions: The application of ClinGen criteria to CHD candidate genes yielded a list that can be used to interpret clinical genetic testing for CHD. Applying this gene list to one of the largest research cohorts of CHD participants provides a lower bound for the yield of genetic testing in CHD.
MeSH term(s)	Adult ; Child ; Humans ; Heart Defects, Congenital/diagnosis ; Heart Defects, Congenital/genetics ; Genetic Testing ; Heart ; Genomics ; DNA Copy Number Variations
Language	English
Publishing date	2023-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2574-8300
ISSN (online)	2574-8300
DOI	10.1161/CIRCGEN.122.003791
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