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Ciccarone Center Research

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Arrhythmias

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
By: Arking DE, Pulit SL, Crotti L, van der Harst P, Munroe PB, Koopmann TT, Sotoodehnia N, Rossin EJ, Morley M, Wang X, Johnson AD, Lundby A, Gudbjartsson DF, Noseworthy PA, Eijgelsheim M, Bradford Y, Tarasov KV, Dörr M, Müller-Nurasyid M, Lahtinen AM, Nolte IM, Smith AV, Bis JC, Isaacs A, Newhouse SJ, Evans DS, Post WS, et al.
This integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, long-QT syndrome, and sudden cardiac death.
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Comparison of the relation between left ventricular anatomy and QRS duration in patients with cardiomyopathy with versus without left bundle branch block.
By: Chan DD, Wu KC, Loring Z, Galeotti L, Gerstenblith G, Tomaselli G, Weiss RG, Wagner GS, Strauss DG.
Increasing left ventricular (LV) anatomical measurements were associated with increasing QRS duration in patients with cardiomyopathy.
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Prevalence and prognostic significance of exercise-induced non-sustained ventricular tachycardia in asymptomatic volunteers: The Baltimore Longitudinal Study of Aging.
By: Marine JE, Shetty V, Chow GV, Wright J, Gerstenblith G, Najjar SS, Lakatta EG, Fleg JL.
This longitudinal cohort analysis suggests that brief asymptomatic runs of exercise-induced non-sustained ventricular tachycardia, in the absence of clinical heart disease, are not uncommon in men, older adults, and those with hypertension, but are not associated with increased mortality after adjusting for baseline risk factors. These findings do not necessarily apply to patients with known structural heart disease.
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Left ventricular mechanical dyssynchrony by cardiac magnetic resonance is greater in patients with strict vs. nonstrict electrocardiogram criteria for left bundle-branch block.
By: Andersson LG, Wu KC, Wieslander B, Loring Z, Frank TF, Maynard C, Gerstenblith G, Tomaselli GF, Weiss RG, Wagner GS, Ugander M, Strauss DG.
This study found there was no significant difference between patients with nonstrict left bundle-branch block and non-left bundle-branch block. The greater observed LV dyssynchrony may explain why patients with strict left bundle-branch block have a better response to cardiac resynchronization therapy.
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Dynamic analysis of cardiac rhythms for discriminating atrial fibrillation from lethal ventricular arrhythmias.
By: DeMazumder D, Lake DE, Cheng A, Moss TJ, Guallar E, Weiss RG, Jones SR, Tomaselli GF, Moorman JR.

Implantable cardioverter-defibrillators (ICDs), the first line of therapy for preventing sudden cardiac death in high-risk patients, deliver appropriate shocks for termination of ventricular tachycardia (VT)/ventricular fibrillation. A common shortcoming of ICDs is imperfect rhythm discrimination, resulting in the delivery of inappropriate shocks for atrial fibrillation (AF). An underexplored area for rhythm discrimination is the difference in dynamic properties between AF and VT/ventricular fibrillation. We hypothesized that the higher entropy of rapid cardiac rhythms preceding ICD shocks distinguishes AF from VT/ventricular fibrillation. This new strategy for AF discrimination based on entropy estimation expands on simpler concepts of variability, performs well at fast heart rates, and has potential for broad clinical application.

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Thyroid hormones and electrocardiographic parameters: findings from the third national health and nutrition examination survey.
By: Zhang Y, Post WS, Cheng A, Blasco-Colmenares E, Tomaselli GF, Guallar E.
Variation in thyroid hormone levels in the general population, even within the normal range, was associated with various changes in electrocardiograms.
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Genome-wide association study of cardiac structure and systolic function in African Americans: the Candidate Gene Association Resource (CARe) study.
By: Fox ER, Musani SK, Barbalic M, Lin H, Yu B, Ogunyankin KO, Smith NL, Kutlar A, Glazer NL, Post WS, et al.
In the largest genome-wide association study of cardiac structure and function to date in African-Americans, researchers identified 4 genetic loci related to left ventricular mass, interventricular septal wall thickness, left ventricular internal diastolic diameter, and ejection fraction, which reached genome-wide significance.
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Associations between NOS1AP single nucleotide polymorphisms (SNPs) and QT interval duration in four racial/ethnic grops in the Multi-Ethnic Study of Atherosclerosis (MESA).
By: Shah SA, Herrington DM, Howard TD, Divers J, Arnett DK, Burke GL, Kao WH, Guo X, Siscovick DS, Chakravarti A, Lima JA, Psaty BM, Tomaselli GF, Rich SS, Bowden DW, Post W.

QT is a risk factor for sudden cardiac death. This study used the Multi-Ethnic Study of Atherosclerosis to examine association of QT with NOS1AP variants in an ethnically diverse cohort.

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Impact of ancestry and common genetic variants on QT interval in African Americans.
By: Smith JG, Avery CL, Evans DS, Nalls MA, Meng YA, Smith EN, Palmer C, Tanaka T, Mehra R, Butler AM, Young T, Buxbaum SG, Kerr KF, Berenson GS, Schnabel RB, Li G, Ellinor PT, Magnani JW, Chen W, Bis JC, Curb JD, Hsueh WC, Rotter JI, Liu Y, Newman AB, Limacher MC, North KE, Reiner AP, Quibrera PM, Schork NJ, Singleton AB, Psaty BM, Soliman EZ, Solomon AJ, Srinivasan SR, Alonso A, Wallace R, Redline S, Zhang ZM, Post WS, Zonderman AB, Taylor HA, Murray SS, Ferrucci L, Arking DE, Newton-Cheh C, et al.; CARe and COGENT consortia.
This study tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia. However, no difference in duration of cardiac repolarization with global genetic indices of African-American ancestry was noted.
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Electrocardiographic and clinical predictors separating atherosclerotic sudden cardiac death from incident coronary heart disease.
By: Soliman EZ, Prineas RJ, Case LD, Russell G, Rosamond W, Rea T, Sotoodehnia N, Post WS, Siscovick D, Psaty BM, Burke GL.
Sudden cardiac death and coronary heart disease have many risk factors in common, including hypertension, race/ethnicity, BMI, and heart rate, that have the potential to separate between the risks of both diseases. These results need to be validated in another cohort.
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