Entropy of cardiac repolarization predicts ventricular arrhythmias and mortality in patients receiving an implantable cardioverter-defibrillator for primary prevention of sudden death

DeMazumder, Deeptankar; Limpitikul, Worawan B.; Dorante, Miguel I.; Dey, Soumen; Mukhopadhyay, Bhasha; Zhang, Yiyi; Moorman, J. Randall; Cheng, Alan; Berger, Ronald D.; Güallar, Eliseo; Jones, Steven R.; Tomaselli, Gordon F.

doi:10.1093/europace/euv399

Cited by 15 publications

(18 citation statements)

References 34 publications

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“…Table 1 shows the univariate and multivariate predictors in a Cox proportional hazards model. In the univariate models (2nd thru 4th columns), heart rate, standard deviation of heart rate, and COSEn all failed to reach statistical significance affirming our previous assertion that COSEn has its main value in atrial fibrillation detection from short segments 10 , 16 rather than as a predictor of mortality. In the univariate model, PIP (chosen to represent all other heart rate fragmentation measures) demonstrated a highly significant ability to predict mortality (p = 1.71E-16).…”

Section: Hr Fragmentation Metrics Are Associated With Survivalsupporting

confidence: 64%

Heart rate fragmentation gives novel insights into non-autonomic mechanisms governing beat-to-beat control of the heart’s rhythm

Lensen

Monfredi

Andris

et al. 2020

JRSM Cardiovascular Disease

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Objectives To demonstrate how heart rate fragmentation gives novel insights into non-autonomic mechanisms of beat-to-beat variability in cycle length, and predicts survival of cardiology clinic patients, over and above traditional clinical risk factors and measures of heart rate variability. Approach: We studied 2893 patients seen by cardiologists with clinical data including 24-hour Holter monitoring. Novel measures of heart rate fragmentation alongside canonical time and frequency domain measures of heart rate variability, as well as an existing local dynamics score were calculated. A proportional hazards model was utilized to relate the results to survival. Main results: The novel heart rate fragmentation measures were validated and characterized with respect to the effects of age, ectopy and atrial fibrillation. Correlations between parameters were determined. Critically, heart rate fragmentation results could not be accounted for by undersampling respiratory sinus arrhythmia. Increased heart rate fragmentation was associated with poorer survival (p ≪ 0.01 in the univariate model). In multivariable analyses, increased heart rate fragmentation and more abnormal local dynamics (p 0.045), along with increased clinical risk factors (age (p ≪ 0.01), tobacco use (p ≪ 0.01) and history of heart failure (p 0.019)) and lower low- to high-frequency ratio (p 0.022) were all independent predictors of 2-year mortality. Significance: Analysis of continuous ECG data with heart rate fragmentation indices yields information regarding non-autonomic control of beat-to-beat variability in cycle length that is independent of and additive to established parameters for investigating heart rate variability, and predicts mortality in concert with measures of local dynamics, frequency content of heart rate, and clinical risk factors.

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Section: Hr Fragmentation Metrics Are Associated With Survivalsupporting

confidence: 64%

Heart rate fragmentation gives novel insights into non-autonomic mechanisms governing beat-to-beat control of the heart’s rhythm

Lensen

Monfredi

Andris

et al. 2020

JRSM Cardiovascular Disease

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“…MitoTEMPO treatment of the ACi animals reduced the dispersion of repolarization (Fig. 5D), as indexed by the QTVI 32, 33 , in parallel with the elimination of SCD.…”

Section: Resultsmentioning

confidence: 85%

Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure

Dey

DeMazumder

Sidor

et al. 2018

Circulation Research

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198

159

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mROS drive both acute emergent events, such as electrical instability responsible for SCD, and those that mediate chronic HF remodeling, characterized by suppression or altered phosphorylation of metabolic, antioxidant, and ion transport protein networks. In vivo reduction of mROS prevents and reverses electrical instability, SCD, and HF. Our findings support the feasibility of targeting the mitochondria as a potential new therapy for HF and SCD while identifying new mROS-sensitive protein modifications.

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“…For example, in a cohort of forty-seven patients with decreased left ventricular function with implantable cardioverter defibrillators, increases in approximate entropy of the interval between the peak of the R-wave and peak of the T-wave, were independently associated with appropriate ICD shocks and mortality ( Perkiomaki et al., 2003 ). More recently, entropy of QT intervals was reported to predict the occurrence of ventricular arrhythmias and mortality in patients who have received implantable cardioverter-defibrillator for primary prevention of sudden death ( DeMazumder et al., 2016 ). Early detection of ventricular arrhythmias well before the actual event is the biggest challenge in cardiology.…”

Section: Discussionmentioning

confidence: 99%

Measures of repolarization variability predict ventricular arrhythmogenesis in heptanol-treated Langendorff-perfused mouse hearts

Tse¹,

Hao²,

Lee³

et al. 2021

Current Research in Physiology

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Background Time-domain and non-linear methods can be used to quantify beat-to-beat repolarization variability but whether measures of repolarization variability can predict ventricular arrhythmogenesis in mice have never been explored. Methods Left ventricular monophasic action potentials (MAPs) were recorded during constant right ventricular 8 Hz pacing in Langendorff-perfused mouse hearts, in the presence or absence of the gap junction and sodium channel inhibitor heptanol (0.1, 0.5, 1 or 2 mM). Results Under control conditions, mean action potential duration (APD) was 39.4 ± 8.1 ms. Standard deviation (SD) of APDs was 0.3 ± 0.2 ms, coefficient of variation was 0.9 ± 0.8% and the root mean square (RMS) of successive differences in APDs was 0.15 ± 0.14 ms. Poincaré plots of APD n+1 against APD n revealed ellipsoid morphologies with a SD along the line-of-identity (SD2) to SD perpendicular to the line-of-identity (SD1) ratio of 4.6 ± 2.1. Approximate and sample entropy were 0.61 ± 0.12 and 0.76 ± 0.26, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.49 ± 0.27 and 0.81 ± 0.36, respectively. Heptanol at 2 mM induced ventricular tachycardia in five out of six hearts. None of the above parameters were altered by heptanol during which reproducible electrical activity was observed (KW-ANOVA, P > 0.05). Contrastingly, SD2/SD1 decreased to 2.03 ± 0.41, approximate and sample entropy increased to 0.82 ± 0.12 and 1.45 ± 0.34, and short-term fluctuation slope decreased to 0.82 ± 0.19 during the 20-s period preceding spontaneous ventricular tachy-arrhythmias (n = 6, KW-ANOVA, P < 0.05). Conclusion Measures of repolarization variability, such as SD2/SD1, entropy, and fluctuation slope are altered preceding the occurrence of ventricular arrhythmogenesis in mouse hearts. Changes in these variables may allow detection of impending arrhythmias for early intervention.

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Entropy of cardiac repolarization predicts ventricular arrhythmias and mortality in patients receiving an implantable cardioverter-defibrillator for primary prevention of sudden death

Abstract: EntropyX measured during ICD implantation strongly and independently predicts appropriate shock and all-cause mortality over follow-up. EntropyX complements conventional risk predictors and has the potential for broad clinical application.

Cited by 15 publications

References 34 publications

Heart rate fragmentation gives novel insights into non-autonomic mechanisms governing beat-to-beat control of the heart’s rhythm

Heart rate fragmentation gives novel insights into non-autonomic mechanisms governing beat-to-beat control of the heart’s rhythm

Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure

Measures of repolarization variability predict ventricular arrhythmogenesis in heptanol-treated Langendorff-perfused mouse hearts

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