QT Variability Index Research Articles

Effect of body fat on temporal dispersion of ventricular repolarization duration assessed by QT variability index in healthy females.

To assess the impact of age as well general and central adiposity indices on QT variability index. The cross-sectional study was conducted at the Department of Physiology, College of Medicine, Mustansiriyah University, Baghdad, Iraq, from September 2020 to April 2021, and comprised healthy adult females having regular menstrual cycle. QT variability index and its association with age, body mass index, waist circumference and waist-height ratio were worked out. Data was analysed using SPSS 14. There were 55 women with mean age 37.4±10.5 years. QT variability index correlated significantly and positively with age, body mass index, waist circumference and waist-height ratio (p<0.05). Aging and obesity increased QT variability index, and could contribute to ventricular arrhythmia and sudden cardiac death.

Investigating the correlation of the second derivative of digital pulse wave (DPW) with QT variability index in women.

To determine the correlation between the second derivative of digital pulse wave and the QT variability index. The cross-sectional study was conducted from October 2021 to May 2022 at the Department of Physiology, College of Medicine, University of Mustansiriyah, Baghdad, Iraq, and comprised healthy women. Samples were raised by simple random technique. Digital pulse waves were captured using a fingertip pulse wave transducer. Lab Chart Pro version 7.2 was used to automatically detect and quantify the amplitude of A, B, C, D and E waves expressed by the second derivative. QT interval of each beat was recorded by electrocardiogram, and was calculated automatically via Lab chart Pro version 7.2 without averaging. Data was spread out on Microsoft Office Excel 2013 and analysed using SPSS version 26. There were 55 women with mean age 37.4±9.9 years and mean body mass index 31.2±7.2kg/m2. Age was positively associated with QT variability index and normalised wave amplitude values of B/A and (B-C-D-E)/A (p<0.05).QT variability index was positively associated with the normalised values of the second derivative of digital pulse wave B/A and (B-C-D-E)/A (p<0.05). QT variability index I was significantly correlated with second derivative of photoplethysmogram, and both were affected by age and arterial stiffness.

Sleep-disordered breathing destabilizes ventricular repolarization: Cross-sectional, longitudinal, and experimental evidence

BackgroundSleep-disordered breathing (SDB) increases the risk of cardiac arrhythmias and sudden cardiac death. ObjectiveThis study sought to characterize the associations between SDB, intermittent hypoxemia, and the beat-to-beat QT variability index (QTVI), a measure of ventricular repolarization lability associated with cardiac arrhythmias and sudden cardiac death. MethodsThree distinct cohorts were used: a matched sample of 122 participants with and without severe SDB for cross-sectional analysis; a matched sample of 52 participants with and without incident SDB for longitudinal analysis; and a sample of 19 healthy adults exposed to acute intermittent hypoxia and ambient air on 2 separate days. The cross-sectional and longitudinal cohorts were the Sleep Heart Health Study participants with no known comorbidities who were not taking any drugs known to affect cardiac repolarization and satisfied the inclusion criteria. Electrocardiographic measures were calculated from 1-lead electrocardiograms. ResultsParticipants with severe SDB had greater QTVI than those without SDB (P = .027). Total sleep time with <90% oxygen saturation, but not the arousal frequency, was a predictor of QTVI. QTVI during sleep was predictive of all-cause mortality. With incident SDB, mean QTVI increased from −1.23 to −0.86 during 5 years (P = .017). Finally, experimental exposure of healthy adults to acute intermittent hypoxia for 4 hours progressively increased QTVI (P = .016). ConclusionThe results show that both prevalent SDB and incident SDB are associated with ventricular repolarization instability and suggest intermittent hypoxemia as the underlying mechanism that may contribute to increased mortality in SDB.

Beat-to-beat cardiac repolarization lability increases during hypoxemia and arousals in obstructive sleep apnea patients.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI), were calculated before, during, and after 20,955 desaturations from lead II electrocardiography signals of 492 patients with suspected OSA (52% men). Variations in repolarization parameters were assessed during and after desaturations, both with and without accompanying arousals, and groupwise comparisons were performed based on desaturation duration and depth. Regression analyses were used to investigate the influence of confounding factors, comorbidities, and medications. The standard deviation (SD) of QT, mean QTc, SDQTc, and STVQT increased significantly (P < 0.01), whereas QTVI decreased (P < 0.01) during and after desaturations. The changes in SDQT, mean QTc, SDQTc, and QTVI were significantly amplified (P < 0.01) in the presence of accompanying arousals. Desaturation depth was an independent predictor of increased SDQTc (β = 0.405, P < 0.01), STVQT (β = 0.151, P < 0.01), and QTVI (β = 0.009, P < 0.01) during desaturation. Desaturations cause acute changes in ventricular repolarization, with deeper desaturations and accompanying arousals independently contributing to increased ventricular repolarization lability. This may partially explain the increased risk of arrhythmias and SCD in patients with OSA, especially when the OSA phenotype includes high hypoxic load and fragmented sleep.NEW & NOTEWORTHY Nocturnal desaturations are associated with increased ventricular repolarization lability. Deeper desaturations with accompanying arousals increase the magnitude of alterations, independent of confounding factors, comorbidities, and medications. Changes associated with desaturations can partially explain the increased risk of arrhythmias and sudden cardiac death in patients with OSA, especially in patients with high hypoxic load and fragmented sleep. This highlights the importance of detailed electrocardiogram analytics for patients with OSA.

Assessment of the human response to acute mental stress-An overview and a multimodal study.

Numerous vital signs are reported in association with stress response assessment, but their application varies widely. This work provides an overview over methods for stress induction and strain assessment, and presents a multimodal experimental study to identify the most important vital signs for effective assessment of the response to acute mental stress. We induced acute mental stress in 65 healthy participants with the Mannheim Multicomponent Stress Test and acquired self-assessment measures (Likert scale, Self-Assessment Manikin), salivary α-amylase and cortisol concentrations as well as 60 vital signs from biosignals, such as heart rate variability parameters, QT variability parameters, skin conductance level, and breath rate. By means of statistical testing and a self-optimizing logistic regression, we identified the most important biosignal vital signs. Fifteen biosignal vital signs related to ventricular repolarization variability, blood pressure, skin conductance, and respiration showed significant results. The logistic regression converged with QT variability index, left ventricular work index, earlobe pulse arrival time, skin conductance level, rise time and number of skin conductance responses, breath rate, and breath rate variability (F1 = 0.82). Self-assessment measures indicated successful stress induction. α-amylase and cortisol showed effect sizes of -0.78 and 0.55, respectively. In summary, the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system were successfully activated. Our findings facilitate a coherent and integrative understanding of the assessment of the stress response and help to align applications and future research concerning acute mental stress.

Time and Frequency Repolarization Domains in Elderly Candidates to Transcatheter Aortic Valve Replacement.

Aortic valve stenosis (AVS) is a well-known risk factor for sudden cardiac death. Therefore, some non-invasive, electrocardiographic markers are capable to stratify the risk of sudden death at rest and during light mental challenge [mini-mental state examination (MMSE) administration]. We compared short period RR, QT and Te intervals variability in 42 candidates to and 12 age-matched hypertensive control patients at rest and during mental challenge. At rest, AVS patients showed a higher QT standard deviation (sd), QT low frequency power (LF), QT High Frequency (HF), Tpeak-Tend intervals sd (Te sd) and Te HF than the control group. During mental challenge AVS group showed a decrease of RR mean and RR HF, expressed in normalized units (NU), and an increase of RR total power (TP), RR LF, RR LF NU, RR LF, HF ratio (LF/HF). During this same mental test, QT sd, QT LF, QT HF, Te sd, Te LF, Te HF, QT variability index (VI), TeVI, QT normalized variance (VN) were higher in AVS patients than the control group. During mental challenge Te LF (r:0.825, p<0.05) was significantly associated to: serum albumin (β:-0.473, p<0.001), MMSE (β:-0.267, p:0.038), diastolic blood pressure (β:-0.443, p:0.03) and cardiac index (β:-0.303, p:0.029). AVS patients showed temporal dispersion of ventricular repolarization phase, useful maker to individuate high risk patients. MMSE administration induced a sympathetic sinus activation and vagal deactivation in AVS subjects. Frailty and mental function influenced Te HF and Te LF.

Analysis of CACNA1C and KCNH2 Risk Variants on Cardiac Autonomic Function in Patients with Schizophrenia.

Cardiac autonomic dysfunction (CADF) is a major contributor to increased cardiac mortality in schizophrenia patients. The aberrant function of voltage-gated ion channels, which are widely distributed in the brain and heart, may link schizophrenia and CADF. In search of channel-encoding genes that are associated with both CADF and schizophrenia, CACNA1C and KCNH2 are promising candidates. In this study, we tested for associations between genetic findings in both genes and CADF parameters in schizophrenia patients whose heart functions were not influenced by psychopharmaceuticals. First, we searched the literature for single-nucleotide polymorphisms (SNPs) in CACNA1C and KCNH2 that showed genome-wide significant association with schizophrenia. Subsequently, we looked for such robust associations with CADF traits at these loci. A total of 5 CACNA1C SNPs and 9 KCNH2 SNPs were found and genotyped in 77 unmedicated schizophrenia patients and 144 healthy controls. Genotype-related impacts on heart rate (HR) dynamics and QT variability indices (QTvi) were analyzed separately in patients and healthy controls. We observed significantly increased QTvi in unmedicated patients with CADF-associated risk in CACNA1C rs2283274 C and schizophrenia-associated risk in rs2239061 G compared to the non-risk allele in these patients. Moreover, unmedicated patients with previously identified schizophrenia risk alleles in KCNH2 rs11763131 A, rs3807373 A, rs3800779 C, rs748693 G, and 1036145 T showed increased mean HR and QTvi as compared to non-risk alleles. We propose a potential pleiotropic role for common variation in CACNA1C and KCNH2 associated with CADF in schizophrenia patients, independent of antipsychotic medication, that predisposes them to cardiac arrhythmias and premature death.

Abstract 12538: Intermittent Hypoxemia Progressively Destabilizes Ventricular Repolarization in Healthy Awake Subjects

Introduction : Obstructive sleep apnea (OSA) is highly prevalent in the general population. OSA is associated with adverse cardiovascular events, including sudden cardiac death, but the mechanism is unclear. Intermittent hypoxemia, a pathognomonic feature of OSA, could increase the propensity for abnormal ventricular repolarization. We previously found that short-term exposure of awake healthy subjects to recurrent hypoxic episodes increased their heart rate (HR) and HR variability. Hypothesis: Exposure to intermittent hypoxia increases ventricular repolarization instability in awake healthy subjects. Methods: Healthy adults (N = 19) were exposed to either intermittent hypoxia or air for 4 hours on two different days in a randomized order. Intermittent hypoxia was induced with exposure to hypoxic gas (95% N 2 and 5% O 2 ) or ambient air in an alternative fashion at a frequency of ⁓ 25 times/hour, mimicking moderate to severe OSA. Repolarization stability was assessed using the QT variability index (QTVI), a validated predictor of cardiac arrhythmias and mortality. HR and QTVI were measured from one-lead ECG over consecutive 5-min epochs. Paired sample t - test was used to assess statistical associations. Results: Mean oxygen saturation levels were lower during exposure to intermittent hypoxia (90.86 ± 0.19%) versus normoxia (97.37 ± 0.20%, P &lt; 10 -13 ). Electrocardiographic measures at baseline were similar between the two conditions. No changes in these measures were noted during the conditions of normoxia. However, with intermittent hypoxia, mean HR and QTVI steadily increased (HR: 63.31 ± 1.51 initial, 69.21 ± 2.14 final, P &lt; 0.001; QTVI: -1.85 ± 0.04 initial, -1.64 ± 0.07 final, P = 0.016). By the end of the 4-hour experiment, QTVI was greater in hypoxia vs. normoxia (final QTVI in hypoxia: -1.64 ± 0.07, in normoxia: -1.86 ± 0.06, P = 0.021). Conclusion: Four hours of intermittent hypoxia in awake normal healthy subjects progressively destabilized ventricular repolarization. Chronic exposure to recurrent periods of intermittent hypoxemia in OSA can increase ventricular repolarization and contribute to the OSA-associated adverse cardiovascular events, including sudden cardiac death.

Abstract 14306: Development of Sleep-Disordered Breathing Destabilizes Ventricular Repolarization

Introduction: Sleep-disordered breathing (SDB) is a prevalent condition associated with adverse cardiovascular events, including nocturnal arrhythmias and sudden cardiac death, but the underlying mechanism is unclear. Hypothesis: Ventricular repolarization instability increases in those who develop SDB. Methods: For the participants of the Sleep Heart Health Study (SHHS), the percentage of sleep time with oxygen saturation levels &lt; 90% (T90) was measured. We identified participants who did not have SDB (T90 &lt; 0.22% = median of the SHHS cohort) during the initial study but developed SDB (T90 &gt; 10%) by the time of the 5-year follow-up. A comparator group was identified as those who matched the first group on age, sex, BMI, and race but had T90 &lt; 0.22% during both the initial and the follow-up sleep studies. Each group consisted of 25 (8 M and 17 F) participants, none of whom had any diagnosed comorbidities or prescriptions that could affect cardiac repolarization. Heart rate (HR), heart rate variability (SDNN), and QT variability index (QTVI, a measure of ventricular repolarization instability) were calculated from one-lead ECG recordings. Paired sample t- test was used to assess statistical associations. Results: The respiratory disturbance index (RDI) for the study group increased from 2.57 ± 0.74 events/hr at baseline to 14.8 ± 3.72 events/hr at follow-up (P = 0.001), while the RDI was not different for the comparators (3.08 ± 0.71 events/hr at baseline, 3.65 ± 0.68 events/hr at follow-up, P = 0.599). In those who developed SDB, HR and SDNN did not change between baseline and follow-up, but QTVI increased from -1.25 ± 0.15 to -0.85 ± 0.15 (P = 0.013). None of the measured electrocardiographic parameters differed between baseline and follow-up in comparators. Conclusion: Over a five-year follow-up, the development of SDB was associated with an increase in QT variability comparable to symptomatic heart failure. Hypoxemia appears to be the main underlying mechanism.

Abstract 13376: Sleep-Disordered Breathing is Associated With Larger Ventricular Repolarization Instability

Introduction: Sleep-disordered breathing (SDB) is a common disorder in the general population that is associated with adverse cardiovascular events, such as sudden cardiac death, but the underlying mechanisms are unclear. Hypothesis: Ventricular repolarization instability is greater in those with severe SDB than those without SDB, independent of other risk factors. Methods: Among the participants of the Sleep Heart Health Study (SHHS), we identified those with SDB who had no diagnosed cardiovascular disease or other factors that could affect cardiac repolarization. Severe SDB was defined as having a respiratory disturbance index (RDI) &gt; 33 events/hour (top 95%ile of the SHHS cohort). We also identified a group of participants matched to the severe SDB group on age, sex, BMI, and race and had RDI &lt; 1.33 events/hour (bottom 25%ile; without SDB). Each group consisted of 61 (45 M and 16 F) participants. Oxygen saturation levels (SpO 2 ) were used to measure hypoxemia burden as the percentage of sleep time with SpO 2 &lt; 90% (T90). Heart rate (HR), heart rate variability (SDNN), and QT variability index (QTVI, a measure of ventricular repolarization instability) were calculated from one-lead ECG recordings. Student’s t- test was used to assess statistical associations. Results: The SDB group had a larger T90 than those without SDB (11.39 ± 1.42% vs 1.32 ± 0.61%, P &lt; 0.001). Participants with SDB also had greater mean HR (P = 0.028), SDNN (P = 0.017), and QTVI (P = 0.027) than those without SDB. Based on a multivariable linear model that included hypoxemia burden, age, BMI, and smoking status, T90 was the only independent predictor of QTVI (P = 0.022). Conclusion: SDB is associated with higher HR, HRV, and QTVI, an indicator of increased instability in ventricular repolarization leading to increased risk for cardiac arrhythmias and sudden cardiac death. The severity of the destabilizing effect of SDB on ventricular repolarization appears to be modified by hypoxemia burden.

Sleep Arousal-Related Ventricular Repolarization Lability Is Associated With Cardiovascular Mortality in Older Community-Dwelling Men

Sleep is fragmented by brief arousals, and excessive arousal burden has been linked to increased cardiovascular (CV) risk, but mechanisms are poorly understood. Do arousals trigger cardiac ventricular repolarization lability that may predispose people to long-term cardiovascular mortality? This study analyzed 407,541 arousals in the overnight polysomnograms of 2,558 older men in the Osteoporotic Fractures in Men sleep study. QT and RR intervals were measured beat-to-beat starting 15s prior to arousal onset until 15s past onset. Ventricular repolarization lability was quantified by using the QT variability index (QTVi). During 10.1 ± 2.5 years of follow-up, 1,000 men died of any cause, including 348 CV deaths. During arousals, QT and RR variability increased on average by 5 and 55ms, respectively, resulting in a paradoxical transient decrease in QTVi from 0.07 ± 1.68 to -1.00 ± 1.68. Multivariable Cox proportional hazards analysis adjusted for age, BMI, cardiovascular and respiratory risk factors, sleep-disordered breathing and arousal, diabetes, and Parkinson disease indicated that excessive QTVi during arousal was independently associated with all-cause and CV mortality (all-cause hazard ratio, 1.20 [95%CI, 1.04-1.38; P= .012]; CV hazard ratio, 1.29 [95%CI, 1.01 -1.65; P= .043]). Arousals affect ventricular repolarization. A disproportionate increase in QT variability during arousal is associated with an increased all-cause and CV mortality and may reflect ventricular repolarization maladaptation to the arousal stimulus. Whether arousal-related QTVi can be used for more tailored risk stratification warrants further study, including evaluating whether arousal suppression attenuates ventricular repolarization lability and reduces subsequent mortality. ClinicalTrials.gov; No.: NCT00070681; URL: www. gov.

Evaluation of electrocardiographic repolarization parameters in patients with polycystic ovary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Research, Development and Innovation Office Introduction Polycystic ovary syndrome (PCOS) is a multifactorial, endocrine disease associated with metabolic disturbances (e.g. hyperinsulinemia, insulin resistance) and increased cardiovascular risk. Recent data strongly suggest that different QT variability parameters characterizing cardiac repolarization instability represent novel markers in proarrhythmic risk assessment. Purpose In the present study we investigated ECG repolarization parameters, including QT variability parameters in patients with polycystic ovary syndrome. Methods Fifty-five PCOS patients (age: 29±6 years) and 55 age-matched healthy volunteers (age: 29±10 years) were enrolled in the study. Five-minute 12-lead resting electrocardiograms were recorded, the ECGs were digitized and evaluated off-line using the Cardiosys-A01 system (Cardiosys-A01). The following parameters were determined: the frequency corrected QT interval (QTc) using Bazett’s, Fridericia, Framingham and the Hodges formulas; QT dispersion (QTd) and T wave peak-to-end distance (Tpeak-Tend). Among QT variability parameters we analyzed the QT variance (QTv), the QT variability index (QTVI), the short-term beat-to-beat QT and RR interval variability (STV-QT, STV-RR) based on constructed Poincaré plots and the variability ratio (VR). Results The RR interval did not differ significantly in PCOS patients compared to controls (821±129 ms vs. 847±99 ms), however the QT interval (373±30 ms vs. 391±27 ms, p&amp;lt;0.01), the QTc calculated with Bazett’s, Framingham, Fridericia and Hodges correction formulas (QTc Bazett’s: 413±18 ms vs. 426±21 ms, p&amp;lt;0.01) and the Tpeak-Tend intervals were significantly shorter (76±10 ms vs. 83±12 ms, p&amp;lt;0.01). The QTd, QTv, and STV-RR did not differ significantly. However, the VR (0.3±0.4 vs. 0.2±0.2, p&amp;lt;0.05), the QTVI (-0,9±0.5 vs. -1,3±0.4, p&amp;lt;0.001), and importantly, the STV-QT were significantly higher in PCOS patients compared to controls (4.0±0.9 ms vs. 3.2±0.9 ms, p&amp;lt;0.0001). Conclusion Some of the alterations in repolarization parameters and the significant increase in the short-term beat-to-beat QT interval variability and the QT variability index may indicate increased repolarization instability in patients with polycystic ovary syndrome compared to age-matched controls, however, further studies are needed to establish the exact relation of this finding to increased arrhythmia propensity in this population.

Influence of sleep bruxism on QTc interval and QT variability in patients with OSA: A pilot study.

Obstructive sleep apnea (OSA) is associated with increases in QT interval corrected for heart rate (QTc interval) and QT variability index (QTVI) and sleep bruxism (SB) is prevalent in OSA patients. To examine whether QTc interval and QT variability were changed during episodes of rhythmic masticatory muscle activities (RMMAs)/SB in SB patients with and without OSA. The RR and QTc intervals, and QTVI during RMMAs with or without accompanied limb movements (RMMAs/LMs) in 10 normal controls and 10 SB patients without OSA and during apneic and recovery periods of OSA in 10 SB patients with OSA were analysed. In the SB patients without OSA and controls, QTc intervals and QTVI were significantly increased during RMMAs/LMs compared with those during the 10s periods (from 10th to 20th s) before the onset and after the offset of RMMAs/LMs, and significantly increased during RMMAs/LMs with awakenings compared with those with microarousals and no arousals. In addition, QTc interval and QTVI were positively correlated with the duration of RMMAs/LMs. Moreover, in the SB patients with OSA, QTc interval and QTVI during the recovery period of OSA events were significantly longer and higher than those during the apneic period regardless of accompanied RMMAs/LMs, and QTc interval and QTVI during the apneic and recovery periods accompanied with RMMAs/LMs were significantly longer and higher than those without accompanied RMMAs/LMs. OSA and RMMAs/LMs events were associated with longer QTc intervals and higher QTVI, and RMMAs/LMs might contribute to these changes associated with OSA events accompanied with RMMAs/LMs.

Evaluation of Variations of Qt Interval in Hypothyroidism Through Autonomic and Vascular Profiling of Cardiac Function

Background Hypothyroidism increases the risk of cardiac disease as well as autonomic dysfunction (abnormalities of the autonomic nervous system). A prospective case-control study was conducted. The purpose of this study was to compare the QT variability and vascular stiffness of SH patients. Materials and Methods:Using ABI, we compared female SH patients to age- and sex-matched normal controls in order to better understand their condition. HF (0.15–0.4 Hz) and LF (0.003–0.04 Hz) frequencies were investigated spectroscopically. The HF represents vagal regulation, whereas the LF reflects both vagal and limbic regulation. Result In this case research 32 women participated who were 28.02+7.8 years old and 28 women in control group who were age-matched (30.2+ 7.1). Patients had greater QT variability indices (P = 0.01) than healthy controls. Cases showed a higher LF/HF ratio than controls (P = 0.03), which was statistically significant. It was shown that there was a 0.02 point difference in left-right ABI between patients and controls. Conclusion In these circumstances, sympathetic activity predominated over parasympathetic activity, with less of the latter. QTvi may be beneficial in determining the risk of cardiovascular mortality in this particular patient population.

Methadone Destabilizes Cardiac Repolarization During Sleep.

Methadone, a widely prescribed medication for chronic pain and opioid addiction, is associated with respiratory depression and increased predisposition for torsades de pointes, a potentially fatal arrhythmia. Most methadone-related deaths occur during sleep. The objective of this study was to determine whether methadone's arrhythmogenic effects increase during sleep, with a focus on cardiac repolarization instability using QT variability index (QTVI), a measure shown to predict arrhythmias and mortality. Sleep study data of 24 patients on chronic methadone therapy referred to a tertiary clinic for overnight polysomnography were compared with two matched groups not on methadone: 24 patients referred for overnight polysomnography to the same clinic (clinic group), and 24 volunteers who had overnight polysomnography at home (community group). Despite similar values for heart rate, heart rate variability, corrected QT interval, QTVI, and oxygen saturation (SpO2 ) when awake, patients on methadone had larger QTVI (P=0.015 vs. clinic, P<0.001 vs. community) and lower SpO2 (P=0.008 vs. clinic, P=0.013 vs. community) during sleep, and the increase in their QTVI during sleep vs. wakefulness correlated with the decrease in SpO2 (r=-0.54, P=0.013). QTVI positively correlated with methadone dose during sleep (r=0.51, P=0.012) and wakefulness (r=0.73, P<0.001). High-density ectopy (>1,000 premature beats per median sleep period), a precursor for torsades de pointes, was uncommon but more frequent in patients on methadone (P=0.039). This study demonstrates that chronic methadone use is associated with increased cardiac repolarization instability. Methadone's pro-arrhythmic impact may be mediated by sleep-related hypoxemia, which could explain the increased nocturnal mortality associated with this opioid.

Psychological factors and cardiac repolarization instability during anger in implantable cardioverter defibrillator patients

BackgroundEvidence indicates that emotions such as anger are associated with increased incidence of sudden cardiac death, but the biological mechanisms remain unclear. We tested the hypothesis that, in patients with sudden death vulnerability, anger would be associated with arrhythmic vulnerability, indexed by cardiac repolarization instability.MethodsPatients with coronary artery disease (CAD) and an implantable cardioverter defibrillator (ICD; n = 41) and healthy controls (n = 26) gave an anger‐inducing speech (anger recall), rated their current (state) anger, and completed measures of trait (chronic) levels of Anger and Hostility. Repolarization instability was measured using QT Variability Index (QTVI) at resting baseline and during anger recall using continuous ECG.ResultsICD patients had significantly higher QTVI at baseline and during anger recall compared with controls, indicating greater arrhythmic vulnerability overall. QTVI increased from baseline to anger recall to a similar extent in both groups. In ICD patients but not controls, during anger recall, self‐rated anger was related to QTVI (r = .44, p = .007). Trait (chronic) Anger Expression (r = .26, p = .04), Anger Control (r = −.26, p = .04), and Hostility (r = .25, p = .05) were each associated with the change in QTVI from baseline to anger recall (ΔQTVI). Moderation analyses evaluated whether psychological trait associations with ΔQTVI were specific to the ICD group. Results indicated that Hostility scores predicted ΔQTVI from baseline to anger recall in ICD patients (β = 0.07, p = .01), but not in controls.ConclusionsAnger increases repolarization lability, but in patients with CAD and arrhythmic vulnerability, chronic and acute anger interact to trigger cardiac repolarization lability associated with susceptibility to malignant arrhythmias.

Absence of Rgs5 Influences the Spatial and Temporal Fluctuation of Cardiac Repolarization in Mice.

AimsThis study investigated the contribution of the regulator of G-protein signaling 5 (Rgs5) knockout to the alteration of the action potential duration (APD) restitution and repolarizing dispersion in ventricle.Methods and ResultsThe effects of Rgs5–/– were investigated by QT variance (QTv) and heart rate variability analysis of Rgs5–/– mice. Monophasic action potential analysis was investigated in isolated Rgs5–/– heart. Rgs5–/– did not promote ventricular remodeling. The 24-h QTv and QT variability index (QTVI) of the Rgs5–/– mice were higher than those of wild-type (WT) mice (P < 0.01). In WT mice, a positive correlation was found between QTv and the standard deviation of all NN intervals (r = 0.62; P < 0.01), but not in Rgs5–/– mice (R = 0.01; P > 0.05). The absence of Rgs5 resulted in a significant prolongation of effective refractory period and APD in isolated ventricle. In addition, compared with WT mice, the knockout of Rgs5 significantly deepened the slope of the APD recovery curve at all 10 sites of the heart (P < 0.01) and increased the spatial dispersions of Smax (COV-Smax) (WT: 0.28 ± 0.03, Rgs5–/–: 0.53 ± 0.08, P < 0.01). Compared with WT heart, Rgs5–/– increased the induced S1–S2 interval at all sites of heart and widened the window of vulnerability of ventricular tachyarrhythmia (P < 0.05).ConclusionOur findings indicate that Rgs5–/– is an important regulator of ventricular tachyarrhythmia in mice by prolonging ventricular repolarization and increasing spatial dispersion in ventricle.

Heart Rate Influence on the QT Variability Risk Factors.

QT interval variability, mostly expressed by QT variability index (QTVi), has repeatedly been used in risk diagnostics. Physiologic correlates of QT variability expressions have been little researched especially when measured in short 10-second electrocardiograms (ECGs). This study investigated different QT variability indices, including QTVi and the standard deviation of QT interval durations (SDQT) in 657,287 10-second ECGs recorded in 523 healthy subjects (259 females). The indices were related to the underlying heart rate and to the 10-second standard deviation of RR intervals (SDRR). The analyses showed that both QTVi and SDQT (as well as other QT variability indices) were highly statistically significantly (p < 0.00001) influenced by heart rate and that QTVi showed poor intra-subject reproducibility (coefficient of variance approaching 200%). Furthermore, sequential analysis of regression variance showed that SDQT was more strongly related to the underlying heart rate than to SDRR, and that QTVi was influenced by the underlying heart rate and SDRR more strongly than by SDQT (p < 0.00001 for these comparisons of regression dependency). The study concludes that instead of QTVi, simpler expressions of QT interval variability, such as SDQT, appear preferable for future applications especially if multivariable combination with the underlying heart rate is used.

Autonomic and Cardiac Repolarization Lability in Long QT Syndrome Patients.

Long QT-Syndrome (LQTS) patients are at risk of arrhythmias and seizures. We investigated whether autonomic and cardiac repolarization measures differed based on LQTS genotypes, and in LQTS patients with vs. without arrhythmias and seizures. We used 24-h ECGs from LQTS1 (n = 87), LQTS2 (n = 50), and LQTS genotype negative patients (LQTS(-), n = 16). Patients were stratified by LQTS genotype, and arrhythmias/seizures. Heart rate variability (HRV) and QT variability index (QTVI) measures were compared between groups during specific physiological states (minimum, middle, & maximum sympathovagal balance, LF/HF). Results were further tested using logistic regression for each ECG measure, and all HRV measures in a single multivariate model. Across multiple physiological states, total autonomic (SDNN) and vagal (RMSSD, pNN50) function were lower and repolarization dynamics (QTVI) were elevated in LQTS(+), LQTS1, and LQTS2, compared to LQTS(-). Many measures remained significant in the regression models. Multivariate modeling demonstrated that SDNN, RMSSD, and pNN50 were independent markers of LQTS(+) vs. LQTS(-), and SDNN and pNN50 were markers for LQTS1 vs. LQTS(-). During sympathovagal balance (middle LF/HF), RMSSD and pNN50 distinguished LQTS1 vs. LQTS2. LQTS1 patients with arrhythmias had lower total (SDNN) and vagal (RMSSD and pNN50) autonomic function, and SDNN remained significant in the models. In contrast, ECG measures did not differ in LQTS2 patients with vs. without arrhythmias, and LQTS1 and LQTS2 with vs. without seizures. Autonomic (HRV) and cardiac repolarization (QTVI) ECG measures differ based on LQTS genotype and history of arrhythmias in LQTS1. SDNN, RMSSD, and pNN50 were each independent markers for LQTS genotype.

QT Variability Index is Correlated with Autonomic Nerve Activity in Healthy Children

The QT variability index (QTVI), which measures the instability of myocardial repolarization, is usually calculated from a single electrocardiogram (ECG) recording and can be easily applied in children. It is well known that frequency analysis of heart rate variability (HRV) can detect autonomic balance, but it is not clear whether QTVI is correlated with autonomic tone. Therefore, we evaluated the association between QTVI and HRV to elucidate whether QTVI is correlated with autonomic nerve activity. Apparently, healthy 320 children aged 0–7 years who visited Fujita Health University Hospital for heart checkup examinations were included. The RR and QT intervals of 60 continuous heart beats were measured, and the QTVI was calculated using the formula of Berger et al. Frequency analysis of HRV, including the QTVI analysis region, was conducted for 2 min and the ratio of low-frequency (LF) components to high-frequency (HF) components (LF/HF) and HF/(LF + HF) ratio was calculated as indicators of autonomic nerve activity. Then, the correlations between QTVI and these parameters were assessed. QTVI showed a significant positive correlation with LF/HF ratio (r = 0.45, p < 0.001) and negative correlation with HF/(LF + HF) ratio (r = −0.429, p < 0.001). These correlations remained after adjustment for sex and age. QTVI, which is calculated from non-invasive ECG and can detect abnormal myocardial repolarization, is significantly correlated with frequency analysis of HRV parameters. QTVI reflects autonomic nerve balance in children.