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 (ß = 0.405, P < 0.01), STVQT (ß = 0.151, P < 0.01), and QTVI (ß = 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.

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

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: In the SB patients without OSA and controls, QTc intervals and QTVI were significantly increased during RMMAs/LMs compared with those during the 10 s 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. CONCLUSION: 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.

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

BACKGROUND: Evidence 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. METHODS: Patients 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. RESULTS: ICD 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 (ß = 0.07, p = .01), but not in controls. CONCLUSIONS: Anger 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.

Time- and frequency-domain analysis of repolarization phase during recovery from exercise in healthy subjects.

BACKGROUND/AIM: Recently, data from temporal dispersion of myocardial repolarization analysis have gained a capital role in the sudden cardiac death risk stratification. Aim of this study was to evaluate the influence of heart rate, autonomic nervous system, and controlled breathing on different myocardial repolarization markers in healthy subjects. METHOD: Myocardial repolarization dispersion markers from short-period (5 minutes) electrocardiogram (ECG) analysis (time and frequency domain) have been obtained in 21 healthy volunteers during the following conditions: free breathing (rest); controlled breathing (resp); the first 5 minutes of postexercise recovery phases (exercisePeak ), maximum sympathetic activation; and during the second 5 minutes of postexercise recovery phases (exerciseRecovery ), intermediate sympathetic activation. Finally, we analyzed the whole repolarization (QTe), the QT peak (QTp), and T peak - T end intervals (Te). RESULTS: During the exercisePeak , major part of repolarization variables changed in comparison to the rest and resp conditions. Particularly, QTe, QTp, and Te standard deviations (QTeSD , QTpSD , and TeSD ); variability indexes (QTeVI and QTpVI), normalized variances (QTeVN, QTpVN, and TeVN); and the ratio between short-term QTe, QTp, and Te variability RR (STVQTe/RR , STVQTp/RR, and STVTe/RR ) increased. During exerciseRecovery , QTpSD (P < .05), QTpVI (P < .05), QTeVN (P < .05), QTpVN (P < .001), TeVN (P < .05), STVQTe/RR (P < .05), STVQTp/RR (P < .001), and STVTe/RR (P < .001) were significantly higher in comparison to the rest. The slope between QTe (0.24 ± 0.06) or QTp (0.17 ± 0.06) and RR were significantly higher than Te (0.07 ± 0.06, P < .001). CONCLUSION: Heart rate and sympathetic activity, obtained during exercise, seem able to influence the time domain markers of myocardial repolarization dispersion in healthy subjects, whereas they do not alter any spectral components.

Hospital mortality in decompensated heart failure. A pilot study.

BACKGROUND/AIM: Heart failure is a leading cause of morbidity and mortality worldwide and it is a major cause of emergency department access for cardiovascular disease patients. Aim of this study was to identify the electrocardiographic (ECG) markers, based on short-term temporal repolarization dispersion, capable to individuate decompensated chronic heart failure (CHF) patients at high mortality risk. METHODS: We obtained the following variables from an ECG recording, monitored via mobile phone, during 5-minute recordings in decompensated CHF patients: RR, QT end (QTe), QT peak (QTp) and T peak to T end (Te) and we calculated mean, standard deviation (SD) and normalized index (N). RESULTS: In-hospital mortality occurred for 25 subjects on 101 studied (25%). Deceased patients showed higher QTeSD (p < 0.01), Te mean (p < 0.01), TeSD (p < 0.05), QTeVN (p < 0.05) than the surviving group. Logistic multivariable analysis evidenced that Te mean was a significant predictor of in-hospital mortality (odd ratio: 0.09, 95% confidence limit: 0.02-0.35, p: 0.001). At multiple regression analysis, TeSD was significantly and positively related only to the NT-pro BNP levels (r: 0.540; p < 0.001). The Te mean (AUC: 0.677 p < 0.01) and TeSD (AUC: 0.647, p: 0.05) showed significant sensitivity/specificity for the event. CONCLUSIONS: The Te mean and TeSD seem to be a promising noninvasive clinical marker able to identify patients with decompensated CHF at high risk of in-hospital mortality.

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.

A new approach for analysis of heart rate variability and QT variability in long-term ECG recording.

BACKGROUND AND PURPOSE: With the emergence of long-term electrocardiogram (ECG) recordings that extend several days beyond the typical 24-48 h, the development of new tools to measure heart rate variability (HRV) and QT variability is needed to utilize the full potential of such extra-long-term ECG recordings. METHODS: In this report, we propose a new nonlinear time-frequency analysis approach, the concentration of frequency and time (ConceFT), to study the HRV QT variability from extra-long-term ECG recordings. This approach is a generalization of Short Time Fourier Transform and Continuous Wavelet Transform approaches. RESULTS: As proof of concept, we used 14-day ECG recordings to show that the ConceFT provides a sharpened and stabilized spectrogram by taking the phase information of the time series and the multitaper technique into account. CONCLUSION: The ConceFT has the potential to provide a sharpened and stabilized spectrogram for the heart rate variability and QT variability in 14-day ECG recordings.

Maturation of the QT Variability Index is Impaired in Preterm Infants.

Reduced heart rate (HR) variability in preterm infants compared with full-term infants suggests that autonomic cardiac control is developmentally delayed. However, the association between developmental changes in myocardial repolarization and gestational age remains unknown. This study investigated the association between the myocardial repolarization lability index, namely the QT variability index (QTVI) = log10 [(QTv/QTm2)/(HRv/HRm2)], and the perinatal profile of healthy 1-month-old infants. We included 209 infants (143 boys and 87 girls; mean gestational weeks at birth, 38.6 ± 1.7) who were born in university hospitals between 2014 and 2015 without apparent cardiac disease. We compared the ECG variability indices in 28 infants born before 37 gestational weeks (mean gestational weeks at birth, 35.6 ± 1.1 as preterm) and 181 infants born at the average number of gestational weeks (mean gestational weeks at birth, 38.8 ± 1.1 as controls). There was a negative correlation between the QTVI and gestational weeks (r = - 0.460, p = 0.035). QTVI values in preterm infants were larger than those in the controls (0.01 ± 0.50 vs. -0.26 ± 0.48, p = 0.023). In conclusion, the QTVI is negatively correlated with gestational age. The QTVI can serve as an index of the maturity of the cardiac autonomic nervous system and myocardial depolarization.

Electrocardiographic RR and QT Interval Variability in Patients with Atrial Septal Defect and Healthy Children.

Atrial septal defect is a common congenital heart disease. In patients with atrial septal defect, left-to-right shunting increases the right atrial and right ventricular preload. This pathological change affects sinus node automaticity and myocardial depolarization and repolarization, and has the potential to evoke arrhythmogenic substrates. We examined the effect of atrial septal defect on sinus node automaticity and myocardial repolarization by investigating the variability in the repolarization interval, namely the QT variability index (QTVI) and variability ratio (VR). This retrospective study included 38 patients (mean age, 2.2 ± 1.9 years; mean left-to-right shunt ratio, 2.1 ± 0.70) and 40 age-matched healthy control subjects evaluated from 2008 to 2015. QTVI was calculated using the ratio of the repolarization parameter variance to heart rate variance, and VR was calculated as the ratio of the standard deviation (SD) of QT intervals to the SD of RR intervals on electrocardiography. There was a significant difference in the SD of all normal RR intervals, heart rate variance, VR, and QTVI of control subjects or patients with low shunt ratio compared with patients with high shunt ratio (all P < 0.05). Linear regression analysis revealed strong positive correlations between the left-to-right shunt ratio and VR (r = 0.662, P < 0.0001) or QTVI (r = 0.808, P < 0.0001). These repolarization indices provide information on alteration of sinus node autonomic control and the pathophysiology of myocardial repolarization, and could be used as a noninvasive indicator of the shunt ratio in children with atrial septal defect.

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

AIMS: The need for a readily available, inexpensive, non-invasive method for improved risk stratification of heart failure (HF) patients is paramount. Prior studies have proposed that distinct fluctuation patterns underlying the variability of physiological signals have unique prognostic value. We tested this hypothesis in an extensively phenotyped cohort of HF patients using EntropyXQT, a novel non-linear measure of cardiac repolarization dynamics. METHODS AND RESULTS: In a prospective, multicentre, observational study of 852 patients in sinus rhythm undergoing clinically indicated primary prevention implantable cardioverter-defibrillator (ICD) implantation (2003-10), exposures included demographics, history, physical examination, medications, laboratory results, serum biomarkers, ejection fraction, conventional electrocardiographic (ECG) analyses of heart rate and QT variability, and EntropyXQT. The primary outcome was first 'appropriate' ICD shock for ventricular arrhythmias. The secondary outcome was composite events (appropriate ICD shock and all-cause mortality). After exclusions, the cohort (n = 816) had a mean age of 60 ± 13 years, 28% women, 36% African Americans, 56% ischaemic cardiomyopathy, and 29 ± 16% Seattle HF risk score (SHFS) 5-year predicted mortality. Over 45 ± 24 months, there were 134 appropriate shocks and 166 deaths. After adjusting for 30 exposures, the hazard ratios (comparing the 5th to 1st quintile of EntropyXQT) for primary and secondary outcomes were 3.29 (95% CI 1.74-6.21) and 2.28 (1.53-3.41), respectively. Addition of EntropyXQT to a model comprised of the exposures or SHFS significantly increased net reclassification and the ROC curve area. CONCLUSIONS: EntropyXQT measured during ICD implantation strongly and independently predicts appropriate shock and all-cause mortality over follow-up. EntropyXQT complements conventional risk predictors and has the potential for broad clinical application.

Heart rate-guided, but not dose-guided titration of beta blockers stabilizes ventricular repolarization in patients with chronic heart failure.

AIMS: We compared the effects of heart rate-guided and dose-guided beta-blocker titration strategies on QT variability in patients with chronic heart failure (CHF). METHODS: In a prospective study we recorded 5-minute resting high-resolution ECGs (HRECG) in 100 patients with CHF and measured heart rate (HR) and ventricular repolarization by QT variability index (QTVI). In a subgroup of patients not reaching target HR (<70bpm) we uptitrated beta blockers and repeated HRECG measurements 3months thereafter. RESULTS: Target HR was present in 46 patients (group A), and in 54 patients HR was above target (group B). The groups did not differ in age, gender, NYHA class, NT pro-BNP, creatinine, or beta blocker dose. Patients in group A displayed significantly lower QTVI than patients in group B (-1.25±0.55 vs. -1.52±0.42, P=0.013). When uptitrating beta-blockers we found a decrease in HR (from 91±15bpm to 71±15bpm, P<0.001), NTpro BNP levels (from 4474±3878pg/ml to 3042±2566pg/ml, P=0.024), and NYHA class (from 3.0±0.8 to 2.5±0.7, P=0.006). With beta-blocker uptitration QTVI decreased in 10 of 24 patients (42%). In these patients HR decreased more than in the remaining cohort (-25±20bpm vs. -15±17bpm, P=0.017). On multivariate analysis, the presence of target HR was a predictor of QTVI decrease (P=0.017), but beta-blocker dose was not. CONCLUSIONS: In patients with CHF treated by beta-blockers, changes in QT variability appear to occur in parallel with changes of heart rate. This suggests that heart rate-guided titration of beta-blockers may be associated with decreased risk of sudden cardiac death.

The presence of electromechanical mismatch in nonischemic dilated cardiomyopathy is associated with ventricular repolarization instability.

BACKGROUND: We analyzed electromechanical mismatch (EMM) and its relationship to ventricular repolarization in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: In 39 DCM patients with left ventricular ejection fraction (LVEF) <40% and New York Heart Association functional class ≥III, electroanatomic mapping was used to quantify areas of EMM. High-resolution electrocardiograph was used to measure heart rate variability (HRV) and QT variability index (QTVI). EMM was present in 22 patients (56%, group 1), whereas 17 patients presented no mismatched segments (44%, group 2). The groups did not differ in age (56 ± 10 years in group 1 vs 57 ± 7 years in group 2; P = .82), sex (male: 82% vs 94%; P = .40), LVEF (27 ± 8% vs 25 ± 6%; P = .18), or N-terminal pro-B-type natriuretic peptide (2,350 pg/mL vs 2,831 pg/mL; P = .32). Although heart rate and HRV were similar in both groups (rate: 80 ± 20 beats/min in group 1 vs 74 ± 19 beats/min in group 2 [P = .47]; standard deviation of normal-to normal RR intervals: 106 ± 79 vs 88 ± 115 [P = .61]), we found significantly higher QTVI values in patients from group 1 (-1.15 ± 0.46 vs -1.62 ± 0.51 in group 2; P = .005). In patients with implantable cardioverter-defibrillators, ventricular arrhythmias recorded ≤1 year before enrollment were more frequent in group 1 than in group 2 (58% vs 13%; P = .02). CONCLUSIONS: EMM is present in a majority of patients with DCM and is associated with ventricular repolarization instability.

Artificial Intelligence Applied to Electrical and Non-Invasive Hemodynamic Markers in Elderly Decompensated Chronic Heart Failure Patients.

OBJECTIVES: The first aim of this study was to assess the predictive power of Tend interval (Te) and non-invasive hemodynamic markers, based on bioimpedance in decompensated chronic heart failure (CHF). The second one was to verify the possible differences in repolarization and hemodynamic data between CHF patients grouped by level of left ventricular ejection fraction (LVEF). Finally, we wanted to check if repolarization and hemodynamic data changed with clinical improvement or worsening in CHF patients. METHODS: Two hundred and forty-three decompensated CHF patients were studied by 5 min ECG recordings to determine the mean and standard deviation (TeSD) of Te (first study). In a subgroup of 129 patients (second study), non-invasive hemodynamic and repolarization data were recorded for further evaluation. RESULTS: Total in-hospital and cardiovascular mortality rates were respectively 19 and 9%. Te was higher in the deceased than in surviving subjects (Te: 120 ± 28 vs. 100 ± 25 ms) and multivariable logistic regression analysis reported that Te was related to an increase of total (χ2: 35.45, odds ratio: 1.03, 95% confidence limit: 1.02-1.05, p < 0.001) and cardiovascular mortality (χ2: 32.58, odds ratio: 1.04, 95% confidence limit: 1.02-1.06, p < 0.001). Subjects with heart failure with reduced ejection fraction (HFrEF) reported higher levels of repolarization and lower non-invasive systolic hemodynamic data in comparison to those with preserved ejection fraction (HFpEF). In the subgroup, patients with the NT-proBNP reduction after therapy showed a lower rate of Te, heart rate, blood pressures, contractility index, and left ventricular ejection time in comparison with the patients without NT-proBNP reduction. CONCLUSION: Electrical signals from ECG and bioimpedance were capable of monitoring the patients with advanced decompensated CHF. These simple, inexpensive, non-invasive, easily repeatable, and transmissible markers could represent a tool to remotely monitor and to intercept the possible worsening of these patients early by machine learning and artificial intelligence tools.

Relationship between Alzheimer dementia and QT interval: A meta-analysis.

While the link between aging and mortality from dementia is widely appreciated, the mechanism is not clear. The objective of this study was to determine whether there is a direct relationship between Alzheimer dementia (AD) and the QT interval, because the latter has been related to cardiac mortality. A systematic review and meta-analysis were conducted after a Medline and EMBASE search using terms "Alzheimer disease or Dementia AND QT interval, QT dispersion or cardiac repolarization." Four studies with control groups were identified. There were significant differences in QT interval between individuals with AD vs individuals without dementia (controls) (odds ratio (OR)1.665 [random effects model] and 1.879 [fixed effect model]) (p < 0.001). There were significant differences in QT interval between individuals with AD vs individuals with mild cognitive impairment (MCI) (OR 1.760 [random effects] and 1.810 [fixed effect]) (p < 0.001). A significant (p <0.001) correlation exists between the QTc and the Mini-Mental State Exam (MMSE), a test of cognitive function. Two studies examined QT variability (the difference between the longest and shortest QT interval on a 12 lead ECG); the OR for QT variability AD vs MCI was 3.858 [random effects model] and 3.712 [fixed effects model] (p < 0.001). When compared to the control group, the OR for QT dispersion in AD was 6.358 [random effects model] or 5.143 ( P< 0.001) [fixed effects model]. A qualitative analysis of the data raised questions about paucity of data defining the nature of the control groups, the pathophysiologic mechanism, and the uniform use of a poor QT heart rate correction factor. The longer QT in AD, greater QT variability in AD, and the direct relationship between QT interval and AD severity supports a brain-heart connection in AD that might be fundamental to aging-induced AD and mortality. Issues with defining the control group, limited number of studies, conflicting data in population studies, and the lack of a strong electrophysiological basis underscore the need for additional research in this field.

Autonomic modulation of repolarization instability in patients with heart failure prone to ventricular tachycardia.

QT variability (QTV) signifies repolarization lability, and increased QTV is a risk predictor for sudden cardiac death. The aim of the present study was to investigate the role of autonomic nervous system activity on QTV. This study was performed in 29 subjects: 10 heart failure (HF) patients with spontaneous ventricular tachycardia [HFVT(+)], 10 HF patients without spontaneous VT [HFVT(-)], and 9 subjects with structurally normal hearts (HNorm). The beat-to-beat QT interval was measured on 3-min records of surface ECGs at baseline and during interventions (atrial pacing and esmolol, isoprenaline, and atropine infusion). Variability in QT intervals was expressed as the SD of all QT intervals (SDQT). The ratio of the SDQT to SD of RR intervals (SDRR) was calculated as an index of QTV normalized to heart rate variability. There was a trend toward a higher baseline SDQT-to-SDRR ratio in the HFVT(+) group compared with the HFVT(-) and HNorm groups (P = 0.09). SDQT increased significantly in the HFVT(+) and HFVT(-) groups compared with the HNorm group during fixed-rate atrial pacing (P = 0.008). Compared with baseline, isoprenaline infusion increased SDQT in HNorm subjects (P = 0.02) but not in HF patients. SDQT remained elevated in the HFVT(+) group relative to the HNorm group despite acute ß-adrenoceptor blockade with esmolol (P = 0.02). In conclusion, patients with HF and spontaneous VT have larger fluctuations in beat-to-beat QT intervals. This appears to be a genuine effect that is not solely a consequence of heart rate variation. The effect of acute autonomic nervous system modulation on QTV appears to be limited in HF patients.

Relationship of QT interval variability to heart rate and RR interval variability.

The study investigated whether the beat-to-beat QT interval variability relationship to the mean heart rate and the RR interval variability depended on the cardiovascular autonomic status changed by postural positioning. Repeated long-term 12-lead Holter recordings were obtained from 352 healthy subjects (mean age 32.7 ± 9.1 years, 176 females) while they underwent postural provocative tests involving supine, unsupported sitting and unsupported standing positions. Each recording was processed as a sequence of overlapping 10-second segments. In each segment, the mean RR interval, the coefficients of variance of the RR intervals (RRCV) and the QT intervals (QTCV) were obtained. In each subject, these characteristics, corresponding to different postural positions, were firstly averaged and secondly used to obtain within-subject correlation coefficients between the different characteristics at different postural positions. While the within-subject means of RRCV generally decreased when changing the position from supine to sitting and to standing (4.53 ± 1.95%, 4.12 ± 1.51% and 3.26 ± 1.56% in females and 3.99 ± 1.44%, 4.00 ± 1.24% and 3.53 ± 1.32% in males respectively), the means of QTCV systematically increased during these position changes (0.96 ± 0.40%, 1.30 ± 0.56% and 1.88 ± 1.46% in females and 0.85 ± 0.30%, 1.13 ± 0.41% and 1.41 ± 0.59% in males, respectively). The intra-subject relationship between QTCV, RRCV and mean RR intervals was highly dependent on postural positions. The study concludes that no universally applicable normalization of the QT interval variability for the heart rate and/or the RR interval variability should be assumed. In future studies of the QT variability, it seems preferable to report on the absolute values of QT variability, RR variability and mean heart rate separately.

QT interval instability and QRS interval dispersion in healthy cats and cats with a hypertrophic cardiomyopathy phenotype.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats. Electrocardiographic (ECG) analysis can help with the diagnosis of HCM and also in the investigation of the secondary consequences of the disease. This study investigated ECG markers of QT interval variability (total instability [TI], short-term instability [STI], long-term instability [LTI], QT variance [QTv]), mean QT interval (QTa) and QT interval corrected for heart rate (QTac), as well as the duration (QRSd) and dispersion (QRSv) of the QRS interval in healthy cats and in those with HCM. METHODS: Data were collected from 63 domestic cats: 40 in the control group and 23 in the HCM group. Fifty consecutive QT intervals were recorded for all cats and then QTa, QTac, QTv, TI, LTI and STI were calculated. QRSd and QRSv were also obtained for all animals. A Mann-Whitney U-test was used for group comparison. Receiver operating characteristic curves were plotted to evaluate the sensitivity and specificity of all markers for HCM. Logistic regression analysis was performed to assess the risks of cats having HCM, based on the studied indexes. RESULTS: QTa (P <0.01), QTac (P <0.01), QRSd (P <0.01) and STI (P = 0.02) were higher in the HCM group. QTa >158.8 ms, QTac >27.4 ms and QRSd >0.045 s had an accuracy of 77.4%, 68.2% and 80.9%, respectively, in detecting HCM. Logistic regression showed that cats with QTa >158 ms, QTac >27.4 ms and QRSd >0.045 s had a 1.58-, 1,23- and 6.5-fold higher risk, respectively, of developing HCM. CONCLUSIONS AND RELEVANCE: Cats with HCM had higher ventricular instability as assessed by STI and showed a prolongation of the QT and QRS intervals via the QTa, QTac and QRSd markers. These markers show potential as ancillary screening tools for identifying the presence of HCM.

QT interval instability and variability in dogs with naturally-occurring hypercortisolism.

Hypercortisolism is one of the most common endocrine diseases in dogs. In humans, it is clearly associated with a higher risk of cardiovascular events, but studies in dogs are scarce. To investigate the arrhythmogenic risk of dogs with naturally-occurring hypercortisolism (NOHC), indices of variability and instability of the QT interval were retrospectively studied in 38 dogs with NOHC and prospectively studied in 12 healthy dogs: variance (QTv), total instability (TI), short-term (STI) and long-term (LTI), and mean (QTm). Except for QTm, all parameters studied were higher in the NOHC group than in the control group. In addition, STI and QTv showed moderate positive correlation with left ventricle wall thickness. The NOHC group was subdivided according to cortisol suppression pattern in the low-dose dexamethasone suppression test. All electrocardiographic indices of partial and absent suppression patterns were numerically higher than healthy dogs. QTv and TI were lower in the control group than in both NOHC subgroups. LTI and STI were lower in the CG than in the group with the partial suppression pattern. There was no statistical difference between sex groups in any of the electrocardiographic parameters studied. This result might indicate that the etiology of NOHC, and its consequent influence on hypothalamus-pituitary-adrenal axis could interfere on the heterogeneity of ventricular repolarization parameters in different ways, especially in the short-term and the long-term stability; however further studies are necessary to understand the role of cortisol on electrical instability in dogs.

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

BACKGROUND: Sleep is fragmented by brief arousals, and excessive arousal burden has been linked to increased cardiovascular (CV) risk, but mechanisms are poorly understood. RESEARCH QUESTION: Do arousals trigger cardiac ventricular repolarization lability that may predispose people to long-term cardiovascular mortality? STUDY DESIGN AND METHODS: 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 15 s prior to arousal onset until 15 s past onset. Ventricular repolarization lability was quantified by using the QT variability index (QTVi). RESULTS: 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 55 ms, 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]). INTERPRETATION: 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT00070681; URL: www. CLINICALTRIALS: gov.

Differences in circadian variation in QT interval of the ECG in women compared to men.

BACKGROUND: Measurement of the QT interval in the ECG (QT interval) is important in evaluating risk for cardiac death and for assessing the impact of drugs on the heart. The objective of this study is to determine whether the time of day affects the QT interval, QT interval variability and whether these relationships are influenced by an individual's sex. METHODS: Twenty-four hour ECGs were analyzed in detail on 50 individuals, 49 years of age, without evidence of coronary artery disease, structural heart disease, or significant arrhythmias. Four different QT-heart rate adjustment formulae were calculated and compared. RESULTS: There were significant (P=0.0014) differences between the QT-heart rate relationship during three different time-periods (night 00:00 to 08:00 h, day 08:00 to 14:00 h and evening 14:00 to 24:00 h). Women, compared to men, had a steeper relation of QT to RR interval indicating that when heart rate slows at night, the QT interval is more prolonged which is consistent with a greater susceptibility to fatal arrhythmias. The variability of the QT interval (the SD) was significantly (P<0.01) greater in men than women at night and in the evening but not during the day. There were differences in the ability of different QT heart rate adjustment formulae to blunt the effect of heart rate changes on the QT interval during the day. CONCLUSION: The time of the day that the QT interval is assessed should be considered. The QT heart rate relationship is different in women than in men especially at night. QT interval variability is greater at night especially in men. There are differences in the ability of QT heart rate adjustment formulae to blunt the effect of heart rate on the QT interval. Differences in the QTc at night might be the basis for the higher prevalence of sudden death in women at night.