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.

OBJECTIVE: 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.
CONCLUSIONS: 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.

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.
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.
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.
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.

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.

Using bio-impedance to deduce some hemodynamic parameters combined with some short-term ECG temporal dispersion intervals, and measuring myocardial depolarization, intraventricular conduction, and repolarization. A total of 65 in-hospital patients (M/F:35/30) were enrolled, 39 with HFrEF and 26 HFpEF, in New York Heart Association (NYHA) class IV. Stroke volume (SVI), cardiac indexes (CI), left ventricular ejection fraction (LVEFBIO), end diastolic volume (LV-EDV), and other systolic and diastolic parameters were noninvasively obtained at enrollment and at hospital discharge. At the same time, QR, QRS, QT, ST, Tpeak-Tend (Te) interval mean, and standard deviation (SD) from 5 min ECG recordings were obtained. At baseline, HFrEF patients reported significantly lower SVI (p < 0.05), CI (p < 0.05), and LVEF (p < 0.001) than HFpEF patients; moreover, HFrEF patients also showed increased LV-EDV (p < 0.05), QR, QRS, QT, ST, and Te means (p < 0.05) and standard deviations (p < 0.05) in comparison to HFpEF subjects. Multivariable logistic regression analysis reported a significant correlation between hospital mortality and Te mean (odds ratio: 1.03, 95% confidence limit: 1.01−1.06, p: 0.01). Fifty-seven percent of patients were considered responders to optimal medical therapy and, at discharge, they had significantly reduced NT-proBNP, (p < 0.001), heart rate (p < 0.05), and TeSD (p < 0.001). LVEF, obtained by transthoracic echocardiography, and LVEFBIO were significantly related (r: 0.781, p < 0.001), but these two parameters showed a low agreement limit. Noninvasive hemodynamic and ECG-derived parameters were useful to highlight the difference between HFrEF and HFpEF and between responders and nonresponders to the optimal medical therapy. Short-period bioimpedance and electrocardiographic data should be deeply evaluated to determine possible advantages in the therapeutic and prognostic approach in severe CHF.

Objective. Beat-to-beat fluctuations in the QT interval-QT variability (QTV)-have been shown to vary amongst the different ECG leads. This study aims to compare the utility of single and multi-lead ECG to disentangle the mechanisms contributing to QTV.Approach. Twelve-lead ECG was analysed in 57 coronary artery disease patients before and after an elective percutaneous transluminal coronary angiography (PTCA) procedure. QT, RR and respiration time series were extracted. QTV was decomposed into contributions by heart rate, respiration and QTV independent of heart rate and respiration using parametric autoregressive modelling. Signal-to-noise ratio, model goodness-of-fit, mean QT, corrected QT, QT variability and RR variability were also computed. Results from two single leads (Lead II and V5) and three one-dimensional representations of 12-lead ECG (principal component analysis (PCA), vector magnitude (VM), and root mean square of the 8 independent leads of the standard 12 leads (RMS8)) were compared during resting conditions, before and after PTCA, and between patients with myocardial infarction and those without.Main results. At baseline, mean QT and corrected QT were significantly lower in VM and RMS8 compared to single leads. While overall QT variability was not different between the leads, QT independent of heart rate and respiration was significantly lower in VM and RMS8. Following PTCA, changes in these variables were similar in all leads. Differences between patients with MI and those without MI were consistent in all leads.Significance. Despite the differences in some QTV components amongst various leads, single-lead ECG could be sufficient for analyzing QTV in populations with pathological cardiovascular conditions compared to those without, or for quantification of intervention effects.

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.

Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality.
Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality.
Eight hundred of 5600 participants were randomly selected. The participants (68 ± 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05).
Sleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality.

Increases in beat-to-beat variability of electrocardiographic QT interval duration have repeatedly been associated with increased risk of cardiovascular events and complications. The measurements of QT variability are frequently normalized for the underlying RR interval variability. Such normalization supports the concept of the so-called immediate RR effect which relates each QT interval to the preceding RR interval. The validity of this concept was investigated in the present study together with the analysis of the influence of electrocardiographic morphological stability on QT variability measurements. The analyses involved QT and RR measurements in 6,114,562 individual beats of 642,708 separate 10-s ECG samples recorded in 523 healthy volunteers (259 females). Only beats with high morphology correlation (r > 0.99) with representative waveforms of the 10-s ECG samples were analyzed, assuring that only good quality recordings were included. In addition to these high correlations, SDs of the ECG signal difference between representative waveforms and individual beats expressed morphological instability and ECG noise. In the intra-subject analyses of both individual beats and of 10-s averages, QT interval variability was substantially more strongly related to the ECG noise than to the underlying RR variability. In approximately one-third of the analyzed ECG beats, the prolongation or shortening of the preceding RR interval was followed by the opposite change of the QT interval. In linear regression analyses, underlying RR variability within each 10-s ECG sample explained only 5.7 and 11.1% of QT interval variability in females and males, respectively. On the contrary, the underlying ECG noise contents of the 10-s samples explained 56.5 and 60.1% of the QT interval variability in females and males, respectively. The study concludes that the concept of stable and uniform immediate RR interval effect on the duration of subsequent QT interval duration is highly questionable. Even if only stable beat-to-beat measurements of QT interval are used, the QT interval variability is still substantially influenced by morphological variability and noise pollution of the source ECG recordings. Even when good quality recordings are used, noise contents of the electrocardiograms should be objectively examined in future studies of QT interval variability.

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.
OBJECTIVE: 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.
CONCLUSIONS: 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.