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.

Electronic cigarettes are often used for smoking cessation as a harm reduction strategy, but studies comparing risks of electronic cigarettes (ECs) and tobacco cigarettes (TCs) are scarce. Ventricular repolarization in people who smoke TCs is abnormal. Baseline repolarization was compared among nonusers (people who do not use TCs or ECs) and people who use ECs or TCs. The acute effects of ECs and TCs on metrics of ventricular repolarization were then compared in people who chronically smoke. A total of 110 participants (59 female), including 35 people (21 females) in the TC cohort, 34 people (17 females) in the EC cohort, and 41 people (21 females) in the nonuser cohort, were included. None of the primary outcomes, Tpeak-end (Tp-e), Tp-e/QT, and Tp-e/QTc, were different among the three cohorts at supine baseline, even when adjusted for sex. When compared with the control exposure standing after acutely using the EC but not the TC, significantly prolonged all three primary indices of ventricular repolarization in people who smoke TCs. The major new finding in this study is that in people who smoke TCs, using an EC compared with a TC significantly prolongs ventricular repolarization. Furthermore, in our subgroup analysis by sex, this adverse effect on repolarization is found only in male, not female, smokers. In summary, chronic TC smoking is the most prevalent, modifiable risk factor for cardiovascular death, including sudden cardiac death. If used for smoking cessation, ECs should only be used in the short term since they too carry their own risks; this risk appears to be greatest in males compared with females who smoke.NEW & NOTEWORTHY The major new finding in this study is that in people who smoke tobacco cigarettes, using an electronic cigarette but not a tobacco cigarette acutely and significantly prolongs several metrics of ventricular repolarization, including Tpeak-Tend, Tpeak-Tend/QT, and Tpeak-Tend/QTc. Furthermore, in our subgroup analysis by sex, this adverse effect on repolarization is found only in male, not female, smokers.

OBJECTIVE: The clinical value of electrocardiogram (ECG) repolarization parameters associated with ventricular arrhythmias (VAs) in tako-tsubo syndrome is still under debate. We aimed to evaluate ECG predictors of subacute VAs, defined as those occurring after the first 48hours from admission.
METHODS: This single-center observational study enrolled patients admitted to the cardiology department between 2012 and 2018 with a confirmed diagnosis of tako-tsubo syndrome. Data collection included a 12-lead ECG on admission and at 48hours, continuous telemetry monitoring, blood testing, transthoracic echocardiography, and coronary angiography during hospitalization. VAs events were defined as: premature ventricular contractions ≥ 2000 within a 24-hour window of telemetry monitoring, ventricular fibrillation, sustained ventricular tachycardia (VT), polymorphic VT, and non-sustained VT.
RESULTS: A total of 87 patients (age 72±12 years) were enrolled. During a median of 8 days of hospitalization, subacute VAs were documented in 22 patients (25%) after a median of 91hours from admission. Subacute VAs were associated with an increase in mortality during hospitalization (P=.030). The corrected global (mean of the 12-lead ECG values) Tpeak-Tend interval at 48hours from admission was an independent predictor of subacute VAs and was statistically superior to the standard corrected QT interval (Z test, P=.040). A cut-off of 108 msec for the corrected global Tpeak-Tend yielded a 71% sensitivity and 72% specificity for subacute VAs.
CONCLUSIONS: In patients with tako-tsubo syndrome, subacute VAs are associated with repolarization alterations that can be identified on conventional ECG using the Tpeak-Tend interval.

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.

BACKGROUND: As previously reported, an increased repolarization temporal imbalance induces a higher risk of total/cardiovascular mortality.
OBJECTIVE: The aim of this study was to assess if the electrocardiographic short period markers of repolarization temporal dispersion could be predictive of the hospital stay length and mortality in patients with acutely decompensated chronic heart failure (CHF).
METHODS: Mean, standard deviation (SD), and normalized variance (VN) of QT (QT) and Tpeak-Tend (Te) were obtained on 5-min ECG recording in 139 patients hospitalized for acutely decompensated CHF, subgrouping the patients for hospital length of stay (LoS): less or equal 1 week (≤1 W) and those with more than 1 week (>1 W).
RESULTS: We observed an increase of short-period repolarization variables (TeSD and TeVN, p < .05), a decrease of blood pressure (p < .05), lower ejection fraction (p < .05), and higher plasma level of biomarkers (NT-proBNP, p < .001; Troponin, p < .05) in >1 W LoS subjects. 30-day deceased subjects reported significantly higher levels of QTSD (p < .05), Te mean (p < .001), TeSD (p < .05), QTVN (p < .05) in comparison to the survivors. Multivariable Cox regression analysis reported that TeVN was a risk factor for longer hospital stay (hazard ratio: 1.04, 95% confidence limit: 1.01-1.08, p < .05); whereas, a longer Te mean was associated with higher mortality risk (hazard ratio: 1.02, 95% confidence limit: 1.01-1.03, p < .05).
CONCLUSIONS: A longer hospital stay is considered a clinical surrogate of CHF severity, we confirmed this finding. Therefore, these electrical and simple parameters could be used as noninvasive, transmissible, inexpensive markers of CHF severity and mortality.

UNASSIGNED: Aging and chronic heart failure (CHF) are responsible for the temporal inhomogeneity of electrocardiogram (ECG) repolarization phase. In the past, short period repolarization-dispersion parameters were used as makers of mortality risk in different heart diseases, yet. Aim of this work was to evaluate risk of mortality or worsening condition in CHF elderly subjects by mean of these repo-larization variables.
UNASSIGNED: An observational, prospective cohort study was performed, collecting 5 minutes ECG recordings to assess the mean and standard deviation (SD) of the following variables: QT end (QTe), QT peak (QTp) and T peak to T end (Te) in 117 decompensated CHF (age range: from 49 to 103 years). 30-day mortality and high levels of NT-pro BNP (<75 percentile) were considered markers of decompensated CHF.
UNASSIGNED: A total of 27 patients (23%) died during the 30-day follow-up (overall mortality rate 23%). Te mean (odd ratio (OR): 1.04, 95% confidence limit (Cl 7u): 1.02-1.09, p<0.01), NT-pro BNP (OR: 1.00, 95% cl: 1.00-1.00, p<0.01) and LVMI (OR : 0.98, 95% cl: 0.96-0.10, p<0.05) were associated to risk of mortality at the multivariable logistic analysis. On the contrary, the same statistical analysis selected TeSD (OR: 1.36, 95% cl: 1.16-1.59, p<0.001) and LVEF (OR: 0.91, 95% cl: 0.87-0.95, p<0.001) as marker of decompensated CHF.
UNASSIGNED: In decompensated CHF elderly subjects, Te mean seem be associated to mortality and TeSD could be considered a risk factor for CHF worsening and complications. These evidences could provide useful tools for telemonitoring CHF elderly patients, amelio-rating treatments and outcomes.

His-bundle pacing (HBP) and left-bundle-area pacing (LBAP) are conduction system pacing (CSP) modalities increasingly used as alternatives to conventional biventricular pacing (BiVP). While effects of CSP on ventricular depolarization have been reported, effects on ventricular repolarization have not.
QRS duration (QRSd) and validated ECG parameters of ventricular repolarization associated with arrhythmic risk (T-peak-to-T-endTransmural , T-peak-to-T-endTotal , T-peak dispersion, QTc, QTc dispersion) were analyzed post-implant in 107 patients: 60 with CSP (HBP: n = 35, LBAP: n = 25) and 47 with BiVP. T-wave memory resolution and QTc shortening were analyzed on ECGs obtained ≥25 days post-implant. Twenty blinded measurements were obtained by both authors to assess Interobserver variability.
Although QRSd was shorter with HBP versus LBAP (119 ± 7 ms vs. 132 ± 9 ms, p = .02), there were no significant differences in any repolarization parameters between these methods of CSP. However, when comparing CSP (HBP + LBAP) to BiVP, both QRSd (125 ± 5 ms vs. 147 ± 7 ms, p < .0001) and repolarization parameters (T-peak-to-T-endTransmural : 83 ± 5 ms vs. 107 ± 8 ms; T-peak-to-T-endTotal : 110 ± 7 ms vs. 137 ± 10 ms; QTc: 470 ± 12 ms vs. 506 ± 12 ms; all p ≤ .0001) were significantly shorter with CSP. Improved T-peak-to-T-end values were unrelated to pre-implant QRSd or LV function. Interobserver variability was 4.6 ± 1.9 ms. Frontal QRS-T angle narrowing (132° to 104°, p = .001) and QTc shortening (483 ± 13 ms to 464 ± 12 ms, p = .008) were seen only with CSP.
In addition to improved depolarization, CSP reduced repolarization heterogeneity and provided greater T-wave memory resolution as compared to BiVP. Both modalities of CSP (HBP + LBAP) resulted in comparably reduced repolarization heterogeneity regardless of baseline QRSd and LV function. These observations may confer lower arrhythmogenic risk and warrant further study.

The association between chronic heart failure (CHF) and permanent atrial fibrillation is very frequent. The repolarization duration was already found predictive for atrial fibrillation. Aim of this study was to evaluate the influence of atrial fibrillation on short period repolarization variables in decompensated CHF patients.
We used 5 min ECG recordings to assess the mean, standard deviation (SD), and normalized variance (NV) of the following variables: QT end (QTe), QT peak (QTp), and T peak to T end (Te) in 121 decompensated CHF, of whom 40 had permanent atrial fibrillation, too. We reported also the 30-day mortality.
QTpSD (p < .01), TeSD (p < .01), QTpVN (p < .01), and TeVN (p < .01) were higher in the atrial fibrillation than among sinus rhythm CHF subjects. Multivariable logistic analysis selected only TeSD (odd ratio, o.r.: 1.32, 95% confidence interval, c.i.: 1.06-1.65, p: .015) associated with atrial fibrillation. A total of 27 patients died during the 30-days follow-up (overall mortality rate 22%), 7 (18%), and 20 (25%) respectively in the atrial fibrillation and sinus rhythm patients. Furthermore, the following variables were associated to the morality risk: NT-pro Brain Natriuretic Peptide (o.r.: 1.00, 95% c.i.: 1.00-1.00, p: .041), left ventricular end diastolic diameter (o.r.: 0.81, 95% c.i.: 0.67-0.96, p: .010), and Te mean (o.r.: 1.04, 95% c.i.: 1.02-1.09, p: .012).
In decompensated CHF subjects, Te mean seems be associated to mortality and TeSD to the permanent atrial fibrillation. We could hypothesize that, during severe CHF, the multi-level ionic CHF channel derangement could be critical in influencing these non-invasive markers. (ClinicalTrials.gov number, NCT04127162).

Women are associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT-prolonging drugs. The purpose of this study was to characterize the differences in cardiac electrophysiology between moxifloxacin and levofloxacin in men and women and to assess the balance of inward and outward currents through the analysis of QT subintervals. Data from 2 TQT studies were used to investigate the impact of moxifloxacin (400 mg) and levofloxacin (1000 and 1500 mg) on QT subintervals using algorithms for measurement of J-Tpeak and Tpeak -Tend intervals. Concentration-effect analyses were performed to establish potential relationships between the ECG effects and the concentrations of the 2 fluoroquinolones. Moxifloxacin was shown to be a more potent prolonger of QT interval corrected by Fredericia (QTcF) and had a pronounced effect on J-Tpeak c. Levofloxacin had little effect on J-Tpeak c. For moxifloxacin, the concentration-effect modeling showed a greater effect for women on QTcF and J-Tpeak c, whereas for levofloxacin the inverse was true: women had smaller QTcF and J-Tpeak c effects. The different patterns in repolarization after administration of both drugs suggested a sex difference, which may be related to the combined IKs and IKr inhibitory properties of moxifloxacin versus IKr suppression only of levofloxacin. The equipotent inhibition of IKs and IKr appears to affect women more than men. Sex hormones are known to influence cardiac ion channel expression and differences in QT duration. Differences in IKr and IKs balances, influenced by sex hormones, may explain the results. These results support the impact of sex differences on the cardiac safety assessment of drugs.

OBJECTIVE: Adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). However, methods for risk stratification are not yet well-defined. The Tpeak -Tend (TpTe) interval, a measure of dispersion of ventricular repolarization, is a risk factor for SCD in non-ACHD patients. We aim to evaluate whether TpTe can be used in risk stratification for SCD in ACHD patients.
METHODS: From an international multicenter cohort of 25 790 ACHD patients, we identified all SCD cases. Cases were matched to controls by age, gender, congenital defect, and (surgical) intervention.
METHODS: TpTe was measured on a standard 12-lead ECG. The maximum TpTe of all ECG leads (TpTe-max), mean (TpTe-mean), and TpTe dispersion (maximum minus minimum) were obtained. Odds ratios (OR) for SCD cases vs controls were calculated using conditional logistic regression analysis.
RESULTS: ECGs were available for 147 cases (median age at death 33.5 years (quartiles 26.2, 48.7), 66% male) and 267 controls. The mean TpTe-max was 97 ± 24 ms in cases vs 84 ± 17 ms in controls (P < .001); TpTe-mean was 70 ± 16 vs 63 ± 10 ms (P < .001); and dispersion was 51 ± 22 ms vs 41 ± 16 ms (P = .02), respectively. Assessing each ECG lead separately, TpTe in lead aVR predicted SCD most accurately. TpTe in lead aVR was 71 ± 23 ms in cases vs 61 ± 13 ms in controls (P < .001). After adjusting for impaired ventricular function, heart failure symptoms, and prolonged QRS duration, the OR of SCD of TpTe in lead aVR at an optimal cutoff of 80 ms was 5.8 (95% CI 2.7-12.4, P < .001).
CONCLUSIONS: The TpTe interval is associated with SCD in ACHD patients. Particularly, TpTe in lead aVR can be used as an independent risk factor for SCD in ACHD patients and may, therefore, add precision to current risk prediction models.