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.

A Longer Tpeak-Tend Interval Is Associated with a Higher Risk of Death: A Meta-Analysis.

A noninvasive tool for cardiovascular risk stratification has not yet been established in the clinical routine analysis. Previous studies suggest a prolonged Tpeak-Tend interval (the interval from the peak to the end of the T-wave) to be predictive of death. This meta-analysis was designed to systematically evaluate the association of the Tpeak-Tend interval with mortality outcomes. Medline (via PubMed), Embase and the Cochrane Library were searched from 1 January 2008 to 21 July 2020 for articles reporting the ascertainment of the Tpeak-Tend interval and observation of all-cause-mortality. The search yielded 1920 citations, of which 133 full-texts were retrieved and 29 observational studies involving 23,114 patients met the final criteria. All-cause deaths had longer Tpeak-Tend intervals compared to survivors by a standardized mean difference of 0.41 (95% CI 0.23-0.58) and patients with a long Tpeak-Tend interval had a higher risk of all-cause death compared to patients with a short Tpeak-Tend interval by an overall odds ratio of 2.33 (95% CI 1.57-3.45). Heart rate correction, electrocardiographic (ECG) measurement methods and the selection of ECG leads were major sources of heterogeneity. Subgroup analyses revealed that heart rate correction did not affect the association of the Tpeak-Tend interval with mortality outcomes, whereas this finding was not evident in all measurement methods. The Tpeak-Tend interval was found to be significantly associated with all-cause mortality. Further studies are warranted to confirm the prognostic value of the Tpeak-Tend interval.

High-rate pacing suppresses Torsade de Pointes arrhythmias and reduces spatial dispersion of repolarization in the chronic AV-block dog model.

Background: An electrical storm of Torsade de Pointes arrhythmias (TdP) can be reproducibly induced in the anesthetized chronic AV-block (CAVB) dog by infusion of the IKr-blocker dofetilide. Earlier studies showed that these arrhythmias 1) arise from locations with high spatial dispersion in repolarization (SDR) and 2) can be suppressed by high-rate pacing. We examined whether suppression of TdP by high-rate pacing is established through a decrease in SDR in the CAVB dog. Methods: Dofetilide (25 µg/kg in 5 min) was administered to 5 anesthetized CAVB dogs to induce TdP arrhythmias. During the experiments, animals were continuously paced from the right ventricular apex at 50 beats/minute (RVA50). Upon TdP occurrence and conversion, RVA pacing was consecutively set to 100, 80 and 60 beats/minute for 2 min, referred to as pacing blocks. To determine the additional anti-arrhythmic effects of HRP over defibrillation alone, the number of arrhythmic events and SDR at RVA100 were compared to data from three previously conducted experiments, in which dogs underwent the same experimental protocol but were paced at RVA60 upon TdP occurrence (RVA60retro). In all experiments, recordings included surface electrocardiogram and mapping by 56 intramural needles, each recording four electrograms, evenly inserted into the ventricular walls and septum. For each pacing block, the number of ectopic beats (EB), and TdP severity were scored. SDR was quantified as the average difference in repolarization time within four squared needles (SDRcubic). Results: In 4 out of 5 animals, pacing at RVA100 suppressed TdP occurrence. One dog could not be converted by defibrillation after the initial TdP. Compared to RVA50, pacing at RVA100, but not RVA80 and RVA60, significantly reduced the TdP score (78 ± 33 vs. 0 ± 0, p < 0.05 and vs. 12.5 ± 25 and 25 ± 50, both p > 0.05). The reduction in TdP score was reflected by a significant decrease in SDRcubic (125 ± 46 ms before TdP vs. 49 ± 18 ms during RVA100, p < 0.05), and SDR was smaller than in the RVA60retro animals (101 ± 52 ms, p < 0.05 vs. RVA100). Conclusion: In CAVB dogs, high-rate pacing effectively suppresses TdP, which, at least in part, results from a spatial homogenization of cardiac repolarization, as reflected by a decrease in SDR.

Noninvasive Hemodynamic Monitoring in Advanced Heart Failure Patients: New Approach for Target Treatments.

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.

QT and Tpeak-Tend interval variability: Predictive electrical markers of hospital stay length and mortality in acute decompensated heart failure. Preliminary data.

BACKGROUND: As previously reported, an increased repolarization temporal imbalance induces a higher risk of total/cardiovascular mortality. HYPOTHESIS: 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). METHOD: 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). CONCLUSION: 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.

Short-Period Temporal Dispersion Repolarization Markers in Elderly Patients with Decompensated Heart Failure.

Objectives: 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. Method: 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. Results: 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. Conclusion: 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.

Sex-Specific Associations of Anxiety With Left Ventricular Hypertrophy and Transmural Dispersion of Repolarization in Hypertensive Patients.

Background: The previous studies have shown that individuals with hypertension and anxiety have a higher mean left ventricular mass index (LVMI) and QTc dispersion. We explored the associations between anxiety and left ventricular hypertrophy (LVH) and between anxiety and transmural dispersion of repolarization (TDR) (as detected by T peak-T end interval/QT interval, Tp-Te/QT ratio) in patients with hypertension. Methods: A total of 353 patients with uncomplicated hypertension from the Shaanxi Provincial People's Hospital were enrolled between 2017 and 2021. Anxiety was defined as a Hamilton Anxiety Scale (HAM-A) score ≥ 14. Logistic regression models were used to estimate the association between HAM-A and LVH. The association between HAM-A score and Tp-Te/QT was estimated using linear regression. Results: Participants were divided into two groups based on the presence of anxiety. LVMI was significantly higher in patients with hypertension and anxiety than in those with hypertension without anxiety (no anxiety: 84.36 ± 23.82, anxiety: 105.75 ± 25.45 g/m2, p < 0.001). HAM-A score was positively correlated with LVMI (r = 0.578, p < 0.001) and with Tp-Te/QT (r = 0.252, p < 0.001). Logistic regression models showed that patients with hypertension and anxiety were at higher risk of LVH than were patients with hypertension without anxiety (adjusted OR, 2.44, 95% CI, 1.35-4.43, p = 0.003). The linear regression analysis showed that the HAM-A score was associated with Tp-Te/QT ratio (adjusted ß, 0.001, 95% CI, 0.001-0.002, p = 0.013). There was an interaction between sex and anxiety for LVH risk (p for interaction = 0.035) and for increased Tp-Te/QT (p for interaction = 0.014). After stratification by sex, anxiety was associated with increased risk for LVH in men with hypertension (adjusted OR, 5.56, 95% CI, 2.07-14.98, p = 0.001), but not in women (adjusted: OR, 1.44, 95% CI, 0.64-3.26, p = 0.377) with hypertension. The HAM-A score was also positively associated with Tp-Te/QT ratio in male (adjusted ß, 0.002, 95% CI, 0.001-0.003, p < 0.001), but not in women (adjusted ß, 0.001, 95% CI, -0.0002-0.002, p = 0.165). Conclusion: Our results indicated that anxiety was associated with LVH and with increased TDR in men with hypertension, but not in women with hypertension.

Effects of ß-blockers on ventricular repolarization documented by 24-hour electrocardiography in long QT syndrome type 2.

BACKGROUND: Long QT syndrome (LQTS) is an inherited arrhythmia disorder characterized by ventricular repolarization abnormalities and a risk of sudden cardiac death. The electrophysiological components generating the high risk of arrhythmias in LQTS are prolonged repolarization, increased dispersion of repolarization, and early afterdepolarizations, which are clinically estimated as QT interval, T-wave peak to T-wave end (TPE) interval, and T2/T1-wave amplitude ratio, respectively. In experimental LQTS type 2 (LQT2) models, ß-blockers decrease dispersion of repolarization and prevent early afterdepolarizations. In clinical studies in patients with LQT2 , ß-blockers are more effective against exercise-induced than arousal-induced cardiac events. OBJECTIVES: The aim of the study was to investigate the effects of ß-blocker therapy on repolarization properties in LQT2. METHODS: QT and TPE intervals and maximal T2/T1-wave amplitude ratios recorded by 24-hour electrocardiograms before and during ß-blocker therapy were evaluated in 25 patients with LQT2. RESULTS: ß-Blocker therapy decreased the maximal T2/T1-wave amplitude ratio from 2.9 ± 1.1 to 1.8 ± 0.7 (P < .001), but did not change the pause-induced T2/T1-wave amplitude ratio. Under medication, abrupt maximal TPE intervals were shorter at heart rates of ≥75 beats/min and maximal QT intervals were shorter at a heart rate of 100 beats/min. CONCLUSION: ß-Blockers stabilize ventricular repolarization in LQT2 by reducing electrocardiographic early afterdepolarizations and by reducing abrupt prolongation of electrocardiographic dispersion of repolarization and ventricular repolarization duration at elevated heart rates. The effect of ß-blockers on pause-induced electrocardiographic early afterdepolarizations is weak. The findings provide electrocardiographic explanation for the protective effects of ß-blockers against exercise-induced cardiac events in LQT2.

Myocardial electrophysiological and mechanical changes caused by moderate hypothermia-A clinical study.

Moderate hypothermia has been used to improve outcomes in comatose out-of-hospital cardiac arrest survivors during the past two decades, although the effects remain controversial. We have recently shown in an experimental study that myocardial electrophysiological and mechanical relationships were altered during moderate hypothermia. Electromechanical window positivity increased, and electrical dispersion of repolarization decreased, both of which are changes associated with decreased arrhythmogenicity in clinical conditions. Mechanical dispersion, a parameter also linked to arrhythmic risk, remained unaltered. Whether corresponding electrophysiological and mechanical changes occur in humans during moderate hypothermia, has not been previously explored. Twenty patients with normal left ventricular function were included. Measurements were obtained at 36 and 32°C prior to ascending aortic repair while on partial cardiopulmonary bypass and at 36°C after repair. Registrations were performed in the presence of both spontaneous and comparable paced heart rate during standardized loading conditions. The following electrical and mechanical parameters were explored: (1) Electromechanical window, measured as time difference between mechanical and electrical systole, (2) dispersion of repolarization from ECG T-wave, and (3) mechanical dispersion, measured as segmental variation in time to peak echocardiographic strain. At moderate hypothermia, mechanical systolic prolongation (425 ± 43-588 ± 67 ms, p < 0.001) exceeded electrical systolic prolongation (397 ± 49-497 ± 79 ms, p < 0.001), whereby, electromechanical window positivity increased (29 ± 30-86 ± 50 ms, p < 0.001). Dispersion of repolarization and mechanical dispersion remained unchanged. Corresponding electrophysiological and mechanical relationships were present at comparable paced heart rates. After rewarming, the increased electromechanical window was reversed in the presence of both spontaneous and paced heart rates. Moderate hypothermia increased electromechanical window positivity, while dispersion of repolarization and mechanical dispersion remained unchanged. This impact of hypothermia may be clinically relevant for selected groups of patients after cardiac arrest.

Interplay between temporal and spatial dispersion of repolarization in the initiation and perpetuation of torsades de pointes in the chronic atrioventricular block dog.

Ventricular arrhythmias, consisting of single ectopic beats (sEB), multiple EB (mEB), and torsades de pointes (TdP, defined as ≥5 beats with QRS vector twisting around isoelectric line) can be induced in the anesthetized chronic atrioventricular block (CAVB) dog by dofetilide (IKr blocker). The interplay between temporal dispersion of repolarization, quantified as short-term variability (STV), and spatial dispersion of repolarization (SDR) in the initiation and perpetuation of these arrhythmias remains unclear. Five inducible (≥3 TdPs/10 min) CAVB dogs underwent one mapping experiment and were observed for 10 min from the start of dofetilide infusion (0.025 mg/kg, 5 min). An intracardiac decapolar electrogram (EGM) catheter and 30 intramural cardiac needles in the left ventricle (LV) were introduced. STVARI was derived from 31 consecutive activation recovery intervals (ARIs) on the intracardiac EGM, using the formula: [Formula: see text]. The mean SDR3D in the LV was determined as the three-dimensional repolarization time differences between the intramural cardiac needles. Moments of measurement included baseline (BL) and after dofetilide infusion before first 1) sEB (occurrence at 100 ± 35 s), 2) mEB (224 ± 96 s), and 3) non-self-terminating TdP (454 ± 298 s). STVARI increased from 2.15 ± 0.32 ms at BL to 3.73 ± 0.99 ms* before the first sEB and remained increased without further significant progression to mEB (4.41 ± 0.45 ms*) and TdP (5.07 ± 0.84 ms*) (*P < 0.05 compared with BL). SDR3D did not change from 31 ± 11 ms at BL to 43 ± 13 ms before sEB but increased significantly before mEB (68 ± 7 ms*) and to TdP (86 ± 9 ms*+) (+P < 0.05 compared with sEB). An increase in STV contributes to the initiation of sEB, whereas an increase in SDR is important for the perpetuation of non-self-terminating TdPs.NEW & NOTEWORTHY This study compared two well-established electrophysiological parameters, being temporal and spatial dispersion of repolarization, and provided new insights into their interplay in the arrhythmogenesis of torsades de pointes arrhythmias. Although it confirmed that an increase in temporal dispersion of repolarization contributes to the initiation of single ectopic beats, it showed that an increase in spatial dispersion of repolarization is important for the perpetuation of non-self-terminating torsades de pointes arrhythmias.

Dynamic spatial dispersion of repolarization is present in regions critical for ischemic ventricular tachycardia ablation.

BACKGROUND: The presence of dynamic substrate changes may facilitate functional block and reentry in ventricular tachycardia (VT). OBJECTIVE: We aimed to study dynamic ventricular repolarization changes in critical regions of the VT circuit during sensed single extrastimulus pacing known as the Sense Protocol (SP). METHODS: Twenty patients (aged 67 ± 9 years, 17 male) underwent VT ablation. A bipolar voltage map was obtained during sinus rhythm (SR) and right ventricular SP pacing at 20 ms above ventricular effective refractory period. Ventricular repolarization maps were constructed. Ventricular repolarization time (RT) was calculated from unipolar electrogram T waves, using the Wyatt method, as the dV/dtmax of the unipolar T wave. Entrainment or pace mapping confirmed critical sites for ablation. RESULTS: The median global repolarization range (max-min RT per patient) was 166 ms (interquartile range [IQR] 143-181 ms) during SR mapping vs 208 ms (IQR 182-234) during SP mapping (P = .0003 vs intrinsic rhythm). Regions of late potentials (LP) had a longer RT during SP mapping compared to regions without LP (mean 394 ± 40 ms vs 342 ± 25 ms, P < .001). In paired regions of normal myocardium there was no significant spatial dispersion of repolarization (SDR)/10 mm2 during SP mapping vs SR mapping (SDR 11 ± 6 ms vs 10 ± 6 ms, P = .54). SDR/10 mm2 was greater in critical areas of the VT circuit during SP mapping 63 ± 29 ms vs SR mapping 16 ± 9 ms (P < .001). CONCLUSION: Ventricular repolarization is prolonged in regions of LP and increases dynamically, resulting in dynamic SDR in critical areas of the VT circuit. These dynamic substrate changes may be an important factor that facilitates VT circuits.

Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model.

INTRODUCTION: Torsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP. METHODS: Dofetilide (25 µg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions. Recordings included surface electrocardiogram and short-term variability (STV) of repolarization from endocardial unipolar electrograms. TdP inducibility (three or more episodes within 10 min after start of dofetilide) and arrhythmic activity scores (AS) were established. Mapping experiments in 10 additional dogs determined the effect of lowering rate on STV and spatial dispersion of repolarization (SDR) in baseline. RESULTS: IVR-tested animals had longer baseline RR-interval (1,403 ± 271 ms) and repolarization intervals than RVA60 animals. Dofetilide increased STV similarly under both rhythm strategies. Nevertheless, TdP inducibility and AS were higher under IVR conditions (6/8 and 37 ± 27 vs. 1/8 and 8 ± 12 in RVA60, respectively, both p < 0.05). Mapping: Pacing from high (128 ± 10 bpm) to middle (88 ± 10 bpm) to experimental rate (61 ± 3 bpm) increased all electrophysiological parameters, including interventricular dispersion, due to steeper left ventricular restitution curves, and intraventricular SDR: maximal cubic dispersion from 60 ± 14 (high) to 69 ± 17 (middle) to 84 ± 22 ms (p < 0.05 vs. high and middle rate). CONCLUSION: In CAVB dogs, severe bradycardia increases the probability and severity of arrhythmic events by heterogeneously causing electrophysiological instability, which is mainly reflected in an increased spatial, and to a lesser extent temporal, dispersion of repolarization.

Short-period temporal repolarization dispersion in subjects with atrial fibrillation and decompensated heart failure.

BACKGROUND/OBJECTIVES: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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).

Different effects of amiodarone and dofetilide on the dispersion of repolarization between well-coupled ventricular and Purkinje fibers1.

Increased transmural dispersion of repolarization is an established contributing factor to ventricular tachyarrhythmias. In this study, we evaluated the effect of chronic amiodarone treatment and acute administration of dofetilide in canine cardiac preparations containing electrotonically coupled Purkinje fibers (PFs) and ventricular muscle (VM) and compared the effects to those in uncoupled PF and VM preparations using the conventional microelectrode technique. Dispersion between PFs and VM was inferred from the difference in the respective action potential durations (APDs). In coupled preparations, amiodarone decreased the difference in APDs between PFs and VM, thus decreasing dispersion. In the same preparations, dofetilide increased the dispersion by causing a more pronounced prolongation in PFs. This prolongation was even more emphasized in uncoupled PF preparations, while the effect in VM was the same. In uncoupled preparations, amiodarone elicited no change on the difference in APDs. In conclusion, amiodarone decreased the dispersion between PFs and VM, while dofetilide increased it. The measured difference in APD between cardiac regions may be the affected by electrotonic coupling; thus, studying PFs and VM separately may lead to an over- or underestimation of dispersion.

Torsade de pointes induced by intravenous amiodarone therapy accompanied by marked augmentation of the transmural dispersion of repolarization in a patient with tachycardia-induced-cardiomyopathy.

We report a 77-year-old human on renal dialysis for end-stage renal disease with heart failure and atrial fibrillation (AF) complicated by a high ventricular frequency. The underlying disease was thought as tachycardia-induced-cardiomyopathy. Intravenous infusion of amiodarone was initiated, and direct current cardioversion succeeded in converting AF to sinus rhythm. Then, excessive increases in the QT and Tpeak-Tend (Tp-e) intervals were seen and hypokalemia induced by hemodialysis led to the development of numerous episodes of torsades de pointes (TdP). Magnesium repletion was effective in preventing TdP, while Tp-e intervals returned to the previous values 2 days after the discontinuation of amiodarone.

Dispersion of ventricular repolarization: Temporal and spatial.

Repolarization heterogeneity (RH) is an intrinsic property of ventricular myocardium and the reason for T-wave formation on electrocardiogram (ECG). Exceeding the physiologically based RH level is associated with appearance of life-threatening ventricular arrhythmias and sudden cardiac death. In this regard, an accurate and comprehensive evaluation of the degree of RH parameters is of importance for assessment of heart state and arrhythmic risk. This review is devoted to comprehensive consideration of RH phenomena in terms of electrophysiological processes underlying RH, cardiac electric field formation during ventricular repolarization, as well as clinical significance of RH and its reflection on ECG parameters. The formation of transmural, apicobasal, left-to-right and anterior-posterior gradients of action potential durations and end of repolarization times resulting from the heterogenous distribution of repolarizing ion currents and action potential morphology throughout the heart ventricles, and the different sensitivity of myocardial cells in different ventricular regions to the action of pharmacological agents, temperature, frequency of stimulation, etc., are being discussed. The review is focused on the fact that RH has different aspects - temporal and spatial, global and local; ECG reflection of various RH aspects and their clinical significance are being discussed. Strategies for comprehensive assessment of ventricular RH using different ECG indices reflecting various RH aspects are presented.

[Effects of hypothermia on the repolarization duration of ventricular myocytes in rats and its mechanism].

Objective: To observe the effects of hypothermia on the repolarization duration and the expression of Kir2.1 protein of ventricular myocytes in isolated rat heart and explore the role of Kir2.1 protein.Methods: Eighteen healthy adult male Sprague-Dawley rats were randomly divided into three groups (n=6 per group): Control group (C group), 35℃ group (H1 group), 32℃ group (H2 group). Langendorff isolated heart models were established. After 15 min 37℃ K-H fluid banlanced perfusion, C group continued to perfuse the K-H solution at 37℃ for 30 minutes, H1 group continued to perfuse the K-H solution at 35℃ for 30 minutes, H2 group continued to perfuse the K-H solution at 32℃ for 30 minutes. At 15 min of balanced perfusion (T1), and 30 min of continuous perfusion (T2), the heart rate,and the MAP in the three layers of the left ventricular anterior wall were recorded, the action potential duration at 50% repolarization (MAPD50), the action potential duration at 90% repolarization (MAPD90) and transmural dispersion of repolarization(TDR) were calculated. At the same time, the occurrence of arrhythmia was recorded. The expression of Kir2.1 protein was measured by Western blot. The average optical density (AOD) and the distribution of Kir2.1 protein were measured by immunohistochemistry in the ventricular tissue measured by electrophysiology. Results: Compared with T0, the heart rate was decreased, MAPD50 and MAPD90 were prolonged significantly (P＜0.05), and TDR was increased significantly (P＜0.05) in H1 group, H2 group at T1. Compared with C group, the HR was decreased, the MAPD90 was prolonged significantly (P＜0.05), TDR was increased significantly (P＜0.05),the expression and the AOD of Kir2.1 protein were decreased significantly (P＜0.05) in H1group, H2group at T1. Compared with H1 group, the heart rate of H2 group was decreased significantly (P＜0.05), MAPD50 and MAPD90 were prolonged significantly (P＜0.05), and TDR was increased significantly (P＜0.05) at T1. The distribution of Kir2.1 protein in group C was normal, while the distribution of Kir2.1 in H1 group and H2 group was disordered. Conclusion: Hypothermia prolonged the ventricular duration of repolarization and increased the dispersion of repolarization. The mechanism is related to the down-regulation the expression of Kir2.1 protein and the disorder of the distribution of Kir2.1 protein.

Left ventricular pacing induced polymorphic ventricular tachycardia via the adaptive left ventricle pacing algorithm.

Providers should be aware of the possibility of cardiac resynchronization therapy-related proarrhythmia which could be life-threatening. His-bundle pacing may serve as an alternative, more physiological, option in the management as it preserves the normal sequence of depolarization from the septum to the lateral wall, and from endocardium to epicardium.

Preventive Administration of Melatonin Attenuates Electrophysiological Consequences of Myocardial Ischemia.

The effect of preventive administration of melatonin on the arrhythmogenic substrate in the myocardium was studied in the rabbit model of acute ischemia/reperfusion in vivo. The animals treated with melatonin 60 min before ischemia induction had shorter median activation time compared to the control group (p=0.039), less pronounced shortening of repolarization durations in the ischemic zone during coronary occlusion (p=0.008), and more complete recovery of repolarization during reperfusion (p=0.027). In the melatonin group, the dispersion of repolarization was less than in the control group during both ischemic period (p=0.043) and reperfusion (p=0.038). Thus, preventive administration of melatonin mitigated the arrhythmogenic substrate in the heart under conditions of ischemia/reperfusion.

Short-Period Temporal Dispersion Repolarization Markers Predict 30-Days Mortality in Decompensated Heart Failure.

BACKGROUND AND OBJECTIVES: Electrocardiographic (ECG) markers of the temporal dispersion of the myocardial repolarization phase have been shown able to identify chronic heart failure (CHF) patients at high mortality risk. The present prospective single-center study sought to investigate in a well-characterized cohort of decompensated heart failure (HF) patients the ability of short-term myocardial temporal dispersion ECG variables in predicting the 30-day mortality, as well as their relationship with N-terminal Pro Brain Natriuretic Peptide (NT-proBNP) plasmatic values. METHOD: One hundred and thirteen subjects (male: 59, 67.8%) with decompensated CHF underwent 5 min of ECG recording, via a mobile phone. We obtained QT end (QTe), QT peak (QTp) and T peak to T end (Te) and calculated the mean, standard deviation (SD), and normalized index (VN). RESULTS: Death occurred for 27 subjects (24%) within 30 days after admission. Most of the repolarization indexes (QTe mean (p < 0.05), QTeSD (p < 0.01), QTpSD (p < 0.05), mean Te (p < 0.05), TeSD (p < 0.001) QTeVN (p < 0.05) and TeVN (p < 0.01)) were significantly higher in those CHF patients with the highest NT-proBNP (>75th percentile). In all the ECG data, only TeSD was significantly and positively related to the NT-proBNP levels (r: 0.471; p < 0.001). In the receiver operating characteristic (ROC) analysis, the highest accuracy for 30-day mortality was found for QTeSD (area under curve, AUC: 0.705, p < 0.01) and mean Te (AUC: 0.680, p < 0.01), whereas for the NT-proBNP values higher than the 75th percentile, the highest accuracy was found for TeSD (AUC: 0.736, p < 0.001) and QTeSD (AUC: 0.696, p < 0.01). CONCLUSION: Both mean Te and TeSD could be considered as reliable markers of worsening HF and of 30-day mortality. Although larger and possibly interventional studies are needed to confirm our preliminary finding, these non-invasive and transmissible ECG parameters could be helpful in the remote monitoring of advanced HF patients and, possibly, in their clinical management. (ClinicalTrials.gov number, NCT04127162).