QT Interval Time Research Articles

QT interval time lag in response to heart rate changes during stress test for Coronary Artery Disease diagnosis

Background: Slow adaptation of the QT interval to abrupt changes in heart rate (HR) can enhance ventricular heterogeneity and has been suggested as a marker of arrhythmic risk. Most investigations on QT rate adaptation lag have been performed in response to step-like HR changes. However, abrupt HR changes are difficult to induce or observe in ECG recordings under ambulatory conditions. Objective:We aim to evaluate the power of indices related to the QT lag in response to ramp-like HR changes in stress test to assess CAD risk. Methods:We quantified the lag between the actual QT series and the memoryless expected QT series, which was obtained by fitting a hyperbolic regression model to the instantaneous QT and HR measurements in stages where their behavior could be assumed stationary. The proposed methodology was applied to analyze ECG stress tests of a subset of 448 patients presenting different risk levels for Coronary Artery Disease (CAD). The QT lag was estimated separately in the exercise and recovery phases. Results:An increase in the estimated QT lag during exercise (from 25 to 36 s) and a decrease during recovery (from 57 to 39 s) were associated with higher CAD risk. The difference between these lags showed significant capacity for CAD risk stratification. Conclusion:The QT lag in response to HR changes can be quantified from a stress test. QT lag values in response to ramp-like HR changes are in ranges comparable to those quantified from abrupt HR changes and show clinical significance to stratify CAD risk.

Sleep disturbance exacerbates the cardiac conduction abnormalities induced by persistent heavy ambient fine particulate matter pollution: A multi-center cross-sectional study

Fine particulate matter (PM2.5) exposure and sleep disturbance have been significantly associated with adverse cardiovascular outcomes, however, the combined effects of these two factors are still unclear. We conducted a multi-center cross-sectional study from November 2018 to May 2019 in the Beijing–Tianjin–Hebei region in China to investigate the potential modifying effects of sleep disturbance on associations between cardiac conduction abnormalities and PM2.5 exposure, as well as the combined effects of sleep disturbance and heavy pollution episodes, which were defined based on the PM2.5 mass concentration (≥75 μg/m3, falling in the 75th/90th percentile) and duration (1 day and ≥2 days). The sleep quality and sleep duration of all participants were evaluated using the Pittsburgh Sleep Quality Index. Standard 12-lead electrocardiogram (ECG) test was performed to measure the heart rate (HR), QRS duration (time taken for ventricular depolarization), HR corrected QT interval (time for ventricular depolarization and repolarization) and PR interval (time for atrioventricular conduction). Multivariable linear regression models were performed to evaluate the associations of PM2.5 and heavy pollution events on ECG parameters and the joint effects with sleep disturbance. We found PM2.5 exposure was independently associated with prolonged QRS and QTc intervals. Association between PM2.5 and the QTc interval was significantly stronger in participants with poor sleep quality. For each 10-μg/m3 increase in PM2.5 concentration, the QTc interval in the participants with poor sleep quality increased by 0.41 % (95 % confidence interval: 0.19, 0.64). In addition, heavy PM2.5 pollution episodes, especially extremely heavy pollution of long duration, were found to have synergistic effects with sleep disturbance on ECG parameters. Our findings provide evidence that PM2.5 exposure, especially heavy pollution episodes, may increase abnormal cardiac conduction and have a synergistic effect with sleep disturbance. Improving sleep hygiene is crucial to protect the heart health of the general population.

Acute promyelocytic leukemia: A single institution's experience.

e19001 Background: Acute Promyelocytic Leukemia (APL) is highly curable but carries high risk of early morbidity and mortality, including hemostatic abnormalities, differentiation syndrome and infection. Induction regimens include all-trans-retinoic acid (ATRA) to promote promyelocyte differentiation and arsenic trioxide (ATO), with chemotherapy added for high-risk patients. Our objective was to characterize clinical characteristics and complications during APL induction. Methods: Electronic medical records were screened for ATRA, ATO, or idarubicin from 2011-2021. APL induction hospitalization records were reviewed for: demographics, white blood cell (WBC) and platelet count at presentation, fibrinogen at presentation, time to ATRA administration, time to complete remission (CR), infection, thrombohemorrhagic complications, ATO related QT interval prolongation, incidence of and time to differentiation syndrome. Results: 56 patients (pts) (median age 50) were analyzed. Mean time from initial presentation at our institution to ATRA administration was 1.5 days (range 0-6 days). Findings upon arrival: median WBC 1.7 K/UL (range 0.3-134.9), median platelets 32 K/UL (range 7-373), hypofibrinogenemia in 39.2% (N = 22) (median 161 MG/DL, range 35-473). 80.3% had documented thrombohemorrhagic complications during induction hospitalization: DIC (N = 24), venous thromboembolism (N = 12), gastrointestinal bleed (N = 6), oral mucosal bleeding (N = 5), vaginal bleeding (N = 3), gross hematuria (N = 3), intracranial hemorrhage (N = 3), epistaxis (N = 2), intraocular hemorrhage (N = 1), cerebral vascular accident (CVA) (N = 1). 21% (N = 12) developed differentiation syndrome with mean time of onset of 8.8 days (range 1-23 days). 55% (N = 31) had clinically significant infections most commonly neutropenic fever (N = 13), bacterial pneumonia (N = 10), skin (N = 5) and bacteremia (N = 5). 48 pts were given ATO during induction and 31% (N = 15) developed QT interval prolongation with no arrhythmias in the cohort. Among 8 pts who did not receive ATO, one died prior to therapy initiation and 7 were treated prior to ATO as standard of care. Among evaluable patients (N = 51): 98% (N = 50) achieved complete remission (CR) or complete remission with incomplete count recovery (CRi). Median time to CR was 35 days (range 27-50). 6 pts did not achieve CR or had unknown status: 1 patient died during induction (CVA) and 5 had post-induction bone marrow evaluations at outside facilities. Conclusions: Thrombohemorrhagic complications, infection and differentiation syndrome are critical to be mindful of during the early phase of treatment in APL. Our data adds to the landscape of knowledge regarding the incidence and timeline of complications. Although we observed prolonged QTc in pts on ATO, there were no arrhythmias detected and all pts were able to quickly resume therapy.

Assesment of Normal ECG Percentiles and Cardiac Rhythm Problems through 12-Lead ECG Screening in School-Age Children

Introduction: Electrocardiography (ECG) is an important non-invasive examination used for the diagnosis of cardiovascular diseases and rhythm problems for nearly hundred years. Many studies showed the important effect of age and gender on electrocardiographic tracings and studies were made to form ECG data normal for age groups. The number of studies on this subject is quite low in children. The aim of this study was to evaluate the standard percentile values of ECG measurement and the prevalence of cardiac rhythm disorders in school children aged 6-18 in our region. Material and Method: 2154 students who were randomly selected from eight elementary, secondary and high schools in Malatya city center were included in the study and informed consent form was taken from their families. Using MAC 2000 (GE Healthcare, Milwaukee, USA) device capable of taking digital ECG record, ECG records with standard 12 derivations were taken for all participating children. ECG records of all children were examined by the same pediatric cardiologists. Using 24 hour Holter ECG and echocardiography, advanced evaluation was performed for the children with problems detected in ECG records. Results: Pathology was detected in the ECG of 110 out of a total of 2154 children whose ECG records were examined. Average age of 2044 children without detected conduction and rhythm disorder was 11.4±2.8 and 56.8% (n=1149) were female. In addition to the heart rate, PR, QT and QTc interval and QRS time, R/S ratio was also checked manually in V1, V2 and V6 precordial derivations together with QTc, P, QRS and T axis for the children participating in the study. These eleven parameters were compared to the other studies in literature. Mean QTc interval was detected below 440 milliseconds in all age groups (6-9, 9-13, 13-18). Mean heart rate per minute was found higher in all age groups in our study compared to other studies. Thus mean QTc interval was found lower than the other studies although QT distance was similar. Conclusion: Data of this study is important for the detection of normal ECG percentiles and the prevalence of rhythm problems in children and would guide other future studies on this subject.

The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity.

Cyclophosphamide (CYP)-induced cardiotoxicity is a common side effect of cancer treatment. Although it has received significant attention, the related mechanisms of CYP-induced cardiotoxicity remain largely unknown. In this study, we used cell and animal models to investigate the effect of CYP on cardiomyocytes. Our data demonstrated that CYP-induced a prolonged cardiac QT interval and electromechanical coupling time courses accompanied by JPH2 downregulation. Moreover, N6-methyladenosine (m6A) methylation sequencing and RNA sequencing suggested that CYP induced cardiotoxicity by dysregulating calcium signaling. Importantly, our results demonstrated that CYP induced an increase in the m6A level of JPH2 mRNA by upregulating methyltransferases METTL3, leading to the reduction of JPH2 expression levels, as well as increased field potential duration and action potential duration in cardiomyocytes. Our results revealed a novel mechanism for m6A methylation-dependent regulation of JPH2, which provides new strategies for the treatment and prevention of CYP-induced cardiotoxicity.

Acute effects of inhaled iloprost on intracardiac conduction in patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is asevere, life-threatening disorder despite the availability of specific drug therapy. Alack of endogenous prostacyclin secondary to downregulation of prostacyclin synthase in PAH may contribute to vascular pathologies. Therefore, prostacyclin and its analogs including inhaled iloprost may decrease pulmonary arterial pressure and ventricular pressure. Here, we studied that acute effects of iloprost used in pulmonary vasoreactivity testing on the intracardiac conduction system in patients with PAH. Atotal of35 (15idiopathic PAH, 20congenital heart disease) patients with PAH were included in this prospective study. Patients were divided into two groups: 22patients with negative pulmonary vasoreactivity in group1 and 13with positive pulmonary vasoreactivity in group2. Electrophysiological parameters including basic cycle length, atrium-His (AH) interval, His-ventricle (HV) interval, PR interval, QT interval, QRS duration, Wenckebach period, and sinus node recovery time (SNRT) were evaluated before and after pulmonary vasoreactivity testing in both groups. The AH interval (81 [74-93]; 80 [65.5-88], p = 0.019) and SNRT (907.7 ± 263.4; 854.0 ± 288.04, p = 0.027) was significantly decreased after pulmonary vasoreactivity testing. Mean right atrium pressure was found to be correlated with baseline AH (r = 0.371, p = 0.031) and SNRT (r = 0.353, p = 0.037). Inhaled iloprost can improve cardiovascular performance in the presence of PAH, primarily through areduction in right ventricular afterload and interventricular pressure. Decreased pressure on the interventricular septum and ventricles leads to conduction system normalization including of the AH interval and SNRT due to resolution of inflammation and edema.

Enhanced Automated Diagnosis of Coronary Artery Disease Using Features Extracted From QT Interval Time Series and ST–T Waveform

There is a growing interest in automated diagnosis of coronary artery disease (CAD) with the application of machine learning (ML) methods to the body surface electrocardiograph (ECG). Although prior studies have documented associations of CAD with increased QT variability and ST–T segment abnormalities such as T-wave inversion and ST-segment elevation or depression, their efficacy in automated CAD detection has not been fully investigated. To validate their usefulness, a dataset containing related clinical characteristics and 5-min single-lead ECGs of 107 healthy controls and 93 CAD patients was first constructed. Based on this dataset, simultaneous analyses were then conducted in five scenarios, in which different ML algorithms were applied to classify the two groups with various features derived from the RR and QT interval time-series and ST–T segment waveforms. Compared with utilizing features obtained from the RR interval time-series, better classification results were achieved utilizing that obtained from the QT interval time-series. The classification results were elevated with combining utilization of features derived from both the RR and QT interval time-series. By further fusing features extracted from ST–T segment waveforms, the best performance was achieved with 96.16% accuracy, 95.75% sensitivity, and 96.40% specificity. Based the best performance, an automated CAD detection system was developed with extreme gradient boosting, an ensemble ML algorithm, and the residual neural network, namely, a deep learning method. The results of this study support the potential of information derived from the QT interval time-series and ST–T segment waveforms in ECG-based automated CAD detection.

Comparison of QT interval variability of coronary patients without myocardial infarction with that of patients with old myocardial infarction

BackgroundThe significant association of myocardial ischemia with elevated QT interval variability (QTV) has been reported in myocardial infarction (MI) patients. However, the influence of the time course of MI on QTV has not been investigated systematically. MethodShort-term QT and RR interval time series were constructed from the 5 min electrocardiograms of 49 coronary patients without MI and 26 patients with old MI (OMI). The QTV, heart rate variability (HRV), and QT–RR coupling of the two groups were analyzed using various time series analysis tools in the time- and frequency-domains, as well as nonlinear dynamics. ResultsNearly all of the tested QTV indices for coronary patients with OMI were higher than those for patients without MI. However, no significant differences were found between the two groups in any of the variables employed to assess the HRV and QT–RR coupling. All of the markers that showed statistical significances in univariate analyses still possessed the capabilities of distinguishing between the two groups even after adjusting for studied baseline characteristics, including the coronary atherosclerotic burden. ConclusionsThe results suggested that the QTV increased in coronary patients with OMI compared to those without MI, which might reflect the influence of post-MI remodeling on the beat-to-beat temporal variability of ventricular repolarization. The non-significant differences in the HRV and QT–RR couplings could indicate that there were no differences in the modulation of the autonomic nervous system and interaction of QT with the RR intervals between the two groups.

Understanding the cardiac toxicity of the anthropogenic pollutant phenanthrene on the freshwater indicator species, the brown trout (Salmo trutta): From whole heart to cardiomyocytes

Freshwater systems are faced with a myriad of stressors including geomorphological alterations, nutrient overloading and pollution. Previous studies in marine fish showed polyaromatic hydrocarbons (PAHs) to be cardiotoxic. However, the cardiotoxicity of anthropogenic pollutants in freshwater fishes is unclear and has not been examined across multiple levels of cardiac organization. Here we investigated the effect of phenanthrene (Phe), a pervasive anthropogenic pollutant on a sentinel freshwater species, the brown trout (Salmo trutta). We first examined the electrical activity of the whole heart and found prolongation (∼8.6%) of the QT interval (time between ventricular depolarization and repolarization) of the electrocardiogram (ECG) and prolongation (∼13.2%) of the monophasic action potential duration (MAPD) following ascending doses of Phe. At the tissue level, Phe significantly reduced trabecular force generation by ∼24% at concentration 15 μM and above, suggesting Phe reduces cellular calcium cycling. This finding was supported by florescent microscopy showing a reduction (∼39%) in the intracellular calcium transient amplitude following Phe exposure in isolated brown trout ventricular myocytes. Single-cell electrophysiology was used to reveal the mechanism underlying contractile and electrical dysfunction following Phe exposure. A Phe-dependent reduction (∼38%) in the L-type Ca2+ current accounts, at least in part, for the lowered Ca2+ transient and force production. Prolongation of the MAPD and QT interval was explained by a reduction (∼70%) in the repolarising delayed rectifier K+ current following Phe exposure. Taken together, our study shows a direct impact of Phe across multiple levels of cardiac organization in a key freshwater salmonid.

Refractory ventricular fibrillations after surgical repair of atrial septal defects in a patient with CACNA1C gene mutation - case report

BackgroundCongenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history.Case presentationA 64-year-old man was diagnosed as having multiple atrial septal defects. He presented with no symptoms of heart failure. His preoperative ECG showed complete right bundle branch block (CRBBB) with a corrected QT interval time of 478 ms. He underwent open-heart surgery to close the defects through median sternotomy access. Three hours after the operation, he developed multiple events of TdP and VFs in the intensive care unit. Cardiopulmonary resuscitation and multiple cardioversions were attempted for his repetitive TdP and VFs. He eventually reverted to sinus rhythm, and intravenous beta-blocker was administered to maintain the sinus rhythm. After this event, his family history was reviewed, and it was confirmed that his daughter and grandson had a medical history of arrhythmia. A genetic test confirmed that he had a missense mutation in CACNA1C, p.K1580 T, which is the cause for type 8.ConclusionsThis case highlights the importance of paying attention to other ECG findings in patients with CRBBB, which can mask prolonged QT intervals.

Multi-Country Evaluation of Safety of Dihydroartemisinin/Piperaquine Post-Licensure in African Public Hospitals with Electrocardiograms.

The antimalarial drug piperaquine is associated with delayed ventricular depolarization, causing prolonged QT interval (time taken for ventricular de-polarisation and re-polarisation). There is a lack of safety data regarding dihydroartemisinin/piperaquine (DHA/PPQ) for the treatment of uncomplicated malaria, which has limited its use. We created a platform where electrocardiograms (ECG) were performed in public hospitals for the safety assessment of DHA/PPQ, at baseline before the use of dihydroartemisinin/piperaquine (Eurartesim®), and on day 3 (before and after administration of the final dose) and day 7 post-administration. Laboratory analyses included haematology and clinical chemistry. The main objective of the ECG assessment in this study was to evaluate the effect of administration of DHA/PPQ on QTc intervals and the association of QTc intervals with changes in blood biochemistry, full and differential blood count over time after the DHA/PPQ administration. A total of 1315 patients gave consent and were enrolled of which 1147 (87%) had complete information for analyses. Of the enrolled patients 488 (42%), 323 (28%), 213 (19%) and 123 (11%) were from Ghana, Burkina Faso, Tanzania and Mozambique, respectively. Median (lower—upper quartile) age was 8 (5–14) years and a quarter of the patients were children under five years of age (n = 287). Changes in blood biochemistry, full and differential blood count were temporal which remained within clinical thresholds and did not require any intervention. The mean QTcF values were significantly higher than on day 1 when measured on day 3 before and after administration of the treatment as well as on day 7, four days after completion of treatment (12, 22 and 4 higher, p < 0.001). In all age groups the values of QT, QTcF and QTcB were highest on day 3 after drug intake. The mean extreme QTcF prolongation from baseline was lowest on day 3 before drug intake (33 ms, SD = 19) and highest on day 3 after the last dose (60 ms, SD = 31). There were 79 (7%) events of extreme mean QTcF prolongation which were not clinically significant. Nearly a half of them (n = 37) were grade 3 and mainly among males (33/37). Patients in Burkina Faso, Mozambique and Tanzania had significantly lower mean QTcF than patients in Ghana by an average of 3, 4 and 11 ms, respectively. We found no evidence that Eurartesim® administered in therapeutic doses in patients with uncomplicated malaria and no predisposing cardiac conditions in Africa was associated with adverse clinically significant QTc prolongation.

Recording duration and short-term reproducibility of heart rate and QT interval variability in patients with myocardial infarction

Beat-to-beat variability of the QT interval (QTV) measured on surface ECG has emerged as a potential marker for ventricular repolarization instability and has been used along with heart rate variability (HRV) to predict arrhythmic risk. Since measurement modalities of QTV have not been standardized, the objective of this study was to investigate the effect of ECG recording duration on QTV as well as HRV. Using a database of 30 min ECG recorded from 500 patients with acute myocardial infraction during rest, we extracted RR and QT interval time series and estimated different HRV and QTV metrics over windows of varying length. Analysis of variance (ANOVA) and intra-class correlation analyses were computed to investigate the effect of recording length on consistency and short-term reproducibility of HRV and QTV variables. Good consistency (non-significant ANOVA results) and short-term reproducibility (intra-class correlation coefficients >0.8) were demonstrated for all but standard deviation based metrics when at least 200 beats were included in the estimation. In conclusion, QTV can be quantified from resting ECG with good short-term consistency and reproducibility that is comparable to that of HRV.

Entropy Analysis of RR and QT Interval Variability during Orthostatic and Mental Stress in Healthy Subjects

Autonomic activity affects beat-to-beat variability of heart rate and QT interval. The aim of this study was to explore whether entropy measures are suitable to detect changes in neural outflow to the heart elicited by two different stress paradigms. We recorded short-term ECG in 11 normal subjects during an experimental protocol that involved head-up tilt and mental arithmetic stress and computed sample entropy, cross-sample entropy and causal interactions based on conditional entropy from RR and QT interval time series. Head-up tilt resulted in a significant reduction in sample entropy of RR intervals and cross-sample entropy, while mental arithmetic stress resulted in a significant reduction in coupling directed from RR to QT. In conclusion, measures of entropy are suitable to detect changes in neural outflow to the heart and decoupling of repolarisation variability from heart rate variability elicited by orthostatic or mental arithmetic stress.

Quantification of the acute effect of a low dose of red wine by nonlinear measures of RR and QT interval series in healthy subjects

The measures of nonlinear properties of RR interval and QT interval time series are sensitive to physiologically- or pathologically-induced complexity/regularity changes, but were not used to estimate the effect of alcohol intake. We wanted to examine the potential of these measures to quantify the acute effect of a low dose of red wine in healthy subjects. In separate experiments, fourteen young volunteers drank 200ml of red wine and a control drink with equal concentration of ethanol. ECG in supine position was recorded 20min before and 60min after drink intake. RR interval and QT interval series were extracted from ECG and we calculated variability, scaling exponents (α1 and α2) and sample entropy (SampEn) for both series. Systolic and diastolic blood pressures (BP) were measured every 10min. The immediate effect of both the drinks was equal: HR, BP and QT variability exhibited a sudden increase and then a decrease. However, the prolonged effect of wine and the control drink was different. Wine decreased both BP (p<0.05) and reduced complexity of RR and QT series (increased scaling exponents and decreased SampEn). The control drink prolonged QT and RR intervals (p<0.05). These results point out that the nonlinear properties of RR and QT interval series could be used to differentiate the effect of wine and ethanol. Changes in RR and QT interval series induced by a low dose of red wine are more detectable by methods that quantify the structure of the series than by methods that quantify their variability.

Decoupling of QT interval variability from heart rate variability with ageing

Ageing has been associated with changes in cardiac electrophysiology that result in QT interval prolongation. The effect of age on rate-adaptation dynamics of the QT interval is less well understood. The aim of this study was to assess age-related changes in the temporal relationship between QT and RR interval variability. Resting ECG of 20 young and 20 elderly healthy subjects were analyzed. Beat-to-beat RR and QT interval time series were automatically extracted. Coupling between QT and RR was assessed by means of the QT variability index, coherence in the frequency domain, rate-corrected QT interval, cross-multiscale entropy, information based similarity index and joint symbolic dynamics. In addition to QT interval prolongation (433 ± 31 versus 405 ± 33 ms, p = 0.008), elderly subjects were characterized by a significantly increased QT variability index (−1.26 ± 0.28 versus −1.52 ± 0.22 ms, p < 0.0001), reduced coherence in high (0.11 ± 0.09 versus 0.29 ± 0.14 ms, p = 0.003), and low frequency bands (0.20 ± 0.16 versus 0.49 ± 0.15 ms, p < 0.0001), reduced information domain synchronization index (0.13 ± 0.07 versus 0.19 ± 0.05 ms, p = 0.001) as well as increased entropy and disparity in joint symbolic dynamics of QT and RR interval time series. In conclusion, ageing is associated with decoupling of QT variability from heart rate variability. Complexity analysis in addition to standard metrics may provide additional insight.

Analysis of pro-arrhythmic effects induced by different routes of administration of bone marrow stem cells

There has been repeated concern that intramyocardial (i.m.) delivery of cells could cause ventricular arrhythmias. The aim of the study was to evaluate the pro-arrhythmic effects of bone marrow stem cell (BMSC) injection and compare different routes of administration. An ischemia reperfusion injury was induced in New Zealand rabbits by temporal ligation of anterior descending coronary artery. Homologous BMSCs were isolated, cultured and re-suspended for injection. We compared different routes of BMSC injections, intramyocardial (i.m.) versus intravenous (i.v.) administration of cells. A control group was treated with i.m. injections of saline. The hourly number of supra- and ventricular premature contractions (VPCs), QT interval time and QTc time were recorded and calculated. At Day 7 after cell injections, VPCs were more frequent in the groups treated with i.m. BMSCs and i.m. saline compared with i.v. BMSCs (132 ±19; 54±14 and 34±9, respectively; P<0.01 within groups), whereas at Day 21 the number of VPCs was higher in the 2 groups treated with either i.m. or i.v. BMSCs compared with saline (96±23; 52±19 and 25±20, respectively; P<0.001 within groups). QTc time interval was prolonged during ischemia, and recovered in control and in the group treated with i.v. cells, whereas it remained longer in rabbits treated with i.m. BMSCs. These findings show that i.m. BMSC injections induced a high number of pre-arrhythmic events suggesting changes in cardiac electrophysiological properties. The i.v. administration of cells resulted in lower VPC beats and in a temporary QT prolongation. These results suggest that the combination of BMS cells and i.m. injections induced an electrical remodeling that contributed to the development of arrhythmias.

Totally Drug Resistant Tuberculosis can be treated with thioridazine in combination with antibiotics to which the patient was initially resistant.

infection is presented. Thioridazine is an old neuroleptic that replaced the first commercial neuroleptic chlorpromazine (trade name lactargil) inasmuch as the former produced fewer serious side effects than the latter. Thioridazine however, is not free of serious side effects. Albeit infrequently, it may produce prolongation of QT interval (time between heart beats), arrhythmia, tordade de pointes, and rarely, even sudden death [2]. However, with proper attention to these potential problems, cardiac monitoring prior to and during initial therapy with thioridazine is commenced at a low dose that is increased slowly, the drug is relatively safe when compared to other newer and more commonly used neuroleptics [2]. The in vitro antitubercular properties of thioridazine were first described more than 15 years ago [3] at the time that resurgence of tuberculosis and its multi-drug resistant forms of infection were noted world-wide. However, the concentrations needed to completely inhibit the in vitro replication of the organism were clinically irrelevant given that these concentrations were in the range of 25 to 30 mg/L and the maximum safe level that can be achieved in the patient is ca. 0.5 mg/L of plasma. Crowle et al. [4] had demonstrated that chlorpromazine enhanced the killing of intracellular Mycobacterium tuberculosis at a concentration in the medium that was in the range present in plasma of a chronically treated with this neuroleptic. Given that tuberculosis is essentially an intracellular infection, the question of whether thioridazine, the equal to chlorpromazine as an in vitro tubercular agent [3], has similar intracellular activity against multi-drug resistant Mycobacterium tuberculosis, was soon investigated and shown to promote the killing of intracellular multi-drug resistant Mycobacterium tuberculosis by non-killing human macrophages at a concentration that was close to that initially used to treat a freshly diagnosed case of pyschosis [5]. Thioridazine has been shown to cure the mouse of an antibiotic susceptible [6] and multi-drug resistant [7] infections and most recently, shown to cure patients infected with extensively drug resistant strains of Mycobacterium tuberculosis when used in combination with antibiotics to which the patients were initially resistant [8]. When used as monotherapy, thioridazine has been +

Abstract 8622: Transmural Dispersion of Repolarization in Febrile Children with Kawasaki Disease

Introduction: The instability of myocardial repolarization is generally mediated by myocardial failure. We assessed the hypothesis that transmural dispersion of repolarization is increased in the inflamed myocardium in patients with acute-phase Kawasaki disease. Method: Consecutive 25 infants (M:F = 15:10 ) with Kawasaki disease aged 2.6 ± 2.2 years and 25 age-matched control infants were included. RR interval, QT interval and Tp-e time (CM5 lead) were calculated using analysis software (Acqknowledge Ver. 3.9, Biopac Systems Inc. CA, USA). Tp-e time was corrected by Fridericia equation (Tp-eC). These parameters were compared in the acute phase (6.9 ± 3.0 days after onset) and recovery phase (23.0 ± 13.3 days after onset) or control. The relationship between Tp-e/QT, Tp-eC and C reactive protein, body temperature on admission were evaluated by regression analysis. Results: 1) The Tp-e/QT in the acute phase were significantly higher than that in the recovery phase (Mean ± SD: 0.248 ± 0.055 vs 0.215 ± 0.022, p&lt;0.05 ) and control group (0.220 ± 0.025, p&lt;0.005). 2) The Tp-eC in the acute phase was significantly higher than that in the recovery phase (89.99 ± 16.86 vs 82.11 ± 7.45, p&lt;0.05) and control group (80.02 ± 10.46, p&lt;0.01). 3) In acute phase, significant positive correlation was observed between Tp-e/QT and C reactive protein or body temperature (r = 0.677 and 0.672, respectively). Further, between Tp-eC and C reactive protein or body temperature (r = 0.482 and 0.583, respectively). Conclusions: Transmural dispersion of repolarization assessed by Tp-e/QT and Tp-eC was increased in the acute phase of Kawasaki disease, which exhibits the sub-clinical lability of ventricular repolarization. These repolarization properties of the myocardium were considered a useful indicator to assess arrhythmogenesis in patients with Kawasaki disease.

Assessment of repolarization heterogeneity in myocardial infarction patients by QT interval time variability (dispersion) and dynamics of the first electrocardiogram derivative

Assessment of repolarization heterogeneity in myocardial infarction patients by QT interval time variability (dispersion) and dynamics of the first electrocardiogram derivative

Multiscale entropy and detrended fluctuation analysis of QT interval and heart rate variability during normal pregnancy

Pregnancy leads to physiological changes in various parameters of the cardiovascular system. The aim of this study was to investigate longitudinal changes in the structure and complexity of heart rate variability (HRV) and QT interval variability during the second half of normal gestation. We analysed 30-min high-resolution ECGs recorded monthly in 32 pregnant women, starting from the 20th week of gestation. Heart rate and QT variability were quantified using multiscale entropy (MSE) and detrended fluctuation analyses (DFA). DFA of HRV showed significantly higher scaling exponents towards the end of gestation (p<0.0001). MSE analysis showed a significant decrease in sample entropy of HRV with progressing gestation on scales 1–4 (p<0.05). MSE analysis and DFA of QT interval time series revealed structures significantly different from those of HRV with no significant alteration during the second half of gestation.In conclusion, pregnancy is associated with increases in long-term correlations and regularity of HRV, but it does not affect QT variability. The structure of QT time series is significantly different from that of RR time series, despite its close physiological dependence.