Ventricular Repolarization Intervals Research Articles

Associations of Cardiac Ventricular Repolarization with Serum Adhesion Molecules and Cognitive Function in Older Adults: The MIND-China Study.

Emerging evidence has linked electrocardiographic parameters with serum adhesion molecules and cognition; however, their interrelationship has not been explored. We sought to investigate the associations of ventricular depolarization and repolarization intervals with serum adhesion molecules and cognitive function among rural-dwelling older adults. This population-based study engaged 4,886 dementia-free participants (age ≥60 years, 56.2% women) in the baseline examination (March-September 2018) of MIND-China. Of these, serum intercellular and vascular adhesion molecules (ICAM-1 and VCAM-1) were measured in 1591 persons. We used a neuropsychological test battery to assess cognitive function. Resting heart rate, QT, JT intervals, and QRS duration were assessed with electrocardiogram. Data were analyzed using general linear models adjusting for multiple confounders. Longer JT interval was significantly associated with lower z-scores of global cognition (multivariable-adjusted β= -0.035; 95% confidence interval = -0.055, -0.015), verbal fluency (-0.035; -0.063, -0.007), attention (-0.037; -0.065, -0.010), and executive function (-0.044; -0.072, -0.015), but not with memory function (-0.023; -0.054, 0.009). There were similar association patterns of QT interval with cognitive functions. In the serum biomarker subsample, longer JT and QT intervals remained significantly associated with poorer executive function and higher serum adhesion molecules. We detected statistical interactions of JT interval with adhesion molecules (pinteraction <0.05), such that longer JT interval was significantly associated with a lower executive function z-score only among individuals with higher serum ICAM-1 and VCAM-1. Longer ventricular depolarization and repolarization intervals are associated with worse cognitive function in older adults and vascular endothelial dysfunction may play a part in the associations.

IL-1β is not critical to chronic heart dysfunction in mice with Chagas disease.

Long after Trypanosoma cruzi infection, 40% of individuals develop a progressive chronic chagasic cardiomyopathy (CCC), with systolic dysfunction and arrhythmias. Since we previously showed IL-1β mediates the development of systolic dysfunction and cardiac arrhythmias in diabetes mellitus and cardiorenal syndrome, and IL-1β remains elevated in Chagas disease patients, here we tested the role of IL-1β in CCC using a mouse model. Mice deficient in IL-1R expression (Il-1r-/- ) survived acute T. cruzi infection with greater parasitemia than controls but did not lose weight as wild-type (WT) did. At the chronic stage, WT presented prolonged ventricular repolarization intervals (QJ), while Il-1r-/- presented intervals like noninfected controls. Infected Il-1r-/- and WT did not differ in stroke volume (SV), the incidence of cardiac arrhythmias on electrocardiography (EKG), whole heart action potential duration (APD), or the incidence of triggered activity after S1-S2 protocol, which is a measure of susceptibility to cardiac arrhythmias. We also treated chronically infected WT mice with an IL-1R antagonist, anakinra. Treatment shortened the QJ interval but did not improve the SV or the incidence of cardiac arrhythmias on EKG. Anakinra failed to reduce triggered activity following the electrical extra-stimulation protocol. In conclusion, the absence of functional IL-1β/IL-1R signaling did not prevent or reverse the decrease of SV or the incidence of cardiac arrhythmias induced by chronic T. cruzi infection, implying this is not a critical mechanism in generating or maintaining CCC. Since similar cardiac abnormalities were previously credited to IL-1β signaling, ruling out this mechanism is important to discourage further attempts of IL-1β blockade as a therapeutical measure.

Proposed stages of Fabry disease: insights from multiparametric cardiac MRI and advanced ECG

Abstract Funding Acknowledgements Type of funding sources: None. Background Staging of Fabry disease (FD) cardiomyopathy uses multiparametric cardiac MRI. Advanced disease is characterized by left ventricular hypertrophy (LVH), myocardial inflammation/oedema (high native T2 mapping) and/or fibrosis (late gadolinium enhancement, LGE). Pre-LVH involvement has been described and includes myocardial sphingolipid storage (low native T1 mapping), impaired LV global longitudinal strain (GLS) and microvascular disease/dysfunction (low stress myocardial blood flow, MBF, in perfusion mapping). We aimed to define (1) the early myocardial phenotype prior to T1 lowering/pre-storage and (2) the stages of cardiac involvement in FD. Methods FD patients and age, sex and heart rate matched healthy controls underwent same-day ECG with advanced analysis and multiparametric CMR (cines, GLS, pre-contrast T1 and T2 mapping, adenosine stress perfusion mapping [for MBF] and LGE). Results 114 Fabry patients (46 ± 13 years, 61% female, 37% [n = 72] had LVH) and 76 controls (49 ± 15 years, 50% female) were included. FD with vs without LVH in brief and as expected, FD with LVH had significantly (p &amp;lt; 0.05) lower MBF, GLS and T1, and higher T2 and %LGE. FD pre-LVH low T1 vs pre-LVH normal T1: low T1 patients (32/72, 44%) had higher LV mass index (67 ± 14 vs 59 ± 10g/m2, P = 0.011), maximum Q wave amplitude (2[1-2] vs 1[1-2]mm, P &amp;lt; 0.001), Sokolow-Lyon index (22[16-28] vs 17[13-23]mm, P = 0.031) and more fractionated QRS complexes (44 vs 18%, P = 0.020). FD pre-LVH normal T1 vs healthy controls: normal T1 pre-LVH Fabry patients (40/72, 56%) had reduced GLS (-18 ± 2 vs -20 ± 2%, P &amp;lt; 0.001), microvascular impairment (lower MBF 2.5 ± 0.7 vs 3.0 ± 0.8mL/g/min, P = 0.028), subtle T2 elevation (50 ± 4 vs 48 ± 2ms, p = 0.027) and limited LGE (%LGE 0.3 ± 1.1 vs 0%, P = 0.004) when compared to healthy controls; ECG abnormalities included shorter P wave duration (88 ± 12 vs 94 ± 15ms, P = 0.010) and T wave peak time (Tonset–Tpeak; 104 ± 28 vs 115 ± 20ms, P = 0.015), resulting in a more symmetric T wave with lower T wave time ratio (Tonset–Tpeak)/(Tpeak–Tend) (1.5 ± 0.4 vs 1.8 ± 0.4, P &amp;lt; 0.001) compared to controls. Conclusion Prior staging of Fabry cardiomyopathy included a pre-LVH stage (accumulation/storage) and two LVH stages (hypertrophy and inflammation; fibrosis and impairment). Here we define an even earlier stage, pre-LVH pre-detectable storage, defined by microvascular dysfunction, impaired GLS and altered atrial depolarization and ventricular repolarization intervals (see Figure). Abstract Figure. Proposed stages of cardiac involvement

The myocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage

Abstract Background Cardiac involvement in Fabry Disease (FD) occurs prior to left ventricular hypertrophy (LVH) and is characterized by low myocardial native T1 with storage reflected by cardiovascular magnetic resonance (CMR) and ECG changes. Objectives We hypothesize that a pre-storage myocardial phenotype might occur even earlier, prior to T1 lowering. Methods FD patients and age, sex and heart rate matched healthy controls underwent same-day ECG with advanced analysis and multiparametric CMR (cines, global longitudinal strain [GLS], T1 and T2 mapping, stress perfusion [myocardial blood flow, MBF] and late gadolinium enhancement [LGE]). Results 114 Fabry patients (46±13 years, 61% female) and 76 controls (49±15 years, 50% female) were included. In pre-LVH FD (n=72, 63%), a low T1 (n=32/72, 44%) was associated with a constellation of ECG and functional abnormalities compared to normal T1 FD patients and controls. However, pre-LVH FD with normal T1 (n=40/72, 56%) also had abnormalities compared to controls: reduced GLS (−18±2 vs −20±2%, P&amp;lt;0.001), microvascular changes (lower MBF 2.5±0.7 vs 3.0±0.8mL/g/min, P=0.028), subtle T2 elevation (50±4 vs 48±2ms, p=0.027) and limited LGE (%LGE 0.3±1.1 vs 0%, P=0.004). ECG abnormalities included shorter P wave duration (88±12 vs 94±15ms, P=0.010) and T wave peak time (Tonset–Tpeak; 104±28 vs 115±20ms, P=0.015), resulting in a more symmetric T wave with lower T wave time ratio (Tonset–Tpeak)/(Tpeak–Tend) (1.5±0.4 vs 1.8±0.4, P&amp;lt;0.001) compared to controls. Conclusions FD has a measurable myocardial phenotype pre-LVH and pre-detectable myocyte storage with microvascular dysfunction, subtly impaired GLS and altered atrial depolarization and ventricular repolarization intervals. Proposed stages of cardiac involvement Funding Acknowledgement Type of funding source: None

Identification of Drug-Induced Multichannel Block and Proarrhythmic Risk in Humans Using Continuous T Vector Velocity Effect Profiles Derived From Surface Electrocardiograms.

We present continuous T vector velocity (TVV) effect profiles as a new method for identifying drug effects on cardiac ventricular repolarization. TVV measures the temporal change in the myocardial action potential distribution during repolarization. The T vector dynamics were measured as the time required to reach p percent of the total T vector trajectory length, denoted as Tr(p), with p in {1, …, 100%}. The Tr(p) values were individually corrected for heart rate at each trajectory length percentage p. Drug effects were measured by evaluating the placebo corrected changes from baseline of Tr(p)c jointly for all p using functional mixed effects models. The p-dependent model parameters were implemented as cubic splines, providing continuous drug effect profiles along the entire ventricular repolarization process. The effect profile distributions were approximated by bootstrap simulations. We applied this TVV-based analysis approach to ECGs available from three published studies that were conducted in the CiPA context. These studies assessed the effect of 10 drugs and drug combinations with different ion channel blocking properties on myocardial repolarization in a total of 104 healthy volunteers. TVV analysis revealed that blockade of outward potassium currents alone presents an effect profile signature of continuous accumulation of delay throughout the entire repolarization interval. In contrast, block of inward sodium or calcium currents involves acceleration, which accumulates during early repolarization. The balance of blocking inward versus outward currents was reflected in the percentage pzero of the T vector trajectory length where accelerated repolarization transitioned to delayed repolarization. Binary classification using a threshold pzero = 43% separated predominant hERG channel blocking drugs with potentially higher proarrhythmic risk (moxifloxacin, dofetilide, quinidine, chloroquine) from multichannel blocking drugs with low proarrhythmic risk (ranolazine, verapamil, lopinavir/ritonavir) with sensitivity 0.99 and specificity 0.97. The TVV-based effect profile provides a detailed view of drug effects throughout the entire ventricular repolarization interval. It enables the evaluation of drug-induced blocks of multiple cardiac repolarization currents from clinical ECGs. The proposed pzero parameter enhances identification of the proarrhythmic risk of a drug beyond QT prolongation, and therefore constitutes an important tool for cardiac arrhythmia risk assessment.

The myocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage.

AimsCardiac involvement in Fabry disease (FD) occurs prior to left ventricular hypertrophy (LVH) and is characterized by low myocardial native T1 with sphingolipid storage reflected by cardiovascular magnetic resonance (CMR) and electrocardiogram (ECG) changes. We hypothesize that a pre-storage myocardial phenotype might occur even earlier, prior to T1 lowering.Methods and resultsFD patients and age-, sex-, and heart rate-matched healthy controls underwent same-day ECG with advanced analysis and multiparametric CMR [cines, global longitudinal strain (GLS), T1 and T2 mapping, stress perfusion (myocardial blood flow, MBF), and late gadolinium enhancement (LGE)]. One hundred and fourteen Fabry patients (46 ± 13 years, 61% female) and 76 controls (49 ± 15 years, 50% female) were included. In pre-LVH FD (n = 72, 63%), a low T1 (n = 32/72, 44%) was associated with a constellation of ECG and functional abnormalities compared to normal T1 FD patients and controls. However, pre-LVH FD with normal T1 (n = 40/72, 56%) also had abnormalities compared to controls: reduced GLS (−18 ± 2 vs. −20 ± 2%, P < 0.001), microvascular changes (lower MBF 2.5 ± 0.7 vs. 3.0 ± 0.8 mL/g/min, P = 0.028), subtle T2 elevation (50 ± 4 vs. 48 ± 2 ms, P = 0.027), and limited LGE (%LGE 0.3 ± 1.1 vs. 0%, P = 0.004). ECG abnormalities included shorter P-wave duration (88 ± 12 vs. 94 ± 15 ms, P = 0.010) and T-wave peak time (Tonset – Tpeak; 104 ± 28 vs. 115 ± 20 ms, P = 0.015), resulting in a more symmetric T wave with lower T-wave time ratio (Tonset – Tpeak)/(Tpeak – Tend) (1.5 ± 0.4 vs. 1.8 ± 0.4, P < 0.001) compared to controls.ConclusionFD has a measurable myocardial phenotype pre-LVH and pre-detectable myocyte storage with microvascular dysfunction, subtly impaired GLS and altered atrial depolarization and ventricular repolarization intervals.

Analysis of changes in cardiac circadian rhythms of RR and QT induced by a 60-day head-down bed rest with and without nutritional countermeasure.

Prolonged weightlessness exposure generates cardiovascular deconditioning, with potential implications on ECG circadian rhythms. Head-down (-6°) tilt (HDT) bed rest is a ground-based analogue model for simulating the effects of reduced motor activity and fluids redistribution occurring during spaceflight. Our aim was to evaluate the impact of 60-day HDT on the circadianity of RR and ventricular repolarization (QTend) intervals extracted from 24-h Holter ECG recordings, scheduled 9days before HDT (BDC-9), the 5th (HDT5), 21st (HDT21) and 58th (HDT58) day of HDT, the 1st (R + 0) and 8th (R + 7) day after HDT. Also, the effectiveness of a nutritional countermeasure (CM) in mitigating the HDT-related changes was tested. RR and QTend circadian rhythms were evaluated by Cosinor analysis, resulting in maximum and minimum values, MESOR (a rhythm-adjusted mean), oscillation amplitude (OA, half variation within a night-day cycle), and acrophase (φ, the time at which the fitting sinusoid's amplitude is maximal) values. RR and QTend MESOR increased at HDT5, and the OA was reduced along the HDT period, mainly due to the increase of the minima. At R + 0, QTend OA increased, particularly in the control group. The φ slightly anticipated during HDT and was delayed at R + 0. 60-Day HDT affects the characteristics of cardiac circadian rhythm by altering the physiological daily cycle of RR and QTend intervals. Scheduled day-night cycle and feeding time were maintained during the experiment, thus inferring the role of changes in the gravitational stimulus to determine these variations. The applied nutritional countermeasure did not show effectiveness in preventing such changes.

Predictive role of ventricular repolarization parameters for the occurrence of complete heart block in patients undergoing transcatheter aortic valve implantation.

BackgroundWe investigated the role of ventricular repolarization parameters to predict complete atrioventricular block in patients undergoing transcatheter aortic valve implantation (TAVI).MethodsA total of 150 patients undergoing TAVI due to severe aortic stenosis were included in this retrospective cohort study. Patients were assigned in two groups based on the presence (n: 49) or absence (n: 101) of complete atrioventricular block after TAVI. Ventricular repolarization intervals (QT, QTc, JT, JTc, TP‐E), indices (QT dispersion), and ratios (TP‐E/QT, TP‐E/QTc, TP‐E/JTc) were measured.ResultsElectrocardiographic repolarization parameters such as Tp‐e interval: 74.2 ± 5.1 versus 59.2 ± 6.1 ms, p < .001; QTc interval: 397.6 ± 3.4 versus 368.1 ± 7.8 ms, p < .001; JTc interval: 317.4 ± 11.3 versus 291.1 ± 6.7 ms, p < .001; Tp‐e/QT ratio: 0.28 ± 0.04 versus 0.20 ± 0.04, p < .001; Tp‐e/QTc ratio: 0.29 ± 0.04 versus 0.19 ± 0.03, p < .001; Tp‐e/JT ratio: 0.32 ± 0.03 versus 0.23 ± 0.03, p < .001; Tp‐e/JTc ratio: 0.30 ± 0.02 versus 0.2 ± 0.03, p < .001; and QT dispersion: 34.4 ± 3.0 versus 17.8 ± 3.6 ms, p < .01 were significantly higher in post‐TAVI permanent pacemaker group. In a univariate regression analysis, pulmonary artery pressure, heart rate, coronary artery disease, Tp‐e/QTc, Tp‐e/JTc, and PR interval were significantly associated with complete heart block. Tp‐e/JTc (OR 0.373, p = .067) and PR interval (OR 0.898, p = .079) were found to be independent predictors of these type of arrhythmias in a multivariate analysis. But it is not statistically significant.ConclusionOur results suggest that repolarization parameters may play a role in predicting complete atrioventricular block. Tp‐e/JTc was found to be potential independent risk marker for this setting.

Comparison of one- and three-lead ECG to measure cardiac intervals and differentiate drug-induced multi-channel block

IntroductionFDA has established initiatives to characterize clinical and non-clinical biomarkers to enable more precise prediction of proarrhythmia risk based upon knowledge of drug effect on multiple cardiac ion channels (Colatsky et al., 2016). The FDA has recently demonstrated superiority of early ventricular repolarization interval (JTp) in differentiating pure hERG block from multi-channel block in human subjects. Preclinical studies often acquire a single lead ECG, whereas FDA measurements of JTp were derived ​from a spatial vectorcardiogram computed using multiple leads. This study compares QT subintervals derived from single lead vs. spatial magnitude (SM) ECG and contrasts information obtained from multilead and single lead ECGs in the canine model. MethodsFour beagle dogs were instrumented with 3-lead Holter monitors to acquire continuous surface ECG recordings for three consecutive days. A 24-h baseline recording was obtained on day 1 followed by administration of dofetilide on day 2 and atropine and dofetilide on day 3. Lead II and SM ECGs were automatically analyzed using the AE-1010 Rhythm Express™ (RE) software (VivaQuant, St. Paul, MN USA) without manual intervention or editing of the results (auto). Five-minute averages of beat-to-beat intervals measured on each lead were compared for agreement assessed by Bland-Altman (BA) statistics and consistency measured as the repeatability standard deviation (SD) from 5-min intervals. The fully automated results were screened by an operator (semi-automated) and compared to automated results. ResultsJTp and TpTe measured using SM lead are less sensitive to changes in posture and respiration related changes in T-wave morphology. The 24-h repeatability SD of 5-min subintervals for JTp and TpTe over the three days was improved by 15.4% and 15.5% respectively with the highest improvements of 23.3% for JTp on day 2 and 25.3% for TpTe on day 3. Drug induced changes in QTcV, QRS, RR, and PR intervals were qualitatively similar between the SM lead and Lead II and in close agreement based on BA statistics. Semi-automated and automated measurements from SM Lead were in close agreement based on BA statistics. DiscussionSingle lead ECG is adequate for PR, RR, QRS, and QT, but produces different and more variable results when assessing QT subintervals relative to the SM lead. Close agreement between automated and semi-automated measurements demonstrates Rhythm Express accuracy and the potential to streamline interval analysis.

Ventricular Repolarization Intervals in Children Previously Treated with Anthracyclines

Ventricular Repolarization Intervals in Children Previously Treated with Anthracyclines

Optimal QT/JT Interval Assessment in Patients with Complete Bundle Branch Block

Prolonged ventricular repolarization duration confers increased risk for malignant ventricular arrhythmias. We sought to clarify the optimal method of QT/JT interval assessment in patients with complete bundle branch block (BBB). Study patients (n = 71) were dual-chamber device recipients with baseline left or right BBB who preserved intrinsic ventricular activation during incremental atrial pacing. Patients were classified according to the presence or not of structural heart disease. The former group received chronic amiodarone therapy. QT and JT intervals were recorded at baseline heart rate of 51 ± 4 beats/min and during atrial pacing at 60, 80, and 100 beats/min. We used linear mixed-effects models to assess the effect of heart rate on the derived QTc and JTc values with the use of six different heart rate correction formulae. Heart rate had a significant effect on the QTc and the JTc intervals regardless of the correction formula used (P < 0.001 for all formulae). The formula of Hodges demonstrated the least variability in QTc and JTc measurements across the different heart rates in both patients groups without (F = 15.05 and F = 13.53, respectively) and with structural heart disease (F = 5.71 and F = 7.69, respectively), followed by the Nomogram and Framingham methods, whereas the uncorrected QT and JT intervals showed comparable heart rate-dependency. The application of Bazett's JTc and QTc led to the most pronounced interval variations in any case with BBB. The Hodges, Nomogram and Framingham correction methods provide best assessment of QT/JT intervals in BBB, whereas Bazett's formula exaggerates heart rate-dependency of ventricular repolarization intervals.

Predicting Torsade de Pointes in Acquired Long QT Syndrome: Optimal Identification of Critical QT Interval Prolongation

Objectives: To determine the optimal method of ventricular repolarization assessment in predicting torsade de pointes (Tdp) in acquired long QT syndrome (LQTS) within the context of the recommended cutoff levels of concern for QT/corrected QT (QTc) interval prolongation. Methods: Twenty-nine patients with LQTS and Tdp (age 66 ± 11 years) and matched controls were studied. Standard 12-lead electrocardiograms were utilized to evaluate ventricular repolarization by using six different QT/JT heart rate correction methods. We compared the distribution of QT/QTc and JT/corrected JT intervals of patients who experienced Tdp with (1) the corresponding intervals in the matched controls and (2) the recommended cutoff levels for QT/JT interval prolongation. Results: Patients with Tdp (23 with narrow QRS, 6 with wide QRS) had longer ventricular repolarization intervals than controls (p < 0.001). For patients with narrow QRS, the QTc interval as determined firstly by the method of Hodges (t = 7.56, c = 0.933, p < 0.001), followed by the Nomogram and Fridericia methods, best discriminated Tdp patients from controls and provided the optimal balance between sensitivity and specificity at all three cutoff levels. For patients with wide QRS, the JT interval or, alternatively, the Hodges method seemed most useful. Conclusions: Assessment of ventricular repolarization by the Hodges, Nomogram and Fridericia methods performs best in identifying subsequent Tdp.

Study of ventricular repolarization changes after carnitine deprivation in rats by contactless magnetocardiography

Carnitine deficiency can be associated with cardiomyopathy and life-threatening arrhythmias. The aim of this study was to assess changes of ventricular repolarization (VR) intervals by contactless magnetocardiographic mapping (MCG), in a rat model of carnitine deficiency. 21 anesthetized Wistar rats (WR), 11 males and 10 females, were investigated, with an unshielded 36-channel MCG instrumentation. After a basal recording 10 animals were randomized to carnitine-deprivation induced by a 3-weeks diet containing N-trimethyl-hydrazine-3-propionate (THP). All WR were restudied 1 week after the end of THP treatment. RR, QRS, QT peak, QT end, JT peak, JT end and T peak-end intervals were measured from MCG waveforms. A prolongation of all HR-corrected VR intervals was observed in THP-treated animals (range 7.6–12.8%), as compared to their basal values. However, only the lengthening of QT end and T peak-end was statistically significant ( p < 0.05). Compared to untreated age-matched controls, the cardiac intervals of TPH-treated WR values were longer, but the differences were not significant. After 3 weeks of THP-induced reduction of cardiac and plasma levels of carnitine, abnormalities in myocardial function are expected. In this study we have found only a prolongation of HR-corrected QT end and T peak-end in THP-treated animals. The lack of significance versus age-matched controls could be either due to too early re-evaluation after deprivation, or to the effect of aging. In fact, age-related prolongation of VR intervals has been reported in WR at the age of 14 months.

Magnetocardiographic estimate of cardiac intervals in guinea pigs. Comparison between conscious and anesthetized conditions

The aim of this study was to assess the feasibility and reliability of Magnetocardiographic mapping (MCG), for the measurement of cardiac intervals and quantitative estimate of other MCG ventricular repolarization (VR) parameters, in unrestrained conscious Guinea pigs (GPs), taking into account possible gender-related differences, and in comparison with MCG of the same animals under anesthesia. 12 adult GPs (6 males and 6 females) were investigated with an unshielded 36-channel MCG system. Two sets of measurements were performed from each animal, at the age of 14 months: 1) awake (prone posture), 2) under anesthesia (supine). RR, PR, QRS, QT peak, QT end, JT peak, JT end and T peak-end intervals were measured. MCG imaging and quantitative analysis were automatically obtained as magnetic field maps (MFMs) and with the Equivalent Current Dipole (ECD) inverse solutions. As concerns interval durations, measured in the two sessions, a statistically significant difference was found only for the T peak-end interval. No gender-related differences of VR intervals were observed. Although MFMs were different as a function of the posture, the ECD localization at the QRSpeak, was properly centered in the heart and coincided within a 3-D uncertainty of less that 10 mm. MCG mapping is reliable for the assessment of cardiac intervals and VR, both in awake and in anaesthetized GPs. In non-aggressive rodents, MCG mapping does not require anesthesia and can be repeated multiple times, for circadian or long-term longitudinal pharmacological studies.

Contactless magnetocardiographic study of age- and gender-related variability of ventricular repolarization parameters in guinea pigs

Guinea pigs (GPs) are used for preclinical investigation of the ability of new drugs to induce QT alterations and arrhythmias. The aim of this study was to evaluate the accuracy of multi-site magnetocardiographic mapping (MCG) for the assessment of age-related variation of ventricular repolarization (VR) maps in GPs. 18 adult GPs (8 males and 10 females) were investigated with an unshielded 36-channel MCG instrumentation, at the age of 5 months. Only 12 survived until the age of 14 months and were restudied. RR, PR, QRS, QT peak, QT end, JT peak, JT end and T peak-end intervals were measured from MCG waveforms. Magnetic field (MF) maps and the Equivalent Current Dipole (ECD) inverse solution were automatically computed. At the age of 5 months, average values of VR intervals were slightly longer in males. At the age of 14 months, a statistically significant age-related prolongation of the PR ( p < 0.05) and of the QRS ( p < 0.01) intervals was found. Neither significant age- nor gender-related variations of VR intervals were appreciable. Statistically significant ( p < 0.01) age-related differences were found for the JT α angle, T peak α angle and for the distance dynamics. At the same age, the strength of the ECD at the peak of the P, QRS and T waves, was stronger ( p < 0.01) than at 5 months. MCG is reliable for VR assessment in GPs. In contrast with findings in rats, age-related changes and gender-related differences of VR parameters were not statistically significant in GPs. More complex variability of MF patterns was observed, which deserves further investigation.

Contactless magnetocardiographic mapping in anesthetized Wistar rats: evidence of age-related changes of cardiac electrical activity

Magnetocardiography (MCG) is the recording of the magnetic field (MF) generated by cardiac electrophysiological activity. Because it is a contactless method, MCG is ideal for noninvasive cardiac mapping of small experimental animals. The aim of this study was to assess age-related changes of cardiac intervals and ventricular repolarization (VR) maps in intact rats by means of MCG mapping. Twenty-four adult Wistar rats (12 male and 12 female) were studied, under anesthesia, with the same unshielded 36-channel MCG instrumentation used for clinical recordings. Two sets of measurements were obtained from each animal: 1) at 5 mo of age (297.5 +/- 21 g body wt) and 2) at 14 mo of age (516.8 +/- 180 g body wt). RR and PR intervals, QRS segment, and QTpeak, QTend, JTpeak, JTend, and Tpeak-end were measured from MCG waveforms. MCG imaging was automatically obtained as MF maps and as inverse localization of cardiac sources with equivalent current dipole and effective magnetic dipole models. After 300 s of continuous recording were averaged, the signal-to-noise ratio was adequate for study of atrial and ventricular MF maps and for three-dimensional localization of the underlying cardiac sources. Clear-cut age-related differences in VR duration were demonstrated by significantly longer QTend, JTend, and Tpeak-end in older Wistar rats. Reproducible multisite noninvasive cardiac mapping of anesthetized rats is simpler with MCG methodology than with ECG recording. In addition, MCG mapping provides new information based on quantitative analysis of MF and equivalent sources. In this study, statistically significant age-dependent variations in VR intervals were found.

Novel indices of ventricular repolarization to screen post myocardial infarction patients

We propose novel indices of ventricular repolarization intervals, the JTp/JT, Tpe/JTp and Tpe/JT ratios. These indices have been compared with the duration of the ventricular repolarization intervals and other ratios in 17 normal subjects and 17 patients with old myocardial infarction. In the intervals and other ratios, the best separation between groups is obtained with the Tpe/QTp and Tpe/QT ratios with 94% sensitivity and 82% specificity, the proposed ratios increased sensitivity to 100% and specificity to 94%. These indices should be further tested to determine their usefulness in discriminating between OMI patients with and without susceptibility to ventricular arrhythmias.

Marginal copper and high fat diet produce alterations in electrocardiograms and cardiac ultrastructure in male rats.

This study investigated whether a high fat diet in tandem with a marginal copper (Cu) diet exerts deleterious effects on copper status, cardiac morphology, and electrophysiology compared to a low-fat marginal copper diet. Male weanling Long-Evans rats were fed diets containing either marginal copper (42.5 mumol/kg) or adequate copper (97.6 mumol/kg), and low fat (50.0 g/kg) or high fat (150.0 g/kg) diet for 12 wk in a 2 x 2 factorial design. To simulate the western diet, fat was composed of a 1:2 polyunsaturated:saturated fatty acids using a coconut and corn oil mixture. High dietary fat increased liver Cu concentration. Marginal copper diets decreased liver Cu,Zn-superoxide dismutase activity. Dietary copper and fat level had no effect on volume densities of mitochondria and myofibril. However, lower mitochondrial pathologic scores were observed in the rats consuming the high fat diets. Marginal copper high fat diet prolonged atrial electric depolarization (PR) and ventricular electric depolarization and repolarization (QT) intervals. This study provided direct evidence that a high fat diet can exert detrimental effects on cardiac ultrastructure and lead to alterations in electrocardiograms. The combination of marginal copper-high fat diet appears to alter cardiac electric conductivity. Longer term studies should provide information more relevant to clinical situations and morphologic changes.

Carotid sinus baroreflex influence on electrophysiologic properties of the canine atrioventricular node and ventricle

This study examines the efferent mechanisms of carotid sinus baroreflex influence on ventricular repolarization and refractory period compared with effects on atrioventricular (AV) nodal conduction. Pressure was controlled in both carotid sinuses by the Moisejeff technique in 16 chloralose-anesthetized dogs. Increases in carotid sinus pressure during pacing produced graded prolongation of AV nodal conduction, ventricular repolarization and refractory period with a threshold at a carotid sinus pressure of 120 mm Hg and a peak response at 200 mm Hg. Atropine, 0.4 mg/kg, attenuated the peak percent change in ventricular repolarization interval by only 12 ± 14% (± standard error of the mean) despite a significantly greater attenuation (48 ± 11%, p <0.05) in peak percent change in AV nodal conduction. However, stellate ganglionectomy attenuated the peak percent change in ventricular repolarization (42 ± 19%), similar to effects on AV nodal conduction (59 ± 21%, p >0.25). Changes in mean arterial pressure, ventricular end-diastolic segment length or segment length shortening with systole (sonomicrometer technique) did not account for the electrophysiologic responses. Latency to peak effect on ventricular repolarization (43 ± 7 seconds) was slower than that on AV nodal conduction (23 ± 6 seconds, p <0.05). This difference in time course was not abolished by atropine. Thus, the carotid sinus baroreflex prolongs ventricular repolarization and refractoriness mainly by withdrawal of sympathetic influence; AV nodal conduction is prolonged by both vagal activation and sympathetic withdrawal. In addition, differences in time course between ventricular and AV nodal electrophysiologic responses are not explained by different efferent autonomic mechanisms.

Cardiac rhythm, rate and ventricular repolarization properties in infants at risk for sudden infant death syndrome: Comparison with age- and sex-matched control infants

Using 24-hour ambulatory electrocardiographic recordings and 120-lead body surface potential maps, prevailing cardiac rate and rhythm, incidence and frequency of dysrhythm and rate and pattern of ventricular repolarization at the body surface were compared in 17 infants at risk for sudden infant death syndrome (SIDS) and 17 age- and sex-matched control subjects. Sinus rhythm was the prevailing rhythm in both study groups and there were no intergroup differences in average overall awake or asleep sinus rates, nor in temporal variability of sinus rate. Atrial and ventricular ectopic activity were equally uncommon in both study groups. Although there were smooth and bipolar body surface distributions of ST-T and QRST time integrals in both study groups, the average rate of ventricular repolarization (QTc), measured from the 12-lead electrocardiogram, 120-lead body surface potential maps and 24-hour electrocardiography, was consistently shorter in the at-risk group than in the control group. However, temporal variability of QTc was not different between the 2 groups. Thus, significant cardiac dysrhythm and QT prolongation are not found in infants at increased risk for SIDS. Rather, there is an abbreviated ventricular repolarization interval in at-risk infants. In combination with the findings of intergroup similarity of average sinus rate and temporal variability of sinus rate and ventricular repolarization rate, the data suggest a subtle, constant difference in cardiac autonomic activity, most likely an Increase in sympathetic tone, in at-risk subjects. The role of this altered cardiac autonomic activity in the causation of SIDS remains undetermined.