Ventricular Repolarization Dynamics Research Articles

Evaluation of electrocardiogram findings and inflammatory parameters in patients with benign paroxysmal positional vertigo.

Benign Paroxysmal Positional Vertigo (BPPV) is a common vestibular disorder characterized by brief episodes of intense vertigo, often accompanied by nausea and nystagmus. The frontal QRS-T (fQRS-T) angle, a novel indicator of ventricular depolarization and repolarization heterogeneity, has garnered attention due to its potential to reveal insights into cardiac function. This study aimed to investigate the potential relationship between the fQRS-T angle and inflammation markers in individuals with BPPV. The study encompassed 49 BPPV patients and 51 healthy individuals as a control group. Laboratory assessments were conducted to measure inflammation parameters. Electrocardiogram (ECG) data was analyzed, focusing on conduction parameters including fQRS-T angle, QRS duration, QT interval, and corrected QT interval. The study revealed that the fQRS-T angle was significantly higher in BPPV patients compared to the control group (p<.001). Moreover, inflammation markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and C-reactive protein-to-albumin ratio (CAR) were notably elevated in BPPV patients (p<.001, for all). The findings of the correlation analysis demonstrated a strong association between NLR and the fQRS-T angle (r=.718, p<.001). Additionally, the results of the linear regression analysis indicated that NLR positively predicted the fQRS-T angle (p<.001). The study's outcomes have underscored a significant increase in the fQRS-T angle among BPPV patients, suggesting altered ventricular repolarization dynamics. The strong correlation between NLR and the fQRS-T angle raises intriguing possibilities of inflammation's potential role in influencing cardiac electrophysiology. The study contributes to the growing body of evidence suggesting that BPPV might have implications beyond its immediate vestibular manifestations.

Drug-induced symmetry effects on ventricular repolarization dynamics

The detection of proarrhythmic effects of many current drugs has prompted the search for complementary non-invasive markers of cardiotoxicity risk. Indices based on studies of cardiac vector dynamics have emerged. We use quaternions to quantify symmetry changes in cardiac vector velocity during ventricular repolarization, which could signal the arrhythmia risk. Principal component analysis is used to homogenize the information and reduce the space to three dimensions. A comparison with the ratio of normalized areas of the repolarization loop (T-wave) and two standard measurements was made: QT and T peak-end intervals. Assessment was conducted by comparing 52 healthy subjects with patients undergoing treatment with Sotalol: 7 recordings with Torsade de Pointes events and 15 without arrhythmic effects. Significant differences (p ¡ 5E-4) were found in both phases of repolarization in terms of absolute velocities and areas. The ratio between the maximums of each parameter in both halves of the T-wave showed a trend towards 1 in the proximity of an arrhythmic event. Angular velocity ratios reached a sensitivity/specificity pair of 100 (95%CI: 59–100)/90 (95%CI: 79–97) with an AUC of 98.6 (95%CI: 95.7–100) in the comparison of healthy population with at-risk patients. Linear discriminant analysis improved the classification by reaching sensitivity and specificity values of 100 (95%CI: 59–100) and 96 (5%CI: 87–100), respectively. The high performance of the method exceeded the diagnostic power of standard measurements, thus showing its potential to contribute to drug evaluation methods. Further research with a larger number of events is required to generalize the method.

QT variability unrelated to RR variability during stress testing for identification of coronary artery disease.

Stress test electrocardiogram (ECG) analysis is widely used for coronary artery disease (CAD) diagnosis despite its limited accuracy. Alterations in autonomic modulation of cardiac electrical activity have been reported in CAD patients during acute ischemia. We hypothesized that those alterations could be reflected in changes in ventricular repolarization dynamics during stress testing that could be measured through QT interval variability (QTV). However, QTV is largely dependent on RR interval variability (RRV), which might hinder intrinsic ventricular repolarization dynamics. In this study, we investigated whether different markers accounting for low-frequency (LF) oscillations of QTV unrelated to RRV during stress testing could be used to separate patients with and without CAD. Power spectral density of QTV unrelated to RRV was obtained based on time-frequency coherence estimation. Instantaneous LF power of QTV and QTV unrelated to RRV were obtained. LF power of QTV unrelated to RRV normalized by LF power of QTV was also studied. Stress test ECG of 100 patients were analysed. Patients referred to coronary angiography were classified into non-CAD or CAD group. LF oscillations in QTV did not show significant differences between CAD and non-CAD groups. However, LF oscillations in QTV unrelated to RRV were significantly higher in the CAD group as compared with the non-CAD group when measured during the first phases of exercise and last phases of recovery. ROC analysis of these indices revealed area under the curve values ranging from 61 to 73%. Binomial logistic regression analysis revealed LF power of QTV unrelated to RRV, both during the first phase of exercise and last phase of recovery, as independent predictors of CAD. In conclusion, this study highlights the importance of removing the influence of RRV when measuring QTV during stress testing for CAD identification and supports the added value of LF oscillations of QTV unrelated to RRV to diagnose CAD from the first minutes of exercise. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

ECG Ventricular Repolarization Dynamics during Exercise: Temporal Profile, Relation to Heart Rate Variability and Effects of Age and Physical Health.

Periodic repolarization dynamics (PRD) is a novel electrocardiographic marker of cardiac repolarization instability with powerful risk stratification capacity for total mortality and sudden cardiac death. Here, we use a time-frequency analysis approach to continuously quantify PRD at rest and during exercise, assess its dependence on heart rate variability (HRV) and characterize the effects of age (young adults/middle-aged adults/older adults), body mass index (non-overweight/overweight) and cardiorespiratory fitness level (fit/unfit). Sixty-six male volunteers performed an exercise test. RR and dT variabilities (RRV, dTV), as well as the fraction of dT variability unrelated to RR variability, were computed based on time-frequency representations. The instantaneous LF power of dT (PdTV), representing the same concept as PRD, and of its RRV-unrelated component (PdTVuRRV) were quantified. dT angle was found to mostly oscillate in the LF band. Overall, 50–70% of PdTV was linearly unrelated to RRV. The onset of exercise caused a sudden increase in PdTV and PdTVuRRV, which returned to pre-exercise levels during recovery. Clustering analysis identified a group of overweight and unfit individuals with significantly higher PdTV and PdTVuRRV values at rest than the rest of the population. Our findings shed new light on the temporal profile of PRD during exercise, its relationship to HRV and the differences in PRD between subjects according to phenotypic characteristics.

Estimation of the second ventilatory threshold through ventricular repolarization profile analysis.

Under the hypothesis that sympathetic control of ventricular repolarization may change once the second ventilatory threshold (VT2) has been reached, a novel methodology for non-invasive VT2 estimation based on the analysis of the T wave from the electrocardiogram (ECG) is proposed, and potential underlying physiological mechanisms are suggested. 25 volunteers (33.4 ± 5.2 years) underwent an incremental power cycle ergometer test (25 W/minute). During the test, respiratory gas exchange and multi-lead ECG were acquired. The former was employed to determine VT2, used here as a reference, whereas the latter was used to compute the temporal profiles of an index of ventricular repolarization instability (dT) and its low-frequency (LF) oscillations (LFdT). The sudden increases observed in dT and LFdT profiles above an established heart rate threshold were employed to derive VT2 estimates, referred to as VT2d T and VT2LF d T , respectively. Estimation errors of -4.7 ± 25.2 W were obtained when considering VT2d T . Errors were lower than the one-minute power increment of 25 W in 68% of the subjects and lower than 50 W in 89.5% of them. When using VT2LF d T , estimation error was of 15.3 ± 32.4 W. Most of the subjects shared common characteristic dT and LFdT profiles, which could be reflecting changes in the autonomic control of ventricular repolarization before and after reaching VT2. The analysis of ventricular repolarization dynamics during exercise allows non-invasive ECG-based estimation of VT2, possibly in relation to changes in the autonomic control of ventricular electrical activity when VT2 is reached.

The Effect of Emotional Valence on Ventricular Repolarization Dynamics Is Mediated by Heart Rate Variability: A Study of QT Variability and Music-Induced Emotions.

BackgroundEmotions can affect cardiac activity, but their impact on ventricular repolarization variability, an important parameter providing information about cardiac risk and autonomic nervous system activity, is unknown. The beat-to-beat variability of the QT interval (QTV) from the body surface ECG is a non-invasive marker of repolarization variability, which can be decomposed into QTV related to RR variability (QTVrRRV) and QTV unrelated to RRV (QTVuRRV), with the latter thought to be a marker of intrinsic repolarization variability.AimTo determine the effect of emotional valence (pleasant and unpleasant) on repolarization variability in healthy volunteers by means of QTV analysis.Methods75 individuals (24.5 ± 3.2 years, 36 females) without a history of cardiovascular disease listened to music-excerpts that were either felt as pleasant (n = 6) or unpleasant (n = 6). Excerpts lasted about 90 s and were presented in a random order along with silent intervals (n = 6). QTV and RRV were derived from the ECG and the time-frequency spectrum of RRV, QTV, QTVuRRV and QTVrRRV as well as time-frequency coherence between QTV and RRV were estimated. Analysis was performed in low-frequency (LF), high frequency (HF) and total spectral bands.ResultsThe heart rate-corrected QTV showed a small but significant increase from silence (median 347/interquartile range 31 ms) to listening to music felt as unpleasant (351/30 ms) and pleasant (355/32 ms). The dynamic response of QTV to emotional valence showed a transient phase lasting about 20 s after the onset of each musical excerpt. QTV and RRV were highly correlated in both HF and LF (mean coherence ranging 0.76–0.85). QTV and QTVrRRV decreased during listening to music felt as pleasant and unpleasant with respect to silence and further decreased during listening to music felt as pleasant. QTVuRRV was small and not affected by emotional valence.ConclusionEmotional valence, as evoked by music, has a small but significant effect on QTV and QTVrRRV, but not on QTVuRRV. This suggests that the interaction between emotional valence and ventricular repolarization variability is mediated by cycle length dynamics and not due to intrinsic repolarization variability.

Cardiovascular Predictive Value and Genetic Basis of Ventricular Repolarization Dynamics.

Early prediction of cardiovascular risk in the general population remains an important issue. The T-wave morphology restitution (TMR), an ECG marker quantifying ventricular repolarization dynamics, is strongly associated with cardiovascular mortality in patients with heart failure. Our aim was to evaluate the cardiovascular prognostic value of TMR in a UK middle-aged population and identify any genetic contribution. We analyzed ECG recordings from 55 222 individuals from a UK middle-aged population undergoing an exercise stress test in UK Biobank (UKB). TMR was used to measure ventricular repolarization dynamics, exposed in this cohort by exercise (TMR during exercise, TMRex) and recovery from exercise (TMR during recovery, TMRrec). The primary end point was cardiovascular events; secondary end points were all-cause mortality, ventricular arrhythmias, and atrial fibrillation with median follow-up of 7 years. Genome-wide association studies for TMRex and TMRrec were performed, and genetic risk scores were derived and tested for association in independent samples from the full UKB cohort (N=360 631). A total of 1743 (3.2%) individuals in UKB who underwent the exercise stress test had a cardiovascular event, and TMRrec was significantly associated with cardiovascular events (hazard ratio, 1.11; P=5×10-7), independent of clinical variables and other ECG markers. TMRrec was also associated with all-cause mortality (hazard ratio, 1.10) and ventricular arrhythmias (hazard ratio, 1.16). We identified 12 genetic loci in total for TMRex and TMRrec, of which 9 are associated with another ECG marker. Individuals in the top 20% of the TMRrec genetic risk score were significantly more likely to have a cardiovascular event in the full UKB cohort (18 997, 5.3%) than individuals in the bottom 20% (hazard ratio, 1.07; P=6×10-3). TMR and TMR genetic risk scores are significantly associated with cardiovascular risk in a UK middle-aged population, supporting the hypothesis that increased spatio-temporal heterogeneity of ventricular repolarization is a substrate for cardiovascular risk and the validity of TMR as a cardiovascular risk predictor.

Abstract 102: Molecular, Cellular and Systemic Mechanism of Nonlinear Dynamic Patterns of Ventricular Repolarization and Spontaneous Arrhythmic Sudden Death in Non-ischemic Heart Failure

Introduction: Sudden cardiac death (SCD) is the leading cause of death in USA. Heart failure (HF) confers high SCD risk, but most SCD victims do not have HF or well-defined genetic abnormalities. The underlying mechanisms are poorly understood, precluding the design of more effective strategies for risk stratification and therapy. We previously showed that distinct non-linear patterns of cardiac repolarization strongly and independently predict SCD in HF patients [PMID: 27044982]. We also showed in a unique guinea pig HF model that increased levels of mitochondrial reactive oxygen species (mROS) drive spontaneous SCD, even before HF onset [PMID: 29898892]. Herein, we further dissect the underlying mechanisms. Hypothesis: Increased mROS levels in pressure overloaded hearts reduce K+ currents, destabilize the resting membrane potential, increase repolarization lability and cause SCD. Methods: Guinea pigs were randomized to Sham, aortic banding (AC), or AC with daily brief low-dose β-adrenergic stress (ACi) with and without in vivo mROS scavenger MitoTEMPO (ACi+MT). We performed time series analyses on recordings of: (1) 24-hour ECG QT interval in freely ambulating animals before sacrifice at 4 weeks; (2) pressure-volume and electrophysiology (EP) in excised perfused hearts; and (3) duration of action potential (APd), calcium transient (CaTd) and sarcomere shortening (SSd) in isolated LV myocytes. Results: About 50% of ACi animals had SCD by 4 weeks. Increased QT entropy in ACi (at 1 week) predicted SCD over followup, similar to HF patients. Compared to Sham and ACi+MT, LV myocytes isolated from AC and ACi had reduced inward (IK1) and delayed slow (IKs) and rapid (IKr) rectifier currents; and increased beat-to-beat lability in APd, CaTd and SSd. The late Na and L-type Ca currents were similar between models. Acute exposure to isoproterenol (Iso) and carbachol (CCh) increased lability in LV myocytes compared to Iso or CCh alone. Conclusions: High mROS levels reduce repolarization reserve in LV myocytes and contribute, at least in part, to the non-linear dynamics of ventricular repolarization (reflected by high QT entropy), leading to spontaneous arrhythmic SCD. These findings provide important new mechanistic insight with direct clinical implications.

Fibrosis and wall thickness affect ventricular repolarization dynamics in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterized by ventricular repolarization abnormalities and risk of ventricular arrhythmias. Our aim was to study the association between the phenotype and ventricular repolarization dynamics in HCM patients. HCM patients with either the MYBPC3-Q1061X or TPM1-D175N mutation (n=46) and control subjects without mutation and hypertrophy (n=35) were studied with 24-hr ambulatory ECG recordings by measuring time intervals of rate-adapted QT (QTe), maximal QT, and T-wave apex to wave end (TPE) intervals and the QTe/RR slope. Findings were correlated to specified echocardiographic and cardiac magnetic resonance imaging (CMRI) findings. Rate-adapted QTe interval was progressively longer in HCM patients with decreasing heart rates compared to control subjects (p=0.020). The degree of hypertrophy correlated with measured QTe values. HCM patients with maximal wall thickness higher than the mean (20.6mm) had longer maximum QTe and median TPE intervals compared to control subjects and HCM patients with milder hypertrophy (p<0.001 and p=0.014, respectively). HCM patients with late gadolinium enhancement (LGE) on CMRI had steeper QTe/RR slopes compared to HCM patients without LGE and control subjects (p=0.044 and p=0.001, respectively). LGE was an independent predictor of QTe/RR slope (p=0.023, B=0.043). Dynamics of ventricular repolarization in HCM are affected by hypertrophy and fibrosis. LGE may confer an independent effect on QT dynamics which may increase the arrhythmogenic potential in HCM.

Effect of Loss of Heart Rate Variability on T-Wave Heterogeneity and QT Variability in Heart Failure Patients: Implications in Ventricular Arrhythmogenesis.

Heart rate variability (HRV) modulates dynamics of ventricular repolarization. A diminishing value of HRV is associated with increased vulnerability to life-threatening ventricular arrhythmias, however the causal relationship is not well-defined. We evaluated if fixed-rate atrial pacing that abolishes the effect of physiological HRV, will alter ventricular repolarization wavefronts and is relevant to ventricular arrhythmogenesis. The study was performed in 16 subjects: 8 heart failure patients with spontaneous ventricular tachycardia [HFVT], and 8 subjects with structurally normal hearts (H Norm). The T-wave heterogeneity descriptors [total cosine angle between QRS and T-wave loop vectors (TCRT, negative value corresponds to large difference in the 2 loops), T-wave morphology dispersion, T-wave loop dispersion] and QT intervals were analyzed in a beat-to-beat manner on 3-min records of 12-lead surface ECG at baseline and during atrial pacing at 80 and 100bpm. The global T-wave heterogeneity was expressed as mean values of each of the T-wave morphology descriptors and variability in QT intervals (QTV) as standard deviation of QT intervals. Baseline T-wave morphology dispersion and QTV were higher in HFVT compared to H Norm subjects (p≤0.02). While group differences in T-wave morphology dispersion and T-wave loop dispersion remained unaltered with atrial pacing, TCRT tended to fall more in HFVT patients compared to H Norm subjects (interaction p value=0.086). Atrial pacing failed to reduce QTV in both groups, however group differences were augmented (p<0.0001). Atrial pacing and consequent loss of HRV appears to introduce unfavorable changes in ventricular repolarization in HFVT subjects. It widens the spatial relationship between wavefronts of ventricular depolarization and repolarization. This may partly explain the concerning relation between poorer HRV and the risk of ventricular arrhythmias.

The Association of Pseudoexfoliation Syndrome with Ventricular Repolarization Dynamics

The Association of Pseudoexfoliation Syndrome with Ventricular Repolarization Dynamics

A multivariate time-frequency approach for tracking QT variability changes unrelated to heart rate variability.

The beat-to-beat variability of the QT interval (QTV) is a marker of ventricular repolarization (VR) dynamics and it has been suggested as an index of sympathetic ventricular outflow and cardiac instability. However, QTV is also affected by RR (or heart rate) variability (RRV), and QTV due to RRV may reduce QTV specificity as a VR marker. Therefore, it would be desirable to separate QTV due to VR dynamics from QTV due to RRV. To do that, previous work has mainly focused on heart rate corrections or time-invariant autoregressive models. This paper describes a novel framework that extends classical multiple inputs/single output theory to the time-frequency (TF) domain to quantify QTV and RRV interactions. Quadratic TF distributions and TF coherence function are utilized to separate QTV into two partial (conditioned) spectra representing QTV related and unrelated to RRV, and to provide an estimates of intrinsic VR dynamics. In a simulation study, a time-varying ARMA model was used to generate signals representing realistic RRV and VR dynamics with controlled instantaneous frequencies and powers. The results demonstrated that the proposed methodology is able to accurately track changes in VR dynamics, with a correlation between theoretical and estimated patterns higher than 0.88. Data from healthy volunteers undergoing a tilt table test were analyzed and representative examples are discussed. Results show that the QTV unrelated to RRV dynamics quickly increased during orthostatic challenge.

Interactive effect of beta-adrenergic stimulation and mechanical stretch on low-frequency oscillations of ventricular action potential duration in humans

Ventricular repolarization dynamics are crucial to arrhythmogenesis. Low-frequency oscillations of repolarization have recently been reported in humans and the magnitude of these oscillations proposed to be a strong predictor of sudden cardiac death. Available evidence suggests a role of the sympathetic nervous system. We have used biophysically detailed models integrating ventricular electrophysiology, calcium dynamics, mechanics and β-adrenergic signaling to investigate the underlying mechanisms. The main results were: (1) Phasic beta-adrenergic stimulation (β-AS) at a Mayer wave frequency between 0.03 and 0.15Hz resulted in a gradual decrease of action potential (AP) duration (APD) with concomitant small APD oscillations. (2) After 3–4minutes of phasic β-AS, the mean APD adapted and oscillations of APD became apparent. (3) Phasic changes in haemodynamic loading at the same Mayer wave frequency (a known accompaniment of enhanced sympathetic nerve activity), simulated as variations in the sarcomere length, also induced APD oscillations. (4) The effect of phasic β-AS and haemodynamic loading on the magnitude of APD oscillations was synergistic. (5) The presence of calcium overload and reduced repolarization reserve further enhanced the magnitude of APD oscillations and was accompanied by afterdepolarizations and/or spontaneous APs. In conclusion, low-frequency oscillations of repolarization recently reported in humans were induced by phasic β-AS and phasic mechanical loading, which acted synergistically, and were greatly enhanced by disease-associated conditions, leading to arrhythmogenic events.

Detecting Subclinical Diabetic Cardiac Autonomic Neuropathy by Analyzing Ventricular Repolarization Dynamics.

In this study, a linear parametric modeling technique was applied to model ventricular repolarization (VR) dynamics. Three features were selected from the surface ECG recordings to investigate the changes in VR dynamics in healthy and cardiac autonomic neuropathy (CAN) participants with diabetes including heart rate variability (calculated from RR intervals), repolarization variability (calculated from QT intervals), and respiration [calculated by ECG-derived respiration (EDR)]. Surface ECGs were recorded in a supine resting position from 80 age-matched participants (40 with no cardiac autonomic neuropathy (NCAN) and 40 with CAN). In the CAN group, 25 participants had early/subclinical CAN (ECAN) and 15 participants were identified with definite/clinical CAN (DCAN). Detecting subclinical CAN is crucial for designing an effective treatment plan to prevent further cardiovascular complications. For CAN diagnosis, VR dynamics was analyzed using linear parametric autoregressive bivariate (ARXAR) and trivariate (ARXXAR) models, which were estimated using 250 beats of derived QT, RR, and EDR time series extracted from the first 5 min of the recorded ECG signal. Results showed that the EDR-based models gave a significantly higher fitting value (p < 0.0001) than models without EDR, which indicates that QT-RR dynamics is better explained by respiratory-information-based models. Moreover, the QT-RR-EDR model fitting values gradually decreased from the NCAN group to ECAN and DCAN groups, which indicate a decoupling of QT from RR and the respiration signal with the increase in severity of CAN. In this study, only the EDR-based model significantly distinguished ECAN and DCAN groups from the NCAN group (p < 0.05) with large effect sizes (Cohen's d > 0.75) showing the effectiveness of this modeling technique in detecting subclinical CAN. In conclusion, the EDR-based trivariate QT-RR-EDR model was found to be better in detecting the presence and severity of CAN than the bivariate QT-RR model. This finding also establishes the importance of adding respiratory information for analyzing the gradual deterioration of normal VR dynamics in pathological conditions, such as diabetic CAN.

Effects of dronedarone on ventricular repolarization and repolarization dynamics in patients with preserved left ventricular systolic function

1. Mean 24-hour heart rate (HR) and normal 24-hour RR-intervals (NNMEAN) 2. Mean 24-hour QT interval (QTe), measured from the beginning of the R-wave to the end of the T-wave 3. Mean heart rate corrected 24-hourQT interval (QTc) using the Bazett correction formula: QTc = RR 4. Standard deviation of mean 24-hour NN-intervals (SDNN), proportion of NN50 divided by total number of NNs (pNN50) and Root

Effect of ECG-derived respiration (EDR) on modeling ventricular repolarization dynamics in different physiological and psychological conditions.

Ventricular repolarization dynamics is an important predictor of the outcome in cardiovascular diseases. Mathematical modeling of the heart rate variability (RR interval variability) and ventricular repolarization variability (QT interval variability) is one of the popular methods to understand the dynamics of ventricular repolarization. Although ECG derived respiration (EDR) was previously suggested as a surrogate of respiration, but the effect of respiratory movement on ventricular repolarization dynamics was not studied. In this study, the importance of considering the effect of respiration and the validity of using EDR as a surrogate of respiration for linear parametric modeling of ventricular repolarization variability is studied in two cases with different physiological and psychological conditions. In the first case study, we used 20 young and 20 old healthy subjects' ECG and respiration data from Fantasia database at Physionet to analyze a bivariate QT-RR and a trivariate [Formula: see text] model structure to study the aging effect on cardiac repolarization variability. In the second study, we used 16 healthy subjects' data from drivedb (stress detection for automobile drivers) database at Physionet to do the same analysis for different psychological condition (i.e., in stressed and no stress condition). The results of our study showed that model having respiratory information (QT-RR-RESP and QT-RR-EDR) gave significantly better fit value (p < 0.05) than that of found from the QT-RR model. EDR showed statistically similar (p > 0.05) performance as that of respiration as an exogenous model input in describing repolarization variability irrespective of age and different mental conditions. Another finding of our study is that both respiration and EDR-based models can significantly (p < 0.05) differentiate the ventricular repolarization dynamics between healthy subjects of different age groups and with different psychological conditions, whereas models without respiration or EDR cannot distinguish between the groups. These results established the importance of using respiration and the validity of using EDR as a surrogate of respiration in the absence of respiration signal recording in linear parametric modeling of ventricular repolarization variability in healthy subjects.

Evaluation of repolarization dynamics using the QT–RR regression line slope and intercept relationship during 24-h Holter ECG

QT-RR linear regression consists of two parameters, slope and intercept, and the aim of this study was to evaluate repolarization dynamics using the QT-RR linear regression slope and intercept relationship during 24-h Holter ECG. This study included 466 healthy subjects (54.6 ± 14.6 years; 200 men and 266 women) and 17 patients with ventricular arrhythmias, consisted of 10 patients with idiopathic ventricular fibrillation (IVF) and 7 patients with torsades de pointes (TDP). QT and RR intervals were measured from ECG waves based on a 15-s averaged ECG during 24-h Holter recording using an automatic QT analyzing system. The QT interval dependence on the RR interval was analyzed using a linear regression line for each subject ([QT] = A[RR] + B; where A is the slope and B is the y-intercept). The slope of the QT-RR regression line in healthy subjects was significantly greater in women than in men (0.185 ± 0.036 vs. 0.161 ± 0.033, p < 0.001) and the intercept was significantly smaller in women than in men (0.229 ± 0.028 vs. 0.240 ± 0.027, p < 0.001). A scatter diagram of the QT-RR regression line slope and intercept among healthy subjects demonstrated a statistically significant negative correlation (B = -0.62A + 0.34, r = -0.79). Distribution of both scatter diagrams of the slope and the intercept of the QT-RR regression line in patients with IVF and TDP was different from healthy subjects (left corner for IVF and upward shift for TDP). The slope and intercept relationship of the QT-RR linear regression line based on 24-h Holter ECG may become a simple useful marker for abnormality of ventricular repolarization dynamics.

Diastolic and autonomic dysfunction in early cirrhosis: a dobutamine stress study

Objective. Presence of cardiac dysfunction in patients with advanced cirrhosis is widely accepted, but data in early stages of cirrhosis are limited. Systolic and diastolic functions, dynamics of QT-interval, and pro-atrial natriuretic peptide (pro-ANP) are investigated in patients with early stage cirrhosis during maximal β-adrenergic drive. Material and methods. Nineteen patients with Child A (n = 12) and Child B cirrhosis (n = 7) and seven matched controls were studied during cardiac stress induced by increasing dosages of dobutamine and atropine. Results. Pharmacological responsiveness was similar in cirrhosis and controls and the heart rate (HR) increased by 66 ± 15 versus 67 ± 8 min−1. HR-blood pressure product increased equally by 115% in both cirrhotic patients and controls. However, time to resume HR of 100 beats/min was significantly longer in cirrhosis, p < 0.01. The QTc interval increased after dobutamine infusion in cirrhosis (0.41 ± 0.02 vs. 0.43 ± 0.02 s, p = 0.001) but similar electrophysiological changes were seen in controls. Cardiac volumes increased with the severity of disease. The increased cardiac output was primarily attributed to increased stroke volume. The ejection fraction was similar in patients and controls. Peak filling rate was longer in cirrhosis compared to controls (1.8 ± 0.4 and 1.4 ± 0.2 end-diastolic volume/s, p < 0.01). Pro-ANP was higher in cirrhosis and increased during stress by 13% compared to 0% in controls, p < 0.01. Conclusions. These findings indicate that patients with early stage cirrhosis exhibit early diastolic and autonomic dysfunction as well as elevated pro-ANP. However, the cardiac chronotropic and inotropic responses to dobutamine stress were normal. The dynamics of ventricular repolarization appears normal in patients with early stage cirrhosis.

The association of premature ovarian failure with ventricular repolarization dynamics evaluated by QT dynamicity

The association between premature ovarian failure (POF) and cardiovascular diseases has been investigated in a few studies, but none have looked at ventricular repolarization abnormalities in these patients. In this study, we aimed to evaluate the ventricular repolarization by QT dynamicity in patients with POF. We enrolled 26 female patients (mean age 37.5 ± 10.1 years) with primary POF and 31 healthy female subjects (mean age 37.5 ± 9.0 years). The linear regression slopes of the QT interval measured to the apex and to the end of the T-wave plotted against RR intervals (QTapex/RR and QTend/RR slopes, respectively) were calculated from 24 h Holter recordings using a standard algorithm. QTapex/RR and QTend/RR slopes were more steeper in the POF patients in contrary to healthy control subjects (QTapex/RR = 0.184 ± 0.022 vs. 0.131 ± 0.019, P < 0.001; QTend/RR = 0.164 ± 0.021 vs. 0.128 ± 0.018, P < 0.001). Pearson's correlation analyses revealed a stronger negative correlation between oestradiol (E2) and QTapex/RR (r = -0.715, P < 0.001). There was also a moderate negative correlation between E2 and QTend/RR (r = -0.537, P < 0.001). Serum follicle-stimulating hormone level was positively correlated with QTapex/RR (r = 0.681, P < 0.001) and QTend/RR (r = 0.531, P < 0.001). Our study results suggest that QT dynamicity is impaired in patients with POF despite the absence of overt cardiovascular involvement. Further studies are needed to elucidate the prognostic significance and clinical implications of impaired ventricular repolarization in patients with POF.

Ventricular Repolarization Dynamics and the Risk of Sudden Cardiac Death after Heart Transplantation

Purpose We analyzed the value of ventricular repolarization dynamics for prediciton of sudden cardiac death (SCD) after heart transplantation. Methods and Materials In a prospective study, we enrolled 54 cardiac transplant recipients who underwent yearly routine surveillance. Patients with recent ( th percentile (high QTV group). Follow-up lasted 5 years. Results High QT variability was present in 14 of 54 patients. Patients in the high QTV group and those in the control group did not differ with regard to age (52±10 years in high QTV group vs. 50±9 years in control group; P =0.42), sex (86% [men] vs. 73%; P =0.60), history of rejection (0.98±1.12 vs. 0.87±0.92; P =0.28), or heart rate variability (standard deviation of normal-to-normal [SDNN]: 11±3 ms vs. 13±5 ms, P =0.33; root mean square successive difference [rMSSD]: 37±7 ms vs. 35±3 ms, P =0.52). Cadriac allograft vasculopathy was more common in high QTV group (79%) than in control group (40%) ( P =0.013). During follow-up, 7 patients (13%) died of SCD, and those patients had significantly higher QT variability compared to survivors (SDNN: 7.3±2.2 ms vs. 4.2±2.2 ms, P =0.001; rMSSD: 8.4±3.2 ms vs. 4.8±2.1, P =0.001; QTRR: 27±4 % vs. 20±6 %, P =0.002; QTVI: −0.65±0.37 vs. −1.31±0.41, P =0.002). Conclusions Increased ventricular repolarization dynamics is related to cardiac allograft vasculopathy and may be predictive of SCD in heart transplant recipients.