[Show abstract][Hide abstract] ABSTRACT: Measurement of QT intervals during atrial flutter (AFL) is relevant to monitor the safety of drug delivery. Our aim is to compare QT and QTc intervals in AFL patients before and after catheter ablation in order to validate QT measurement during AFL.
25 patients suffering from AFL underwent catheter ablation; 9 were in sinus rhythm and 16 were in AFL at the time of the procedure. Holter ECGs were continuously recorded before, during and after the procedure. In AFL signals, flutter waves were subtracted using a previously-validated deconvolution-based method. Fridericia's QTc was computed before and after ablation after hysteresis reduction.
Comparing QTc values obtained before and after ablation showed that (1) the intervention did not significantly affect QTc, and (2) the QTc during AFL was concordant with the QTc value in sinus rhythm.
QTc can be reliably measured in patients with AFL using flutter wave subtraction and hysteresis reduction.
Journal of electrocardiology 11/2013; 47(2). DOI:10.1016/j.jelectrocard.2013.11.002 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: In experimental models, ranolazine exerts a synergistic effect which enhances amiodarone's potential to suppress atrial fibrillation (AF). The clinical effect of ranolazine added to amiodarone for AF conversion has only undergone minimal investigation.
Purpose: This study compared the safety and effectiveness of ranolazine in combination with amiodarone versus amiodarone alone for conversion of paroxysmal AF.
Methods: We prospectively enrolled all consecutive patients with paroxysmal AF who were deemed eligible for pharmacologic cardioversion. Exclusion criteria were QTc>440msec, hepatic, renal, or thyroid disorders, acute coronary syndrome, prior use of ranolazine, and use of strong CYP3A inhibitors which could affect ranolazine's metabolism. Patients were randomized to either iv amiodarone alone (loading dose of 5md/kg followed by a maintenance dose of 50mg/h for 24h), or to the combination of iv amiodarone plus a single oral dose of ranolazine 1500mg. Patients remained on continuous ECG monitoring. We measured the time to conversion to sinus rhythm, and the proportion of patients with AF conversion within 12h and within 24h.
Results: 72 patients were enrolled (mean age 59±7 years): 35 in the amiodarone-only group and 37 in the amiodarone plus ranolazine combination group. The two groups did not differ in terms of clinical characteristics and echocardiographic parameters, including left atrium diameter. Time to conversion was shorter in the combination group compared with the amiodarone-only group (8.4±3.8h vs.15.1±4.8 h; p<0.001). Conversion was achieved in more patients in the combination group as compared to the amiodarone-only group (57% vs. 20% at 12h, respectively, p=0.001; and 86% vs. 68% at 24h, respectively, p=0.07). There were no cases of excessive QT prolongation (>550msec) and no proarrhythmic events in either treatment group.
Conclusions: The addition of ranolazine to standard amiodarone treatment is safe, and it leads to faster conversion of paroxysmal AF. Consistent with substantial preclinical research on ranolazine's AF-suppressing potential, the present clinical study demonstrates a synergistic effect of ranolazine and amiodarone for conversion of paroxysmal AF.
[Show abstract][Hide abstract] ABSTRACT: Aims:
To quantify the sensitivity of QT heart-rate correction methods for detecting drug-induced QTc changes in thorough QT studies.
Twenty-four-hour Holter ECGs were analyzed in 66 normal subjects during placebo and moxifloxacin delivery (single oral dose). QT and RR time series were extracted. Three QTc computation methods were used: (1) Fridericia's formula, (2) Fridericia's formula with hysteresis reduction, and (3) a subject-specific approach with transfer function-based hysteresis reduction and three-parameter non-linear fitting of the QT-RR relation. QTc distributions after placebo and moxifloxacin delivery were compared in sliding time windows using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) served as a measure to quantify the ability of each method to detect moxifloxacin-induced QTc prolongation.
Moxifloxacin prolonged the QTc by 10.6 ± 6.6 ms at peak effect. The AUC was significantly larger after hysteresis reduction (0.87 ± 0.13 vs. 0.82 ± 0.12, p<0.01) at peak effect, indicating a better discriminating capability. Subject-specific correction further increased the AUC to 0.91 ± 0.11 (p<0.01 vs. Fridericia with hysteresis reduction). The performance of the subject-specific approach was the consequence of a substantially lower intra-subject QTc standard deviation (5.7 ± 1.1 ms vs. 8.8 ± 1.2 ms for Fridericia).
The ROC curve provides a tool for quantitative comparison of QT heart rate correction methods in the context of detecting drug-induced QTc prolongation. Results support a broader use of subject-specific QT correction.
Journal of electrocardiology 09/2012; 45(6). DOI:10.1016/j.jelectrocard.2012.07.004 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The QT interval in the electrocardiogram (ECG) is a measure of total duration of depolarization and repolarization. Correction for heart rate is necessary to provide a single intrinsic physiological value that can be compared between subjects and within the same subject under different conditions. Standard formulas for the corrected QT (QTc) do not fully reproduce the complexity of the dependence in the preceding interbeat intervals (RR) and inter-subject variability. In this paper, a subject-specific, nonlinear, transfer function-based correction method is formulated to compute the QTc from Holter ECG recordings. The model includes five parameters: three describing the static QT-RR relationship and two representing memory/hysteresis effects that intervene in the calculation of effective RR values. The parameter identification procedure is designed to minimize QTc fluctuations and enforce zero correlation between QTc and effective RR. Weighted regression is used to better handle unbalanced or skewed RR distributions. The proposed optimization approach provides a general mathematical framework for further extensions of the model. Validation, robustness evaluation and comparison with existing QT correction formulas is performed on ECG signals recorded during sinus rhythm, atrial pacing, tilt-table tests, stress tests and atrial flutter (29 subjects in total). The resulting average modeling error on the QTc is 4.9 ± 1.1 ms with a sampling interval of 2 ms, which outperforms correction formulas currently used. The results demonstrate the benefits of subject-specific rate correction and hysteresis reduction.
[Show abstract][Hide abstract] ABSTRACT: The combined effect of a β2-antagonist and an α2-agonist on the release of adrenal catecholamines was studied in the anaesthetized and vagotomized dog. The electrical stimulation of the splanchnic nerve (5-V pulses of 2 ms duration for 3 min at a frequency of 3 Hz) produced a significant rise in adrenal catecholamine release in the adrenal vein. Intravenous injection of a β2-antagonist significantly reduced this response and a subsequent injection of an α2-agonist further reduced the release of catecholamines. However, if the α2-agonist is injected first, the release is not different compared with the control stimulation, and the subsequent injection of the β2-antagonist also did not modify the release in response to electrical stimulation. These results suggest that the blockade of presynaptic β2-receptors reduces the release of adrenal catecholamines without interfering with the activation of the α2-adrenoceptors. In contrast, the pretreatment with the α2-agonist, which does not modify the release of catecholamine at 3 Hz, seems to interfere with the inhibitory effect of the β2-antagonist.
Canadian Journal of Physiology and Pharmacology 02/2011; 66(10):1340-1343. DOI:10.1139/y88-219 · 1.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Analysis of T waves in the ECG is an essential clinical tool for diagnosis, monitoring, and follow-up of patients with heart dysfunction. During atrial flutter, this analysis has been so far limited by the perturbation of flutter waves superimposed over the T wave. This paper presents a method based on missing data interpolation for eliminating flutter waves from the ECG during atrial flutter. To cope with the correlation between atrial and ventricular electrical activations, the CLEAN deconvolution algorithm was applied to reconstruct the spectrum of the atrial component of the ECG from signal segments corresponding to TQ intervals. The locations of these TQ intervals, where the atrial contribution is presumably dominant, were identified iteratively. The algorithm yields the extracted atrial and ventricular contributions to the ECG. Standard T-wave morphology parameters (T-wave amplitude, T peak-T end duration, QT interval) were measured. This technique was validated using synthetic signals, compared to average beat subtraction in a patient with a pacemaker, and tested on pseudo-orthogonal ECGs from patients in atrial flutter. Results demonstrated improvements in accuracy and robustness of T-wave analysis as compared to current clinical practice.
[Show abstract][Hide abstract] ABSTRACT: Chronotropic "vagal responses" elicited by high-frequency stimulation have been used to identify atrial targets for ablative treatment of atrial tachyarrhythmias (AT), whereas an anatomic approach consisting of extensive ablation of the ganglionated plexus areas has been proposed as an alternative. Therefore, there is a need for precise delineation of juxtacardiac nerves involved in AT initiation and clarification of their regional influences throughout the atria in relation to AT sites of origin, beyond chronotropic effects related to sinus node modulation.
Unipolar electrograms were recorded from 191 biatrial epicardial sites in 13 anesthetized canines, with concomitant left atrial endocardial recording from 63 sites in 5 of 13 animals. When electric stimuli were delivered to dorsal mediastinal nerves during the atrial refractory period, atrial premature depolarizations initiating AT were elicited in all animals, most frequently without prior sinus cycle length modification. Among 63 episodes, the sites of origin of early AT beats were localized to (1) the posterolateral left atrial wall in the pulmonary vein region (33%), (2) superior left atrial loci along the Bachmann bundle (55%), and (3) the region of Bachmann bundle insertion into the superior right atrial wall (11%). Moreover, the AT sites of origin were spatially concordant with regional waveform changes during the repolarization phase of unipolar recordings. AT induction and repolarization changes were abolished after atropine administration.
Activation of individual dorsal mediastinal nerves induces AT arising from distinct sites of origin which are spatially concordant with regional atrial repolarization changes.
[Show abstract][Hide abstract] ABSTRACT: This paper reports two attempts at estimating the magni-tude of atrial flutter amplitude modulation caused by atrial motion during heart contraction. The first approach con-sists in analyzing the ECG of a patient in flutter with atrio-ventricular block and an implanted pacemaker. These con-ditions facilitate QRST cancellation, even in the presence of time-varying flutter wave amplitude. The second ap-proach is based on a computer model of atrial flutter em-bedded in a torso model featuring predetermined motion of the atria. The results suggests that this lead-dependent effect is usually not large enough to preclude reasonably accurate QRST cancellation or T-wave extraction.
[Show abstract][Hide abstract] ABSTRACT: Health-related quality of life (QoL) is reduced in patients with recurrent vasovagal (VVS) or unexplained (US) syncope. Little
is known regarding these patients’ QoL as pertains to their capacity to attain their life goals. Factors influencing QoL,
such as sex, syncope type and illness representations have not been studied. Our objective is to examine the relationship
between illness representations and QoL, as well as possible sex and syncope type differences. One hundred and four patients
undergoing tilt-table testing (TTT) for recurrent syncope were interviewed one month before TTT, using questionnaires. Data
were analysed using ANCOVAs, a-priori Helmert contrasts for illness representations, and regressions. Patients with US had
a poor QoL compared to those with VVS [F(1, 91) = 10.46; p < 0.01], particularly in men (p < 0.01). Patients with higher perceived syncope severity showed an impoverished QoL relative to those with less severe perceptions
[F(1, 91) = 5.47; p < 0.05]. A hierarchical regression revealed that illness representations mediate the impact of lifetime number of syncope
on QoL. In conclusion, QoL is reduced in these patients, and is influenced by illness representations. Helping patients change their
perceptions about their syncope may be an efficient way to promote QoL.
Applied Research in Quality of Life 12/2009; 3(4):235-249. DOI:10.1007/s11482-009-9058-x · 0.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Syncope is experienced by a third of the population, and in the absence of cardiac pathology is most commonly of vasovagal (VVS) or unexplained origin (US). Psychiatric morbidity has been observed in up to 81% of patients with US but findings with VVS are contradictory. Little is known regarding the chronicity of their psychiatric morbidity.
To determine the psychological profile of patients with recurrent syncope prior to and following diagnostic head-up tilt testing (HUT), and whether it predicts syncope recurrence.
Seventy-three women and 43 men (mean age=48+/-16.6) were recruited from all consenting patients referred for HUT. Psychological status (Psychiatric Symptom Index, Anxiety Sensitivity Index (ASI), Fear of Blood Injury Subscale) and presence of mood/anxiety disorders (Primary Care Evaluation of Mental Disorders) were evaluated 1 month prior to and 6 months following HUT. Follow-up data were collected for 83 patients (mean age=48+/-17.34).
At baseline, clinically significant levels of distress were observed in 60% of patients. Those with US (negative HUT) had a fivefold greater risk of suffering from a depressive or anxiety disorder compared to VVS (positive HUT) after controlling for significant covariates. There was no significant change in distress level over follow-up, although psychiatric morbidity dropped from 33% to 22% (P=.049). Syncope recurrence was predicted by elevations in baseline psychological distress (OR=1.544, P=.013) independently of lifetime number of syncopes.
Patients exhibited high levels of psychological distress and psychiatric morbidity despite reassurance and education received after HUT. Improved screening for and treatment of psychological distress in these patients is critical.
Journal of psychosomatic research 10/2009; 67(3):213-22. DOI:10.1016/j.jpsychores.2009.03.012 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effect of age on autonomic nervous system was assessed at rest and while standing using systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, and power spectral analysis of the time duration between 2 consecutive R waves of an electrocardiogram (RR) interval variability, as well as on plasma norepinephrine and epinephrine levels in mild to moderate hypertensive patients (DBP, 90-110 mm Hg). Patients younger than 60 years (n=57) and older than 60 years (n=32), were evaluated after a 3- to 4-week placebo period. Plasma catecholamines were measured in the supine position at rest and after 10 minutes of standing. Power spectral analysis of the RR interval variability was performed in each condition using the high-frequency (HF) band (0.15-0.4 Hz) as an index of parasympathetic activity and the low-frequency (LF) band (0.05-0.15 Hz) and LF-HF ratio to estimate sympathetic activity. The total power was calculated as the sum of LF and HF power. supine SBP was significantly higher in older patients (P<.05). SBP and DBP increased significantly only in younger patients during standing (P<.05), while the changes were smaller and nonsignificantly lower in older patients. HR was similar in both groups at rest and increased similarly during standing. Norepinephrine and epinephrine levels were similar at rest and increased similarly in both groups of patients during standing. At rest, lower LF and HF components were observed in older patients. The LF component increased less and the HF component decreased less in older patients during standing. A lower sympathetic and parasympathetic basal cardiac tone was observed at rest in older hypertensive patients. Moreover, reduced hemodynamic and sympathetic responses to standing as assessed by SBP, DBP, and the LF component of HR variability were observed in older hypertensives in the presence of a normal catecholamine response. These observations could reflect a decreased sensitivity of cardiac beta-adrenoceptors with aging.
[Show abstract][Hide abstract] ABSTRACT: Previous studies have shown that the diagnosis and localization of previous non-Q wave myocardial infarction (NQMI) is possible by body surface potential mapping (BSPM), but the criteria for the discrimination between anteroseptal and inferoseptal middle regions remain to be determined.
BSPM using 63 unipolar leads was recorded in 119 patients with previous NQMI (36 to 76 years of age, average 61 years; 85 men). Localization of anteroseptal or inferior middle NQMI occurred in 70 cases (44 to 76 years of age, average 61 years, 53 men) by determining early anterior minimum potential with only slight negativity. In these cases, isopotential maps obtained at additional time points were investigated to discriminate between anteroseptal and inferoseptal NQMI. The clinical localization was based on the concordance of two of the following tests: wall motion disturbances on echocardiography, coronary angiogram and repolarization changes in the acute-phase electrocardiogram.
Two milliseconds before the appearance of the first anterior minimum, a more accentuated superior negativity indicated anteroseptal NQMI (32 of 70 cases), while a more pronounced inferior negativity indicated inferoseptal NQMI (38 of 70 cases). Fisher's exact test showed statistically significant associations between the above BSPM localizations and the clinical localizations (P<0.001). Occlusion or stenosis of the expected infarct-related coronary artery was detected in all patients either as a single lesion or together with other coronary artery lesions.
The BSPM criteria proposed here are suitable to detect the most frequent NQMI localizations. The narrowing of the infarct-related coronary arteries, the left anterior descending or the posterior descending coronary artery, can be thus differentiated.
The Canadian journal of cardiology 02/2008; 24(1):53-5. DOI:10.1016/S0828-282X(08)70549-X · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The electrocardiogram (ECG) obtained during stress testing often shows a typical pattern of primary ST depression. A similar pattern can occur in unstable angina. Current textbooks consider ST depression as a direct result of partial occlusion of a coronary artery. However, animal models could not reproduce this phenomenon. An alternative explanation for ST depression specific to stress testing involves global subendocardial ischemia. In this study, we evaluated both explanations with a realistic mathematical model of the human heart.
The ECG was simulated with an anisotropic reaction-diffusion model of the human heart and an inhomogeneous boundary-element model of the human torso.
Limited subendocardial ischemic zones caused small ST depression in ECG leads not overlying the ischemic region. An ischemic zone of 50% transmural extent covering the entire left ventricular subendocardium caused an ST-depression pattern similar to that observed during stress test.
In contrast to regional subendocardial ischemia, global subendocardial ischemia can explain ST depression in our model.
Anadolu kardiyoloji dergisi: AKD = the Anatolian journal of cardiology 08/2007; 7 Suppl 1:145-7. · 0.93 Impact Factor