Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment ...elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death.
Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca(v)1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours. Three probands displaying ST-segment elevation and corrected QT intervals < or = 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Ca(v)1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca(v beta2b)-subunits.
This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.
Activation mapping using noninvasive electrocardiographic imaging (ECGi) has recently been used to describe the physiology of different cardiac abnormalities. These descriptions differ from prior ...invasive studies, and both methods have not been thoroughly confronted in a clinical setting.
The goal of the present study was to provide validation of noninvasive activation mapping in a clinical setting through direct confrontation with invasive epicardial contact measures.
Fifty-nine maps were obtained in 55 patients and aligned on a common geometry. Nearest-neighbor interpolation was used to avoid map smoothing. Quantitative comparison was performed by computing between-map correlation coefficients and absolute activation time errors.
The mean activation time error was 20.4 ± 8.6 ms, and the between-map correlation was poor (0.03 ± 0.43). The results suggested high interpatient variability (correlation −0.68 to 0.82), wide QRS patterns, and paced rhythms demonstrating significantly better mean correlation (0.68 ± 0.17). Errors were greater in scarred regions (21.9 ± 10.8 ms vs 17.5 ± 6.7 ms; P < .01). Fewer epicardial breakthroughs were imaged using noninvasive mapping (1.3 ± 0.5 vs 2.3 ± 0.7; P < .01). Primary breakthrough locations were imaged 75.7 ± 38.1 mm apart. Lines of conduction block (jumps of ≥50 ms between contiguous points) due to structural anomalies were recorded in 27 of 59 contact maps and were not visualized at these same sites noninvasively. Instead, artificial lines appeared in 33 of 59 noninvasive maps in regions of reduced bipolar voltage amplitudes (P = .03). An in silico model confirms these artificial constructs.
Overall, agreement of ECGi activation mapping and contact mapping is poor and heterogeneous. The between-map correlation is good for wide QRS patterns. Lines of block and epicardial breakthrough sites imaged using ECGi are inaccurate. Further work is required to improve the accuracy of the technique.
Introduction
Radiofrequency (RF) lesion metrics are influenced by underlying parameters like RF power, duration, and contact force (CF), and utilization of lesion metric indices (ablation index AI) ...is a proposed strategy to predict lesion quality. The aim of this study was to analyze the influence of underlying parameters on lesion metrics of high‐power short‐duration (HPSD) and standard RF applications using an in silico and ex vivo model.
Methods and Results
An in silico simulation study was designed to simulate HPSD and standard ablations, in which ablation parameters could systematically be varied. For each simulated ablation process (n = 5732), the corresponding AI value was calculated. HPSD and standard RF settings were then applied in a porcine ex vivo model (
n = 120 lesions). The resulting lesion metrics were compared and analyzed regarding underlying parameters. RF applications of 50 W/13 seconds, 60 W/10 seconds, 70 W/7 seconds, and 80 W/6 seconds resulted in lesion volumes not significantly different from standard RF applications (30 W/30 seconds,
P > 0.05). HPSD lesion diameters were significantly larger and lesion depths were significantly smaller (
P < 0.01) when compared with standard settings. Prolonging RF duration from 5 to 10 seconds resulted in a +27.5% increase, whereas a prolongation of RF duration from 35 to 40 seconds resulted in a +4.8% increase of AI value only. An increase of CF from 1 to 10 g resulted in a +73.0%, an increase of CF from 20 to 30 g resulted in a +10.1% increase of AI value.
Conclusion
HPSD RF applications resulted in similar lesion volumes but significantly different lesion geometries when compared with standard setting RF applications.
The mechanisms responsible for perpetuation of human persistent atrial fibrillation (AF) are controversial and probably vary between individuals. A wide spectrum of mechanisms have been described in ...experimental studies, ranging from a single localized stable (focal/reentrant) source, to multiple sources, up to diffuse bi‐atrial wavelets. We characterized AF drivers in patients with persistent AF (lasting less than 1 year) using novel high resolution mapping, imaging and modelling approaches with the objective of evaluating their relationship to atrial structural heterogeneities. Using panoramic non‐invasive mapping in humans, focal or reentrant sources driving AF waves were identified, originating from multiple distinct regions and exhibiting short lifespans and periodic recurrences in the same locations. The reentrant driver regions harboured long, fractionated electrograms covering most of the fibrillatory cycle lengths with varying beat‐to‐beat sequences suggestive of unstable trajectories attached to slow conducting heterogeneous tissue. MRI atrial imaging demonstrated that such drivers preferentially clustered at the borders of fibrotic atrial regions. In patient‐specific computer simulations, sustained AF was shown to be driven by meandering transitory reentries attached to fibrosis borders expressing specific metrics in density and extent. Finally, random microstructural alterations devoid of cellular electrical changes were modelled, showing that a percolation mechanism could also explain atrial reentries and complex fractionated electrograms. These data from clinical, imaging and computational studies strongly suggest that intermittent and spatially unstable drivers anchoring to structural heterogeneities are a major pathophysiological mechanism in human persistent atrial fibrillation.
Anchoring of AF drivers from mapping, imaging and computational studies.
Atrial Fibrosis on MRI in Patients
Introduction
We studied the extent and distribution of left atrial (LA) fibrosis on delayed‐enhanced (DE) MRI in a general cardiology population.
Methods and ...Results
One hundred ninety consecutive patients referred for cardiac MRI underwent DE imaging using a free breathing method. The population comprised 60 AF patients and 130 patients without AF, including 75 with structural heart disease (SHD). DE was quantified using histogram thresholding, expressed in % of the wall. Regression analysis was performed to identify predictors of DE. Additionally, DE was registered on a template to study its distribution in subpopulations. In the total population, age, AF, and SHD were independently associated with DE. DE was increasingly observed from 11.1 ± 4.7% in patients with no SHD nor AF, 18.8 ± 7.8% in SHD and no AF history, 22.9 ± 7.8% in paroxysmal AF, to 27.8 ± 7.7% in persistent AF. Among non‐AF patients, age and SHD were independently associated with DE. Among AF patients, female gender and AF persistence were independently associated with DE. DE was variably distributed but more frequently detected in the posterior wall.
Conclusion
Age, history of AF, and SHD are the most powerful predictors of atrial fibrosis, as detected by MRI, in a general cardiology population. Atrial fibrosis predominates in the posterior LA wall.
BACKGROUND—Brugada syndrome (BrS) is a highly arrhythmogenic cardiac disorder, associated with an increased incidence of sudden death. Its arrhythmogenic substrate in the intact human heart remains ...ill-defined.
METHODS AND RESULTS—Using noninvasive ECG imaging, we studied 25 BrS patients to characterize the electrophysiological substrate and 6 patients with right bundle-branch block for comparison. Seven healthy subjects provided control data. Abnormal substrate was observed exclusively in the right ventricular outflow tract with the following properties (in comparison with healthy controls; P<0.005)(1) ST-segment elevation and inverted T wave of unipolar electrograms (2.21±0.67 versus 0 mV); (2) delayed right ventricular outflow tract activation (82±18 versus 37±11 ms); (3) low-amplitude (0.47±0.16 versus 3.74±1.60 mV) and fractionated electrograms, suggesting slow discontinuous conduction; (4) prolonged recovery time (381±30 versus 311±34 ms) and activation-recovery intervals (318±32 versus 241±27 ms), indicating delayed repolarization; (5) steep repolarization gradients (Δrecovery time/Δx=96±28 versus 7±6 ms/cm, Δactivation-recovery interval/Δx=105±24 versus 7±5 ms/cm) at right ventricular outflow tract borders. With increased heart rate in 6 BrS patients, reduced ST-segment elevation and increased fractionation were observed. Unlike BrS, right bundle-branch block had delayed activation in the entire right ventricle, without ST-segment elevation, fractionation, or repolarization abnormalities on electrograms.
CONCLUSIONS—The results indicate that both slow discontinuous conduction and steep dispersion of repolarization are present in the right ventricular outflow tract of BrS patients. ECG imaging could differentiate between BrS and right bundle-branch block.
Within the span of a few years, watches have functionally morphed from objects that tell time to wearable minicomputers that allow real-time recording of electrocardiograms (ECGs). Considerable ...information can be deduced from these single lead tracings, and it is now not uncommon to see patients in whom diagnostic tracings of clinically relevant but elusive arrhythmias are captured using a smartwatch. Empowering individuals to record their own ECG tracings in scenarios such as palpitations, syncope, and for risk stratification of sudden death intuitively has considerable potential, but its value remains to be robustly demonstrated. The main objective of this review is to describe the information that can be obtained from smartwatch-based single-lead ECG recordings beyond simply differentiating between sinus rhythm and atrial fibrillation. We also review the strengths and limitations of using these devices in clinical settings and offer potential solutions to address the latter.
The Early Repolarization Pattern: A Consensus Paper Macfarlane, Peter W; Antzelevitch, Charles; Haissaguerre, Michel ...
Journal of the American College of Cardiology,
07/2015, Letnik:
66, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The term early repolarization has been in use for more than 50 years. This electrocardiographic pattern was considered benign until 2008, when it was linked to sudden cardiac arrest due to idiopathic ...ventricular fibrillation. Much confusion over the definition of early repolarization followed. Thus, the objective of this paper was to prepare an agreed definition to facilitate future research in this area. The different definitions of the early repolarization pattern were reviewed to delineate the electrocardiographic measures to be used when defining this pattern. An agreed definition has been established, which requires the peak of an end-QRS notch and/or the onset of an end-QRS slur as a measure, denoted Jp, to be determined when an interpretation of early repolarization is being considered. One condition for early repolarization to be present is Jp ≥0.1 mV, while ST-segment elevation is not a required criterion.
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