Purpose
There is a relative paucity of data on ante-mortem clinical characteristics of young (age 1 to 35 years) sudden death (SD) victims. The aim of the study was to characterize ante-mortem ...characteristics of SD victims, in a selected national cohort identified by a web search.
Methods
A dataset of all SD (January 2010 and December 2015) was built from national forensic data and medical records, integrated with Google search model. Families were contacted to obtain consent for interviews. Data were obtained on ante-mortem symptoms. ECG characteristics and autopsy data were available.
Results
Out of 301 SD cases collected, medical and family history was available in 132 (43.9%). Twenty-eight (21.1%) had a positive family history for SD. SD occurred during sport/effort in 76 (57.6%). One hundred twelve (85%) SD cases had no prior reported symptoms. Autopsy data were available in 100/132 (75.8%) cases: an extra cardiac cause was identified in 20 (20%). Among the 61 cases with a cardiac diagnosis, 21 (34%) had hypertrophic cardiomyopathy. Among the 19 (19%) victims without structural abnormalities, molecular autopsy identified pathogenic variants for channelopathies in 9 cases. Ten (10%) victims had no identifiable cause.
Conclusions
Most SD were due to cardiac causes and occurred in previously asymptomatic patients. SD events mainly occurred during strenuous activity. In a minority of cases, no cause was identified. The web-based selection criteria, and incomplete data retrieval, need to be carefully taken into account for data interpretation and reproducibility.
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.
Abstract Background The underlying mechanisms sustaining human persistent atrial fibrillation (PsAF) is poorly understood. Objectives This study sought to investigate the complexity and distribution ...of AF drivers in PsAF of varying durations. Methods Of 135 consecutive patients with PsAF, 105 patients referred for de novo ablation of PsAF were prospectively recruited. Patients were divided into 3 groups according to AF duration: PsAF presenting in sinus rhythm (AF induced), PsAF <12 months, and PsAF >12 months. Patients wore a 252-electrode vest for body surface mapping. Localized drivers (re-entrant or focal) were identified using phase-mapping algorithms. Results In this patient cohort, the most prominent re-entrant driver regions included the pulmonary vein (PV) regions and inferoposterior left atrial wall. Focal drivers were observed in 1 or both PV regions in 75% of patients. Comparing between the 3 groups, with longer AF duration AF complexity increased, reflected by increased number of re-entrant rotations (p < 0.05), number of re-entrant rotations and focal events (p < 0.05), and number of regions harboring re-entrant (p < 0.01) and focal (p < 0.05) drivers. With increased AF duration, a higher proportion of patients had multiple extra-PV driver regions, specifically in the inferoposterior left atrium (p < 0.01), superior right atrium (p < 0.05), and inferior right atrium (p < 0.05). Procedural AF termination was achieved in 70% of patients, but decreased with longer AF duration. Conclusions The complexity of AF drivers increases with prolonged AF duration. Re-entrant and focal drivers are predominantly located in the PV antral and adjacent regions. However, with longer AF duration, multiple drivers are distributed at extra-PV sites. AF termination rate declines as patients progress to longstanding PsAF, underscoring the importance of early intervention.
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.
Many patients with sleep apnea syndrome have nocturnal bradycardia, paroxysmal tachyarrhythmias, or both, which can be prevented by permanent atrial pacing. We evaluated the effect of using cardiac ...pacing to increase the heart rate during sleep in patients with sleep apnea syndrome.
We studied 15 patients (11 men and 4 women; mean +/-SD age, 69+/-9 years) with central or obstructive sleep apnea who had received permanent atrial-synchronous ventricular pacemakers for symptomatic sinus bradycardia. All patients underwent three polysomnographic evaluations on consecutive nights, the first night for base-line evaluation and then, in random order, one night in spontaneous rhythm and one in dual-chamber pacing mode with atrial overdrive (basic rate, 15 beats per minute faster than the mean nocturnal sinus rate). The total duration and number of episodes of central or obstructive sleep apnea or hypopnea were analyzed and compared.
The mean 24-hour sinus rate during spontaneous rhythm was 57 +/- 5 beats per minute at base line, as compared with 72 +/- 3 beats per minute with atrial overdrive pacing (P<0.001). The total duration of sleep was 321 +/- 49 minutes in spontaneous rhythm, as compared with 331 +/- 46 minutes with atrial overdrive pacing (P=0.48). The hypopnea index (the total number of episodes of hypopnea divided by the number of hours of sleep) was reduced from 9 +/- 4 in spontaneous rhythm to 3 +/-3 with atrial overdrive pacing (P<0.001). For both apnea and hypopnea, the value for the index was 28 +/- 22 in spontaneous rhythm, as compared with 11 +/- 14 with atrial overdrive pacing (P<0.001).
In patients with sleep apnea syndrome, atrial overdrive pacing significantly reduces the number of episodes of central or obstructive sleep apnea without reducing the total sleep time.
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.
...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.
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.
The mainstay of treatment for atrial fibrillation (AF) remains pharmacological; however, catheter ablation has increasingly been used over the last decade. The relative merits of each strategy have ...not been extensively studied.
We conducted a randomized multicenter comparison of these 2 treatment strategies in patients with paroxysmal AF resistant to at least 1 antiarrhythmic drug. The primary end point was absence of recurrent AF between months 3 and 12, absence of recurrent AF after up to 3 ablation procedures, or changes in antiarrhythmic drugs during the first 3 months. Ablation consisted of pulmonary vein isolation in all cases, whereas additional extrapulmonary vein lesions were at the discretion of the physician. Crossover was permitted at 3 months in case of failure. Echocardiographic data, symptom score, exercise capacity, quality of life, and AF burden were evaluated at 3, 6, and 12 months by the supervising committee. Of 149 eligible patients, 112 (18 women 16%; age, 51.1+/-11.1 years) were enrolled and randomized to ablation (n=53) or "new" antiarrhythmic drugs alone or in combination (n=59). Crossover from the antiarrhythmic drugs and ablation groups occurred in 37 (63%) and 5 patients (9%), respectively (P=0.0001). At the 1-year follow-up, 13 of 55 patients (23%) and 46 of 52 patients (89%) had no recurrence of AF in the antiarrhythmic drug and ablation groups, respectively (P<0.0001). Symptom score, exercise capacity, and quality of life were significantly higher in the ablation group.
This randomized multicenter study demonstrates the superiority of catheter ablation over antiarrhythmic drugs in patients with AF with regard to maintenance of sinus rhythm and improvement in symptoms, exercise capacity, and quality of life.
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.
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