Circulation. Arrhythmia and electrophysiology最新文献

Background: Atrial tachyarrhythmia recurrence remains the primary end point of clinical trials evaluating therapeutic pharmacological and nonpharmacological interventions for atrial fibrillation (AF). We sought to examine the relationship between the timing of first atrial tachyarrhythmia recurrence and subsequent AF burden.

Methods: We performed a patient-level analysis of 2 multicenter prospective parallel-group, single-blinded randomized clinical trials that used continuous rhythm monitoring after rhythm intervention. Patients with paroxysmal AF were stratified based on the month where the first recurrence of atrial tachyarrhythmia was observed, after a 2-month blanking period. AF burden was calculated as the time spent in AF at 1 year after first recurrence and over 3 years of follow-up.

Results: A total of 51.7% of patients experienced a recurrence of atrial tachyarrhythmia in the first year of follow-up. A first recurrence of atrial tachyarrhythmia occurred in 56.5% of patients within the third month post treatment initiation, with 79.5% of all recurrences detected by month 6 and 90.2% detected by month 9. The median postrecurrence AF burden was significantly greater in those with first recurrence in month 3 (1.04% [interquartile range, 0.23-5.05]) when compared with those patients with first recurrence between months 4 to 12 (0.13% [interquartile range, 0.04-0.63]; P<0.0001 versus month 3) and those with first recurrence after month 12 (0.05% [interquartile range, 0.01-0.20]; P<0.0001 versus month 3).

Conclusions: Atrial tachyarrhythmia recurrence after rhythm control intervention for paroxysmal AF is not uniform, with earlier recurrences being associated with higher AF burden on follow-up. These findings suggest that the timing of arrhythmia recurrence is of critical importance, with later recurrences being of progressively lesser clinical significance.

Background: Bradyarrhythmia is a common and potentially serious cause of syncope, often difficult to detect due to its intermittent nature. Traditional ECG monitoring methods either provide low diagnostic accuracy or delay diagnosis, increasing the risk of recurrence. We hypothesized that a deep learning-enabled, 24-hour, single-lead ECG could detect past episodes of bradyarrhythmia.

Methods: Using unselected 14-day single-lead ambulatory ECG recordings, we developed a deep learning model to identify patients with prior asystole from sinus arrest or complete heart block. The model was trained using the last 24 hours of each recording, free of bradyarrhythmias, to identify daytime sinus pause of ≥3 s, anytime sinus pause of ≥6 s, complete heart block, or a composite of these bradyarrhythmias from the previous 13 days.

Results: A total of 320 959 unselected 14-day ambulatory ECG recordings (mean age, 60.5±17.8 years; 60% female) were split into training (n=189 414), tuning (n=45 982), internal validation (n=43 390), and external validation (n=42 173) sets. External validation of prior daytime sinus pause ≥3 s, anytime sinus pause ≥6 s, complete heart block, and a composite end point demonstrated an area under the receiver operating characteristic curve of 0.89, 0.87, 0.93, and 0.89, respectively, with negative predictive values between 97.9 and 99.9%. In addition to this approach of uncovering past events, our model was also tested for its ability to predict bradyarrhythmias within the following 13 days using the first 24 hours of ECG data, achieving an AUC of 0.88 for the composite end point.

Conclusions: A deep learning-enabled ambulatory ECG is capable of unmasking underlying conduction tissue system disease. This tool may help identify patients with significant intermittent bradyarrhythmia, potentially improving timely diagnosis and management.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia, with pathogenic variants in the RYR2 gene responsible for 60% of clinically well-defined CPVT cases. Diagnosis of CPVT often occurs after a major cardiac event, posing a severe threat to the patient's life. A data set of patients with CPVT would improve the diagnosis and treatment of patients with CPVT.

Methods: This review cataloged clinical data on patients with RYR2-related CPVT variants from articles published up to October 2020 from PubMed, Scopus, and Embase. Variants were mapped to the structural domains of RYR2. Differences in the age of onset based on variant location and incidence of CPVT symptoms, and differences in treatment strategies were analyzed.

Results: In 221 publications analyzed, 964 patients with CPVT (351 male, 463 female) were identified with 263 RYR2 protein-coding variants and a median age of onset of CPVT of 11 years (interquartile range, 7-14 years). A web app was developed to allow users to query the database and is available at https://markslab-cpvtdb.org. The proportion of patients requiring treatments in addition to β-blockers varied between variants. The age of onset of CPVT differed significantly between RYR2 variants located in different exons, domains, and subdomains. Patients with variants in the core solenoid at the domain level, and the core solenoid (exEF-hand) and channel pore at the subdomain level, tended to have a lower age of onset compared with other regions.

Conclusions: This study compiled a comprehensive data set of CPVT-associated RYR2 variants and their clinical phenotypes. The age of onset in certain domains (core solenoid) and subdomains (core solenoid[exEF-hand], channel pore) tended to be lower compared with other regions. Variability in patient phenotypes, such as age of onset and treatment efficacy, along with structural information on variants, suggests that patients may benefit from personalized interventions based on their variant.

Background: Atrial fibrillation (AF) is a progressive disease involving both structural and functional remodeling. Although over the past decade, digital twin-guided therapy has been proposed and applied, accounting for cardiomyocyte functional remodeling remains challenging. We aimed to investigate the contribution of functional remodeling at the cellular level to AF pathogenesis in patients with fibrotic remodeling and to develop novel techniques to predict the location of reentrant drivers.

Methods: To investigate the contribution of cell-scale functional remodeling to AF pathogenesis under the conditions of fibrotic remodeling, we combined 3-dimensional atrial digital twins with pathology-specific single-cell models. The latter were developed using recordings in myocytes isolated from patients in sinus rhythm, paroxysmal, postoperative, and persistent AF. To quantify AF dynamics in the digital twins, we developed a novel algorithm for locating reentrant drivers by backtracking the conduction velocity field from the wavebreak regions.

Results: We demonstrate that our novel algorithm is at least 700× faster than the traditional phase singularity analysis. The inducibility of simulated AF was not pathology-dependent, but pathological models demonstrate a more extensive arrhythmogenic substrate than the sinus rhythm. We observed a correlation between wavebreak probability and fibrosis density, with the highest regression slope for the persistent AF model and the lowest for the sinus rhythm model.

Conclusions: AF driver locations in atrial fibrotic substrates depend on electrophysiological remodeling; differences between pathology-specific models are explained by differences in wavebreak patterns. Specifically, reentrant drivers tend to dwell in the regions with the highest wavebreak probability.

Background: Catheter ablation of scar-dependent ventricular tachycardia (VT) is frequently hampered by hemodynamic instability, long procedure duration, and high recurrence rates. Magnetic resonance imaging-based personalized heart digital twins may overcome these challenges by noninvasively predicting VT circuits and optimum ablation lesion sites. In this combined clinical and digital twin study, we investigated the relationship between digital twin-predicted VTs and optimum ablation lesion sets with their invasively mapped counterparts during clinical VT ablation.

Methods: A total of 18 patients with scar-dependent VT underwent digital twin creation based on preprocedural, contrast-enhanced cardiac magnetic resonance imaging. Using rapid pacing protocols, VT was simulated and ablation targets were derived that would terminate all possible VTs in the models. Patients subsequently underwent invasive VT ablation, including targeting of diastolic activity and optimum entrainment sites. Digital twin-predicted VT circuits and ablation lesions were compared with their invasive clinical counterparts.

Results: Forty-three clinical VTs and 92 digital twin VTs were induced. Diastolic activity was seen in 16 of 43 (37.2%) clinical VTs. Sensitivity, specificity, positive predictive, and negative predictive values for the detection of critical VT sites by digital twins were 81.3%, 83.8%, 21.7%, and 98.8%, respectively. At an American Heart Association-segment level, agreement between clinical VT critical sites and digital twin primary predicted sites was moderate, with a κ coefficient of 0.46 (±0.32; P≤0.001). Termination of VT with ablation was achieved at a digital twin-predicted site in 4 of 5 (80%) cases where attempted. A total of 426 of 709 (60.1%) lesions were within 5 mm of a predicted target site. In total, 54.0% (±28.9%) of the digital twin-predicted area was ablated per patient based on conventional mapping criteria.

Conclusions: Heart digital twin VT circuits and ablation targets accurately predict many features of their respective clinical counterparts but have some limitations in spatial resolution. Our findings demonstrate the significant potential of digital twin technology in guiding catheter ablation for scar-dependent VT.

Background: Inflammation is a common mechanism for atrial fibrillation (AF). 2-Hydroxybenzylamine (2-HOBA) is a novel therapeutic that scavenges isolevuglandins-a downstream mediator of inflammation and oxidative stress. 2-HOBA is safe and reduces AF in mice, prompting a first-in-human pilot clinical trial.

Methods: Participants were enrolled and randomized 1:1 to placebo or 2-HOBA (750 mg p.o. TID) 3 days before a planned AF ablation. Participants were monitored for 28 days after their ablation for recurrence of AF as detected by smartwatch single-lead ECG recordings. Blood was collected at the time of ablation for measurement of isolevuglandin levels. The study drug was stopped at 28 days. A 12-month extended follow-up period was used to monitor for any residual effect of the study drug on AF recurrence.

Results: 2-HOBA increased the risk of AF recurrence in the postablation population (odds ratio, 3.65 [95% CI, 1.31-10.16]; P=0.013) after prespecified adjustment for potential confounders. This increased risk of recurrence remained despite post hoc adjustment for other clinical risk factors. There was no difference in isolevuglandin levels between the 2-HOBA and placebo groups. After the study drug was stopped, there was no difference in AF recurrence between the 2-HOBA and placebo groups during the 12-month extended follow-up.

Conclusions: 2-HOBA was associated with a higher risk of AF recurrence when tested early after AF ablation. This result was unexpected based on preclinical data, but paradoxical associations with AF have been previously reported for other drugs that target inflammation and oxidative stress pathways, such as omega-3 fatty acids. The mechanisms for AF immediately following ablation may be different from AF that occurs under other conditions, and the generalizability of these results to all forms of AF remains unknown.

Background: In patients with nonischemic cardiomyopathy and no late gadolinium enhancement (LGE) on cardiac magnetic resonance, risk prediction for the occurrence of sustained ventricular arrhythmias (VA) is challenging. Global and regional sympathetic denervation has been associated with VA in patients with ischemic cardiomyopathy. Its prognostic relevance in nonischemic cardiomyopathy is unknown.

Methods: Consecutive patients from the Leiden Nonischemic Cardiomyopathy Study who underwent programmed electrical stimulation, LGE-cardiac magnetic resonance, and 123-iodine meta-iodobenzylguanidine imaging between 2011 and 2019 were included. The presence of LGE and global and regional sympathetic denervation on 123-iodine meta-iodobenzylguanidine were evaluated, and patients were followed for the occurrence of VA. Global denervation was assessed using the heart-to-mediastinum ratio. Regional denervation was evaluated by calculating the number of denervated segments (DS), the ratio of DS, the summed defect score, and the weighted denervation size.

Results: Of 75 included patients (median age 63 years [25th-75th interquartile range (IQR) 54-68], 79% male, left ventricular ejection fraction 36% [IQR, 27-44], 37% inducible for VA), 35 had no LGE. During 4.5±1.6 years of mean follow-up, VA occurred in 8 of 35 (23%) patients without LGE and in 18 of 40 (45%) patients with LGE. Among patients without LGE, those with VA had greater regional sympathetic denervation (median number of DS 8 [IQR, 7-10] versus 2 [IQR, 1-5], P=0.004; median ratio of DS 0.5 [IQR, 0.5-0.7] versus 0.2 [IQR, 0.1-0.4], P=0.007; median defect score 36 [IQR, 30-41] versus 18 [IQR, 14-24], P=0.01; median weighted denervation size 47 [IQR, 38-54] versus 22 [IQR, 14-30]; P=0.01). In bivariate analysis, the number of DS (hazard ratio, 1.25 [95% CI, 1.06-1.46]; P=0.006) was associated with the occurrence of VA in patients without LGE. Denervation of ≥7 segments identified patients without LGE at risk for VA (area under the curve, 0.83; sensitivity, 88%; specificity, 89%). Among patients with LGE, the innervation state was not associated with VA during follow-up.

Conclusions: In patients with nonischemic cardiomyopathy without LGE the extent of regional denervation may contribute to risk stratification for VA.