Circulation. Arrhythmia and electrophysiology最新文献

Background: Atrial fibrillation (AF) events in cardiac implantable electronic devices (CIEDs) are temporally associated with stroke risk. This study explores temporal differences in AF burden associated with HF hospitalization risk in patients with CIEDs.

Methods: Patients with HF events from the Optum de-identified Electronic Health Records from 2007 to 2021 and 120 days of preceding CIED-derived rhythm data from a linked manufacturer's data warehouse were included. AF burden ≥5.5 h/d was defined as an AF event. The AF event burden in the case period (days 1-30 immediately before the HF event) was considered temporally associated with the HF event and compared with the AF event burden in a temporally dissociated control period (days 91-120 before the HF event). The odds ratio for temporally associated HF events and the odds ratio associated with poorly rate-controlled AF (>110 bpm) were calculated.

Results: In total, 7257 HF events with prerequisite CIED data were included; 957 (13.2%) patients had AF events recorded only in either their case (763 [10.5%]) or control (194 [2.7%]) periods, but not both. The odds ratio for a temporally associated HF event was 3.93 (95% CI, 3.36-4.60). This was greater for an HF event with a longer stay of >3 days (odds ratio, 4.51 [95% CI, 3.57-5.68]). In patients with AF during both the control and case periods, poor AF rate control during the case period also increased HF event risk (1.78 [95% CI, 1.22-2.61]). In all, 222 of 4759 (5%) patients without AF events before their HF event had an AF event in the 10 days following.

Conclusions: In a large real-world population of patients with CIED devices, AF burden was associated with HF hospitalization risk in the subsequent 30 days. The risk is increased with AF and an uncontrolled ventricular rate. Our findings support AF monitoring in CIED algorithms to prevent HF admissions.

Success rates for catheter ablation of atrial fibrillation (AF), particularly persistent AF, remain suboptimal. Pulmonary vein isolation has been the cornerstone for catheter ablation of AF for over a decade. While successful for most patients, pulmonary vein isolation alone is still insufficient for a substantial minority. Frustratingly, multiple clinical trials testing a diverse array of additional ablation approaches have led to mixed results, with no current strategy that improves AF outcomes beyond pulmonary vein isolation in all patients. Nevertheless, this large collection of data could be used to extract important insights regarding AF mechanisms and the diversity of the AF syndrome. Mechanistically, the general model for arrhythmogenesis prompts the need for tools to individually assess triggers, drivers, and substrates in individual patients. A key goal is to identify those who will not respond to pulmonary vein isolation, with novel approaches to phenotyping that may include mapping to identify alternative drivers or critical substrates. This, in turn, can allow for the implementation of phenotype-based, targeted approaches that may categorize patients into groups who would or would not be likely to respond to catheter ablation, pharmacological therapy, and risk factor modification programs. One major goal is to predict individuals in whom additional empirical ablation, while feasible, may be futile or lead to atrial scarring or proarrhythmia. This work attempts to integrate key lessons from successful and failed trials of catheter ablation, as well as models of AF, to suggest future paradigms for AF treatment.

Background: The clinical outcome of pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) is suboptimal. Mapping studies have demonstrated atrial sites outside of the pulmonary veins displaying focal activation patterns during AF. We sought to determine whether adding catheter ablation of focal activation sites to PVI improves clinical outcomes of catheter ablation for persistent AF.

Methods: In this multicenter, randomized, single-blinded trial, we assigned patients with persistent AF to either PVI alone or to mapping-guided ablation of focal activation sites in addition to PVI in a 1:1 ratio. In the mapping-guided group, both atria were mapped after PVI using a Pentaray catheter (Biosense-Webster) and focal activation sites identified by CARTOFINDER (Biosense-Webster) were ablated. The primary end point was freedom from AF or atrial tachycardia without antiarrhythmic drugs beyond a 90-day blanking period.

Results: A total of 98 patients were assigned to the mapping-guided group and 102 to the PVI alone group. In the mapping-guided group, focal activation sites were identified at 2.6±0.3 and 2.5±0.2 sites per patient in the left and right atrium, respectively. Patients were followed up for 768.5 (interquartile range, 723.75-915.75) and 755.5 days (interquartile range, 728.5-913.75) in the mapping-guided ablation and the PVI alone groups, respectively. Freedom from AF/atrial tachycardia without antiarrhythmic drugs at 2-year follow-up was 66.8% and 75.2% in the mapping-guided ablation and the PVI alone groups, respectively (hazard ratio, 1.26 [95% CI, 0.76-2.10]; P=0.37). Adverse events occurred in 3 patients (3.0%) and none (0%) in the mapping-guided ablation and the PVI alone groups, respectively (P=0.12).

Conclusions: In patients with persistent AF, the addition of mapping-guided ablation of focal activation sites to PVI did not improve clinical outcomes compared with PVI alone.

Registration: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/index.cgi?function=02; Unique identifier: UMIN000037569.

Background: During pulsed field ablation (PFA), relationships between ablation parameters (contact force [CF], number of burst pulses, impedance decrease, and electrode temperature) and lesion size in beating hearts have not been well validated.

Methods: A 7.5F-catheter with a 3.5-mm ablation electrode and CF sensor (ThermoCool SmartTouch SF-Dual-Energy, Biosense Webster, Inc, Irwindale, CA) was connected to a PFA system (TRUPULSE2, Biosense Webster, Inc). In 11 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and the skin patch at 219 sites in left ventricle and right ventricle using 12, 18, and 24 burst pulses with 4 different levels of CF: (1) low (n=57; CF, 4-15g; median, 10g); (2) moderate (n=60; CF, 16-30g; median, 22.5g); (3) high (n=68; CF, 32-65g; median, 40g); and (4) no electrode contact (n=34), 2 mm away from the endocardium. Swine were euthanized 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining.

Results: All PFA lesions with electrode-myocardium contact were well demarcated with triphenyl tetrazolium chloride staining, demonstrating (1) pale central zone (contraction band necrosis with minimal coagulation necrosis), (2) dark brown zone (contraction band necrosis with hemorrhage), and (3) hyperstained red zone by triphenyl tetrazolium chloride (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). Lesion depth increased significantly with increasing CF and the number of PFA burst pulses. An exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlated lesion depth with high accuracy: R=0.809, P<0.0001, ±1.0-mm accuracy in 128 of 163 (79%) lesions, and ±1.5-mm accuracy in 153 of 163 (94%) lesions. Impedance decrease and electrode temperature were poor predictors of lesion size. There were no detectable lesions resulting from ablation without electrode contact.

Conclusions: Acute PFA ventricular lesions demonstrate irreversible and reversible lesion boundaries. Electrode-tissue contact is required for effective lesion formation. Lesion depth increases significantly with increasing CF and PFA burst pulses. A new exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlates lesion depth with high accuracy.

Background: Differentiating wide complex tachycardias (WCTs) into ventricular tachycardia (VT) and supraventricular wide tachycardia via 12-lead ECG interpretation is a crucial but difficult task. Automated algorithms show promise as alternatives to manual ECG interpretation, but direct comparison of their diagnostic performance has not been undertaken.

Methods: Two electrophysiologists applied 3 manual WCT differentiation approaches (ie, Brugada, Vereckei aVR, and VT score). Simultaneously, computerized data from paired WCT and baseline ECGs were processed by 5 automated WCT differentiation algorithms (WCT Formula, WCT Formula II, VT Prediction Model, Solo Model, and Paired Model). The diagnostic performance of automated algorithms was compared with manual ECG interpretation approaches.

Results: A total of 212 WCTs (111 VT and 101 supraventricular wide tachycardia) from 104 patients were analyzed. WCT Formula demonstrated superior accuracy (85.8%) and specificity (87.1%) compared with Brugada (75.2% and 57.4%, respectively) and Vereckei aVR (65.3% and 36.4%, respectively). WCT Formula II achieved higher accuracy (89.6%) and specificity (85.1%) against Brugada and Vereckei aVR. Performance metrics of the WCT Formula (accuracy 85.8%, sensitivity 84.7%, and specificity 87.1%) and WCT Formula II (accuracy 89.8%, sensitivity 89.6%, and specificity 85.1%) were similar to the VT score (accuracy 84.4%, sensitivity 93.8%, and specificity 74.2%). Paired Model was superior to Brugada in accuracy (89.6% versus 75.2%), specificity (97.0% versus 57.4%), and F1 score (0.89 versus 0.80). Paired Model surpassed Vereckei aVR in accuracy (89.6% versus 65.3%), specificity (97.0% versus 75.2%), and F1 score (0.89 versus 0.74). Paired Model demonstrated similar accuracy (89.6% versus 84.4%), inferior sensitivity (79.3% versus 93.8%), but superior specificity (97.0% versus 74.2%) to the VT score. Solo Model and VT Prediction Model accuracy (82.5% and 77.4%, respectively) was superior to the Vereckei aVR (65.3%) but similar to Brugada (75.2%) and the VT score (84.4%).

Conclusions: Automated WCT differentiation algorithms demonstrated favorable diagnostic performance compared with traditional manual ECG interpretation approaches.

Background: CaM (calmodulin)-mediated long-QT syndrome is a genetic arrhythmia disorder (calmodulinopathies) characterized by a high prevalence of life-threatening ventricular arrhythmias occurring early in life. Three distinct genes (CALM1, CALM2, and CALM3) encode for the identical CaM protein. Conventional pharmacotherapies fail to adequately protect against potentially lethal cardiac events in patients with calmodulinopathy.

Methods: Five custom-designed CALM1-, CALM2-, and CALM3-targeting short hairpin RNAs (shRNAs) were tested for knockdown (KD) efficiency using TSA201 cells and reverse transcription-quantitative polymerase chain reaction. A dual-component suppression and replacement (SupRep) CALM gene therapy (CALM-SupRep) was created by cloning into a single construct CALM1-, CALM2-, and CALM3-specific shRNAs that produce KD (suppression) of each respective gene and a shRNA-immune CALM1 cDNA (replacement). CALM1-F142L, CALM2-D130G, and CALM3-D130G induced pluripotent stem cell-derived CMs were generated from patients with CaM-mediated long-QT syndrome. A voltage-sensing dye was used to measure action potential duration at 90% repolarization (APD90).

Results: Following shRNA KD efficiency testing, a candidate shRNA was identified for CALM1 (86% KD), CALM2 (71% KD), and CALM3 (94% KD). The APD90 was significantly prolonged in CALM2-D130G (647±9 ms) compared with CALM2-WT (359±12 ms; P<0.0001). Transfection with CALM-SupRep shortened the average APD90 of CALM2-D130G to 457±19 ms (66% attenuation; P<0.0001). Additionally, transfection with CALM-SupRep shortened the APD90 of CALM1-F142L (665±9 to 410±15 ms; P<0.0001) and CALM3-D130G (978±81 to 446±6 ms; P<0.001).

Conclusions: We provide the first proof-of-principle suppression-replacement gene therapy for CaM-mediated long-QT syndrome. The CALM-SupRep gene therapy shortened the pathologically prolonged APD90 in CALM1-, CALM2-, and CALM3-variant CaM-mediated long-QT syndrome induced pluripotent stem cell-derived CM lines. The single CALM-SupRep construct may be able to treat all calmodulinopathies, regardless of which of the 3 CaM-encoding genes are affected.

Background: Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown.

Methods: The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method.

Results: Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61-1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59-1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56-0.98] and 0.65 [95% CI, 0.44-0.97], respectively).

Conclusions: In an older population with additional stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.