Efficacy of Computed Tomography-Based Evaluation of Myocardial Extracellular Volume Combined With Red Flags for Early Screening of Concealed Cardiac Amyloidosis in Patients With Atrial Fibrillation.

BACKGROUND: The prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) in atrial fibrillation (AF) patients remains unclear. We explored the efficacy of computed tomography-based myocardial extracellular volume (CT-ECV) combined with red flags for the early screening of concealed ATTR-CM in AF patients undergoing catheter ablation. METHODS AND RESULTS: Patients referred for AF ablation at Oita University Hospital were prescreened using the red-flag signs defined by echocardiographic or electrocardiographic findings, medical history, symptoms, and blood biochemical findings. Myocardial CT-ECV was quantified in red flag-positive patients using routine pre-AF ablation planning cardiac CT with the addition of delayed-phase cardiac CT scans. Patients with high (>35%) ECV were evaluated using technetium pyrophosphate (99 mTc-PYP) scintigraphy. A cardiac biopsy was performed during the planned AF ablation procedure if 99 mTc-PYP scintigraphy was positive. Between June 2022 and June 2023, 342 patients were referred for AF ablation. Sixty-seven (19.6%) patients had at least one of the red-flag signs. Myocardial CT-ECV was evaluated in 57 patients because of contraindications to contrast media, revealing that 16 patients had high CT-ECV. Of these, 6 patients showed a positive 99 mTc-PYP study, and 6 patients were subsequently diagnosed with wild-type ATTR-CM via cardiac biopsy and genetic testing. CONCLUSIONS: CT-ECV combined with red flags could contribute to the systematic early screening of concealed ATTR-CM in AF patients undergoing catheter ablation.

Atrial Structural Remodeling in Patients With Atrial Fibrillation Is a Diffuse Fibrotic Process: Evidence From High-Density Voltage Mapping and Atrial Biopsy.

Background Low-voltage areas (LVAs) in the atria of patients with atrial fibrillation are considered local fibrosis. We hypothesized that voltage reduction in the atria is a diffuse process associated with fibrosis and that the presence of LVAs reflects a global voltage reduction. Methods and Results We examined 140 patients with atrial fibrillation and 13 patients with a left accessory pathway (controls). High-density bipolar voltage mapping was performed using a grid-mapping catheter during high right atrial pacing. Global left atrial (LA) voltage (VGLA) in the whole LA and regional LA voltage (VRLA) in 6 anatomic regions were evaluated with the mean of the highest voltage at a sampling density of 1 cm2. Patients with atrial fibrillation were categorized into quartiles by VGLA. LVAs were evaluated at voltage cutoffs of 0.1, 0.5, 1.0, and 1.5 mV. Twenty-eight patients with atrial fibrillation also underwent right atrial septum biopsy, and the fibrosis extent was quantified. Voltage at the biopsy site (Vbiopsy) was recorded. VGLA results by category were Q1 (<4.2 mV), Q2 (4.2-5.6 mV), Q3 (5.7-7.0 mV), and Q4 (≥7.1 mV). VRLA at any region was reduced as VGLA decreased. VGLA and VRLA did not differ between Q4 and controls. The presence of LVAs increased as VGLA decreased at any voltage cutoff. Biopsies revealed 11±6% fibrosis, which was inversely correlated with both Vbiopsy and VGLA (r=-0.71 and -0.72, respectively). Vbiopsy was correlated with VGLA (r=0.82). Conclusions Voltage reduction in the LA is a diffuse process associated with fibrosis. Presence of LVAs reflects diffuse voltage reduction of the LA.

Sequence determination of phosphorothioated oligonucleotides using MALDI-TOF mass spectrometry for controlling gene doping in equestrian sports.

In human and equestrian sporting events, one method of gene doping is the illegal use of therapeutic oligonucleotides to alter gene expression. In this study, we aimed to identify therapeutic oligonucleotides via sequencing using matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF MS). As a model of therapeutic oligonucleotides, 22 bp-long phosphorothioated oligonucleotides (PSOs) were used. By using a Clarity OTX kit for extracting short-length oligonucleotides, a spectrum of singly charged PSO with a mean intensity of 6.08 × 104 (standard deviation: 4.34 × 103 ) was detected from 500 pmol PSO in 1 ml horse plasma using the linear negative mode of MALDI-TOF MS. In addition, a 17 bp sequence was determined using in-source decay (ISD) mode, indicating that 500 pmol of a PSO in 1 ml plasma is the detection limit for sequencing. Using the determined sequences (17 bp), a targeted gene for PSO was singly identified on the horse reference genome, EquCab2.0, via a GGGenome search. These procedures can be potentially used to identify therapeutic oligonucleotides, whose nucleotides are unknown, for gene doping control.

Digital PCR detection of plasmid DNA administered to the skeletal muscle of a microminipig: a model case study for gene doping detection.

OBJECTIVE: Doping control is an important and indispensable aspect of fair horse racing; genetic doping has been recently included to this. In this study, we aimed to develop a detection method of gene doping. A plasmid cloned with human erythropoietin gene (p.hEPO, 250 µg/head) was intramuscularly injected into a microminipig. Subsequently, p.hEPO was extracted from 1 mL of plasma and detected by droplet digital polymerase chain reaction. RESULTS: The results confirmed that the maximum amount of plasmid was detected at 15 min after administration and the majority of the plasmid was degraded in the bloodstream within 1-2 days after administration. In contrast, low amounts of p.hEPO were detected at 2-3 weeks after administration. These results suggest that the proposed method to detect gene doping can help obtain information for experiments using horses.

Feasibility of total intravenous anesthesia by cardiologists with the support of anesthesiologists during catheter ablation of atrial fibrillation.

BACKGROUND: The optimal methodology for sedation and anesthesia during atrial fibrillation (AF) ablation has not been well established. We assessed the feasibility of total intravenous anesthesia (TIVA) by cardiologists with support from anesthesiologists during AF ablation and quality of pulmonary vein isolation (PVI) and single procedure success rate at 12 months. METHODS: TIVA was performed by cardiologists using IV propofol and fentanyl under controlled ventilation via i-gel™ without neuromuscular blocking drugs in 160 consecutive patients (80 nonparoxysmal) with no anticipated difficult airway or other severe diseases. Anesthesiologists were requested to be on standby during the procedure. The incidence of anesthesia-associated complications and ablation-associated complications were assessed. To evaluate the quality of PVI, the prevalence of acute adenosine triphosphate (ATP)-provoked PV reconnections and late PV reconnections among those requiring a redo procedure was analyzed. RESULTS: TIVA was successfully completed in 152 patients (95%). In five (3%), we requested help from anesthesiologists, and in three (2%), TIVA was abandoned. No major anesthesia-associated complications were observed. Ablation-associated complications were observed in seven patients (4%). ATP provocation test was performed in 141 patients, and no acute PV reconnections were observed in 134 (95%). Success rates at 12 months were 85% of patients off antiarrhythmic drugs. Twenty-one of 24 patients with recurrence underwent a redo session, and 18 (86%) had no PV reconnections. CONCLUSIONS: TIVA by cardiologists with support from anesthesiologists during AF ablation may be feasible. The success rate at 12 months was high, and prevalence of acute and late PV reconnection was very low.