Interventricular septal thickness on cardiac computed tomography as a novel risk factor for conduction disturbances in patients undergoing transcatheter aortic valve replacement.

AIMS: We examined whether thickness of the basal muscular interventricular septum (IVS), as measured by pre-procedural computed tomography (CT), could be used to identify the risk of conduction disturbances following transcatheter aortic valve replacement (TAVR). The IVS is a pivotal region of the electrical conduction system of the heart where the atrioventricular conduction axis is located. METHODS AND RESULTS: Included were 78 patients with severe aortic stenosis who underwent CT imaging prior to TAVR. The thickness of muscular IVS was measured in the coronal view, in systolic phases, at 1, 2, 5, and 10 mm below the membranous septum (MS). The primary endpoint was a composite of conduction disturbance following TAVR. Conduction disturbances occurred in 24 out of 78 patients (30.8%). Those with conduction disturbances were significantly more likely to have a thinner IVS than those without conduction disturbances at every measured IVS level (2.98 ± 0.52 mm vs. 3.38 ± 0.52 mm, 4.10 ± 1.02 mm vs. 4.65 ± 0.78 mm, 6.11 ± 1.12 mm vs. 6.88 ± 1.03 mm, and 9.72 ± 1.95 mm vs. 10.70 ± 1.55 mm for 1, 2, 5 and 10 mm below MS, respectively, P < 0.05 for all). Multivariable logistic regression analysis showed that pre-procedural IVS thickness (<4 mm at 2 mm below the MS) was a significant independent predictor of post-procedural conduction disturbance (adjOR 7.387, 95% CI: 2.003-27.244, P = 0.003). CONCLUSION: Pre-procedural CT assessment of basal IVS thickness is a novel predictive marker for the risk of conduction disturbances following TAVR. The IVS thickness potentially acts as an anatomical barrier protecting the underlying conduction system from mechanical compression during TAVR.

Detection of Epicardial Connection Through Intercaval Bundle Involving Right Pulmonary Veins After Ipsilateral Circumferential Ablation by Intra-Atrial Activation Sequence Pacing From the Right Pulmonary Vein.

BACKGROUND: An epicardial connection (EC) through the intercaval bundle (EC-ICB) between the right pulmonary vein (RPV) and right atrium (RA) is one of the reasons for the need for carina ablation for PV isolation and may reduce the acute and chronic success of PV isolation. We evaluated the intra-atrial activation sequence during RPV pacing after failure of ipsilateral RPV isolation and sought to identify specific conduction patterns in the presence of EC-ICB. METHODS AND RESULTS: This study included 223 consecutive patients who underwent initial catheter ablation of atrial fibrillation. If the RPV was not isolated using circumferential ablation or reconnected during the waiting period, an exit map was created during mid-RPV carina pacing. If the earliest site on the exit map was the RA, the patient was classified into the EC-ICB group. The exit map, intra-atrial activation sequence, and RPV-high RA time were evaluated. First-pass isolation of the RPV was not achieved in 36 patients (16.1%), and 22 patients (9.9%) showed reconnection. Twelve and 28 patients were classified into the EC-ICB and non-EC-ICB groups, respectively, after excluding those with multiple ablation lesion sets or incomplete mapping. The intra-atrial activation sequence showed different patterns between the 2 groups. The RPV-high RA time was significantly shorter in the EC-ICB than in the non-EC-ICB group (69.2±15.2 versus 148.6±51.2 ms; P<0.001), and RPV-high RA time<89.0 ms was highly predictive of the existence of an EC-ICB (sensitivity, 91.7%; specificity, 89.3%). CONCLUSIONS: An EC-ICB can be effectively detected by intra-atrial sequencing during RPV pacing, and an RPV-high RA time of <89.0 ms was highly predictive.

Opioids-Induced Long QT Syndrome: A Challenge to Cardiac Health.

The challenge posed by opioid overdose has become a significant concern for health systems due to the complexities associated with drug prohibition, widespread clinical use, and potential abuse. In response, healthcare professionals have primarily concentrated on mitigating the hallucinogenic and respiratory depressant consequences of opioid overdose to minimize associated risks. However, it is crucial to acknowledge that most opioids possess the capacity to prolong the QT interval, particularly in cases of overdose, thereby potentially resulting in severe ventricular arrhythmias and even sudden death if timely intervention is not implemented. Consequently, alongside addressing the typical adverse effects of opioids, it is imperative to consider their cardiotoxicity. To enhance comprehension of the correlation between opioids and arrhythmias, identify potential targets for prompt intervention, and mitigate the hazards associated with clinical utilization, an exploration of the interaction between drugs and ion channels, as well as their underlying mechanisms, becomes indispensable. This review primarily concentrates on elucidating the impact of opioid drugs on diverse ion channels, investigating recent advancements in this domain, and attaining a deeper understanding of the mechanisms underlying the prolongation of the QT interval by opioid drugs, along with potential interventions.

3D models of the cardiac conduction system in healthy neonatal human hearts.

Iatrogenic damage to the cardiac conduction system (CCS) remains a significant risk during congenital heart surgery. Current surgical best practice involves using superficial anatomical landmarks to locate and avoid damaging the CCS. Prior work indicates inherent variability in the anatomy of the CCS and supporting tissues. This study introduces high-resolution, 3D models of the CCS in normal pediatric human hearts to evaluate variability in the nodes and surrounding structures. Human pediatric hearts were obtained with an average donor age of 2.7 days. A pipeline was developed to excise, section, stain, and image atrioventricular (AVN) and sinus nodal (SN) tissue regions. A convolutional neural network was trained to enable precise multi-class segmentation of whole-slide images, which were subsequently used to generate high- resolution 3D tissue models. Nodal tissue region models were created. All models (10 AVN, 8 SN) contain tissue composition of neural tissue, vasculature, and nodal tissues at micrometer resolution. We describe novel nodal anatomical variations. We found that the depth of the His bundle in females was on average 304 µm shallower than those of male patients. These models provide surgeons with insight into the heterogeneity of the nodal regions and the intricate relationships between the CCS and surrounding structures.

Curvature-mediated source and sink effects on the genesis of premature ventricular complexes in long QT syndrome.

Premature ventricular complexes (PVCs) are spontaneous excitations occurring in the ventricles of the heart that are associated with ventricular arrhythmias and sudden cardiac death. Under long QT conditions, PVCs can be mediated by repolarization gradient (RG) and early afterdepolarizations (EADs), yet the effects of heterogeneities or geometry of the RG or EAD regions on PVC genesis remain incompletely understood. In this study, we use computer simulation to systematically investigate the effects of the curvature of the RG border region on PVC genesis under long QT conditions. We show that PVCs can be either promoted or suppressed by negative or positive RG border curvature depending on the source and sink conditions. When the origin of oscillation is in the source region and the source is too strong, a positive RG border curvature can promote PVCs by causing the source area to oscillate. When the origin of oscillation is in the sink region, a negative RG border curvature can promote PVCs by causing the sink area to oscillate. Furthermore, EAD-mediated PVCs are also promoted by negative border curvature. We also investigate the effects of wavefront curvature and show that PVCs are promoted by convex but suppressed by concave wavefronts; however, the effect of wavefront curvature is much smaller than that of RG border curvature. In conclusion, besides the increase of RG and occurrence of EADs caused by QT prolongation, the geometry of the RG border plays important roles in PVC genesis, which can greatly increase the risk of arrhythmias in cardiac diseases.NEW & NOTEWORTHY The effects of the curvature or geometry of the repolarization gradient region and wavefront curvature on the genesis of premature ventricular complexes are systematically investigated using computer modeling and simulation. Premature ventricular complexes can be promoted by either positive or negative curvature of the gradient region depending on the source and sink conditions. The underlying mechanisms of the curvature effects are revealed, which provides mechanistic insights into arrhythmogenesis in cardiac diseases.

Defining the blanking period, using continuous ECG monitoring, after cryoballoon pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. A blanking period (BP) of 3 months is used in clinical trials and practice. However, the optimal BP duration after PVI remains undefined. OBJECTIVE: The aim of this study was to objectively define, using continuous monitoring by an implantable loop recorder, the optimal BP duration after cryoballoon PVI. METHODS: We enrolled consecutive patients who had cryoballoon PVI and an implantable loop recorder. We determined the time of the last confirmed episode of AF within the blanking period. This was then correlated with AF recurrence in the first year after ablation. RESULTS: There were 210 patients (66 ± 9 years; 138 [66%] male; 116 [55%] paroxysmal AF; CHA2DS2-VASc score, 2.5 ± 1.6). We defined 4 distinct groups based on the last AF episode within the BP: no AF days 0-90 (n = 96 [46%]) and last AF 0-30 days (n = 46 [22%]), 31-60 days (n = 18 [9%]), and 61-90 days (n = 50 [24%]). After the 3-month BP, 101 (48%) patients had AF recurrence at 160 ± 86 days. Compared with patients with no AF in the BP, those with recurrent AF and AF burden >0% 30 days after ablation had a significantly greater AF recurrence during long-term follow-up (P = .001). CONCLUSION: Our data show that the approximately one-third of patients in whom AF occurs and who have a burden of >0% after the first month that follows PVI are at significantly higher risk of long-term recurrent AF. We therefore suggest that the blanking period be limited to a month after cryoballoon PVI.

Artificial intelligence-adjudicated spatiotemporal dispersion: A patient-unique fingerprint of persistent atrial fibrillation.

BACKGROUND: Spatiotemporal dispersion-guided ablation is a tailored approach for patients in persistent atrial fibrillation (PsAF). The characterization of dispersion extent and distribution and its association with common clinical descriptors of PsAF patients has not been studied. OBJECTIVES: Artificial intelligence-adjudicated dispersion extent and distribution (AI-DED) was obtained with a machine/deep learning classifier (VX1 Software, Volta Medical) in PsAF patients undergoing ablation. The purpose of this study was to test the hypothesis that AI-DED is unique to each patient and independent of common procedural and clinical parameters. METHODS: In a subanalysis of the Ev-AIFib study (NCT03434964), spatiotemporal dispersion maps were built with VX1 software in 78 consecutive persistent and long-standing PsAF patients. AI-DED was quantified using 2 distinct approaches (visual regional characterization or automated global quantification of AI-DED). RESULTS: AI-DED paired-subregion Euclidean distance measurements between 78 patients (average distance 5.07 ± 0.60; min 2.23; max 9.75) demonstrate that AI-DED is a patient-unique characteristic of PsAF. Importantly, both AF type and AF history do not correlate with AI-DED levels (R2 = 0.006, P = .53; and R2 = 0.03, P = .25, respectively). The most extensive AI-DED levels are not associated with poorer procedural (83%, 81%, and 83% of AF termination in low, medium, and high dispersion groups, respectively; P = .954) and long-term (88%, 75%, and 91% of freedom from AF/atrial tachycardia after multiple procedures; P = .517) outcomes. CONCLUSION: The atrial distribution and extent of multipolar electrogram spatiotemporal dispersion follow a nonrandom, albeit patient-unique, distribution in PsAF patients. AI-DED may represent a procedure-implementable fingerprint of the PsAF substrate.

Clinical characteristics of electrical storm in patients with early repolarization syndrome.

BACKGROUND: Early repolarization syndrome (ERS) is an idiopathic ventricular fibrillation (VF) associated with inferolateral J waves. While electrical storm (ES) in ERS is not rare, their characteristics and risk factors are not fully understood. OBJECTIVE: This study aimed to clarify the significance of ES in ERS. METHODS: We evaluated 44 patients with ERS who experienced VF/sudden cardiac death or arrhythmic syncope. We assessed clinical characteristics to identify the risk factors for ES. RESULTS: In total, 13 patients (30%) experienced ES (ES group). Of these, 11 patients (85%) experienced ES during the acute phase of initial VF episodes and 2 patients (2%) experienced ES during follow-up. VF associated with ES occurred during therapeutic hypothermia in 6 of 13 patients (46%). The J-wave voltage during therapeutic hypothermia was higher in the ES group than that in the patients without ES. Isoproterenol was used in 5 patients (38%), which decreased J-wave voltage and relieved ES. Among the clinical markers, shorter QT and QTp intervals (the interval from QRS onset to the peak of T wave), pilsicainide-induced ST elevation, and high scores on the Shanghai Score System were associated with ES. Although pilsicainide induced ST elevation in 6 of 34 patients (18%), spontaneous Brugada electrocardiographic patterns did not appear to be associated with VF. Therapeutic hypothermia was also a risk factor for acute phase ES. CONCLUSION: Patients with ERS in the ES group frequently had short QT and QTp intervals, pilsicainide-induced ST elevations, and high Shanghai Score System scores. Therapeutic hypothermia was also associated with acute phase ES.

Characterization of conduction system activation in the postinfarct ventricle using ripple mapping.

BACKGROUND: Three-dimensional (3D) mapping of the ventricular conduction system is challenging. OBJECTIVE: The purpose of this study was to use ripple mapping to distinguish conduction system activation to that of adjacent myocardium in order to characterize the conduction system in the postinfarct left ventricle (LV). METHODS: High-density mapping (PentaRay, CARTO) was performed during normal rhythm in patients undergoing ventricular tachycardia ablation. Ripple maps were viewed from the end of the P wave to QRS onset in 1-ms increments. Clusters of >3 ripple bars were interrogated for the presence of Purkinje potentials, which were tagged on the 3D geometry. Repeating this process allowed conduction system delineation. RESULTS: Maps were reviewed in 24 patients (mean 3112 ± 613 points). There were 150.9 ± 24.5 Purkinje potentials per map, at the left posterior fascicle (LPF) in 22 patients (92%) and at the left anterior fascicle (LAF) in 15 patients (63%). The LAF was shorter (41.4 vs 68.8 mm; P = .0005) and activated for a shorter duration (40.6 vs 64.9 ms; P = .002) than the LPF. Fourteen of 24 patients had left bundle branch block (LBBB), with 11 of 14 (78%) having Purkinje potential-associated breakout. There were fewer breakouts from the conduction system during LBBB (1.8 vs 3.4; 1.6 ± 0.6; P = .039) and an inverse correlation between breakout sites and QRS duration (P = .0035). CONCLUSION: We applied ripple mapping to present a detailed electroanatomic characterization of the conduction system in the postinfarct LV. Patients with broader QRS had fewer LV breakout sites from the conduction system. However, there was 3D mapping evidence of LV breakout from an intact conduction system in the majority of patients with LBBB.

Biomarkers associated with rhythm status after cardioversion in patients with atrial fibrillation.

Biomarkers may help to improve our knowledge about the complex pathophysiology of atrial fibrillation (AF). In this study we sought to identify significant changes in biomarkers and clinical measures in patients with and without AF recurrence after electrical cardioversion. We measured 21 conventional and new biomarkers before and 30 days after electrical cardioversion and assessed the associations of changes in biomarker levels with rhythm status at follow-up. Significant between-group changes were observed for bone morphogenetic protein 10 (BMP10), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin. Their respective changes were - 10.4%, - 62.0% and - 25.6% in patients with sinus rhythm, and 3.1%, 1.1% and - 9.4% in patients with recurrent AF, for a between-group difference of - 13.5% (95% confidence interval [CI] - 19.3% to - 7.6%; P < 0.001), - 63.1% (95% CI - 76.6% to - 49.6%; P < 0.001) and - 16.3% (95% CI - 27.9% to - 4.7%; P = 0.007). In multivariable models, the reductions of BMP10 and NT-proBNP were significantly associated with follow-up rhythm status (ß coefficient per 1 - SD decrease, - 3.85; 95% CI - 6.34 to - 1.35; P = 0.003 for BMP10 and - 5.84; 95% CI - 10.22 to - 1.47; P = 0.009 for NT-proBNP. In conclusion, changes in BMP10 und NT-proBNP levels were independently associated with rhythm status after cardioversion, suggesting that these markers may be dependent on the actual heart rhythm.

Cardiac Autonomic Modulation in Subjects with Amyotrophic Lateral Sclerosis (ALS) during an Upper Limb Virtual Reality Task: A Prospective Control Trial.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. As a result of the rapid progression and severity of the disease, people with ALS experience loss of functionality and independence. Furthermore, it has already been described presence of autonomic dysfunction. Despite the increasing use of virtual reality (VR) in the treatment of different diseases, the use of virtual reality environment as an intervention program for ALS patients is innovative. The benefits and limitations have not yet been proven. Our objective was to evaluate the autonomic function of individuals with amyotrophic lateral sclerosis throughout the virtual reality task. The analysis of autonomic function was completed before, during, and after the virtual reality task using the upper limbs; also, all steps lasted ten minutes in a sitting position. Heart rate variability (HRV) was taken via the Polar® RS800CX cardiofrequencymeter. The following questionnaire was enforced: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS) and Fatigue Severity Scale (FSS). Different types of HRV were revealed for the groups, indicating that the ALS group has reduced HRV, with most of the representative indices of the sympathetic nervous system. Besides, the physiological process of reducing parasympathetic activity from rest to VR activity (vagal withdrawal), with reduction in HF (ms2) and an increase in HR from rest to activity, and a further increase throughout recovery, with withdrawal of sympathetic nervous system, occurs just for the control group (CG), with no alterations between rest, activity, and recovery in individuals with ALS. We could conclude that patients with ALS have the reduction of HRV with the sympathetic predominance when equated to the healthy CG. Besides that, the ALS individuals have no capability to adapt the autonomic nervous system when likened to the CG during therapy based on VR and their recovery.

The best QT correction formula in a non-hospitalized population: the Fasa PERSIAN cohort study.

BACKGROUND: QT interval as an indicator of ventricular repolarization is a clinically important parameter on an electrocardiogram (ECG). QT prolongation predisposes individuals to different ventricular arrhythmias and sudden cardiac death. The current study aimed to identify the best heart rate corrected QT interval for a non-hospitalized Iranian population based on cardiovascular mortality. METHODS: Using Fasa PERSIAN cohort study data, this study enrolled 7071 subjects aged 35-70 years. Corrected QT intervals (QTc) were calculated by the QT interval measured by Cardiax® software from ECGs and 6 different correction formulas (Bazett, Fridericia, Dmitrienko, Framingham, Hodges, and Rautaharju). Mortality status was checked using an annual telephone-based follow-up and a minimum 3-year follow-up for each participant. Bland-Altman, QTc/RR regression, sensitivity analysis, and Cox regression were performed in IBM SPSS Statistics v23 to find the best QT. Also, for calculating the upper and lower limits of normal of different QT correction formulas, 3952 healthy subjects were selected. RESULTS: In this study, 56.4% of participants were female, and the mean age was 48.60 ± 9.35 years. Age, heart rate in females, and QT interval in males were significantly higher. The smallest slopes of QTc/RR analysis were related to Fridericia in males and Rautaharju followed by Fridericia in females. Thus, Fridericia's formula was identified as the best mathematical formula and Bazett's as the worst in males. In the sensitivity analysis, however, Bazett's formula had the highest sensitivity (23.07%) among all others in cardiac mortality. Also, in the Cox regression analysis, Bazett's formula was better than Fridericia's and was identified as the best significant cardiac mortality predictor (Hazard ratio: 4.31, 95% CI 1.73-10.74, p value = 0.002). CONCLUSION: Fridericia was the best correction formula based on mathematical methods. Bazett's formula despite its poorest performance in mathematical methods, was the best one for cardiac mortality prediction. Practically, it is suggested that physicians use QTcB for a better evaluation of cardiac mortality risk. However, in population-based studies, QTcFri might be the one to be used by researchers.