Heart Rhythm

Background Substrate mapping using multielectrode catheters is increasingly used for post-myocardial infarction (MI) ventricular tachycardia (VT) avoiding repeated VT induction and mapping during VT. However, these catheters may mechanically induce ventricular arrhythmias with hemodynamic compromise. This study compares pro-arrhythmogenicity between single-tip and multi-spline catheters during functional substrate mapping. Methods Thirty post-MI patients (age 68{+/-}8 years, 97% male, LVEF 40% [IQR 33-46]) referred for VT ablation at two centers (2021-2024) underwent endocardial mapping during baseline rhythm in random order with both a multi-spline catheter (Octaray, n=4; Pentaray, n=26) and a single-tip QDOT catheter. The protocol was prematurely terminated if (i) two mechanically induced VTs required ECV, (ii) recurrent ATP-treated mechanical VTs caused hemodynamic compromise, or (iii) excessive mechanically induced ectopy impaired catheter contact. Mapping time, point density, and mechanically induced arrhythmias were assessed. Results Multi-spline catheters enabled faster mapping (26{+/-}9 vs 60{+/-}16 minutes, p<0.001) with more acquired points (p<0.001). VTs were more frequently mechanically induced with multi-spline catheters (median 2 [IQR 1-4] vs 0 [0-3], p<0.05) and these VTs were faster (304ms, IQR 292-320] vs 373ms, IQR [316-405], p=0.01) and degenerated more often into VF (3 vs. 0). Overall, 17 patients (57%) experienced at least one mechanically induced VT; seven (23%) required cardioversion, and mapping was prematurely terminated in eight (27%), all while using multi-spline catheters. Conclusion Multi-spline catheters allow rapid substrate mapping but with substantial risk of mechanically induced arrhythmias, requiring premature termination of substrate mapping because of safety concerns. Their use in post-MI VT ablation warrants careful risk?benefit assessment.

Background. Durable mitral isthmus (MI) block remains challenging in persistent atrial fibrillation (PeAF) ablation. Recent epicardial vein of Marshall (VoM) recordings have shown incomplete MI transmurality and time-dependent conduction recovery after pulsed field ablation (PFA). Whether systematic VoM ethanol infusion (VoM-EI) followed by focal PFA provides stable acute MI block remains unknown. **Objectives.** To assess the incidence, timing, and procedural implications of early MI conduction recovery after systematic VoM-EI followed by focal Sphere-9 PFA. Methods.In this prospective single-center study, 55 consecutive patients undergoing first ablation for symptomatic PeAF with planned MI ablation were screened. VoM-EI was systematically attempted before left atrial access and successfully performed in 51 (92.7%), who constituted the study cohort. Pulmonary vein isolation, roof-line, and MI ablation were performed with the Sphere-9? lattice-tip catheter. After bidirectional MI block, conduction was systematically reassessed during a standardized 30-minute waiting period. Results.Mean age was 70.3 {+/-} 8.2 years, and 36 patients (70.6%) were men. Initial bidirectional MI block was achieved in 50/51 patients (98.0%). During the waiting period, conduction recovered in 9/50 (18.0%; 95% CI, 9.8%-30.8%), at a median of 16 minutes (IQR, 10-20; range, 8?23). Six of 9 patients with recovery (66.7%) required targeted coronary sinus (CS) ablation. Block was restored in all 9, yielding a final block rate of 50/51 (98.0%). Median procedure duration was 82 minutes (IQR, 73-95), with no major complications. Conclusions. Immediate bidirectional MI block was not synonymous with stable block. Despite systematic VoM-EI followed by focal Sphere-9 PFA, conduction recovered in approximately one in five patients, including beyond 20 minutes, and two thirds required targeted CS ablation. These findings support standardized 30-minute reassessment and targeted CS interrogation rather than reliance on immediate block. Chronic invasive remapping is required to determine whether this strategy improves long-term MI block durability.

Background: Vagally mediated syncope and functional bradyarrhythmias can cause recurrent symptoms, injury and a need for permanent pacing, yet standard therapies do not address the underlying autonomic reflex. Cardioneuroablation (CNA) targets this mechanism, but adoption has been limited by uncertainty about patient selection, procedural endpoints and durable outcomes. Methods: We studied 95 consecutive patients with vagally mediated syncope (n=78) or functional bradyarrhythmia (n=17) who underwent CNA at a single center by a single lead operator under a uniform, prospectively maintained protocol. Extracardiac vagal stimulation (ECVS) was performed before and after ablation to confirm vagally mediated sinus or atrioventricular (AV) nodal responses and to verify their attenuation. Outcomes through 1 year included clinical recurrence, quality of life, pacing burden and pacemaker extraction. Results: Before ablation, ECVS provoked sinus pauses in 95.8% of patients and AV block in 91.6%; after ablation, sinus pauses were abolished in every patient and residual AV block was present in 4.2%. One-year freedom from recurrent syncope and from bradyarrhythmia-related events was 93.8% and 94.1%. Syncope burden fell from a median of 2.7 episodes per year to none, and disease-specific quality of life improved substantially (P<0.001). Among patients with pre-existing devices, atrial pacing burden fell from a median of 22% to 0%. There were no strokes, deaths or myocardial infarctions. Conclusions: In this single-center cohort, physiology-guided CNA was associated with durable symptom control, improved quality of life and reduced pacing across vagally mediated bradyarrhythmia syndromes. Multicenter controlled studies are needed to confirm these findings.

Background: Anatomic isthmus 3 (AI 3) is defined as the myocardium between the pulmonary valve annulus and the ventricular septal defect patch that persists after tetralogy of Fallot (ToF) repair. Ventricular tachycardia (VT) propagated through slow conducting AI 3 (SCAI 3) represents a significant cause of morbidity in ToF. There is an unmet need for non-invasive identification of SCAI 3 in patients with ToF. Objectives: To assess whether the anatomic features of AI 3 as derived from cardiac computed tomography (CT) can predict slow conduction velocity during EP study. Methods: This retrospective single-center study included patients with ToF who underwent an electrophysiologic study and had AI 3 width measured from the pre-procedure cardiac CT. All patients underwent programmed ventricular stimulation, and electroanatomic. Logistic regression was performed to assess the relationship between AI 3 width and the presence of SCAI 3. Results: Of 27 consecutive patients with ToF, twelve patients were found to have SCAI 3, and ten patients were found to have SCAI 3 mediated VT. The AI 3 was significantly narrower in patients with SCAI 3 compared to those with normal AI 3 conduction (18.4 +/- 6.6 mm vs. 29.2 +/- 9.0 mm; p = 0.001). An AI 3 width above 21.5 mm carried a negative predictive value of 80.0%. Conclusion: In adults with repaired ToF referred for electrophysiology study, a narrower CT-derived AI 3 width was associated with SCAI 3 identification. AI 3 width measured on a CT obtained before PV replacement could help guide invasive risk stratification.

Background: Atrial fibrillation (AF) has been observed in adults with anomalous pulmonary venous return (APVR), but data on catheter ablation outcomes in this population remain limited to case reports and small series. Methods: We retrospectively reviewed 14 adult patients with confirmed APVR who underwent catheter ablation for AF at three tertiary academic centers in the United States between July 2003 and May 2025. Baseline, procedural, electroanatomic mapping, and outcome data were collected. Freedom from atrial arrhythmia recurrence was estimated by Kaplan-Meier analysis. Results: Mean age was 56 +/- 13 years and 79% were male. Heart failure was present in 64%, and hypertension and coronary artery disease in 43% each. Most had partial APVR (86%), and 57% had prior surgical correction. Radiofrequency ablation was used in all patients, combined with pulsed-field ablation in one. Acute success was achieved in all patients, although areas with residual pulmonary vein or SVC electrical activity were left untreated in 3 (21%). Non-pulmonary-vein electrical activity was more common in patients with prior surgical correction than in those without (43% vs 17%). Median follow-up was 3.4 years (IQR, 2.0-9.6). Freedom from arrhythmia recurrence was 78.6% at 1 year and 53.9% at 5 years. Two patients (14%) required reablation; complications occurred in 3 (21%) without long-term sequelae. Conclusions: Catheter ablation was acutely successful in all patients in this largest reported APVR cohort, despite substantial comorbidity burden and anatomic complexity. The arrhythmogenic substrate often extended beyond the anomalous vein, particularly in surgically corrected patients, supporting individualized, substrate-guided ablation in this population.

Background Pulsed-field ablation (PFA) has recently been approved in the USA as a new method for treating atrial fibrillation (AF). PFA provides a promising new approach in the treatment of atrial fibrillation (AF), which historically has a high recurrence rate post-ablation. Of significance, PFA has shown promising data in terms of safety and procedural efficiency to radiofrequency ablation (RFA). Objective The purpose of this study was to compare the procedural and health outcomes in patients with recurrent AF undergoing ablation using PFA or RFA. Methods Consecutive patients with a history of previous radiofrequency ablation and recurrent AF undergoing redo ablation with PFA or RFA were included. Patients were seen for follow-up in the clinic ranging from 4 months to a year and we reported ablation strategy and arrhythmia type. The primary outcome was recurrence of any atrial arrhythmia after a 90-day blanking period. Results A total of 242 patients with recurrent AF underwent redo ablation using PFA (n = 54, 22.5%) or RFA (n = 188, 77.5%). The PFA cohort was younger on average (66 vs. 70 years) with a lower mean CHA2DS2-VASc score (2.2 vs. 3.06, p=0.001) compared to the RFA cohort. PFA procedures were shorter (162{+/-}53 vs 206{+/-}60 minutes, p<0.001) but required more fluoroscopy (13.9{+/-}8.9 vs 8.7{+/-}6.3 minutes, p<0.001). Among patients seen on follow-up, recurrence occurred in 28% of PFA versus 55% of RFA patients, with longer arrhythmia-free survival after PFA (log-rank p=0.03). PFA remained associated with lower recurrence after multivariable adjustment (HR 0.4, 95% CI 0.2?0.9, p=0.04). Adverse events, predominantly vascular access?related, were similar. Conclusion Among patients with recurrent atrial arrhythmias after prior RFA, repeat PFA was associated with shorter procedures, greater fluoroscopy use, and lower arrhythmia recurrence, with comparable safety.

Instability of the cardiac electrical system is a major cause of life-threatening arrhythmias. Current safety guidelines have traditionally emphasized QT interval prolongation on the electrocardiogram (ECG) as a primary biomarker of proarrhythmic risk. However, this approach does not capture all forms of electrical instability. In this study, we demonstrate that beat-to-beat variability in action potential duration (APD), a cellular surrogate of the QT interval, better stratifies proarrhythmic risk than mean APD prolongation alone. Using a validated computational model of a human ventricular myocyte, we simulated the effects of the {beta}-adrenergic agonist isoproterenol (ISO). Increasing the ISO concentration shortened mean APD but paradoxically increased beat-to-beat APD variability, measured as the standard deviation of APDs. In our simulations, the emergence of early afterdepolarizations (EADs), abnormal oscillations of the membrane potential during the plateau phase of the action potential, at higher ISO concentrations was consistently preceded by a marked rise in APD variability, even while mean APD was reduced. Mechanistic analysis revealed that ISO-induced enhancement of L-type Ca2+ current (ICaL) and slow delayed rectifier K+ current (IKs) steepens the APD restitution slope, which reflects action potential instability, even when the net effect is a reduction in APD. These results support APD variability as a more sensitive and mechanistically plausible marker of proarrhythmic risk than APD prolongation alone. Our findings suggest that QT interval variability may improve risk stratification and provide a more robust mechanistic foundation for drug safety evaluation.

BackgroundEmerging evidence in humans has linked Xp22.31 genetic deletions to an increased risk of stress-induced arrhythmias, and association analysis across Xp22.31 has shown enrichment for atrial fibrillation genetic risk variants around STS (steroid sulfatase). MethodsWe compared heart rhythm in homozygous STS-knockout (STS-KO) adult mice (n=19) to wildtype (WT) mice (n=11) under baseline (Tyrodes solution), and {beta}-adrenergic stimulation (stress), conditions using ex vivo perfused-heart electrocardiography (ECG). Ventricular ectopic beats (VEBs) were manually-identified, and rhythm abnormalities were quantified using a semi-automated approach. ResultsAt baseline, the groups displayed comparable sinus cycle length and ECG intervals; all WT hearts showed stable sinus rhythm, whereas [~]30% of STS-KO hearts developed spontaneous VEBs. WT hearts typically maintained steady rhythm under {beta}-adrenergic stimulation; in contrast, [~]60% of STS-KO hearts displayed VEBs. Under baseline and stimulated conditions the QRS interval was greater during VEBs than normal beats in STS-KO hearts, consistent with a ventricular origin. We identified a higher frequency of any abnormal beats in STS-KO hearts than in WT hearts under baseline (1.9{+/-}0.7% vs. 0.3{+/-}0.1%, p=0.038) and stimulated (5.3{+/-}2.2% vs. 0.5{+/-}0.3%, p=0.047) conditions. Under stimulated conditions, abnormal beats only occurred singly in WT hearts, whereas in STS-KO hearts, [~]50% of the time they occurred in runs of two or more. ConclusionSTS deficiency in mice predisposes to arrhythmias, and the STS-KO mouse represents a tractable model for mechanistic investigation. These data support the contention that STS activity influences arrhythmic vulnerability in humans and that STS should be considered for inclusion in arrhythmia-related gene panels.

Background: Pacing-induced cardiomyopathy (PICM) is a major complication of chronic right ventricular pacing and develops in up to 25% of patients. Reliable prediction of PICM may facilitate individualized pacing strategy selection; however, currently available approaches demonstrate limited discriminative performance. This study aimed to develop and validate machine learning (ML) models for predicting PICM in patients with atrioventricular block (AVB) underlying heart failure with mildly reduced or preserved ejection fraction. Methods: In this multicenter prospective study derived from the RISK-PICM registry (January 2002 to January 2026), 125 patients with AVB who underwent pacemaker implantation were analyzed. PICM was defined as a ?10% reduction in left ventricular ejection fraction (LVEF) resulting in an LVEF <50%. Four ML algorithms, including logistic regression, support vector machine, random forest, and XGBoost, were trained using stratified 4-fold cross-validation with hyperparameter optimization and model discrimination was evaluated. Results: PICM developed in 41 patients (32.8%) during a median follow-up of 4.8 years. Male sex, pre-implant minimum QTc interval, and post-implant maximum QRS duration were significantly associated with PICM in univariable Cox regression. XGBoost achieved the highest discriminative performance (AUROC 0.831; sensitivity 0.805; specificity 0.845). Feature importance analysis identified baseline LVEF and post-implant maximum QRS duration as the most influential features. Model-derived risk stratification significantly differentiated high-risk and low-risk groups on Kaplan-Meier analysis (P < 0.001). Conclusions: ML-based models, particularly XGBoost, demonstrated clinically meaningful performance for PICM and may support individualized pacing strategy selection in patients with AVB and underlying heart failure with mildly reduced or preserved ejection fraction.

Background: Loss- and gain-of-function variants in SCN5A, encoding the cardiac sodium channel Nav1.5, are major causes of inherited cardiac channelopathies. Their pathophysiology has almost exclusively been attributed to altered cardiomyocyte excitability and cardiac conduction. However, growing evidence indicates that autonomic dysfunction contributes to these disorders, raising the possibility that Nav1.5 dysfunction may also affect the intrinsic cardiac nervous system. Objectives: We investigated whether Nav1.5 is functionally expressed in murine intrinsic cardiac neurons and evaluated its contribution to neuronal excitability. Methods: Scn5a expression was investigated by digital PCR and immunocytochemistry in isolated murine intracardiac neurons. Whole-cell patch-clamp recordings were used to characterize sodium currents and action potential properties in wild-type and Scn5a+/- mice. Results: Scn5a transcripts and Nav1.5 protein were detected in intrinsic cardiac neurons. Voltage-clamp recordings identified a tetrodotoxin-resistant sodium current accounting for approximately 8% of the total sodium current and displaying pharmacological and biophysical properties consistent with Nav1.5. Activation and inactivation analyses indicated that Nav1.5 is the predominant sodium conductance available at most polarized membrane potentials. Accordingly, Scn5a haploinsufficiency selectively altered action potential threshold, maximal upstroke velocity, overshoot and duration in neurons resting below -60 mV, whereas more depolarized neurons were essentially unaffected. No structural or neurochemical remodeling of intrinsic cardiac ganglia was detected. Conclusion: Nav1.5 is a functional determinant of intrinsic cardiac neuronal excitability. These findings identify the intrinsic cardiac nervous system as a new cellular target of SCN5A dysfunction and suggest that inherited cardiac sodium channelopathies could involve alterations in both myocardial and intrinsic neuronal electrophysiology.

Background: Several Schedule I substances have demonstrated potential benefits for refractory psychiatric conditions and addiction. Some have been legalized at the state level, while others like kratom (mitragynine) are available over-the-counter in some states and illegal in others. A recent presidential executive order directs certain federal agencies to accelerate development and facilitate access to psychedelic drugs through increased funding and expedited FDA review. Studies investigating the therapeutic potential of these drugs are limited and focused disproportionately on efficacy over safety. Rigorous evaluation of cardiovascular safety, including potential arrhythmia liability, is essential. Methods: We analyzed reports from the FDA Adverse Event Reporting System from 2000-2024. involving Schedule 1 and other unscheduled drugs with purported therapeutic potential including 3,4-methylenedioxy-methamphetamine (MDMA), mitragynine, ibogaine, lysergic acid diethylamide (LSD), mescaline, psilocybin, tetrahydrocannabinol (THC), and dimethyltryptamine (DMT). We used FDA-approved drugs (e.g., dofetilide, naltrexone) as quasi-experimental positive and negative controls respectively, then calculated proportional reporting ratios (PRR) for the composite of ventricular arrhythmia and cardiac arrest, ventricular arrhythmia only, and QTc-prolongation. Results: Among 18,499,626 unique cases, 61,961 (0.3%) mentioned at least one psychoactive drug of interest. The psychedelic drugs ibogaine, MDA, MDMA, and LSD and the non-psychedelic mitragynine exhibited a significant PRR for ventricular arrhythmia/cardiac arrest; the strongest signals were observed for mitragynine (PRR 8.8; 84/1171 reports), and ibogaine (PRR 38.8; 7/25 reports). When restricting analysis to ventricular arrhythmia alone (excluding potential non-arrhythmic cardiac arrest), the signal remained significant for mitragynine (PRR 4.4, 8/1171 reports) and was markedly higher for ibogaine (PRR 142.0, 5/25 reports), approximately 6-fold higher than dofetilide (PRR 24.0; 533/11,950 reports). This corresponded with QTc-prolongation signals for ibogaine (PRR 121.0; 6/25 reports) and mitragynine (PRR 15.9; 38/1171 reports), which were comparable to dofetilide (PRR 30.9; 771/11,950 reports) and methadone (PRR 12.4; 1428/55,895 reports). MDA, MDA, and LSD did not show ventricular arrhythmia signal, and although MDMA was associated with disproportionate reporting of QTc-prolongation (PRR 9.9; 10/474 reports). Conclusions: Ibogaine and mitragynine demonstrated disproportionate reporting of ventricular arrhythmia similar to or exceeding established proarrhythmic drugs. These data suggest that robust cardiac safety evaluations will be a regulatory priority given accelerated development of psychedelic drugs.

BACKGROUND: Radiofrequency catheter ablation (RFCA) uses rigid metallic electrodes whose fixed geometry limits tissue contact, lesion continuity, and safe energy delivery near vulnerable structures. We evaluated a moldable, tissue-conforming conductive hydrogel as an RFCA electrode ex vivo. METHODS: Poly(ether urethane diacrylamide) hydrogels with saline-tuned conductivity were molded into plugs, disks, and bars and affixed to an irrigated 8-Fr catheter. Ablations were performed on excised porcine tissue in circulated saline at 37 C under fixed contact force and irrigation. Lesion geometry, intramural temperatures, and steam pops were compared with bare-metal (BM) electrodes and size-matched metallic analogs; an atrioesophageal stack model assessed collateral injury. Lesions were delineated using triphenyltetrazolium chloride staining. RESULTS: Hydrogel bars produced wide, ellipsoidal lesions (width 10.51 {+/-} 1.40 versus 8.71 {+/-} 1.65 mm for BM; P=0.031; aspect ratio 1.72); size-matched metal bars produced none. Hydrogel disks produced lesions statistically indistinguishable from BM in depth (4.54 {+/-} 0.90 versus 4.84 {+/-} 0.55 mm) and width (9.47 {+/-} 0.89 versus 11.41 {+/-} 2.39 mm), whereas metal disks produced significantly shallower lesions (2.30 {+/-} 1.70 mm; P=0.015 versus BM). In the atrioesophageal model, hydrogel plugs achieved transmural atrial lesions with a reduced esophageal lumen temperature (56.33 {+/-} 3.80 versus 61.30 {+/-} 5.14 C; P=0.046), total lesion depth (4.03 {+/-} 1.25 versus 7.58 {+/-} 0.78 mm; P<0.001), and esophageal lesion width (3.05 {+/-} 2.35 versus 8.70 {+/-} 2.69 mm; P<0.001) compared with BM. Hydrogel electrodes reduced steam-pop risk (relative risk 0.34; 95% CI 0.13-0.88). Plug characterization confirmed saline-dependent conductivity and attenuated energy delivery, with lower subsurface peak temperatures and shallower lesions than BM. CONCLUSIONS: Moldable, conductivity-tunable hydrogels shape RF lesions and may improve ablation safety, supporting evaluation for contiguous or linear lesion sets and ablation near sensitive structures.

Brugada syndrome (BrS) is an inherited arrhythmia disorder with limited drug therapy, quinidine being the principal agent. Loss-of-function variants in SCN5A reduce the cardiac sodium current (INa), but the arrhythmogenic imbalance also depends on the transient outward potassium current (Ito). Here we generated human induced pluripotent stem cell-derived cardioids with right-ventricular identity from a patient carrying an SCN5A frameshift variant (p.A665Gfs*16) and characterised them by patch-clamp and optical mapping. BrS cardioids showed 60% lower peak INa, more than doubled Ito, 38% slower conduction and 76% longer spontaneous cycle length. We then tested AR-788, a benzylaminothiazole-benzimidazole carboxamide of the ARumenamide class. In wild-type (WT) cardiomyocytes AR-788 inhibited Ito concentration-dependently (12%, 30% and 42% at 5, 10 and 20 uM; extrapolated IC50 25.4 uM), and at 10 uM it returned BrS Ito to the level of untreated WT cells (21.71 vs 21.48 pA/pF, p = 0.9716) without reducing INa. It also reduced the rapid delayed-rectifier current (IKr) tail current by 40%, a liability requiring formal proarrhythmia profiling. These data identify AR-788 as an Ito-suppressing member of the ARumenamide class and provide proof of concept that a small molecule can correct the potassium-current excess in a human BrS model.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by stress- or catecholamine-induced ventricular arrhythmias in the absence of overt structural heart disease. Mutations in RYR2 and CASQ2 account for most genetically defined cases, although pathogenic variants in the three genes encoding calmodulin (CALM1-3) have also been linked to CPVT. Because all three CALM genes encode an identical calmodulin protein, pathogenic calmodulin variants are expected to be expressed in only a small fraction of total cellular calmodulin, raising the question of whether this limited abundance is sufficient to produce an arrhythmogenic phenotype in vivo. We generated a heterozygous mouse model carrying the human disease-associated N54I-equivalent mutation, N54I, in Calm1. Mutant calmodulin accounted for 13.7% of total cardiac calmodulin, consistent with expression from one of six Calm alleles. Under basal conditions, N54I/+ mice exhibited normal growth, survival, cardiac morphology, and surface electrocardiogram parameters. However, cardiomyocytes isolated from N54I/+ mice had increased rates of RyR2-mediated spontaneous calcium release. Following catecholaminergic challenge with isoproterenol and caffeine, N54I/+ mice exhibited significantly more premature ventricular contractions and arrhythmias than wild-type littermates. Exercise challenge in conscious mice similarly provoked ventricular ectopy and ventricular tachycardia. In addition, N54I/+ mice exhibited abnormalities of atrial and sinoatrial electrical activity, including premature atrial contractions, ectopic P waves, atrioventricular conduction slowing, and beat-to-beat variability. These findings demonstrate that expression of the N54I calmodulin variant from a single Calm1 allele is sufficient to produce a CPVT phenotype in vivo. This model provides experimental evidence linking a human disease-associated calmodulin variant to arrhythmogenesis and demonstrates the functional dominance of mutant calmodulin in the heart.

Introduction. Hypertrophic cardiomyopathy (HCM) is characterized by clinical and genetic heterogeneity. Age of manifestation, clinical and anatomical phenotypes of HCM vary significantly. This study discusses genetic causes and reconstructive surgery results for patients with particular intracardiac phenotype - diffused generalized HCM (DG-HCM). Methods: personal and familial medical history, general examination, 12-lead resting ECG, 24-hour ECG Holter monitoring, transthoracic and transesophageal EchoCG, cardiac MRI with gadolinium enhancement. A ten-gene panel was sequenced by IonTorrent PGM. Mutational screening in patients with suspected multisystemic diseases was performed by Sanger sequencing. Results: 170 patients with obstructive HCM (oHCM) requesting genetic counseling and surgical correction of HCM were evaluated. We distinguished particular DG-HCM subtype of oHCM (diffuse hypertrophy of IVS, LV free walls, papillary muscles displaced towards the LV apex) in 34 patients; 31 out of 34 underwent open heart reconstructive surgery. Patients with DG-HCM were younger at the time of surgery, had higher risk of SCD, and connective tissue dysplasia of the mitral valve. Hemodynamics normalization was observed in 1, 3, and 5 years after surgery. Eighteen ICDs were implanted; five patients experienced appropriate shocks. The genetic spectrum was enriched up to 30% by multisystem disorders. Mutations in "sarcomeric" genes were detected in 15%. Conclusion: Intracardiac phenotype of HCM may correlate with genetic cause and long-term prognosis. DG-HCM phenotype accounts for 20% oHCM patients and indications for open-heart surgery. Extended myectomy with parietal resection of papillary muscles and correction of mitral valve insufficiency provides long-term benefits for DG-HCM patients. Multisystem disorders in patients with DG-HCM should be of special attention. Study was supported by research project FURG-2024-0004.

Background: In obstructive hypertrophic cardiomyopathy, surgical myectomy is highly effective but carries a recognized risk of postoperative conduction disturbances. Percutaneous intramyocardial septal radiofrequency ablation (Liwen procedure) is a less invasive alternative, but head-to-head comparisons of longitudinal hemodynamic trajectories and conduction system safety remain scarce, limiting evidence-based treatment selection. Methods: This single-center retrospective cohort included 211 patients treated 2018?2023 (124 Liwen, 87 modified Morrow myectomy). The primary longitudinal analysis included 133 patients with 1-year follow-up and serial data (75 Liwen, 58 modified Morrow myectomy). Repeated outcomes were analyzed using linear mixed-effects models and generalized estimating equations, adjusted for baseline covariates. Results: Both procedures reduced LVOT gradient, but trajectories differed (interaction P=0.002). At 1 year, the covariate-adjusted mean LVOT gradient remained higher after Liwen than after myectomy (16.1 vs 1.3 mmHg, P<0.001). However, the adjusted 1-year predicted probability of new conduction abnormalities was markedly lower after Liwen (5% vs 62%, P<0.001), with no permanent pacemaker implantations in the Liwen group. Most patients achieved gradient <30 mmHg in both groups (82% vs 96%; nominal P=0.308). Liwen had shorter procedure duration (80 vs 185 min) and hospital stay (11 vs 16 days). Serious adverse event rates were similar (8.1% vs 9.2%) but profiles differed. Conclusions: Modified Morrow myectomy achieved more complete LVOT gradient reduction at 1 year, whereas Liwen ablation had fewer conduction abnormalities, shorter procedure duration, and shorter hospital stay. These findings highlight a clinically relevant trade-off between more complete hemodynamic relief and lower conduction-system injury and require prospective confirmation.

Background Implantable loop recorders (ILRs) provide continuous rhythm monitoring. Professional society guidelines and expert consensus statements recommend ILR use for patients with recurrent syncope and cryptogenic stroke, but recommendations are weaker for other indications. We assessed ILR use over time and concordance between indication and clinical guidance. Methods We conducted a retrospective cohort study using Epic Cosmos data from 1/1/2020-12/31/2025. Among active patients with at least one of 13 diagnoses potentially eligible for ILR placement, we identified ILR placements and classified them by concordance with professional society guidance: concordant, possibly, or non-addressed. Annual incidence was estimated overall and by indication. We also described the proportion of patients who received longer-term (>7 days) rhythm monitoring in the year prior to placement. Results Of 47,046,706 patients with diagnoses potentially eligible for ILR placement, 201,103 (0.4%) had an ILR placed. ILR placements increased from 3.08 ILRs per 100,000 patient-days in 2020 to 4.13 in 2025 (5.9% annual growth). The most common indications were cryptogenic stroke (28.6%) and atrial fibrillation without prior ablation (21.4%). Overall, 43.9% were guidance concordant, 28.5% possibly concordant, and 24.8% non-addressed. Relative annual growth in ILR placements per 100,000 patient-days was significant across all guidance categories: concordant (1.3%, 95% CI, 0.9%-1.7%), possibly concordant (5.5%, 95% CI, 5.0%-6.0%) and non-addressed (7.4%, 95% CI, 6.8%-8.0%). Among 125,631 outpatient placements, 50,181 (39.9%) had any prior long-term rhythm monitoring. Conclusion ILR placements are uncommon but increasing, with faster annual growth for indications that may not be guidance concordant. More than half of patients lacked long-term rhythm monitoring prior to outpatient ILR placement.

Background: Sleep disturbance has been associated with atrial fibrillation (AF), but prior studies have largely relied on sleep assessed at a single time point or examined specific sleep disorders. Whether changes in sleep disturbance over time predict AF and, conversely, whether AF predicts subsequent sleep disturbance within the same population is not well established. Methods: We conducted a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), which enrolled adults with hypertension and increased cardiovascular risk without diabetes. Two prospective analytic cohorts were constructed to examine each direction of the association: 7,232 participants without baseline AF for the analysis of sleep disturbance and incident AF, and 6,079 participants without clinically significant sleep disturbance at baseline for the reciprocal analysis. Sleep disturbance was assessed repeatedly using a 0-3 patient-reported symptom score, with clinically significant sleep disturbance defined as a score [&ge;]2. AF was ascertained from protocol 12-lead ECGs. Time-dependent Cox models evaluated time-updated sleep disturbance in relation to incident AF and time-updated AF in relation to incident clinically significant sleep disturbance, with adjustment for demographic, lifestyle, and cardiovascular risk factors. Results: During a median follow-up of 3.3 years, 189 incident AF events occurred. Time-updated clinically significant sleep disturbance was associated with a 78% higher adjusted risk of incident AF (HR, 1.78; 95% CI, 1.27-2.51). Each 1-point increase in the time-updated sleep score was associated with a 26% higher risk of AF (HR, 1.26; 95% CI, 1.09-1.46). Compared with a sleep score of 0, the adjusted HRs were 1.20 (95% CI, 0.85-1.70), 2.05 (95% CI, 1.33-3.15), and 1.72 (95% CI, 1.03-2.88) for scores of 1, 2, and 3, respectively. In the reciprocal analysis, 1,422 incident clinically significant sleep-disturbance events occurred during a median follow-up of 3.2 years. Time-updated AF was associated with a 59% higher adjusted risk of incident clinically significant sleep disturbance (HR, 1.59; 95% CI, 1.16-2.16). Associations in both directions were consistent across prespecified subgroups, with no significant effect modification. Conclusion: In adults with hypertension, sleep disturbance and AF were prospectively and reciprocally associated when evaluated longitudinally. These findings support a bidirectional relationship between sleep disturbance and AF and highlight the potential clinical relevance of assessing sleep health in patients with or at risk for AF.

Background: Pulsed field ablation (PFA) has been rapidly adopted for atrial fibrillation (AF) on the premise of greater safety than thermal ablation. Real-world signals of hemolysis, coronary spasm, and neurologic events have since emerged, and prior Manufacturer and User Facility Device Experience (MAUDE) analyses relied on term matching without prospective signal detection. Methods: We queried MAUDE for AF ablation catheter reports received January 2016 through June 2026 and assigned each to PFA, radiofrequency ablation (RFA), or cryoballoon ablation. We adjudicated injury and death narratives into predefined complication families and severity tiers with a large language model, checked against a larger model and by physician review. We calculated reporting odds ratios (ROR) and Bayesian shrinkage estimators compared against an empirical null, applied interrupted time series and prospective sequential detection, and repeated estimates on a 2026 hold-out. Results: Among 44,623 reports, 30.1% were PFA, 50.9% RFA, and 19.0% cryoballoon, with 91.8% model agreement on event occurrence (? = 0.83). PFA carried an ROR of 527 (95% CI, 33, 8,509) for hemolysis, 2.83 (2.55, 3.16) for arrhythmia, 2.83 (2.30, 3.48) for coronary, and 2.39 (2.10, 2.73) for cerebrovascular events, against 0.024 (0.008, 0.075) for esophageal and 0.34 (0.32, 0.37) for pericardial events. The cerebrovascular excess was largest for VARIPULSE, but without it the class proportional reporting ratio was 1.36 (1.13, 1.65), concordant with the 1.56 measured in EMBOL-AF. In the hold-out, the cerebrovascular, arrhythmia and hemolysis signals replicated, and coronary events kept their direction without meeting the signal rule. Prospective detection flagged cerebrovascular events 13 months before AVANT GUARD published its neurologic events. Conclusions: PFA showed disproportionate reporting of hemolysis, cerebrovascular, coronary, and arrhythmic events across sequential testing. Machine learning methods allowed for flagging these signals months before confirmatory trials, demonstrating a scalable tool for early detection of procedural risk.

Background: Human induced pluripotent stem cell-derived cardiomyocytes are valuable for cardiac disease modelling and drug testing but remain limited by immature structural and electrophysiological properties in conventional two-dimensional cultures. Three-dimensional cardiac models, including cardioids, provide a more physiological environment through multicellular organization and enable tissue-level functional analysis. Their electrophysiological properties and maturation, however, remain incompletely characterized. Methods: We performed an integrated electrophysiological characterization of human cardioids over the first three weeks of maturation using sharp microelectrode recordings, calcium transient measurements, whole-cell patch clamp recordings, immunofluorescence, transcriptomic analysis, and pharmacological interventions. Results: During maturation, cardioids exhibited progressive electrophysiological maturation, characterized by more physiological resting membrane potentials (-54.0{+/-}3.1mV to -68.1{+/-}1.2mV), increased action potential amplitude (73.5{+/-}4.8mV to 101.7{+/-}2.1mV) and upstroke velocity (44.3{+/-}5mV/ms to 86.6{+/-}8.4mV/ms), and shorter action potential duration (178.9{+/-}8.7ms to 144.0{+/-}4.8ms at 1Hz stimulation). These changes were associated with progressively increased INa density and enhanced SCN5A mRNA and Nav1.5 protein expression, consistent with progressive maturation of cardiac excitability. IKr current and KCNH2/hERG expression were already present at early maturation stages and remained stable, as evidenced by preserved sensitivity to dofetilide-blockade. Pharmacological inhibition of barium- and HMR-sensitive currents altered resting membrane and/or action potential characteristics in intact cardioids, whereas in isolated cardiomyocytes classical IK1 remained undetectable and IKs was small, highlighting a certain degree of persisting immaturity of the model. Conclusions: These findings demonstrate that human cardioids undergo progressive electrophysiological maturation and provide complementary tissue- and cellular-level insights into cardiac function, establishing their suitability for investigating INa and IKr-related cardiac pathologies.