Muller SA, Murray B, Tichnell C
… +14 more, Salavati A, Loh P, Carrick RT, Cox M, van der Harst P, Cramer MJ, Oerlemans MIFJ, Gasperetti A, Asatryan B, Zimmerman S, van Tintelen JP, Calkins H, James CA, Te Riele ASJM
BACKGROUND: Current guidelines recommend regular screening for first-degree relatives of gene-elusive arrhythmogenic right ventricular cardiomyopathy (ARVC) patients using a similar regimen as for genotype-positive/pheno...BACKGROUND: Current guidelines recommend regular screening for first-degree relatives of gene-elusive arrhythmogenic right ventricular cardiomyopathy (ARVC) patients using a similar regimen as for genotype-positive/phenotype-negative relatives. However, the multifactorial nature of gene-elusive ARVC may necessitate a different approach. This study aimed to determine the yield of cardiac screening in first-degree relatives of ARVC probands without a validated genetic cause. METHODS: We included all first-degree relatives of probands who (1) met the 2010 Task Force Criteria, (2) underwent next-generation sequencing that included all genes with at least moderate evidence for ARVC causation per Clinical Genome Resource appraisal (validated ARVC genes), and (3) had no pathogenic/likely pathogenic (P/LP) variants identified in these genes. The primary and secondary end points were definite ARVC by the 2010 Task Force Criteria and ventricular arrhythmia, respectively. RESULTS: We included 44 relatives (39.0 [22.3-45.8] years; 36% male) from 24 families. In 4 (17%) families, a P/LP variant was identified in a different cardiomyopathy/arrhythmia gene (, , , ). Overall, 10 (23%) relatives had definite ARVC at baseline evaluation. Of the 20 relatives without definite ARVC who had follow-up available, 8/20 (40%) relatives progressed to definite ARVC during 9.0 (5.8-14.4) years of follow-up. No statistical difference in the yield of baseline screening or serial evaluation between relatives from families with a P/LP variant and relatives from families without a P/LP variant was observed. Of the 27 relatives who had follow-up available, ventricular arrhythmia was observed in 2/27 (7%) relatives and occurred 6.3 and 13.8 years after definite ARVC diagnosis. Both of those relatives were from families without a P/LP variant. CONCLUSIONS: These findings highlight the importance of managing first-degree relatives of ARVC probands without a validated genetic cause similarly to genotype-positive ARVC relatives. Furthermore, using a broad cardiomyopathy and arrhythmia gene panel in ARVC probands, rather than limiting testing to validated ARVC genes alone, is warranted.
BACKGROUND: Exercise training improves contractile function and can reduce arrhythmia burden after a myocardial infarction (MI). How exercise modifies the proarrhythmic status is uncertain. METHODS: In this study, rats 6...BACKGROUND: Exercise training improves contractile function and can reduce arrhythmia burden after a myocardial infarction (MI). How exercise modifies the proarrhythmic status is uncertain. METHODS: In this study, rats 6 weeks post-MI were randomized to an 8-week high-intensity exercise program (MI-EX) or to a sedentary control group (MI-SED) and compared with a sedentary sham group (Sham-SED). After the exercise program, in vivo and ex vivo programmed electrical stimulation was performed on the rat hearts. Subsequently, optical mapping was conducted to electrophysiologically characterize the MI hearts. RESULTS: Exercise significantly improved maximal oxygen uptake (O; MI-EX, 67 mL·min·kg versus MI-SED, 47 mL·min·kg). In vivo cardiac stimulation protocols indicated reduced inducibility of ventricular arrhythmias in MI-EX compared with MI-SED. This anti-arrhythmic effect was retained ex vivo in Langendorff-perfused hearts. Optical mapping of the noninfarcted left ventricle indicated a prolonged average action potential (AP) duration at 4.5 Hz pacing frequency in both MI groups compared with Sham-SED. As pacing frequency increased (6.5 Hz and ≈8 Hz), AP duration remained significantly longer in the MI-SED group but decreased in the MI-EX group, demonstrating a negative frequency dependency. Spatial heterogeneity of AP duration in the noninfarcted left ventricle area was increased post-MI but was significantly reduced following exercise. Optical AP recorded from the remnant myocardium within the scar showed similar AP duration characteristics at low stimulation frequencies, but AP upstroke time was shorter in the MI-EX group compared with MI-SED. CONCLUSIONS: Post-MI exercise was associated with electrophysiological changes in both the noninfarcted region and the remnant myocardium within the scar. These changes suggest a mechanism for the anti-arrhythmic effects of exercise following MI.
Jones O, Linton N, Bissett S
… +23 more, Koutsoftidis S, Kay J, Wu H, Chow JJ, Qureshi N, Baykaner T, Zaman J, Lewalter T, Demircali A, Zheng Q, Heaney F, Jose I, Malcolme-Lawes L, Koa-Wing M, Lim B, Arnold A, Peters N, Keene D, Ng FS, Whinnett Z, Temelkuran B, Drakakis E, Kanagaratnam P
BACKGROUND: Conventional activation mapping of atrial fibrillation (AF) during clinical procedures is limited by low-amplitude, fractionated electrograms and cycle length variability. The Tau20-RETROmapping stimulator-re...BACKGROUND: Conventional activation mapping of atrial fibrillation (AF) during clinical procedures is limited by low-amplitude, fractionated electrograms and cycle length variability. The Tau20-RETROmapping stimulator-recorder system (TauRhythm Therapies, United Kingdom) is an investigational device used to identify nonpulmonary vein AF drivers by real-time, high-density activation mapping of uniform wavefronts during AF. We validated the accuracy of the system and applied it to left atrial mapping for evidence of AF drivers. METHODS: Left atrial geometry was acquired using a 3-dimensional electroanatomic mapping system with high-density mapping catheters (CARTO 3 with Optrell, or EnSite X with HD Grid). Electrograms were recorded for 30 seconds at multiple left atrial sites. The Tau20-RETROmapping system generates activation maps of organized wavefronts. System performance was manually validated against randomly sampled local electrograms using a grid sweep of thresholds to identify Pareto-optimal parameters in sinus rhythm, atrial pacing, atrial tachycardia (AT), and AF. The system was then applied to identify putative driver activation patterns during persistent AF. RESULTS: We studied 24 patients undergoing pulmonary vein isolation for AF. Six patients presented in sinus rhythm or AT, in whom the system demonstrated a sensitivity of 100.0% (95% CI, 80.5%-100.0%) and a specificity of 100.0% (85.2%-100.0%). Eighteen patients were mapped in AF: the system had a sensitivity of 94.4% (86.2%-98.4%) and a specificity of 97.1% (89.9%-99.6%) when identifying organized AF wavefronts, and accurately identified the earliest activation in 89.6% (79.7%-95.7%) of waves. Stable propagation originating from the left atrial appendage (LAA) was observed in 3/18 patients, while 8/18 demonstrated competing propagation toward and away from the LAA. Conduction away from the LAA was detected along the anterior (8/18 patients), lateral (8/18 patients), and posterior (7/18 patients) walls. No propagation near the LAA was observed in 6/18 patients. CONCLUSIONS: The Tau20-RETROmapping system enables real-time activation mapping of AF, with the most convincing driver-like areas being identified around the LAA.
Nasilli G, Lin X, Swiatlowska P
… +10 more, Meraviglia V, Pérez-Hernández M, Zhang M, Sanchez-Alonso JL, Bellin M, Gorelik J, Rothenberg E, Casini S, Delmar M, Remme CA
BACKGROUND: Alterations in microtubule dynamics have been shown to affect cardiomyocyte membrane stiffness and modulate ion channels, including the cardiac sodium channel. While conditions, such as heart failure and Duch...BACKGROUND: Alterations in microtubule dynamics have been shown to affect cardiomyocyte membrane stiffness and modulate ion channels, including the cardiac sodium channel. While conditions, such as heart failure and Duchenne muscular dystrophy, are associated with increased detyrosination of microtubules and reduced sodium current, a potential role for microtubule detyrosination in arrhythmogenic cardiomyopathy has not been explored. We here investigated the impact of microtubule detyrosination on membrane stiffness, cardiac sodium channel distribution, and function in mouse and human models of arrhythmogenic cardiomyopathy. METHODS: Isolated ventricular cardiomyocytes from mice with cardiomyocyte-specific, tamoxifen-activated knockout of PKP2 (plakophilin-2), as well as -c.2013delC, and isogenic control human-induced pluripotent stem cell-derived-cardiomyocytes were incubated for 2 to 4 hours with compounds known to decrease microtubule detyrosination (parthenolide, 10 µmol/L; EpoY, 20 µmol/L) or vehicle (dimethyl sulfoxide). Immunocytochemistry, mechano-scanning ion conductance microscopy, patch-clamp analysis, and stochastic optical reconstruction microscopy were performed. RESULTS: Cardiomyocyte-specific, tamoxifen-activated knockout of PKP2 cardiomyocytes displayed increased microtubule detyrosination and membrane stiffness, which were both attenuated by parthenolide treatment. Parthenolide significantly increased whole-cell sodium current density in cardiomyocyte-specific, tamoxifen-activated knockout of PKP2 mouse cardiomyocytes, with macropatch measurements demonstrating that this increase occurred both at the intercalated disc and lateral membrane. Stochastic optical reconstruction microscopy analysis revealed that parthenolide increased cardiac sodium channel cluster density at the intercalated disc of cardiomyocyte-specific, tamoxifen-activated knockout of PKP2 mouse cardiomyocytes. In contrast, parthenolide had no effect on sodium current, cardiac sodium channel cluster size, or density in cardiomyocytes from control mice. -c.2013delC human-induced pluripotent stem cell-derived-cardiomyocytes displayed increased microtubule detyrosination and reduced sodium current compared with isogenic control human-induced pluripotent stem cell-derived-cardiomyocytes, which were both prevented by parthenolide and EpoY. CONCLUSIONS: Increased microtubule detyrosination secondary to loss of PKP2 impacts cardiomyocyte (dys)function beyond the desmosome, contributing to both electrical and mechanical alterations in the setting of arrhythmogenic cardiomyopathy. Our findings identify microtubule detyrosination as a novel therapeutic target in pathophysiological conditions, such as arrhythmogenic cardiomyopathy, aimed at improving both contractile and electrical function.
BACKGROUND: Spontaneous automaticity of sinoatrial node cells (SANCs) is driven by a system that couples ion channels, membrane clock and Caclock, the sarcoplasmic reticulum generated LCRs (local subsarcolemmal Carelease...BACKGROUND: Spontaneous automaticity of sinoatrial node cells (SANCs) is driven by a system that couples ion channels, membrane clock and Caclock, the sarcoplasmic reticulum generated LCRs (local subsarcolemmal Careleases). Although LCRs are critically dependent on high basal cAMP and both PKA (protein kinase A)- and CaMKII (Ca2+/calmodulin dependent protein kinase II)-dependent protein phosphorylation, the link between cAMP and CaMKII remains unclear. Here, we tested a hypothesis that high cAMP activates EPAC (exchange protein directly activated by cAMP) which increases basal CaMKII activity, reinforcing the coupled clock pacemaker system, to boost LCRs and accelerate spontaneous SANC firing. METHODS: Real-time quantitative polymerase chain reaction, Western blot, immunostaining, whole-cell patch clamp, and line-scan confocal microscopy were employed to study EPAC-dependent regulation of rabbit SANC firing. RESULTS: Both EPAC isoforms were expressed and active in SANC. Selective inhibition of EPAC1 (CE3F4) or EPAC2 (HJC0350) similarly suppressed basal CaMKII activity, CaMKII-dependent phosphorylation of Ca-cycling proteins (PLB [phospholamban] and RyR [ryanodine receptors]) and reduced the amplitude of L-type Cacurrent. EPAC1 and EPAC2 inhibitors significantly decreased LCR number, size, and prolonged the LCR period (interval between prior AP-induced Catransient and LCR) reducing spontaneous SANC firing by ≈30%. In contrast, EPAC activator (8-pCPT) increased LCR number and size, shortened the LCR period and accelerated spontaneous firing by≈18%. EPAC-mediated effects were implemented in PKC-dependent manner via EPAC-PLC-PKC-CaMKII signaling pathway, since PKC inhibitor reproduced effects of EPAC inhibition on CaMKII activity, CaMKII-dependent phosphorylation of Ca-cycling proteins, LCR parameters, and spontaneous SANC firing. CONCLUSIONS: EPAC is an essential component of basal cardiac pacemaker function, which accelerates spontaneous automaticity of SANC via an increase in basal CaMKII-dependent phosphorylation of Ca-cycling proteins (PLB, RyR, L-type Cachannels, and likely others), leading to amplification of LCR parameters, shortening of LCR timing and resultant spontaneous cycle length. Consequently, EPAC might represent a novel therapeutic target to regulate resting heart rate and treat sinoatrial node dysfunction.
BACKGROUND: The origins of left ventricular outflow tract premature ventricular contractions (PVCs) differ in depth and may involve preferential pathways, potentially requiring complex ablation. However, a noninvasive me...BACKGROUND: The origins of left ventricular outflow tract premature ventricular contractions (PVCs) differ in depth and may involve preferential pathways, potentially requiring complex ablation. However, a noninvasive method to preprocedurally estimate ablation complexity has not been established. METHODS: Sixteen patients with idiopathic left ventricular outflow tract PVCs (V2 transition ratio ≥0.6) underwent 2-dimensional speckle-tracking echocardiography during monomorphic PVCs. Endocardial peak systolic strain timing in 18 left ventricular segments was displayed on a bull's-eye map using 8 color-coded intervals (0-800 ms). Patients were classified as localized (n=6) when the earliest interval appeared in 1 segment and nonlocalized (n=10) when it involved ≥2 segments. Ablation outcomes were compared according to whether a simple ablation approach (PVC elimination within 30 s at a single site) was achieved. RESULTS: Baseline electrocardiographic characteristics were comparable between the groups. Ablation-related parameters, including contact force, power output, and impedance drop at the initial ablation site, were also similar. However, the nonlocalized group required statistically significantly greater total radiofrequency energy to eliminate the targeted PVCs (median, 22 206 versus 10 409 J; =0.031) and demonstrated a statistically significantly lower rate of successful simple ablation approach compared with the localized group (20.0% versus 83.3%; =0.035). Nonlocalized patterns may reflect conduction from deeper origins with preferential pathways, thereby requiring more complex ablation strategies. CONCLUSIONS: A localized earliest-strain pattern was associated with successful PVC elimination using a simple ablation approach, whereas a nonlocalized pattern indicated the need for more complex ablation. This simple, noninvasive metric may aid preprocedural planning for left ventricular outflow tract PVC ablation.
De Gaspari M, Pilichou K, Zorzi A
… +13 more, Bueno Marinas M, Cason M, Celeghin R, Sarto P, Fedeli U, Rigato I, Cipriani A, Perazzolo Marra M, Bauce B, Corrado D, Thiene G, Rizzo S, Basso C
BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a major cause of sudden cardiac death (SCD) in competitive athletes. We aimed to evaluate the prevalence and characteristics of ACM with the increased awareness of the d...BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a major cause of sudden cardiac death (SCD) in competitive athletes. We aimed to evaluate the prevalence and characteristics of ACM with the increased awareness of the disease at preparticipation screening after the introduction of the 1994 and 2010 diagnostic criteria. METHODS: The North-East Italy registry of juvenile SCD (≤40 years old) was searched for competitive athletes dying due to ACM in the time interval from 1985 to 2024. Cases referred from other regions were also included. Clinical and pathology data were analyzed according to guidelines. RESULTS: ACM was the cause of SCD in 29% of athletes. The incidence rate of SCD in athletes was 0.43 (0.27-0.65) versus 0.14 (0.05-0.33) per 100 000/y before and after 2010, respectively. Fifty-one athletes with ACM (50 male, 25±6.4 years) were enrolled. The pattern was right ventricular/biventricular in 74.5% and left ventricular in 25.5% (41% after 2010). Fibrofatty replacement was transmural in 63% of right ventricular/biventricular ACM and exclusively subepicardial-midmural in left ventricular ACM. First-line preparticipation screening revealed abnormalities in 62.7% (83.3% before 1994 and 40.9% after 2010). Twelve-lead ECG abnormalities were present in 50.9% (60.5% in right ventricular/biventricular ACM and 23% in left ventricular ACM), with negative T waves in 39.2% and low QRS voltage in 25.5%. Premature ventricular complexes/nonsustained ventricular tachycardia with left bundle-branch block or multiple morphologies were present on basal or limited exercise ECG in 35.3%. Maximal stress test, Holter, and 2-dimensional echocardiography were positive in 55%, 45.4%, and 5.8% of cases, respectively. In the only case who underwent contrast-enhanced cardiac magnetic resonance, late gadolinium enhancement was detected. CONCLUSIONS: ACM-related SCD incidence appeared lower in the post-2010 period. A phenotypic shift toward the left ventricular variant is observed, with ECG changes in a minority of cases and usually normal 2-dimensional echocardiography. If the index of suspicion is high, contrast-enhanced cardiac magnetic resonance is crucial for early identification and SCD prevention.
Kato R, Takigawa M, Kawamura I
… +12 more, Toda M, Honda M, Negishi M, Tateishi R, Iwakawa H, Yamao K, Goto K, Nishimura T, Tao S, Miyazaki S, Watanabe H, Sasano T
Kucera C, Ramalingam AR, Raph SM
… +6 more, Paily R, Srivastava S, Lorkiewicz PK, Bhatnagar A, Nystoriak MA, Carll AP
Circ Arrhythm Electrophysiol
· 2026 Jun · PMID 42290371
·
Full text
BACKGROUND: Despite the growing popularity of electronic cigarettes, evidence is mounting that vaping induces autonomic nervous system imbalance, cardiac arrhythmia, and potentially even cardiac arrest. The ingredients m...BACKGROUND: Despite the growing popularity of electronic cigarettes, evidence is mounting that vaping induces autonomic nervous system imbalance, cardiac arrhythmia, and potentially even cardiac arrest. The ingredients menthol, WS-3, and WS-23 are cooling agents that enhance the appeal of electronic cigarettes (e-cigs) but bear unknown risks when inhaled. METHODS: We systematically evaluated how these coolants influence the impacts of e-cigs on cardiac and cellular electrophysiology in mice and human induced pluripotent stem cell-derived cardiomyocytes, respectively. Mice were exposed by inhalation to e-cig aerosols generated from standard e-liquid solvents and 2.5% nicotine benzoate (vehicle), or from vehicle plus menthol, WS-3, or WS-23, at increasing concentrations throughout exposure. Telemetry-derived electrocardiograms were analyzed for changes in heart rate, heart rate variability, morphology, and ventricular premature beat arrhythmias. Human induced pluripotent stem cell-derived cardiomyocytes were evaluated for the effects of serially increasing coolant concentrations on beat rate, electric field potential duration, and rate-corrected field potential duration from a newly validated formula, in the absence and presence of norepinephrine to simulate basal physiology and nicotine-evoked sympathoexcitation. RESULTS: Upon e-cig aerosol inhalation, all coolants acutely enhanced vehicle-induced autonomic imbalance, but only the synthetic coolants, WS-3 and WS-23, potentiated ventricular arrhythmogenesis. Ventricular premature beats during e-cig exposures correlated with sympathetic dominance and transient delays in ventricular repolarization measured by heart rate variability and rate-corrected QT interval, respectively; however, correlations were strongest for WS-23 despite no significant impact of coolants on nicotine intake. Conversely, in human induced pluripotent stem cell-derived cardiomyocytes, coolants did not affect basal physiology but slowed beat rate and shortened rate-corrected field potential duration during norepinephrine stimulation. CONCLUSIONS: Together, these data indicate that coolants dose-dependently enhance the arrhythmogenicity of e-cigs, likely through acute alterations in autonomic modulation and repolarization. Pending confirmation by human studies, these common non-nicotine additives may exacerbate e-cig cardiotoxicity and pose unique cardiovascular risks, particularly in those with arrhythmogenic susceptibility to sympathetic stimulation or slowed ventricular repolarization.
Kerkouri F, Clementy N, Defaye P
… +44 more, Ait Said M, Andorin A, Anselme F, Aoudjeghout W, Badoz M, Behar N, Benhenda N, Ben Kilani M, Bodin A, Bordachar P, Bouzeman A, Citerne O, Deharo JC, Dommerc C, Echivard M, Extramiana F, Fauchier L, Garcia R, Gitenay E, Guenancia C, Guy-Moyat B, Jacon P, Jesel L, Juin C, Khoueiry Z, Kubala M, Leclercq C, Mansourati V, Marquié C, Mechulan A, Mondoly P, Narayanan K, Ollitrault P, Pasquié JL, Peret A, Poty H, Sebag F, Villejoubert O, Waintraub X, Waldmann V, Boveda S, Mansourati J, Marijon E, AV-CESAR Investigators
BACKGROUND: Evidence supporting the Micra AV leadless pacing system has largely derived from highly experienced centers, potentially limiting generalizability to routine clinical practice. METHODS: The AV-CESAR study (Fr...BACKGROUND: Evidence supporting the Micra AV leadless pacing system has largely derived from highly experienced centers, potentially limiting generalizability to routine clinical practice. METHODS: The AV-CESAR study (French Cohort Evaluating the Effectiveness of Atrioventricular Synchrony by the micRa AV) is a nationwide retrospective cohort, including the first 1000 patients implanted with a Medtronic Micra AV leadless pacemaker in France (2020-2024). Mean follow-up was 13.4±10.6 months. Primary end points were early (in-hospital) and late (postdischarge) device-related major complications; pacemaker syndrome and need for implantation of a new pacing system were centrally adjudicated. RESULTS: Among 1003 patients, device implantation was successful in 1000 (99.7%). Mean age was 72.0±15 years; 62.8% were men, 44.0% had ≥2 comorbidities, and 62.4% were unsuitable for transvenous pacemakers. The primary indication was permanent complete atrioventricular block with preserved sinus rhythm (78.0%). Early major complications occurred in 2.4%, including pericardial effusion (0.8%; 3 requiring surgery), access-site complications (0.8%), and thromboembolism (0.3%). Late major complications included pacemaker syndrome (2.5%), pacing-induced cardiomyopathy (1.2%), high thresholds (>4 V/0.24ms, 0.3%), and premature battery depletion (0.2%). No device infections or dislodgements were observed. Overall, 2.5% of patients required implantation of a new pacing system (pacing-induced cardiomyopathy n=11; pacemaker syndrome n=7; high threshold n=3; battery/software failure n=3; tricuspid regurgitation n=1) and 12.7% were permanently reprogrammed to ventricular paced/sensed, inhibited (VVI) mode. In pacing-dependent patients with ambulatory Holter monitoring (>3.4 million paced cycles), mean atrioventricular synchrony was 67.6±17.3% and correlated with device-reported AM-VP (74.8±17.1%; =0.92; <0.001). Atrioventricular synchrony declined at heart rates >90 beats per minute (5.6% of monitored time). All-cause mortality was 13.8%, with 0.2% directly device-related; 41.7% of deaths were cardiovascular. CONCLUSIONS: The Micra AV system is primarily used as an alternative when dual-chamber conventional pacemakers are not feasible. It demonstrated acceptable safety and clinical performance in a high-risk population. The marked reduction in atrioventricular synchrony at higher heart rates may suggest limited clinical benefit in patients with higher exertional heart rates. REGISTRATION:URL: https://clinicaltrials.gov/study/NCT05953558; Unique identifier: NCT05953558.
BACKGROUND: Intracardiac echocardiography (ICE) is increasingly used to guide left atrial appendage occlusion as an alternative to transesophageal echocardiography (TEE), particularly in elderly patients for whom general...BACKGROUND: Intracardiac echocardiography (ICE) is increasingly used to guide left atrial appendage occlusion as an alternative to transesophageal echocardiography (TEE), particularly in elderly patients for whom general anesthesia may pose additional risks. Real-world comparative safety data in older adults remain limited, with prior studies including only small ICE cohorts. We aimed to compare short- and long-term outcomes of ICE- versus TEE-guided left atrial appendage occlusion in adults aged ≥80 years. METHODS: We queried the TriNetX US Collaborative Network to identify patients aged ≥80 years with atrial fibrillation who underwent percutaneous left atrial appendage occlusion from 2015 to 2025. Patients were stratified by imaging modality: ICE- versus TEE-guided approach. Propensity score matching (1:1) was performed across demographics and comorbidities, yielding 2913 patients per group. Outcomes were assessed from the index procedure through 7 days, 90 days, and 1 year using Cox proportional hazards models to generate hazard ratios with 95% CIs. Outcomes included mortality, stroke, device thrombosis, pericardial effusion, pericardiocentesis, tamponade, and device leak. RESULTS: Baseline characteristics were well balanced after matching, with a mean age of 83 years and 44% women. At 90 days, ICE and TEE demonstrated no significant differences in mortality (hazard ratio, 1.18 [95% CI, 0.81-1.73]), stroke, device thrombosis, pericardial effusion, pericardiocentesis, tamponade, or device leak. At 1-year follow-up, mortality (hazard ratio, 0.93 [95% CI, 0.76-1.13]), stroke, and device thrombosis remained similar between groups. However, ICE was associated with a higher incidence of device leak compared with TEE (hazard ratio, 1.81 [95% CI, 1.11-2.97]). CONCLUSIONS: In this large propensity-matched cohort of very elderly patients undergoing left atrial appendage occlusion, ICE and TEE demonstrated comparable rates of mortality, stroke, and device thrombosis at 90 days and 1 year. ICE was associated with a higher rate of device leak at 1 year, warranting careful procedural technique and follow-up surveillance. Prospective studies are needed to define optimal intraprocedural imaging strategies in this high-risk population.
BACKGROUND: Early repolarization syndrome (ERS) is diagnosed in survivors of unexplained cardiac arrest (UCA) who exhibit a distinct ECG pattern of early repolarization (ER), defined as J-point elevation ≥0.1 mV in ≥2 co...BACKGROUND: Early repolarization syndrome (ERS) is diagnosed in survivors of unexplained cardiac arrest (UCA) who exhibit a distinct ECG pattern of early repolarization (ER), defined as J-point elevation ≥0.1 mV in ≥2 contiguous inferolateral leads. UCA survivors without ER or another identifiable cause are classified as idiopathic ventricular fibrillation (IVF). This study evaluated long-term outcomes in ERS compared with IVF. METHODS: This retrospective cohort study analyzed patients from the CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) who survived UCA and had structurally normal hearts with an Implantable Cardioverter Defibrillator. Of 709 patients, 186 with explanatory diagnoses and no ER pattern were excluded. The remaining 523 were categorized as ERS (n=48), IVF (n=463), or UCA with ER plus an additional diagnosis (Dx+ER, n=12). Patients were followed for the primary outcome of appropriate Implantable Cardioverter Defibrillator therapy, and logistic regression identified predictors of arrhythmia recurrence. RESULTS: Corrected QT interval intervals were significantly shorter in ERS than in IVF (412±25 ms versus 431±41 ms; <0.01). Over a median follow-up of 5.6 years, appropriate Implantable Cardioverter Defibrillator interventions occurred in 23% of ERS and 13% of IVF patients (=0.09), with incidence rates of 3.0 and 1.5 per 100 person-years, respectively. Four deaths occurred (0.8%), with no significant difference between groups (=0.39). In Dx+ER, appropriate Implantable Cardioverter Defibrillator therapies occurred in 42% of patients (incidence rate, 4.5 per 100 person-years). Arrhythmia-free survival was lower in ERS than in IVF (=0.03). After adjusting for age, sex, and ethnicity, ER was an independent predictor of arrhythmia recurrence (odds ratio, 2.59 [95% CI, 1.33-4.85]; =0.004). CONCLUSIONS: ERS is associated with shorter corrected QT interval intervals and reduced arrhythmia-free survival compared with IVF, with an incidence rate of 3.0 per 100 person-years. These findings underscore the importance of careful ECG review in patients with apparent UCA, to detect ER and undertake individualized risk assessment in affected individuals.
Bessière F, Kronborg MB, Sommer P
… +12 more, Almorad A, Rodrigues G, Scherr D, Sebag FA, De Potter T, Grimaldi M, Reichlin T, Knecht S, Sohns C, Chierchia GB, Gardey K, Ernst S
Transvenous pacing is increasingly recognized as problematic in patients with prior or concomitant tricuspid valve intervention, owing to risks of leaflet interference, prosthetic dysfunction, and progression of tricuspi...Transvenous pacing is increasingly recognized as problematic in patients with prior or concomitant tricuspid valve intervention, owing to risks of leaflet interference, prosthetic dysfunction, and progression of tricuspid regurgitation. Leadless pacemakers offer a valve-sparing alternative; however, their safety and performance in structurally altered right heart anatomy remain incompletely defined. We conducted a systematic review to evaluate procedural feasibility, electrical performance, device-valve interaction, and clinical outcomes of leadless pacemaker implantation in patients undergoing surgical or transcatheter tricuspid valve interventions. Thirty-four studies comprising 272 patients were included, encompassing surgical repair, bioprosthetic replacement, valve-in-valve procedures, transcatheter edge-to-edge repair, and transcatheter tricuspid valve replacement. Leadless pacemakers were implanted via transfemoral, transjugular, or direct surgical approaches, achieving a procedural success rate of 99.3%. Electrical performance was consistently favorable, with stable capture thresholds, sensing amplitudes, and impedance during follow-up. Device-valve interaction was infrequent and generally manageable. Leadless pacemaker-related complications were rare (1.1%), with no device-related mortality. Within the included studies of patients undergoing surgical or transcatheter tricuspid valve interventions, no study demonstrated worsening tricuspid regurgitation attributable to the leadless pacemaker or its delivery system. Across a broad spectrum of complex tricuspid anatomies, leadless pacemakers demonstrated excellent feasibility, durable electrical performance, and a low complication profile, supporting their role as a valve-sparing pacing strategy in this population. These findings support leadless pacing in patients with prior tricuspid intervention, although prospective comparative data are required to define its role relative to alternative pacing modalities.
BACKGROUND: Permanent pacemaker (PPM) implantation after heart transplantation (HT) is common, but contemporary data regarding utilization, outcomes, and emerging pacing technologies are limited. METHODS: We studied PPM...BACKGROUND: Permanent pacemaker (PPM) implantation after heart transplantation (HT) is common, but contemporary data regarding utilization, outcomes, and emerging pacing technologies are limited. METHODS: We studied PPM placement among 1225 bicaval HT recipients (28% women) treated at our institution from 2010 to 2025 and compared PPM recipients with HT patients without PPMs matched on sex, age, and transplant year. RESULTS: Median age at HT was 58 years (interquartile range, 48-65 years). Sixty-six (5%) patients received a PPM, with stable implantation rates over time. Median HT-to-PPM time was 4.3 months (interquartile range, 2 weeks to 4.8 years). The main indications were sinus node dysfunction (41 patients, 62%) or atrioventricular block (19 patients, 29%). Median post-HT survival was similar between PPM and non-PPM recipients (12.8 versus 11.5 years, =0.14). Older organ donor age independently predicted PPM placement (odds ratio, 1.75; =0.04). After 3.2 years of median follow-up, 1 transvenous PPM had a major complication requiring device extraction. Thirteen (20%) patients received leadless PPMs, including 3 atrial leadless PPMs and 1 dual-chamber leadless PPM. Leadless PPMs had no short-term complications over 1 year of median follow-up. CONCLUSIONS: Post-HT PPM implantation rates were low and unchanged since 2010. Most devices were implanted for sinus node dysfunction, with 44% implanted within 1 month post-HT. PPM placement was not associated with post-HT survival. Advanced organ donor age was associated with risk of PPM placement. Transvenous PPM complication rates were comparable to rates described in general populations. Leadless PPMs accounted for a substantial minority of PPM placements since their introduction in 2018, with no complications to date. Longer follow-up is needed to establish their long-term outcomes and safety in patients with HT.