An assessment of rapamycin for weakening binge-eating memories via reconsolidation: a pre-registered, double-blind randomised placebo-controlled experimental study.

BACKGROUND: Maladaptive learning linking environmental food cues to high-palatability food reward plays a central role in overconsumption in obesity and binge eating disorders. The process of memory reconsolidation offers a mechanism to weaken such learning, potentially ameliorating over-eating behaviour. Here we investigated whether putatively interfering with synaptic plasticity using the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, could weaken retrieved chocolate reward memories through blockade of reconsolidation. METHODS: Seventy five healthy volunteers with a tendency to binge eat chocolate were randomised to retrieve chocolate reward memory under 10 mg rapamycin (RET + RAP, active condition), or placebo (RET + PBO), or they received 10 mg rapamycin without subsequent retrieval (NO RET + RAP). Indices of chocolate reward memory strength were assessed one week pre and post manipulation and at one month follow-up. RESULTS: Contrary to hypotheses, the RET + RAP group did not show any greater reduction than control groups on indices of motivational salience of chocolate cues, motivation to consume chocolate or liking of chocolate. Mild evidence of improvement in the RET + RAP group was found, but this was limited to reduced chocolate binge episodes and improved healthy food choices. CONCLUSIONS: We did not find convincing evidence of comprehensive naturalistic chocolate reward memory reconsolidation blockade by rapamycin. The effects on chocolate bingeing and food choices may warrant further investigation. These limited positive findings may be attributable to insufficient interference with mTOR signalling with 10 mg rapamycin, or failure to destabilise chocolate memories during retrieval.

Long-term behavioural rewriting of maladaptive drinking memories via reconsolidation-update mechanisms.

BACKGROUND: Alcohol use disorders can be conceptualised as a learned pattern of maladaptive alcohol-consumption behaviours. The memories encoding these behaviours centrally contribute to long-term excessive alcohol consumption and are therefore an important therapeutic target. The transient period of memory instability sparked during memory reconsolidation offers a therapeutic window to directly rewrite these memories using targeted behavioural interventions. However, clinically-relevant demonstrations of the efficacy of this approach are few. We examined key retrieval parameters for destabilising naturalistic drinking memories and the ability of subsequent counterconditioning to effect long-term reductions in drinking. METHODS: Hazardous/harmful beer-drinking volunteers (N = 120) were factorially randomised to retrieve (RET) or not retrieve (No RET) alcohol reward memories with (PE) or without (No PE) alcohol reward prediction error. All participants subsequently underwent disgust-based counterconditioning of drinking cues. Acute responses to alcohol were assessed pre- and post-manipulation and drinking levels were assessed up to 9 months. RESULTS: Greater long-term reductions in drinking were found when counterconditioning was conducted following retrieval (with and without PE), despite a lack of short-term group differences in motivational responding to acute alcohol. Large variability in acute levels of learning during counterconditioning was noted. 'Responsiveness' to counterconditioning predicted subsequent responses to acute alcohol in RET + PE only, consistent with reconsolidation-update mechanisms. CONCLUSIONS: The longevity of behavioural interventions designed to reduce problematic drinking levels may be enhanced by leveraging reconsolidation-update mechanisms to rewrite maladaptive memory. However, inter-individual variability in levels of corrective learning is likely to determine the efficacy of reconsolidation-updating interventions and should be considered when designing and assessing interventions.

A left ventricular assist device interfering with leadless pacemaker implantation.

Left ventricular assist devices (LVAD) produce electromagnetic interference (EMI) which can have implications when patients require cardiac implantable electronic devices. Leadless pacemakers have been successfully implanted in patients with Heartmate 2 and Heartmate 3 LVADs without evidence of EMI or device-to-device interaction. Here we report a case of a Heartmate 3 LVAD and Micra VR transcatheter pacing system interaction requiring device repositioning.

The Subjective Response to Nitrous Oxide is a Potential Pharmaco-Endophenotype for Alcohol Use Disorder: A Preliminary Study with Heavy Drinkers.

Background: Healthy people with a family history of alcohol problems show a pattern of subjective responses to alcohol that resemble those of affected probands. Studies on ketamine suggest that up-regulation of N-methyl-D-aspartate receptors (NMDARs) underlies these effects, and point to a pharmacologically-responsive endophenotype reflecting enhanced risk for alcohol-use disorders. Methods: Subjective stimulant and sedative effects were assessed before and during nitrous oxide (N2O; 50%) inhalation in heavy drinkers who were otherwise healthy. Results: Participants with an ostensible family history of alcohol-use disorders (n = 23) were distinguishable from those without such familial risk (n = 37) by an enhanced stimulation-to-sedation ratio during N2O inhalation. Conclusion: The pattern of subjective effects of N2O according to familial risk is remarkably similar to that previously seen with ketamine, supporting the idea of a common, NMDAR-mediated mechanism of action. N2O may prove to be a safe and accessible alternative to ketamine for probing heritable NMDAR dysregulation in neuropsychiatric disorders.

Mutation of a common amino acid in NKX2.5 results in dilated cardiomyopathy in two large families.

BACKGROUND: The genetic basis for dilated cardiomyopathy (DCM) can be difficult to determine, particularly in familial cases with complex phenotypes. Next generation sequencing may be useful in the management of such cases. METHODS: We report two large families with pleiotropic inherited cardiomyopathy. In addition to DCM, the phenotypes included atrial and ventricular septal defects, cardiac arrhythmia and sudden death. Probands underwent whole exome sequencing to identify potentially causative variants. RESULTS: Each whole exome sequence yielded over 18,000 variants. We identified distinct mutations affecting a common amino acid in NKX2.5. Segregation analysis of the families support the pathogenic role of these variants. CONCLUSION: Our study emphasizes the utility of next generation sequencing in identifying causative mutations in complex inherited cardiac disease. We also report a novel pathogenic NKX2.5 mutation.

Transtracheal Pressure for Evaluation of Decannulation Readiness.

BACKGROUND: Pediatric tracheostomy decannulation protocols vary among institutions and may include toleration of Passy Muir Valve (PMV), microlaryngoscopy and bronchoscopy (MLB) findings, and polysomnography evaluation. Transtracheal pressure (TTP) is an objective measurement utilized to evaluate PMV toleration. We aimed to investigate the role of TTP in decannulation candidates and compare TTP measurements with polysomnography and MLB findings. METHODS: A retrospective cohort study of children who underwent TTP measurement during PMV trial between December 2012 and November 2022. RESULTS: A total of 79 patients underwent TTP measurement and MLB evaluation; of these, 16 (20.3%) patients had a capped polysomnography. Twenty-eight (35.4%) patients had TTPs ≤10 cm H2O, and 51 (64.6%) patients had TTPs >10 cm H2O. The most common indication for tracheostomy was upper airway obstruction (n = 41, 51.9%), followed by a need for mechanical ventilation (n = 24, 30.4%). Twenty-five (31.6%) patients were decannulated. Patients with TTPs ≤10 cm H2O had a mean Apnea-Hypopnea Index of 0.17 ± 0.26/h compared with 6.93 ± 7.67/h in those with TTPs >10 cm H2O, p = 0.0365. Patients with TTPs >10 cm H2O were found to have a significantly higher occurrence of airway obstruction (96.1% vs. 46.4%, p < 0.0001) and multilevel airway obstruction (70.6% vs. 21.4%, p < 0.0001) on MLB. Neither TTP measured at time of PMV assessment nor capped polysomnography was associated with successful decannulation. CONCLUSIONS: TTP measurements at time of PMV evaluation are associated with polysomnography and MLB findings. One-time PMV measurements were not indicative of decannulation success. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3377-3383, 2024.

The therapeutic benefit of upgrade to cardiac resynchronization therapy in patients with pacing-induced cardiomyopathy.

Background: Pacing-induced cardiomyopathy (PICM) is an important cause of heart failure in patients with a right ventricular pacing burden. Recent evidence suggests that an upgrade to cardiac resynchronization therapy (CRT) may confer benefit in PICM. Objective: To assess the extent and identify predictors of improvement following upgrade to CRT in patients with PICM. Methods: We retrospectively analyzed 43 patients undergoing CRT upgrade for PICM over the 10-year period of 2011 to 2021 at our center. All patients with PICM who underwent device upgrade from a dual- or single-chamber ventricular pacemaker to CRT were included. PICM was defined as a decrease of ≥10% in left ventricular ejection fraction (LVEF), resulting in an LVEF <50% among patients with ≥20% Right ventricular pacing burden without an alternative cause for cardiomyopathy. Results: LVEF significantly improved from 28.7% preupgrade to 44.3% post-CRT upgrade (P < .01). Of 37 patients with severe LV dysfunction, 34 (91.9%) improved to an LVEF >35% and 13 (35.1%) improved to an LVEF >50%. The LV end-diastolic diameter decreased from 5.9 cm preupgrade to 5.4 cm postupgrade (P < .01). Using linear regression, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use was associated with significant LVEF improvement (+7.21%, P = .05). We observed a low rate of complications, and 1 in 4 CRT upgrades required venoplasty (n = 10 of 43, 23.3%). Conclusion: We provide further evidence for the benefit of CRT upgrade in the management of patients with PICM.

Establishing Normative Values for Healthy Term Infant Feeding Performance: Neonatal Eating Assessment Tool-Mixed, Oral Feeding Scale, and Early Feeding Skills Assessment.

PURPOSE: Infants with perceived feeding problems are frequently referred for assessment of their feeding abilities. However, little is known regarding how healthy nondysphagic infants perform on commonly used assessments, making determination of impairment difficult. The aim of this investigation was to elucidate the characteristics of healthy term infant feeding performance using three commonly employed clinical assessments: Neonatal Eating Assessment Tool-Mixed (NeoEat-Mixed), Oral Feeding Scale, and Early Feeding Skills (EFS). METHOD: In this prospective case-control study, we recruited 30 infants without feeding impairments to undergo video-monitored bottle feeds under their normal feeding conditions. Caregiver perception of infant feeding was evaluated using the NeoEat-Mixed. Milk ingestion was monitored real time using the Oral Feeding Scale for rate of milk transfer and modified proficiency as characterized by the total volume consumed out of the total volume the caregiver provided. Videos were analyzed by two speech pathologists using the EFS assessment. Descriptive statistics were used to characterize performance. RESULTS: Participants underwent feeding monitoring at an average chronological age of 4 ± 2 months. Caregivers primarily reported normal, nonconcerning feeding patterns across all of the NeoEAT-Mixed outcomes. Infants consumed milk at an average rate of transfer of 7 ± 3 ml/min, a modified proficiency of 50 ± 21%, and achieved the highest OFS score of 4 (93%, n = 28). The majority of infants scored the best EFS score (mature-3) as it related to the absence of color changes during the feed (97%, n = 29), although commonly scored in the worst EFS score (immature-1) in their presentation of one or more compelling stress cues (63%, n = 19). CONCLUSION: Establishing healthy term infant normative values for commonly used feeding assessments is critical in accurately distinguishing infants with feeding impairments from those with normal developmental variants.

Presence of sinus rhythm at time of ablation in patients with persistent atrial fibrillation undergoing pulmonary vein isolation is associated with improved long-term arrhythmia outcomes.

BACKGROUND: Adverse structural and electrical remodeling underlie persistent atrial fibrillation (PersAF). Restoration of sinus rhythm (SR) prior to ablation in PersAF may improve the underlying substrate, thus improving arrhythmia outcomes. The aim of this study was to evaluate if the presence of SR at time of ablation is associated with improved long-term arrhythmia outcomes of a limited catheter ablation (CA) strategy in PersAF. METHODS: Patients with PersAF undergoing pulmonary vein isolation at our institution from 2014-2018 were included. We compared patients who presented for ablation in SR (by cardioversion and/or antiarrhythmic drugs [AADs]) to those who presented in AF. Primary outcome of interest was freedom from atrial arrhythmias (AAs) on or off AADs at 1 year after single ablation. Secondary outcomes included freedom from AAs on or off AADs overall, freedom from AAs off AADs at 1 year, and time to recurrent AF. RESULTS: Five hundred seventeen patients were included (322 presented in AF, 195 SR). The primary outcome was higher in those who presented for CA in SR as compared to AF (85.6% vs. 77.0%, p = 0.017). Freedom from AAs off AAD at 12 months was also higher in those presenting in SR (59.0% vs. 44.4%; p = 0.001) and time to recurrent AF was longer (p = 0.008). Presence of SR at CA was independently associated with the primary outcome at 12 months (OR 1.77; 95% CI 1.08-2.90) and overall (OR 1.89; 95% CI 1.26-2.82). CONCLUSIONS: Presence of SR at time of ablation is associated with improved long-term arrhythmia outcomes of limited CA in PersAF.

Lightning and severe thunderstorms in event management.

There are a few national position stands/guidelines that address environmental conditions in athletics, yet they do not govern all outdoor sports. Extreme heat and cold, lightning, and severe wind can all be fatal, yet the majority of outdoor sports have no published guidelines addressing these conditions in relation to activity. Available research on extreme heat and cold conditions in athletics provides prevention strategies, to include acclimatization. Lightning and severe wind are two environmental conditions to which humans cannot accommodate, and they both can be deadly. There are strong positions on extreme heat/cold and lightning safety in athletics, but none affiliated with severe winds. Medical personnel involved in planning large outdoor sporting events must know of the presence of nationally published weather-related documents and apply them to their event. In addition, research needs to be expanded in the realm of establishing guidelines for safety to participants and spectators in severe wind conditions.

Pharmacological modelling of dissociation and psychosis: an evaluation of the Clinician Administered Dissociative States Scale and Psychotomimetic States Inventory during nitrous oxide ('laughing gas')-induced anomalous states.

RATIONALE: A significant obstacle to an improved understanding of pathological dissociative and psychosis-like states is the lack of readily implemented pharmacological models of these experiences. Ketamine has dissociative and psychotomimetic effects but can be difficult to use outside of medical and clinical-research facilities. Alternatively, nitrous oxide (N2O) - like ketamine, a dissociative anaesthetic and NMDAR antagonist - has numerous properties that make it an attractive alternative for modelling dissociation and psychosis. However, development and testing of such pharmacological models relies on well-characterized measurement instruments. OBJECTIVES: To examine the factor structures of the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) administered during N2O inhalation in healthy volunteers. METHODS: Secondary analyses of data pooled from three previous N2O studies with healthy volunteers. RESULTS: Effect sizes for N2O-induced dissociation and psychotomimesis were comparable to effects reported in experimental studies with sub-anaesthetic ketamine in healthy volunteers. Although, like ketamine, a three-factor representation of N2O-induced dissociation was confirmed, and a more parsimonious two-factor model might be more appropriate. Bayesian exploratory factor analysis suggested that N2O-induced psychosis-like symptoms were adequately represented by two negative and two positive symptom factors. Hierarchical cluster analysis indicated minimal item overlap between the CADSS and PSI. CONCLUSION: N2O and ketamine produce psychometrically similar dissociative states, although parallels in their psychosis-like effects remain to be determined. The CADSS and PSI tap largely non-overlapping experiences under N2O and we propose the use of both measures (or similar instruments) to comprehensively assess anomalous subjective states produced by dissociative NMDAR antagonists.

Sinus rhythm QRS amplitude and fractionation in patients with nonischemic cardiomyopathy to identify ventricular tachycardia substrate and location.

BACKGROUND: Ventricular tachycardia (VT) substrate in left ventricular (LV) nonischemic cardiomyopathy (NICM) consists of fibrosis with surviving myocardium. OBJECTIVE: The purpose of this study was to determine whether, in patients with LV NICM and sustained VT, reduced QRS amplitude and QRSf during sinus rhythm can identify the presence and location of abnormal septal (S-NICM) and/or free-wall (FW-NICM) VT substrate. METHODS: We compared patients with NICM and VT (group 1) with electroanatomic mapping septal (S-NICM; n = 21) or free-wall (FW-NICM; n = 20) VT substrate to a 38-patient reference cohort (group 2) with cardiac magnetic resonance imaging (cMRI) and NICM but no VT referred for primary prevention implantable cardioverter-defibrillator (26 [68.4%] with late gadolinium enhancement). RESULTS: Group 1 had lower QRS amplitude in leads II (0.60 ± 0.22 vs 0.86 ± 0.35, P <.001), aVR (0.60 ± 0.24 vs 0.75 ± 0.31, P = .002), aVF (0.48 ± 0.20 vs 0.70 ± 0.28, P <.001), and V2 (1.09 ± 0.52 vs 1.38 ± 0.55, P = .001) than group 2. QRS <0.55 mV in lead aVF identified VT and accompanying substrate with sensitivity 70% and specificity 71%. Most group 1 and group 2 patients had 12-lead ECG QRS fractionation (QRSf) in ≥2 contiguous leads (78% vs 63.2%, P = .14). Sensitivity and specificity for ≥2 QRSf leads identifying respective regional electroanatomic or cMRI abnormalities were 76% and 50% for inferior, 44% and 87% for lateral, and 21% and 89% for anterior leads. CONCLUSION: In LV NICM, low frontal plane QRS (<0.55 mV in aVF) is associated with VT substrate. Although multilead QRS fractionation is associated with the presence and location of VT substrate, it is frequently identified in patients without VT with cMRI abnormalities.

Characterization of the right ventricular substrate participating in postinfarction ventricular tachycardia.

BACKGROUND: The right ventricle (RV) is uncommonly implicated in postinfarction ventricular tachycardia (VT). The prevalence and features of the RV substrate participating in postinfarction VT are undefined. OBJECTIVES: The purpose of this study was to characterize critical right ventricular substrate (CRVS) involvement in patients with postinfarction VT. METHODS: We retrospectively reviewed 1279 patients with postinfarction VT undergoing catheter ablation at our center from January 2000 through May 2020. Cases with CRVS defined by conclusive demonstration of participation in VT with activation, entrainment, and/or pacemapping during sinus rhythm were identified. RESULTS: CRVS was identified in 27 of 1279 patients (2.1%): age 65 ± 13 years, 96% male, median left ventricular (LV) ejection fraction 25%, and 93% with left bundle branch block (LBBB) morphology VT. CRVS was identified by RV activation and/or entrainment mapping (n = 19) or by the presence of low-voltage abnormal electrograms with excellent pacemap for the targeted VT and noninducibility after ablation (n = 8). VT termination during RV ablation occurred in 15 patients. After median follow-up of 20 months (interquartile range 9-53 months) and median of 2 procedures (interquartile range 1-3), 22 of 27 patients (80%) had no VT recurrence and 11 (41%) died. CONCLUSION: The RV contains critical substrate elements of postinfarction VT in at least 2.1% of cases. RV mapping should be considered in cases in which LV mapping fails to demonstrate adequate targets, particularly in patients with LBBB morphology VT.

Classification of Left Atrial Diseased Tissue Burden Determined by Automated Voltage Analysis Predicts Outcomes after Ablation for Atrial Fibrillation.

BACKGROUND: The burden and persistence of atrial fibrillation (AF) have been associated with the presence and extent of left atrial (LA) fibrosis. Recent reports have implicated an association between the extent of LA fibrosis and the outcome of pulmonary vein isolation (PVI). We aimed to analyse the value of an automated scar quantification method in the prediction of success following PVI. METHODS: One hundred and nine consecutive patients undergoing PVI for paroxysmal or persistent AF were included in our observational study with a 2-year follow-up. Prior to PVI, patients underwent high-definition LA electroanatomical mapping, and scar burden was quantified by automated software (Voltage Histogram Analysis, CARTO 3, Biosense Webster), then classified into 4 subgroups (Dublin Classes I-IV). Recurrence rates were analysed on and off antiarrhythmic drug therapy (AAD), respectively. RESULTS: The overall success rate was 74% and 67% off AAD at 1- and 2-year follow-up, respectively. Patients with Dublin Class IV had significantly lower success rates (p = 0.008, off AAD). Dublin Class IV (OR = 2.27, p = 0.022, off AAD) and the presence of arrhythmia in the blanking period (OR = 3.28, p = 0.001, off AAD) were the only significant predictors of recurrence. The use of AAD did not affect these results. CONCLUSIONS: We propose a classification of low voltage areas based on automated quantification by software during 3D mapping prior to PVI. Patients with high burden of low voltage areas (>31% of <0.5 mV, Dublin Class IV) have a higher risk of recurrence following PVI. Information gathered during electroanatomical mapping may have important prognostic value.

Substrate Characterization and Outcome of Catheter Ablation of Ventricular Tachycardia in Patients With Nonischemic Cardiomyopathy and Isolated Epicardial Scar.

BACKGROUND: The substrate for ventricular tachycardia (VT) in left ventricular (LV) nonischemic cardiomyopathy may be epicardial. We assessed the prevalence, location, endocardial electrograms, and VT ablation outcomes in LV nonischemic cardiomyopathy with isolated epicardial substrate. METHODS: Forty-seven of 531 (9%) patients with LV nonischemic cardiomyopathy and VT demonstrated normal endocardial (>1.5 mV)/abnormal epicardial bipolar low-voltage area (LVA, <1.0 mV and signal abnormality). Abnormal endocardial unipolar LVA (≤8.3 mV) and endocardial bipolar split electrograms and predictors of ablation success were assessed. RESULTS: Epicardial bipolar LVA (27.3 cm2 [interquartile range, 15.8-50.0]) localized to basal (40), mid (8), and apical (3) LV with basal inferolateral LV most common (28/47, 60%). Of 44 endocardial maps available, 40 (91%) had endocardial unipolar LVA (24.5 cm2 [interquartile range, 9.4-68.5]) and 29 (67%) had characteristic normal amplitude endocardial split electrograms opposite the epicardial LVA. At mean of 34 months, the VT-free survival was 55% after one and 72% after multiple procedures. Greater endocardial unipolar LVA than epicardial bipolar LVA (hazard ratio, 10.66 [CI, 2.63-43.12], P=0.001) and number of inducible VTs (hazard ratio, 1.96 [CI, 1.27-3.00], P=0.002) were associated with VT recurrence. CONCLUSIONS: In patients with LV nonischemic cardiomyopathy and VT, the substrate may be confined to epicardial and commonly basal inferolateral. LV endocardial unipolar LVA and normal amplitude bipolar split electrograms identify epicardial LVA. Ablation targeting epicardial VT and substrate achieves good long-term VT-free survival. Greater endocardial unipolar than epicardial bipolar LVA and more inducible VTs predict VT recurrence.

A Smartwatch Heart Rate Monitor Prompts an Unusual Diagnosis.

We report the case of a 54-year-old woman who presented for cardiological evaluation having noted a decline in her heart rate on her wearable heart rate monitor. She was found to be in 2:1 atrioventricular block. Subsequent evaluation revealed cardiac and pulmonary sarcoidosis, treated with steroids and implantable cardioverter-defibrillator placement. (Level of Difficulty: Beginner.).

Quantitative assessment of left atrial scar using high-density voltage mapping and a novel automated voltage analysis tool.

PURPOSE: Left atrial (LA) fibrosis plays an important role in the pathogenesis and perpetuation of atrial fibrillation (AF). It may be identified by bipolar voltage (BiV) mapping, but quantification of fibrosis which previously relied on visual estimation of scar has been shown to be inaccurate. Our aim was to use a novel automated voltage histogram analysis (VHA) tool to quantify LA scar burden accurately in patients with AF. METHODS: LA voltage was assessed in 100 consecutive patients undergoing first pulmonary vein isolation (PVI) for paroxysmal or persistent AF using a circular multielectrode catheter to create high-density LA BiV maps which were analysed using the VHA tool after the procedure. RESULTS: High-density electro-anatomic maps took 10 min to create and contained a median of 1049 points. The VHA algorithm accurately quantified the burden of Diseased LA Tissue (≤ 0.5 mV) and Dense LA Scar (≤ 0.2 mV) with a median of 17.8% and 3.5% respectively. A quartile classification was applied based on diseased LA tissue burden. Patients in class IV with the highest diseased LA burden were older (p < 0.0001), more likely female (p = 0.0095), had higher CHA2DS2-VASc scores (p = 0.0024) and were more likely to have persistent rather than paroxysmal AF (p = 0.0179) than those in classes I-III. CONCLUSIONS: The VHA algorithm is able to quantify percentage surface area voltage rapidly and according to preset ranges for the first time. The algorithm offers the potential for classification of patients undergoing AF ablation into different classes of diseased LA burden, which may have diagnostic, therapeutic and prognostic implications.

Author Correction: Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ablation of Ventricular Arrhythmias From the Left Ventricular Apex in Patients Without Ischemic Heart Disease.

OBJECTIVES: This study aimed to characterize the incidence, clinical characteristics, and electrocardiographic and electrophysiologic features of LVA VA in the absence of CAD and to describe the experience with catheter ablation (CA) in this group. BACKGROUND: The left ventricular apex (LVA) is a well-described source of ventricular arrhythmias (VAs) in patients with coronary artery disease (CAD) and history of apical infarction but is a rare source of VA in the absence of CAD. METHODS: Patients referred for CA of VA at our institution were retrospectively reviewed, and those with LVA VA in the absence of CAD were identified. RESULTS: Of 3,710 consecutive patients undergoing VA ablation, CA of LVA VA was performed in 24 patients (20 with monomorphic ventricular tachycardia, 4 with premature ventricular contractions or nonsustained ventricular tachycardia; 18 men; mean age: 54 ± 15 years). These cases comprised 10 of 35 (29%) hypertrophic cardiomyopathy, 9 of 789 (1.2%) nonischemic cardiomyopathy, and 5 of 1,432 (0.4%) idiopathic VA ablation procedures. VA QRS morphology was predominantly right bundle with slurred upstroke and right superior frontal plane axis with precordial transition ≤V3. Epicardial ablation was performed in 14 of 24 (58%). After a median of 1 procedure (range 1 to 4) at this institution and median follow-up of 47 months (range 0-176), VA recurred in 1 patient (4%). CONCLUSIONS: LVA VA in the absence of CAD is unusual and may occur in patients with hypertrophic cardiomyopathy or nonischemic cardiomyopathy or, rarely, in the absence of structural heart disease. It can be recognized by characteristic ECG features. CA of LVA VA is challenging; multiple procedures, including epicardial approaches, may be required to achieve VA control over long-term follow-up.