CXCR3 expression in regulatory T cells drives interactions with type I dendritic cells in tumors to restrict CD8+ T cell antitumor immunity.

Infiltration of regulatory T (Treg) cells, an immunosuppressive population of CD4+ T cells, into solid cancers represents a barrier to cancer immunotherapy. Chemokine receptors are critical for Treg cell recruitment and cell-cell interactions in inflamed tissues, including cancer, and thus are an ideal therapeutic target. Here, we show in multiple cancer models that CXCR3+ Treg cells were increased in tumors compared with lymphoid tissues, exhibited an activated phenotype, and interacted preferentially with CXCL9-producing BATF3+ dendritic cells (DCs). Genetic ablation of CXCR3 in Treg cells disrupted DC1-Treg cell interactions and concomitantly increased DC-CD8+ T cell interactions. Mechanistically, CXCR3 ablation in Treg cells increased tumor antigen-specific cross-presentation by DC1s, increasing CD8+ T cell priming and reactivation in tumors. This ultimately impaired tumor progression, especially in combination with anti-PD-1 checkpoint blockade immunotherapy. Overall, CXCR3 is shown to be a critical chemokine receptor for Treg cell accumulation and immune suppression in tumors.

Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.

BACKGROUND: Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma. METHODS: In this phase 2 study, we sought to confirm the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma. Patients with disease after at least three previous regimens including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody were enrolled. Patients received ide-cel target doses of 150 × 106 to 450 × 106 CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses). RESULTS: Of 140 patients enrolled, 128 received ide-cel. At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. Minimal residual disease (MRD)-negative status (<10-5 nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion. CONCLUSIONS: Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 toxic effects, most commonly hematologic toxic effects and cytokine release syndrome. (Funded by bluebird bio and Celgene, a Bristol-Myers Squibb company; KarMMa ClinicalTrials.gov number, NCT03361748.).

The Current Landscape of Ventricular Tachycardia Trials: A Systematic Review of Registered Studies.

BACKGROUND: Although there are evolving techniques and technologies for treating ventricular tachycardia (VT), the current landscape of clinical trials for managing VT remains understudied. OBJECTIVE: The objective of this study was to provide a systematic characterisation of the interventional management of VT through an analysis of the ClinicalTrials.gov, clinicaltrialsregister.eu, anzctr.org.au and chictr.org.cn databases. METHODS: We queried all phase II to IV interventional trials registered up to November 2023 that enrolled patients with VT. Published, completed but unpublished, terminated, or ongoing trials were included for final analysis. RESULTS: Of the 698 registered studies, 135 were related to VT, with 123 trials included in the final analysis. Among these trials, 25 (20%) have been published, enrolling a median of 35 patients (interquartile range [IQR] 20-132) over a median of 43 months (IQR 19-62). Out of the published trials, 14 (56%) were randomised, and 12 (48%) focused on catheter ablation. Twenty-two (18%) have been completed but remain unpublished, even after a median of 36 months (IQR 15-60). Furthermore, 27 (22%) trials were terminated or withdrawn, with the most common cause being poor enrolment. Currently, 49 (40%) trials are ongoing and novel non-ablative technologies, such as radioablation and autonomic modulation, account for 35% and 8% of ongoing trials, respectively. CONCLUSIONS: Our analysis revealed that many registered trials remain unpublished or incomplete, and randomised controlled trial evidence is limited to only a few studies. Furthermore, many ongoing trials are focused on non-catheter ablation-based strategies. Therefore, larger pragmatic trials are needed to create stronger evidence in the future.

Accuracy of a Single-Lead ECG Device for Diagnosis of Cardiac Arrhythmias Compared Against Cardiac Electrophysiology Study.

BACKGROUND: Single-lead electrocardiogram (ECG) devices may allow detection and diagnosis of cardiac rhythms. However, data on their accuracy for detecting cardiac arrhythmias beyond atrial fibrillation are limited. We aimed to determine the accuracy of the AliveCor KardiaMobile (AC) (AliveCor Inc, Mountain View, CA, USA) for the diagnosis of arrhythmias against gold standard cardiac electrophysiology study (EPS). METHOD: Patients undergoing clinically indicated EPS underwent simultaneous rhythm recording with an AC, standard 12-lead ECG, and EP catheters for intracardiac electrograms. Rhythms recorded during EPS were classified based on electrogram, 12-lead ECG, and clinical findings. Blinded reviewers provided differential diagnoses for the single-lead AC tracings; a separate reviewer compared diagnoses made between the AC tracings and EPS findings. RESULTS: In 49 patients, 843 cardiac rhythms were captured during 502 AC recordings. Analysis of tracings containing sinus rhythm (n=273) returned an overall accuracy of 92%, with sensitivity and specificity values of 93% and 92%, respectively. Accuracy for tracings per rhythm was atrial fibrillation 91% (n=51); supraventricular tachycardia accuracy was 89% (n=191), ventricular tachycardia 91% (n=198), ventricular fibrillation 98% (n=11), and asystole 100% (n=5). Accuracy for supraventricular ectopy was 93% (n=28) and for premature ventricular complexes was 91% (n=86). Overall accuracy was 94% for solitary rhythms and 93% in tracings from patients with baseline bundle branch block. CONCLUSIONS: When compared against the gold standard EPS diagnosis, the interpretation of arrhythmias recorded by an AliveCor single-lead ECG device had reasonable diagnostic accuracy.

Correlation of spatial patterns of endocardial pace mapping to underlying scar topography in patients with scar-related ventricular tachycardia.

INTRODUCTION: Endocardial pace mapping (PM) can identify conducting channels for ventricular tachycardia (VT) circuits in patients with structural heart disease (SHD). Recent findings show the temporal and spatial pattern of PM may aid identification of the surface harboring VT isthmii. The specific correlation of PM patterns to scar topography has not been examined. OBJECTIVE: To correlate the pattern of endocardial PMs to underlying scar topography in SHD patients with VT. METHODS: Data from patients undergoing VT ablation from August 2018 to February 2022 were reviewed. RESULTS: Sixty-three patients with SHD-related VT (mean age 65 ± 14 years) with 83 endocardial PM correlation maps were analysed. Two main correlation patterns were identified, an "abrupt-change correlation pattern (AC-pattern)" and "centrifugal-attenuation correlation pattern (CA-pattern)." AC-pattern had lower scar ratio (unipolar/bipolar % scar area; 1.1 vs. 1.5, p < .001), had longer maximal stimulus-QRS intervals (97.5 vs. 68 ms, p = .002), and higher likelihood of endocardial dominant scar (11/21 [52%] vs. 3/38 [8%], p < .001) than CA-pattern seen on intracardiac echocardiography (ICE). In contrast, CA-pattern was more likely to have epicardial dominant scar or mid-intramural scar on ICE (epicardial dominant scar; CA-pattern: 12/38 [32%] vs. AC-pattern: 1/21 [5%], p = .02, mid-intramural scar; CA-pattern: 15/38 [39%] vs. AC-pattern: 1/21 [5%], p = .005). CONCLUSIONS: The spatial pattern of endocardial PM in SHD-related VT directly correlates with scar topography. AC-pattern is associated with endocardial dominant scar on ICE with lower scar ratio and longer stimulus-QRS intervals, whereas CA-pattern is strongly associated with epicardial dominant or mid-intramural scar with higher scar ratio and shorter stimulus-QRS intervals.

Correlation of exit sites of inducible ventricular tachycardia post-ST elevation myocardial infarction on electrophysiology study, with region of infarct.

BACKGROUND: Ventricular arrhythmia (VA) is the most common cause of sudden cardiac death post-ST elevation myocardial infarction (STEMI). Ventricular tachycardia (VT) may be inducible in electrophysiology studies (EPS) early (<40 days) post-STEMI. Whether it originates from the infarct site remains unknown. We examined the correlation between inducible VT and infarct location post-STEMI. AIMS: To investigate the correlation between inducible VT and infarct location post-STEMI. METHODS: We retrospectively analysed 46 patients from 2005 to 2017 with STEMI who underwent early programmed ventricular stimulation through EPS (>48 h post-STEMI and <40 days from admission). Gated heart pool scans were used to visualise infarct scar regions, and VT exit sites were derived from induction 12-lead electrocardiography. Patients were followed up for primary outcomes of recurrent VA and all-cause mortality. RESULTS: Forty-six patients were included for analysis, with 50 uniquely induced VT exit sites. Mean left ventricular ejection fraction was 30 ± 8.7% and 22% had impaired right ventricular ejection fraction. Mean time from presentation to EPS was 16 ± 31.3 days. Of the induced VT, 44 (88%) were from within scar and scar-border regions, whereas 6 (12%) of the induced VT were found to be remote to imaging-derived scar. Over a median follow-up period of 75 months, 6 (13%) patients died, and 7 (15%) patients had recurrent VA. No deaths occurred in patients with remote VT. CONCLUSION: The majority of early inducible post-infarct VT arises from acute myocardial scar; however, a small portion arises from sites remote from scars with a possible focal aetiology.

Somatic symptoms, psychological distress and trauma after disasters: lessons from the 2014 Hazelwood mine fire and 2019-20 Black Summer bushfires.

BACKGROUND: Wildfires cause significant physical and mental ill-health. How physical and mental symptoms interact following wildfire smoke exposure is unclear, particularly in the context of repeated exposures. In this cross-sectional study we investigated how posttraumatic stress and general psychological distress associated with somatic symptoms in a community exposed to multiple smoke events. METHODS: A random weighted sample of 709 adults exposed to smoke during the 2014 Hazelwood coal mine fire in south-eastern Australia completed a survey in 2020. The survey coincided with the Black Summer wildfires that caused a similar period of smoke haze in the region. Participants self-reported somatic symptoms (PHQ-15) and mine fire-related posttraumatic stress (IES-R) experienced over the previous week, general psychological distress (K10) experienced over the previous four weeks, lifetime health diagnoses and demographic information. Associations between posttraumatic stress, general psychological distress, and each PHQ-15 somatic symptom were analysed using ordinal logistic regression models. RESULTS: Overall, 36.2% of participants reported moderate- or high-level somatic symptomology. The most frequent somatic symptoms were fatigue, limb pain, trouble sleeping, back pain, headaches, and shortness of breath. After controlling for confounding factors, general psychological distress and posttraumatic stress were independently associated with all somatic symptoms (except menstrual problems in females for posttraumatic stress). CONCLUSIONS: Results highlight the high prevalence of somatic symptoms and their association with general psychological distress and posttraumatic stress within a community in the midst of a second large-scale smoke event. It is essential that healthcare providers and public health authorities consider the interconnections of these conditions when supporting communities affected by climate-related disasters.

Sociodemographic circumstances, health, and life experience shape posttraumatic distress trajectories among individuals exposed to smoke during a large-scale coal mine fire.

The 2014 Hazelwood coal mine fire in the Latrobe Valley, Australia, distributed toxic smoke into surrounding communities over 45 days. This study investigated risk and protective factors associated with four trajectories of posttraumatic distress (resilient, recovery, delayed-onset, chronic) among exposed adults. Participants (N = 709) completed surveys in 2016-2017 and 2019-2020 assessing mine fire-related particulate matter (PM2.5 ) exposure; sociodemographic, physical, and mental health variables; and exposure to other traumatic and recent stressful events. Mine fire-related posttraumatic distress was measured using the IES-R; trajectories were determined according to established clinical significance thresholds. Relative risk ratios (RRRs) were generated from multivariate multinomial regressions. The resilient trajectory was most common (77.0%). The chronic trajectory (8.5%) was associated with loneliness, RRR = 2.59, 95% CI [1.30, 5.16], and physical health diagnoses, RRR = 2.31, 95% CI [1.32, 4.02]. The delayed-onset trajectory (9.1%) was associated with multiple recent stressful events, RRR = 2.51, 95% CI [1.37, 4.59]; mental health diagnoses, RRR = 2.30, 95% CI [1.25, 4.24]; loneliness, RRR = 2.05, 95% CI [1.09, 3.88]; and male gender, RRR = 2.01, 95% CI [1.18, 3.44]. Socioeconomic advantage protected against chronic, RRR = 0.68, 95% CI [0.53, 0.86], and delayed-onset trajectory membership, RRR = 0.68, 95% CI [0.50, 0.94]; social support protected against chronic trajectory membership, RRR = 0.67, 95% CI [0.49, 0.92]. PM2.5 exposure did not determine trajectory. These findings enhance understanding of longer-term posttraumatic responses to large-scale smoke events and can inform mental health initiatives within at-risk communities.

A Prospective, Multicentre Randomised Controlled Trial Comparing Catheter Ablation Versus Antiarrhythmic Drugs in Patients With Structural Heart Disease Related Ventricular Tachycardia: The CAAD-VT Trial Protocol.

IMPORTANCE: Randomised trials have shown that catheter ablation (CA) is superior to medical therapy for ventricular tachycardia (VT) largely in patients with ischaemic heart disease. Whether this translates to patients with all forms and stages of structural heart disease (SHD-e.g., non-ischaemic heart disease) is unclear. This trial will help clarify whether catheter ablation offers superior outcomes compared to medical therapy for VT in all patients with SHD. OBJECTIVE: To determine in patients with SHD and spontaneous or inducible VT, if catheter ablation is more efficacious than medical therapy in control of VT during follow-up. DESIGN: Randomised controlled trial including 162 patients, with an allocation ratio of 1:1, stratified by left ventricular ejection fraction (LVEF) and geographical region of site, with a median follow-up of 18-months and a minimum follow-up of 1 year. SETTING: Multicentre study performed in centres across Australia. PARTICIPANTS: Structural heart disease patients with sustained VT or inducible VT (n=162). INTERVENTION: Early treatment, within 30 days of randomisation, with catheter ablation (intervention) or initial treatment with antiarrhythmic drugs only (control). MAIN OUTCOMES, MEASURES, AND RESULTS: Primary endpoint will be a composite of recurrent VT, VT storm (≥3 VT episodes in 24 hrs or incessant VT), or death. Secondary outcomes will include each of the individual primary endpoints, VT burden (number of VT episodes in the 6 months preceding intervention compared to the 6 months after intervention), cardiovascular hospitalisation, mortality (including all-cause mortality, cardiac death, and non-cardiac death) and LVEF (assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months post intervention). CONCLUSIONS AND RELEVANCE: The Catheter Ablation versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT) trial will help determine whether catheter ablation is superior to antiarrhythmic drug therapy alone, in patients with SHD-related VT. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry (ANZCTR) TRIAL REGISTRATION ID: ACTRN12620000045910 TRIAL REGISTRATION URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377617&isReview=true.

The Montreal cognitive assessment as a cognitive screening tool in sickle cell disease: Associations with clinically significant cognitive domains.

Adults with sickle cell disease (SCD) are at risk for cognitive impairment, which causes significant morbidity. Guidelines support routine cognitive screening, but no screening test is validated in this population. We explored the Montreal Cognitive Assessment (MoCA) as a possible screening test in SCD. We administered the MoCA; a literacy test, the Wide Range Achievement Test, fourth edition (WRAT-4); and a health literacy test, the Shortened Test of Functional Health Literacy in Adults (S-TOFHLA) to adults with SCD and gathered clinical variables through chart review. Spearman's rho, Mann-Whitney, and Kruskal-Wallis tests and quantile regression models were used. Among our sample of 49 adults with SCD, the median MoCA score was 25.0 [interquartile range (IQR) 22.0-28.0]. Higher educational attainment was associated with MoCA scores (p = 0.001). In multivariable models, MoCA scores were associated with S-TOFHLA (p = 0.001) and WRAT-4 Reading (p = 0.002) scores, and overt stroke (p = 0.03) at the median. This pilot study adds to the limited literature of cognitive screening tests in adults with SCD and demonstrates a relationship between MoCA scores and measures of literacy and health literacy. The MoCA is a promising option for briefly screening for cognitive impairment in adults with SCD, though further study is needed to confirm its validity.

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma.

BACKGROUND: Preclinical studies suggest that bb2121, a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA), has potential for the treatment of multiple myeloma. METHODS: In this phase 1 study involving patients with relapsed or refractory multiple myeloma, we administered bb2121 as a single infusion at doses of 50×106, 150×106, 450×106, or 800×106 CAR-positive (CAR+) T cells in the dose-escalation phase and 150×106 to 450×106 CAR+ T cells in the expansion phase. Patients had received at least three previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or were refractory to both drug classes. The primary end point was safety. RESULTS: Results for the first 33 consecutive patients who received a bb2121 infusion are reported. The data-cutoff date was 6.2 months after the last infusion date. Hematologic toxic effects were the most common events of grade 3 or higher, including neutropenia (in 85% of the patients), leukopenia (in 58%), anemia (in 45%), and thrombocytopenia (in 45%). A total of 25 patients (76%) had cytokine release syndrome, which was of grade 1 or 2 in 23 patients (70%) and grade 3 in 2 patients (6%). Neurologic toxic effects occurred in 14 patients (42%) and were of grade 1 or 2 in 13 patients (39%). One patient (3%) had a reversible grade 4 neurologic toxic effect. The objective response rate was 85%, including 15 patients (45%) with complete responses. Six of the 15 patients who had a complete response have had a relapse. The median progression-free survival was 11.8 months (95% confidence interval, 6.2 to 17.8). All 16 patients who had a response (partial response or better) and who could be evaluated for minimal residual disease (MRD) had MRD-negative status (≤10-4 nucleated cells). CAR T-cell expansion was associated with responses, and CAR T cells persisted up to 1 year after the infusion. CONCLUSIONS: We report the initial toxicity profile of a BCMA-directed cellular immunotherapy for patients with relapsed or refractory multiple myeloma. Antitumor activity was documented. (Funded by Bluebird Bio and Celgene; CRB-401 ClinicalTrials.gov number, NCT02658929.).

Influence of respiration and tissue contact on ventricular substrate identification during high density mapping: Results from an ovine infarct model.

INTRODUCTION: Multielectrode mapping (MEM) and automated point collection are important enhancements to substrate mapping in ventricular tachycardia ablation. The effects of tissue contact and respiration on electrogram voltage with differing depolarization wavefronts with MEM catheters are unclear. METHODS: Bipolar and unipolar voltages were collected from control (n = 5) and infarcted (n = 7) animals with a multispline MEM catheter. Electro-anatomic maps were created in sinus rhythm, and right and left ventricular pacing. Analysis was performed across three collections: standard settings (SS), respiratory-phase gating (RG), and electrode-tissue proximity (TP). Comparison was made to scar detected by cardiac MRI (cMRI). RESULTS: Compared to SS and RG acquisition, median bipolar and unipolar voltages were higher using TP, regardless of the depolarization wavefront. In infarct animals, bipolar voltages were 30.7%-50.5% higher for bipolar and 8.7%-13.8% higher on unipolar voltages with TP, compared to SS. The effect of RG on bipolar and unipolar voltages was minimal. Percentage of local abnormal ventricular activities was not impacted by acquisition settings or wavefront direction in infarct animals. Compared with cMRI defined scar, all three acquisition settings overestimated scar area using standard voltage-based cutoffs. RG improved the low voltage area concordance with MRI by 1.6%-5.1% whereas TP improved by 5.9%-8.4%. CONCLUSIONS: High density voltage mapping with a MEM catheter is influenced by point collection settings. Tissue contact filters reduced low voltage areas and improved agreement with cMRI fibrosis in infarcted ovine hearts. These findings have critical implications for optimizing filter settings for high density substrate mapping in the left ventricle.

Clinical, electroanatomic and electrophysiologic characterization and outcomes of catheter ablation for ventricular tachycardia following valvular intervention.

INTRODUCTION: Ventricular tachycardia (VT) can occur following valvular interventions. There are limited data describing substrate and ablation approaches in such patients. We sought to describe the clinical, electrophysiologic, electroanatomic features and catheter ablation outcomes of patients with VT following aortic and/or mitral valve intervention. METHODS: Over 12-years, consecutive patients with aortic valve replacement (AVR) and/or mitral valve replacement (MVR) or repair, undergoing VT ablation, were identified from two centers. Clinical and procedural parameters and outcomes are described. RESULTS: Twenty-three patients (age 66 ± 14years, 78% male, left ventricular ejection fraction 37 ± 16%), with prior AVR (mechanical n = 6, bioprosthetic n = 2, transcatheter n = 1), MVR (mechanical n = 5, bioprosthetic n = 1), mitral valve repair (n = 6) and both mechanical AVR and MVR (n = 2), underwent VT ablation. Sixteen had concurrent ischemic cardiomyopathy, 10 with prior bypass surgery. Left ventricular access was obtained in 21/23 (91%) patients (transseptal n = 14, retrograde aortic n = 5, transapical n = 2), with perivalvular scar identified in 17/21 (81%). Re-entrant VT isthmi involved the perivalvular regions in 12/23 (52%) patients, and regions remote from the valve in the remainder; 9% had nonscar-related VT. Intramural substrate was ablated from adjacent chambers in 5/23 (22%) patients and with half-normal saline irrigation in 8/23 (35%) patients. There were no instances of catheter entrapment. Following final ablation, VA-free survival was 78% at 13-months. CONCLUSION: Only half of VT circuits following valvular interventions involve the valve regions themselves, while the remainder involves unrelated regions. Catheter ablation is safe and efficacious at treating VT following valvular intervention, but novel strategies may be required.

Confirmation and variability of the Allee effect inDictyostelium discoideumcell populations, possible role of chemical signaling within cell clusters.

In studies of the unicellular eukaryoteDictyostelium discoideum, many have anecdotally observed that cell dilution below a certain 'threshold density' causes cells to undergo a period of slow growth (lag). However, little is documented about the slow growth phase and the reason for different growth dynamics below and above this threshold density. In this paper, we extend and correct our earlier work to report an extensive set of experiments, including the use of new cell counting technology, that set this slow-to-fast growth transition on a much firmer biological basis. We show that dilution below a certain density (around 104cells ml-1) causes cells to grow slower on average and exhibit a large degree of variability: sometimes a sample does not lag at all, while sometimes it takes many moderate density cell cycle times to recover back to fast growth. We perform conditioned media experiments to demonstrate that a chemical signal mediates this endogenous phenomenon. Finally, we argue that while simple models involving fluid transport of signal molecules or cluster-based signaling explain typical behavior, they do not capture the high degree of variability between samples but nevertheless favor an intra-cluster mechanism.

Catheter Ablation for Ventricular Tachycardia in Ischaemic Versus Non-Ischaemic Cardiomyopathy: A Systematic Review and Meta-Analysis.

BACKGROUND: There are differences in substrate and ablation approaches for ventricular tachycardia (VT) in ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM). OBJECTIVE: To perform a systematic review and meta-analysis comparing clinical and procedural characteristics/outcomes of VT ablation in ICM versus NICM. METHODS: Electronic databases were searched for comparative studies reporting outcomes of VT ablation in patients with ICM and NICM. Primary outcomes were acute procedural success, VT recurrence and long-term mortality. Meta-analyses were performed using random-effects modelling. RESULTS: Thirty-one (31) studies (7,473 patients; 4,418 ICM and 3,055 NICM) were included. Patients with ICM were significantly older (67.0 vs 55.3 yrs), more commonly male (89% vs 79%), had lower left ventricular ejection fraction (29% vs 38%) were less likely to undergo epicardial access (11% vs 36%) and were more likely to require haemodynamic support during ablation (relative risk [RR] 1.30; 95% CI 1.01-1.69). Acute procedural success (i.e. non-inducibility of VT) was higher in the ICM cohort (RR 1.10, 95% CI 1.05-1.15). Recurrence of VT at follow-up was significantly lower in the ICM cohort (RR 0.77; 95% CI 0.70-0.84). Peri-procedural mortality, incidence of procedural complications and long-term mortality were not significantly different between the cohorts. CONCLUSIONS: NICM and ICM patients undergoing VT ablation are fundamentally different in their clinical characteristics, ablation approaches, acute procedural outcomes and likelihood of VA recurrence. VT ablation in NICM has a lower likelihood of procedural success with increased risk of VA recurrence, consistent with known challenging arrhythmia substrate.

The Role of Contemporary Wearable and Handheld Devices in the Diagnosis and Management of Cardiac Arrhythmias.

Cardiac arrhythmias are associated with significant morbidity, mortality and economic burden on the health care system. Detection and surveillance of cardiac arrhythmias using medical grade non-invasive methods (electrocardiogram, Holter monitoring) is the accepted standard of care. Whilst their accuracy is excellent, significant limitations remain in terms of accessibility, ease of use, cost, and a suboptimal diagnostic yield (up to ∼50%) which is critically dependent on the duration of monitoring. Contemporary wearable and handheld devices that utilise photoplethysmography and the electrocardiogram present a novel opportunity for remote screening and diagnosis of arrhythmias. They have significant advantages in terms of accessibility and availability with the potential of enhancing the diagnostic yield of episodic arrhythmias. However, there is limited data on the accuracy and diagnostic utility of these devices and their role in therapeutic decision making in clinical practice remains unclear. Evidence is mounting that they may be useful in screening for atrial fibrillation, and anecdotally, for the diagnosis of other brady and tachyarrhythmias. Recently, there has been an explosion of patient uptake of such devices for self-monitoring of arrhythmias. Frequently, the clinician is presented such information for review and comment, which may influence clinical decisions about treatment. Further studies are needed before incorporation of such technologies in routine clinical practice, given the lack of systematic data on their accuracy and utility. Moreover, challenges with regulation of quality standards and privacy remain. This state-of-the-art review summarises the role of novel ambulatory, commercially available, heart rhythm monitors in the diagnosis and management of cardiac arrhythmias and their expanding role in the diagnostic and therapeutic paradigm in cardiology.

Electrophysiologic and electroanatomic characterization of ventricular arrhythmias in non-compaction cardiomyopathy: A systematic review.

BACKGROUND: Non-compaction cardiomyopathy (NCCM) is a form of structural heart disease prone to ventricular arrhythmias (VAs) and sudden cardiac death. Non-compacted myocardium may harbor VA substrate, though some reports suggest otherwise. OBJECTIVE: This study aimed to characterize the electrophysiologic (EP) features of VA in NCCM. METHODS: We performed a systematic review of case reports, case series, and observational studies. RESULTS: One hundred and thirty-five cases of NCCM from studies between 2000 and 2020 were included. Mean age was 34 ± 20 years, mean left ventricular (LV) ejection fraction was 42 ± 15% with two cases having late gadolinium enhancement on magnetic resonance imaging. The LV apex was the most common non-compacted segment (86%); 10% involved the right ventricle (RV). Antiarrhythmic failure was documented in 16 cases, of which 50% failed more than one agent. Only 23% of monomorphic VAs localized to regions of non-compaction on electrocardiogram. Most frequently, VAs localized to the RV outflow tract (n = 21), posterior fascicle (n = 19), and anterolateral LV apex (n = 9). All cases with apical exits arose from the non-compacted myocardium. On EPS, 83% of sustained VTs were due to re-entry, 17% due to focal mechanism. Catheter ablation was performed in 39 cases, with 7 requiring more than 1 procedure. Acute VA non-inducibility was achieved in 82% and VA-free survival was reported in 85% over a mean follow-up of 24 months. CONCLUSION: The majority of VAs in NCCM arise remotely from non-compacted myocardium, and non-re-entrant mechanism seen in ~1/5th of sustained VTs. Catheter ablation outcomes appear favorable. Further study is needed to understand the pathophysiology of VA in NCCM.

Prevalence of mental illness among parents of children receiving treatment within child and adolescent mental health services (CAMHS): a scoping review.

People affected by mental illness often come from families with patterns of mental illness that span across generations. Hence, child and adolescent mental health services (CAMHS) likely provide treatment to many children with parents who also experience mental illness. The aim of this scoping review was to: (1) identify the prevalence of mental illness among parents of children in CAMHS; (2) identify and appraise the methodologies that have been implemented to assess the prevalence of parental mental illness in CAMHS; (3) identify additional circumstances associated with families where both parent and child experience mental illness; and (4) present recommendations that have been made for CAMHS practice based on these findings. English language, peer-reviewed studies (2010-2018) that had investigated the mental health of parents in CAMHS were included in the review. Literature searching yielded 18 studies which were found to have utilised diverse methodologies to assess parental mental health. Overall, reported prevalence of parental mental illness ranged from 16 to 79%; however, a single study that was deemed to be comprehensive reported prevalence rates of 36% for mothers and 33% for fathers. Across studies, parent and child mental illness was found to be associated with additional adversities impacting family functioning and wellbeing. For children who receive treatment for mental illness, having a parent who also experiences mental illness is a frequent family circumstance that has implications for their prospects for recovery. Accordingly, the mental health of parents should be an important consideration within the mental health care CAMHS provide to children.

Ventricular Tachycardia in a Patient With Dilated Cardiomyopathy Caused by a Novel Mutation of Lamin A/C Gene: Insights From Features on Electroanatomic Mapping, Catheter Ablation and Tissue Pathology.

Lamin A/C (LMNA) cardiomyopathy forms an important and increasingly recognised group within the broad spectrum of non-ischaemic cardiomyopathies. LMNA cardiomyopathy typically presents with atrioventricular block followed by recurrent ventricular arrhythmias with a high tendency to progression to end stage heart failure. We present a case of recurrent ventricular tachycardia in a patient with dilated cardiomyopathy caused by a novel mutation of LMNA gene. Through electroanatomic mapping, catheter ablation and tissue pathology we provide detailed insights into this highly pathogenic inherited cardiomyopathy.