Persistence of left atrial thrombus in patients with hypertrophic cardiomyopathy and atrial fibrillation.

BACKGROUND: We recently demonstrated that patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM) have an increased risk of left atrial (LA) thrombus. In this study, we aimed to evaluate thrombus management, thrombus persistence, and thromboembolic events for HCM and non-HCM patients with AF and LA thrombus. METHODS: From a cohort of 2,155 AF patients undergoing transesophageal echocardiography (TEE) for any indication, this study included 122 patients with LA thrombus (64 HCM patients and 58 non-HCM controls). RESULTS: There was no difference in mean CHA2DS2-VASc scores between HCM and control patients (3.9 ± 2.2 vs 3.8 ± 2.0, p = 0.88). Ten (16%) and 4 (7%) patients in the HCM and control groups, respectively, were in sinus rhythm at the time of TEE identifying the LA thrombus (p = 0.13). In all patients, the anticoagulation strategy was modified after the LA thrombus diagnosis. A total of 36 (56%) HCM patients and 34 (59%) control patients had follow-up TEE at median 90 and 62 days, respectively, after index TEE. The HCM group had significantly higher 90-day rates of persistent LA thrombus compared to the control group (88% vs 29%; p < 0.001). In adjusted models, HCM was independently associated with LA thrombus persistence. Among patients with LA thrombus, the 5-year cumulative incidence of thromboembolic events was 11% and 2% in HCM and control groups, respectively (p = 0.22). CONCLUSIONS: Among patients with AF with LA thrombus identified by TEE, those with HCM appear to have a higher risk of LA thrombus persistence than non-HCM patients despite anticoagulation.

Personalized Care in Long QT Syndrome: Better Management, More Sports, and Fewer Devices.

Long QT Syndrome (LQTS) is a potentially life-threatening yet highly treatable inherited cardiac channelopathy. When evaluating these patients, it is important to consider patient-specific as well as genotype-specific factors in order to adequately encompass the many nuances to care that exist in its management. The tendency to follow a "one-size-fits-all" approach needs to be replaced by treatment strategies that embrace the unique considerations of the individual patient in the context of their genotype. Herein, the authors aim to review the spectrum of LQTS, including the considerations when tailoring a personalized, genotype-tailored treatment program for a patient's LQTS.

Fatal Cardiac Arrhythmias During Electronic Gaming in Patients With Genetically Mediated Heart Diseases.

BACKGROUND: Recently, electronic gaming has been reported as a precipitant of life-threatening cardiac arrhythmias in susceptible individuals. However, the prevalence of cardiac events in genetic heart diseases (GHDs) in the setting of electronic gaming has not been established. OBJECTIVES: In this study, we sought to define the prevalence of cardiac events occurring in the setting of electronic gaming in GHDs. METHODS: Retrospective review of all patients evaluated and treated at Mayo Clinic's genetic heart rhythm clinic from July 2000 to November 2022 was performed to identify patients with a history of playing electronic games at the time of their cardiac event. Cardiac event was used to define events occurring before diagnosis, and breakthrough cardiac event (BCE) was used for events occurring after diagnosis. RESULTS: Of the 3,370 patients with a GHD (mean age at first evaluation 27 ± 19 years, 55% female), 1,079 (32%) had a cardiac event before diagnosis, with 5 patients (0.5%) having an electronic gaming-associated event (3 catecholaminergic polymorphic ventricular tachycardia, 1 long QT syndrome, and 1 premature ventricular contraction-triggered ventricular fibrillation). After diagnosis and treatment, 431 patients (13%) experienced ≥1 BCE during follow-up, of which 1 electronic gaming-associated BCE (0.2%) occurred in a patient with catecholamine-sensitive right outflow tract ventricular tachycardia. CONCLUSIONS: Although anecdotal cases of electronic gaming-associated life-threatening arrhythmias have been reported, in this largest single-center study to date, we show that these are extremely rare occurrences. While electronic gaming can have adverse health consequences, the threat of electronic gaming-triggered sudden death should not be used to try to curb time spent gaming.

Cardiac fludeoxyglucose-18 positron emission tomography in genotype-positive arrhythmogenic cardiomyopathy.

BACKGROUND: Myocardial inflammation contributes to the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a clinically and genetically heterogenous disorder. Due to phenotypic overlap, some patients with genetic ACM may be evaluated for an underlying inflammatory cardiomyopathy. However, the cardiac fludeoxyglucose (FDG) positron emission tomography (PET) findings in ACM patients have not been elucidated. METHODS: All genotype-positive patients in the Mayo Clinic ACM registry (n = 323) who received a cardiac FDG PET were included in this study. Pertinent data were extracted from the medical record. RESULTS: Collectively, 12/323 (4%; 67% female) genotype-positive ACM patients received a cardiac PET FDG scan as part of their clinical evaluation (median age at scan 49 ± 13 years). Amongst these patients, pathogenic/likely pathogenic variants were detected in LMNA (n = 7), DSP (n = 3), FLNC (n = 1) and PLN (n = 1). Of note, 6/12 (50%) had abnormal myocardial FDG uptake, including diffuse (entire myocardium) uptake in 2/6 (33%), focal (1-2 segments) uptake in 2/6 (33%) and patchy (3+ segments) in 2/6 (33%). Median myocardial standardized uptake value ratio was 2.1. Interestingly, LMNA-positive patients accounted for 3 out of 6 (50%) positive studies (diffuse uptake in 2 and focal uptake in 1). CONCLUSION: Abnormal myocardial FDG uptake is common in genetic ACM patients undergoing cardiac FDG PET. This study further supports the role of myocardial inflammation in ACM. Further investigation is needed to determine role of FDG PET in diagnosis and management of ACM and investigate the role of inflammation in ACM.

Defining idiopathic ventricular fibrillation: A systematic review of diagnostic testing yield in apparently unexplained cardiac arrest.

BACKGROUND: Idiopathic ventricular fibrillation (IVF) is diagnosed in patients with apparently unexplained cardiac arrest (UCA) after varying degrees of evaluation. This is largely due to the lack of a standardized approach to UCA. OBJECTIVE: We sought to develop an evidence-based diagnostic algorithm for IVF by systematically examining the yield of diagnostic testing in UCA probands. METHODS: Studies reporting the yield of diagnostic testing in UCA were identified in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and conference abstracts. Their methodological quality was assessed by the National Institutes of Health quality assessment tool. Meta-analyses were performed using the random effects model. RESULTS: A total of 21 studies were included. The pooled comprehensive diagnostic testing yield was 43% (95% confidence interval 39%-48%). A lower yield was seen when only definite diagnoses based on the prespecified criteria were used (32% vs 47%; P = .15). Epinephrine challenge, Holter monitoring, and family screening were associated with low yield (<5%), whereas cardiac magnetic resonance imaging, exercise treadmill test, and sodium-channel blocker challenge were associated with high yield (≥5%). Coronary spasm provocation, electrophysiology study, and systematic genetic testing were reported to be abnormal in a high proportion of UCA probands (>10%). CONCLUSION: We developed a stepwise algorithm for UCA evaluation and criteria to assess the strength of IVF diagnosis on the basis of the diagnostic yield of UCA testing.

Prospective Assessment of an Automated Intraprocedural 12-Lead ECG-Based System for Localization of Early Left Ventricular Activation.

BACKGROUND: To facilitate ablation of ventricular tachycardia (VT), an automated localization system to identify the site of origin of left ventricular activation in real time using the 12-lead ECG was developed. The objective of this study was to prospectively assess its accuracy. METHODS: The automated site of origin localization system consists of 3 steps: (1) localization of ventricular segment based on population templates, (2) population-based localization within a segment, and (3) patient-specific site localization. Localization error was assessed by the distance between the known reference site and the estimated site. RESULTS: In 19 patients undergoing 21 catheter ablation procedures of scar-related VT, site of origin localization accuracy was estimated using 552 left ventricular endocardial pacing sites pooled together and 25 VT-exit sites identified by contact mapping. For the 25 VT-exit sites, localization error of the population-based localization steps was within 10 mm. Patient-specific site localization achieved accuracy of within 3.5 mm after including up to 11 pacing (training) sites. Using 3 remotes (67.8±17.0 mm from the reference VT-exit site), and then 5 close pacing sites, resulted in localization error of 7.2±4.1 mm for the 25 identified VT-exit sites. In 2 emulated clinical procedure with 2 induced VTs, the site of origin localization system achieved accuracy within 4 mm. CONCLUSIONS: In this prospective validation study, the automated localization system achieved estimated accuracy within 10 mm and could thus provide clinical utility.

Guidance on Minimizing Risk of Drug-Induced Ventricular Arrhythmia During Treatment of COVID-19: A Statement from the Canadian Heart Rhythm Society.

The COVID-19 pandemic has led to efforts at rapid investigation and application of drugs which may improve prognosis but for which safety and efficacy are not yet established. This document attempts to provide reasonable guidance for the use of antimicrobials which have uncertain benefit but may increase risk of QT interval prolongation and ventricular proarrhythmia, notably, chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir. During the pandemic, efforts to reduce spread and minimize effects on health care resources mandate minimization of unnecessary medical procedures and testing. We recommend that the risk of drug proarrhythmia be minimized by 1) discontinuing unnecessary medications that may also increase the QT interval, 2) identifying outpatients who are likely to be at low risk and do not need further testing (no history of prolonged QT interval, unexplained syncope, or family history of premature sudden cardiac death, no medications that may prolong the QT interval, and/or a previous known normal corrected QT interval [QTc]), and 3) performing baseline testing in hospitalized patients or those who may be at higher risk. If baseline electrocardiographic testing reveals a moderately prolonged QTc, optimization of medications and electrolytes may permit therapy. If the QTc is markedly prolonged, drugs that further prolong it should be avoided, or expert consultation may permit administration with mitigating precautions. These recommendations are made while there are no known effective treatments for COVID-19 and should be revisited when further data on efficacy and safety become available.

Intentional nontherapy in long QT syndrome.

BACKGROUND: International guidelines advise universal beta-blocker therapy as either a class I (symptomatic or QTc ≥470 ms) or class II (asymptomatic and QTc <470 ms) recommendation for treatment of long QT syndrome (LQTS). OBJECTIVE: The purpose of this study was to evaluate the outcomes of a highly selected cohort of patients with LQTS managed with an observation-only (intentional nontreatment) strategy. METHODS: The cohort was derived from a comprehensive retrospective registry of patients with LQTS. Clinical phenotype and genotype data were collected via review of electronic health records. RESULTS: Among 661 patients with LQTS, 55 (8.3%) asymptomatic patients (53% female; 16 age <18 years) were managed with intentional nontherapy. Only preventative measures were advised. Mean age at diagnosis was 37.8 ± 21.2 years. Mean QTc was 448 ± 30 ms. None of the patients experienced an LQTS-triggered cardiac event over mean follow-up of 7.5 ± 4.3 years. Compared to the larger treated cohort, this intentionally untreated cohort was less symptomatic, was older at diagnosis, and had lower resting QTc values (P <.0001). CONCLUSION: After careful clinical evaluation, risk assessment, and institution of precautionary measures, an observation-only strategy may be considered in a highly selected group of LQTS patients with a clinical profile that includes asymptomatic status, older age at diagnosis, and QTc <470 ms, with excellent outcomes and better quality of life than LQTS patients treated with beta-blocker. LQTS patients with this low-risk profile should not receive a prophylactic implantable cardioverter-defibrillator.

Automated intraprocedural localization of origin of ventricular activation using patient-specific computed tomographic imaging.

BACKGROUND: To facilitate catheter ablation of ventricular tachycardia (VT), we previously developed an automated method to identify sources of left ventricular (LV) activation in real time using 12-lead electrocardiography (ECG), the accuracy of which depends on acquisition of a complete electroanatomic (EA) map. OBJECTIVE: The purpose of this study was to assess the feasibility of using a registered cardiac computed tomogram (CT) rather than an EA map to permit real-time localization and avoid errors introduced by incomplete maps. METHODS: Before LV VT ablation, 10 patients underwent CT imaging and 3-dimensional reconstruction of the cardiac surface to create a triangle mesh surface, which was registered to the EA map during the procedure and imported into custom localization software. The software uses QRS integrals from leads III, V2, and V6; derives personalized regression coefficients from pacing at ≥5 sites with known locations; and estimates the location of unknown activation sites on the 3-dimensional patient-specific LV endocardial surface. Localization accuracy was quantified for VT exit sites in millimeters by comparing the calculated against the known locations. RESULTS: The VT exit site was identified for 20 VTs using activation and entrainment mapping, supplemented by pace-mapping at the scar margin. The automated localization software achieved incremental accuracy with additional pacing sites and had a mean localization error of 6.9 ± 5.7 mm for the 20 VTs. CONCLUSION: Patient-specific CT geometry is feasible for use in real-time automated localization of ventricular activation and may avoid reliance on a complete EA map.

The Effect of Shock Burden on Heart Failure and Mortality.

BACKGROUND: Prior studies have demonstrated an association between appropriate implantable cardioverter defibrillator (ICD) shocks and mortality in clinical trials. The effect of shock burden on heart failure and mortality has not been previously studied in a large population-based cohort. METHODS: The cohort was derived using a comprehensive prospective ICD registry in the province of Nova Scotia with a mean follow-up of 4 ± 2.3 years. With the use of time-varying analysis, the relationship among shock burden, mortality, and heart failure hospitalization was determined. RESULTS: A total of 776 patients (mean age of 64.8 years) were included in the study, of whom 37% received appropriate therapy during follow-up. A single ICD shock did not confer an increased mortality risk compared with no therapy (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.84-1.79; P = 0.3), but mortality risk was significantly increased with ≥ 2 shocks (HR, 3.23; 95% CI, 2.04-5.09; P < 0.0001). There was a significant increase in heart failure hospitalization associated with receiving 1 ICD shock (HR, 2.05; 95% CI, 1.46-2.89; P < 0.0001) or more than 1 ICD shock (HR, 4.36; CI, 2.53-7.52; P < 0.0001) compared with patients receiving no ICD therapy. Patients who received antitachycardia pacing alone showed no difference in heart failure hospitalization (HR, 0.93; CI, 0.67-1.29; P = 0.7) and improved survival (HR, 0.69; CI, 0.5-0.96; P = 0.03) compared with those receiving no ICD therapy. CONCLUSION: Ventricular arrhythmia treated with appropriate ICD shocks is associated with an increased risk of heart failure hospitalization, whereas recurrent episodes of ventricular arrhythmia requiring shocks are associated with both higher mortality and higher heart failure hospitalization rates.

CONTEXTE: Des études menées antérieurement ont révélé l'existence d'un lien entre l'administration appropriée de décharges électriques au moyen d'un défibrillateur cardioverteur implantable (DCI) et la mortalité au cours des essais cliniques. L'effet de telles décharges sur l'insuffisance cardiaque et la mortalité n'avait encore jamais été étudié au sein d'une cohorte d'envergure représentative de la population. MÉTHODOLOGIE: La cohorte a été établie au moyen d'un registre prospectif exhaustif des DCI implantés chez des patients de la Nouvelle-Écosse ayant fait l'objet d'un suivi moyen de 4 ± 2,3 ans. La relation entre le fardeau imposé par les décharges, la mortalité et l'hospitalisation pour insuffisance cardiaque a été déterminée au moyen d'une analyse en fonction du temps. RÉSULTATS: Au total, 776 patients (âge moyen : 64,8 ans) ont été admis dans l'étude; 37 % d'entre eux avaient reçu un traitement approprié au cours de la période de suivi. Une seule décharge délivrée par un DCI n'augmentait pas le risque de mortalité par rapport à l'absence de traitement (rapport des risques instantanés [RRI] de 1,23; intervalle de confiance [IC] à 95 %, de 0,84 à 1,79; p = 0,3), mais le risque de mortalité était significativement accru chez les patients ayant reçu ≥ 2 décharges (RRI de 3,23; IC à 95 %, de 2,04 à 5,09; p < 0,0001). Le risque d'hospitalisation pour insuffisance cardiaque s'est révélé significativement supérieur chez les sujets ayant reçu 1 décharge par DCI (RRI de 2,05; IC à 95 %, de 1,46 à 2,89; p < 0,0001) ou plus de 1 décharge par DCI (RRI de 4,36; IC à 95 %, de 2,53-7,52; p < 0,0001), comparativement à ceux n'ayant reçu aucun traitement par DCI. On n'a observé aucune différence quant à l'hospitalisation pour insuffisance cardiaque (RRI de 0,93; IC à 95 %, de 0,67 à 1,29; p = 0,7) et à l'amélioration de la survie (RRI de 0,69; IC à 95 %, de 0,5 à 0,96; p = 0,03) chez les patients qui ont reçu uniquement une stimulation antitachycardie comparativement à ceux qui n'ont reçu aucun traitement par DCI. CONCLUSION: L'arythmie ventriculaire traitée de façon appropriée au moyen de décharges électriques délivrées par un DCI est associée à un risque accru d'hospitalisation pour insuffisance cardiaque, tandis que des épisodes récurrents d'arythmie ventriculaire exigeant un traitement par décharge électrique sont associés à des taux supérieurs de mortalité et d'hospitalisation pour insuffisance cardiaque.

Clinical utility of endomyocardial biopsies in the diagnosis of arrhythmogenic right ventricular cardiomyopathy in children.

BACKGROUND: Histomorphometry of endomyocardial biopsies is one component of arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis, although there is a need for stricter diagnostic criteria for this disease in pediatrics. The clinical utility of biopsy analysis as a component of ARVC diagnosis was evaluated in pediatric patients. METHODS: Histomorphometric analysis of fibrofatty infiltrate was completed on pediatric right ventricular endomyocardial biopsy samples. Myocardial replacement by fat and fibrosis was quantified. ARVC diagnosis was established using the 2010 ARVC Task Force criteria, with the biopsy measures compared across various ARVC diagnoses (definite, borderline, possible, or no ARVC). Receiver-operating characteristic (ROC) curve analysis was also completed using biopsy measures. RESULTS: The greatest proportion of fat, fibrosis, and myocardial replacement was in the definite ARVC cohort, and was significantly larger than for the other diagnosis cohorts. ROC curve analysis (with the biopsy analysis removed from the diagnostic classification) produced cutoff values of 15 and 25% myocardial replacement, which is lower than current adult diagnosis criteria. CONCLUSION: We propose modifications in pediatric major and minor biopsy diagnosis criteria to allow for improved sensitivity. This study suggests that biopsy analysis in children is most significant for subjects with a more severe disease presentation.

Treatment of persistent ventricular tachycardia: Drugs or ablation?

Implantable cardioverter defibrillators (ICDs) reduce the mortality risk associated with recurrent ventricular tachycardia (VT) and can frequently terminate VT episodes painlessly, but do not prevent recurrent episodes. For patients with symptomatic recurrences, frequent asymptomatic recurrences, ICD shocks, or VT storm, most clinicians recommend strategies to suppress VT. The proarrhythmic mortality risk of antiarrhythmic drugs (AADs) may be mitigated by the presence of an ICD, but these medications are limited by high recurrence rates, and unfavorable side effect profiles. Catheter ablation is an alternative or adjunctive option, but is also limited by incomplete efficacy and procedural risk.

Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers.

BACKGROUND: Mutations in LMNA are variably expressed and may cause cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and ventricular arrhythmias (VA). Detailed natural history studies of LMNA-associated arrhythmic and nonarrhythmic outcomes are limited, and the prognostic significance of the index cardiac phenotype remains uncertain. OBJECTIVES: This study sought to describe the arrhythmic and nonarrhythmic outcomes of LMNA mutation carriers and to assess the prognostic significance of the index cardiac phenotype. METHODS: The incidence of AVB, AA, sustained VA, left ventricular systolic dysfunction (LVD) (= left ventricular ejection fraction ≤50%), and end-stage heart failure (HF) was retrospectively determined in 122 consecutive LMNA mutation carriers followed at 5 referral centers for a median of 7 years from first clinical contact. Predictors of VA and end-stage HF or death were determined. RESULTS: The prevalence of clinical manifestations increased broadly from index evaluation to median follow-up: AVB, 46% to 57%; AA, 39% to 63%; VA, 16% to 34%; and LVD, 44% to 57%. Implantable cardioverter-defibrillators were placed in 59% of patients for new LVD or AVB. End-stage HF developed in 19% of patients, and 13% died. In patients without LVD at presentation, 24% developed new LVD, and 7% developed end-stage HF. Male sex (p = 0.01), nonmissense mutations (p = 0.03), and LVD at index evaluation (p = 0.004) were associated with development of VA, whereas LVD was associated with end-stage HF or death (p < 0.001). Mode of presentation (with isolated or combination of clinical features) did not predict sustained VA or end-stage HF or death. CONCLUSIONS: LMNA-related heart disease was associated with a high incidence of phenotypic progression and adverse arrhythmic and nonarrhythmic events over long-term follow-up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis and subsequent follow-up, including anticipatory planning for therapies to prevent sudden death and manage HF, is warranted.

Multicenter Experience With Catheter Ablation for Ventricular Tachycardia in Lamin A/C Cardiomyopathy.

BACKGROUND: Lamin A/C (LMNA) cardiomyopathy is a genetic disease with a proclivity for ventricular arrhythmias. We describe the multicenter experience with percutaneous catheter ablation of sustained monomorphic ventricular tachycardia (VT) in LMNA cardiomyopathy. METHODS AND RESULTS: Twenty-five consecutive LMNA mutation patients from 4 centers were included (mean age, 55±9 years; ejection fraction, 34±12%; VT storm in 36%). Complete atrioventricular block was present in 11 patients; 3 patients were on mechanical circulatory support for severe heart failure. A median of 3 VTs were inducible per patient; in 82%, mapping was consistent with origin from scar in the basal left ventricle, particularly the septum, but also basal inferior wall and subaortic mitral continuity. After multiple procedures (median 2/patient; transcoronary alcohol in 6 and surgical cryoablation in 2 patients), acute success (noninducibility of any VT) was achieved in only 25% of patients. Partial success (inducibility of a nonclinical VT only: 50%) and failure (persistent inducibility of clinical VT: 12.5%) was attributed to intramural septal substrate in 13 of 18 patients (72%). Complications occurred in 25% of patients. After a median follow-up of 7 months after the last procedure, 91% experienced ≥1 VT recurrence, 44% received or were awaiting mechanical circulatory support or transplant for end-stage heart failure, and 26% died. CONCLUSIONS: Catheter ablation of VT associated with LMNA cardiomyopathy is associated with poor outcomes including high rate of arrhythmia recurrence, progression to end-stage heart failure, and high mortality. Basal septal scar and intramural VT origin makes VT ablation challenging in this population.

Catheter ablation for ventricular tachycardia in structural heart disease.

The management of ventricular tachyarrhythmias has changed significantly over the past several decades. The advent of readily available implantable cardioverter defibrillators (ICDs) has had the greatest effect, with important mortality effects in patients with ventricular tachycardia and structural heart disease. ICDs have been shown to reduce sudden death in patients with ischemic and nonischemic cardiomyopathies; evidence of adverse consequences of ICD shocks, however, is mounting. In addition to the negative effects on patient-reported quality of life, anxiety, and depression, frequent ventricular arrhythmias and ICD shocks have also been associated with increased mortality. It is therefore important to identify and implement effective ventricular tachycardia-suppressive strategies. Antiarrhythmic drugs represent one such method, but are challenged by unfavourable side effect profiles and proarrhythmic risk. Catheter ablation of ventricular tachycardia is now a well-accepted intervention, which has been demonstrated to reduce recurrent arrhythmias. Questions persist regarding the optimal role for ablation compared with drug therapy.