2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.

2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.

Dronedarone for the Treatment of Atrial Arrhythmias in Adults With Congenital Heart Disease.

BACKGROUND: Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart disease, but data are limited about its use in adults with congenital heart disease of moderate to great complexity. METHODS: A single-center, retrospective chart review of 21 adults with congenital heart disease of moderate to great complexity who were treated with dronedarone for atrial tachyarrhythmias was performed. RESULTS: The median (IQR) age at dronedarone initiation was 35 (27.5-39) years. Eleven patients (52%) were male. Ten patients (48%) had New York Heart Association class I disease, 10 (48%) had class II disease, and 1 (5%) had class III disease. Ejection fraction at initiation was greater than 55% in 11 patients (52%), 35% to 55% in 9 patients (43%), and less than 35% in 1 patient (5%). Prior treatments included ß-blockers (71%), sotalol (38%), amiodarone (24%), digoxin (24%), and catheter ablation (38%). Rhythm control was complete in 5 patients (24%), partial in 6 (29%), and inadequate in 10 (48%). Two patients (10%) experienced adverse events, including nausea in 1 (5%) and cardiac arrest in 1 (5%), which occurred 48 months after initiation of treatment. There were no deaths during the follow-up period. The median (IQR) follow-up time for patients with complete or partial rhythm control was 20 (1-54) months. CONCLUSION: Dronedarone can be effective for adult patients with congenital heart disease and atrial arrhythmias for whom more established therapies have failed, and with close monitoring it can be safely tolerated.

Effects of aging on attachment of Candida albicans to conventional heat-polymerized, CAD-CAM milled, and CAD-CAM 3D-printed acrylic resin bases.

PURPOSE: The aim of this study was to assess Candida albicans attachment on conventionally fabricated (polymethylmethacrylate, PMMA), CAD-CAM milled, and 3D-printed acrylic resin bases pre- and post-simulated thermal aging, along with examining material surface changes after aging. MATERIALS AND METHODS: Forty-six samples (10 mm × 10 mm × 2 mm) for each of four material groups (conventional heat-polymerized PMMA, CAD-CAM milled acrylic resin base, CAD-CAM 3D-printed methacrylate resin base, CAD-CAM 3D-printed urethane methacrylate resin base) were subjected to 0, 1, or 2 years of simulated thermal aging. Microscopic images were taken before and after aging, and C. albicans attachment was quantified using cell proliferation assay (XTT). Statistical analysis employed analysis of variance (α = 0.05). RESULTS: Two-way factorial analysis showed no significant differences based on acrylic resin type or thermal aging (p = 0.344 and p = 0.091 respectively). However, C. albicans attachment significantly differed between 0- and 2-year thermally aged groups (p = 0.004), mainly due to elevated initial attachments on CAD-CAM milled acrylic resin base and CAD-CAM 3D-printed urethane methacrylate resin base. CONCLUSIONS: Regardless of the fabrication technique and material combination, no significant differences were found in C. albicans adhesion pre- or post- thermal aging. Milled and 3D-printed bases compared favorably with heat- polymerized PMMA in their affinity for C. albicans attachment and surface characteristics after aging. These findings indicate that the risk of patients developing denture stomatitis might not be linked to the type of acrylic resin or fabrication method used.

The Many Faces of Arrhythmogenic Cardiomyopathy: An Overview.

Arrhythmogenic cardiomyopathy (AC) is a disease that involves electromechanical uncoupling of cardiomyocytes. This leads to characteristic histologic changes that ultimately lead to the arrhythmogenic clinical features of the disease. Initially thought to affect the right ventricle predominantly, more recent data show that it can affect both the ventricles or the left ventricle alone. Throughout the recent era, diagnostic modalities and criteria for AC have continued to evolve and our understanding of its clinical features in different age groups as well as the genotype to the phenotype correlations have improved. In this review, we set out to detail the epidemiology, etiologies, presentations, evaluation, and management of AC across the age continuum.

Decreased Heart Rate Variability in Children with Acute Decompensated Heart Failure is Associated with Poor Outcomes.

Heart rate variability (HRV) is a noninvasive indicator of the health of neurocardiac interactions of the autonomic nervous system. In adults, decreased HRV correlates with increased cardiovascular mortality. However, the relationship between HRV and outcomes in children with acute decompensated heart failure (ADHF) has not been described. Patients < 21 years old hospitalized with ADHF from 2013 to 2019 were included (N = 79). Primary outcome was defined as death, heart transplant, or mechanical circulatory support (MCS). The median standard deviation of the R-to-R interval in 5-min intervals (SDNN) was calculated from telemetry data obtained across the first 24 h of admission. Patients who met the primary outcome had significantly lower median SDNN (13.8 [7.8, 29.1]) compared to those who did not (24.6 [15.3, 84.4]; p = 0.004). A median SDNN of 20 ms resulted in a sensitivity of 68% and specificity of 69%. Median SDNN < 20 ms represented decreased freedom from primary outcome (p = 0.043) and a hazard ratio of 2.2 in multivariate analysis (p = 0.016). Pediatric patients with ADHF who died, underwent heart transplant, or required MCS had significantly decreased HRV at presentation compared to those that did not. This supports HRV as a noninvasive tool to improve prognostication in children in ADHF.

PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study.

BACKGROUND: 1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor PRDM16. Early studies suggest that deletion of PRDM16 may underlie cardiomyopathy in patients with 1p36 deletion; however, the prognostic impact of PRDM16 loss is unknown. METHODS: This retrospective cohort included subjects with 1p36 deletion syndrome from 4 hospitals. Prevalence of cardiomyopathy and freedom from death, cardiac transplantation, or ventricular assist device were analyzed. A systematic review cohort was derived for further analysis. A cardiac-specific Prdm16 knockout mouse (Prdm16 conditional knockout) was generated. Echocardiography was performed at 4 and 6 to 7 months. Histology staining and qPCR were performed at 7 months to assess fibrosis. RESULTS: The retrospective cohort included 71 patients. Among individuals with PRDM16 deleted, 34.5% developed cardiomyopathy versus 7.7% of individuals with PRDM16 not deleted (P=0.1). In the combined retrospective and systematic review cohort (n=134), PRDM16 deletion-associated cardiomyopathy risk was recapitulated and significant (29.1% versus 10.8%, P=0.03). PRDM16 deletion was associated with increased risk of death, cardiac transplant, or ventricular assist device (P=0.04). Among those PRDM16 deleted, 34.5% of females developed cardiomyopathy versus 16.7% of their male counterparts (P=0.2). We find sex-specific differences in the incidence and the severity of contractile dysfunction and fibrosis in female Prdm16 conditional knockout mice. Further, female Prdm16 conditional knockout mice demonstrate significantly elevated risk of mortality (P=0.0003). CONCLUSIONS: PRDM16 deletion is associated with a significantly increased risk of cardiomyopathy and cardiac mortality. Prdm16 conditional knockout mice develop cardiomyopathy in a sex-biased way. Patients with PRDM16 deletion should be assessed for cardiac disease.

Atrioventricular Nodal Ablation Is Not an Effective Treatment Strategy in Catecholaminergic Polymorphic Ventricular Tachycardia.

Catecholaminergic polymorphic ventricular tachycardia is a rare but lethal heritable arrhythmia syndrome associated with both atrial and ventricular arrhythmias. Treatment includes antiarrhythmics, sympathetic denervation, and implantable cardioverter-defibrillators. The use of atrioventricular nodal ablation as a treatment strategy to prevent ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia was not found in the literature. This report describes a teenager with a presenting rhythm of atrial and ventricular fibrillation and cardiac arrest. Her clinical arrhythmia was predominantly atrial dysrhythmias, which delayed her diagnosis of catecholaminergic polymorphic ventricular tachycardia. Before her diagnosis, she underwent atrioventricular nodal ablation in an effort to prevent ventricular arrhythmias, which was ultimately ineffective. This report highlights the importance of recognizing atrial arrhythmias in catecholaminergic polymorphic ventricular tachycardia and provides evidence that atrioventricular nodal ablation is not an effective treatment strategy for this disease.

Reduction in Junctophilin 2 Expression in Cardiac Nodal Tissue Results in Intracellular Calcium-Driven Increase in Nodal Cell Automaticity.

BACKGROUND: Spontaneously depolarizing nodal cells comprise the pacemaker of the heart. Intracellular calcium (Ca2+) plays a critical role in mediating nodal cell automaticity and understanding this so-called Ca2+ clock is critical to understanding nodal arrhythmias. We previously demonstrated a role for Jph2 (junctophilin 2) in regulating Ca2+-signaling through inhibition of RyR2 (ryanodine receptor 2) Ca2+ leak in cardiac myocytes; however, its role in pacemaker function and nodal arrhythmias remains unknown. We sought to determine whether nodal Jph2 expression silencing causes increased sinoatrial and atrioventricular nodal cell automaticity due to aberrant RyR2 Ca2+ leak. METHODS: A tamoxifen-inducible, nodal tissue-specific, knockdown mouse of Jph2 was achieved using a Cre-recombinase-triggered short RNA hairpin directed against Jph2 (Hcn4:shJph2). In vivo cardiac rhythm was monitored by surface ECG, implantable cardiac telemetry, and intracardiac electrophysiology studies. Intracellular Ca2+ imaging was performed using confocal-based line scans of isolated nodal cells loaded with fluorescent Ca2+ reporter Cal-520. Whole cell patch clamp was conducted on isolated nodal cells to determine action potential kinetics and sodium-calcium exchanger function. RESULTS: Hcn4:shJph2 mice demonstrated a 40% reduction in nodal Jph2 expression, resting sinus tachycardia, and impaired heart rate response to pharmacologic stress. In vivo intracardiac electrophysiology studies and ex vivo optical mapping demonstrated accelerated junctional rhythm originating from the atrioventricular node. Hcn4:shJph2 nodal cells demonstrated increased and irregular Ca2+ transient generation with increased Ca2+ spark frequency and Ca2+ leak from the sarcoplasmic reticulum. This was associated with increased nodal cell AP firing rate, faster diastolic repolarization rate, and reduced sodium-calcium exchanger activity during repolarized states compared to control. Phenome-wide association studies of the JPH2 locus identified an association with sinoatrial nodal disease and atrioventricular nodal block. CONCLUSIONS: Nodal-specific Jph2 knockdown causes increased nodal automaticity through increased Ca2+ leak from intracellular stores. Dysregulated intracellular Ca2+ underlies nodal arrhythmogenesis in this mouse model.

Atrial Standstill in the Pediatric Population: A Multi-Institution Collaboration.

BACKGROUND: Atrial standstill (AS) is a rare condition characterized by absence of electrical activity within the atria. Studies to date have been limited. OBJECTIVES: The authors sought to describe the clinical characteristics, genetics, and outcomes of patients with AS. METHODS: This was a retrospective multicenter study of patients <18 years at AS diagnosis, defined as absence of atrial activity documented during an electrophysiology study, device placement, or noninvasive rhythm tracings and confirmed by echocardiogram. Patients with acquired disorders were excluded. Clinical details and genetic variants were recorded and analyzed. RESULTS: Twenty patients were diagnosed at a median age of 6.6 years (IQR: 2.9-10.8 years). Arrhythmias included 16 (80%) with atrial/supraventricular arrhythmias and 8 (40%) with ventricular tachycardia, including 4 with cardiac arrests. A type 1 Brugada pattern was documented in 4. Pacemakers were implanted in 18 (90%). Although atrial leads were attempted in 15, only 4 achieved pacing at implantation. During a median follow-up of 6.9 years (IQR: 1.2-13.3 years), 7 (35%) had thromboembolic events. Of these, none had atrial pacing, 6 were not on anticoagulation, and 1 was on aspirin. Genetic testing identified SCN5A variants in 13 patients (65%). Analyses suggest SCN5A loss-of-function may be one mechanism driving AS. Ventricular arrhythmias and cardiac arrest were more commonly seen in patients with biallelic SCN5A variants. CONCLUSIONS: AS may be associated with loss-of-function SCN5A variants. Patients demonstrate atrial and ventricular arrhythmias, and may present challenges during device placement. Patients without the capacity for atrial pacing are at risk for thromboembolic events and warrant anticoagulation.

Atrial tachyarrhythmias after lung transplantation in children: A common occurrence.

BACKGROUND: Atrial arrhythmia's (AA) following lung transplant in adults are a well-described clinical finding. In pediatrics, however, there are limited data with some reports suggesting that arrhythmias are rare. METHODS: We performed a single-center retrospective review of lung transplant recipients from January 2013 to June 2020. A detailed evaluation of clinical characteristics, presence of arrhythmias, and outcomes was completed. Arrhythmias were documented based on inpatient telemetry or remote Holter monitoring. Analyses assessing risk factors for arrhythmias and associations with clinical outcomes were performed. RESULTS: Ninety-one lung transplants were performed in 90 patients. Post-operative AA occurred following 19% transplants. Ectopic atrial tachycardia was seen in 14%, atrial flutter in 2%, and a combination in 2%. The majority of these arrhythmias occurred within the first 45 days post-operatively. Antiarrhythmic treatment was required in 59%, but none required ablation or electrical cardioversion. In patients followed for a year or more, 88% had resolution of their arrhythmia. Arrhythmias were not associated with mortality. In further analysis, however, the presence of arrhythmia was associated with an increased length of ICU stay (median of 12 days (IQR 6, 23) versus 5 days (IQR 4, 9); p = .019) and overall length of hospital stay (median of 26 days (IQR 19, 36) versus 17 days (IQR 19, 36); p = .043). CONCLUSIONS: Atrial tachyarrhythmias after lung transplantation are common in the pediatric population and usually occur early. Although they frequently require medical therapy and are associated with longer stays, there is no associated increased mortality. In addition, the arrhythmias typically self-resolve.

Natural history of TANGO2 deficiency disorder: Baseline assessment of 73 patients.

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD. METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review. RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at the time of data collection was 9.0 years (interquartile range = 5.3-15.9 years, range = fetal to 31.8 years). A total of 24 different TANGO2 alleles were observed. Patients showed normal development in early infancy, with progressive delay in developmental milestones thereafter. Symptoms included ataxia, dystonia, and speech difficulties, typically starting between the ages of 1 to 3 years. A total of 46/71 (65%) patients suffered metabolic crises, and of those, 30 (65%) developed cardiac crises. Metabolic crises were significantly decreased after the initiation of B-complex or multivitamin supplementation. CONCLUSION: We provide the most comprehensive review of natural history of TDD and important observational data suggesting that B-complex or multivitamins may prevent metabolic crises.

Clinical Predictors of Recurrent Supraventricular Tachycardia in Infancy.

BACKGROUND: Data regarding recurrence risk among infants with supraventricular tachycardia (SVT) are limited. OBJECTIVES: The purpose of this study was to determine incidence and factors associated with SVT recurrence. METHODS: This was a retrospective single-center study (1984-2020) with prospective phone follow-up of infants with structurally normal hearts diagnosed at age ≤1 year with re-entrant SVT. Primary outcome was first SVT recurrence after hospital discharge. Classification and regression tree analysis was performed to determine a risk algorithm. RESULTS: Among 460 infants (62% male), 87% were diagnosed at ≤60 days of age (median 13 days; IQR: 1-31 days). During a median follow-up of 5.2 years (IQR: 1.8-11.2 years), 33% had recurrence. On multivariable analysis, factors associated with recurrence included: fetal or late (>60 days) diagnosis (HR: 1.90; 95% CI: 1.26-2.86; and HR: 1.73; 95% CI: 1.07-2.77, respectively), Wolff-Parkinson-White (WPW) syndrome (HR: 2.46; 95% CI: 1.75-3.45), and need for multi-antiarrhythmic or second-line therapy (HR: 2.08; 95% CI: 1.45-2.99). Based on the classification and regression tree analysis, WPW incurred the highest risk. Among those without WPW, age at diagnosis was the most important factor predicting risk. Fetal or late diagnosis incurred higher risk, and if multi-antiarrhythmic or second-line therapy was also required, risk nearly doubled. Infants without WPW, who were diagnosed early (0-60 days), and who were discharged on propranolol were at lowest recurrence risk. CONCLUSIONS: Infants with SVT are most likely to be diagnosed at ≤60 days and be male. Risk factors for recurrence (occurred in 33%), present at time of diagnosis, include WPW, fetal or late diagnosis, and multi-antiarrhythmic or second-line therapy. Infants with early diagnosis, without WPW, and discharged on first-line monotherapy are at lowest recurrence risk.

Cardiac crises: Cardiac arrhythmias and cardiomyopathy during TANGO2 deficiency related metabolic crises.

BACKGROUND: TANGO2 deficiency disorder (TDD) is an autosomal recessive disease associated with metabolic crisis, lethal cardiac arrhythmias, and cardiomyopathy. Data regarding treatment, management, and outcomes of cardiac manifestations of TDD are lacking. OBJECTIVE: The purpose of this study was to describe TDD-related cardiac crises. METHODS: Retrospective multicenter chart review was made of TDD patients admitted with cardiac crises, defined as development of ventricular tachycardia (VT), cardiomyopathy, or cardiac arrest during metabolic crises. RESULTS: Twenty-seven children were admitted for 43 cardiac crises (median age 6.4 years; interquartile range [IQR] 2.4-9.8 years) at 14 centers. During crisis, QTc prolongation occurred in all (median 547 ms; IQR 504-600 ms) and a type I Brugada pattern in 8 (26%). Arrhythmias included VT in 21 (78%), supraventricular tachycardia in 3 (11%), and heart block in 1 (4%). Nineteen patients (70%) developed cardiomyopathy, and 20 (74%) experienced a cardiac arrest. There were 10 deaths (37%), 6 related to arrhythmias. In 5 patients, recalcitrant VT occurred despite use of antiarrhythmic drugs. In 6 patients, arrhythmias were controlled after extracorporeal membrane oxygenation (ECMO) support; 5 of these patients survived. Among 10 patients who survived VT without ECMO, successful treatment included intravenous magnesium, isoproterenol, and atrial pacing in multiple cases and verapamil in 1 patient. Initiation of feeds seemed to decrease VT events. CONCLUSION: TDD-related cardiac crises are associated with a high risk of arrhythmias, cardiomyopathy, cardiac arrest, and death. Although further studies are needed, early recognition and appropriate treatment are critical. Acutely, intravenous magnesium, isoproterenol, atrial pacing, and ECMO as a last resort seem to be the best current treatment options, and early initiation of feeds may prevent VT events.

Distribution and frequency of tyrosine kinase inhibitor-associated long-term complications in children with chronic myeloid leukemia.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) improve outcomes for pediatric malignancies characterized by specific gene rearrangements and mutations; however, little is known about the long-term impact of TKI exposure. Our objective was to assess the incidence and type of late-onset TKI-related toxicities in children with chronic myeloid leukemia (CML). METHODS: We reviewed medical records from patients diagnosed with CML between 2006 and 2019 at <21 years of age and prescribed one or more TKIs. Patients treated with stem cell transplant were excluded. Outcomes were captured beginning at 1 year after CML diagnosis. Outcome incidence was described overall and stratified by TKI exposure during the data-capture period. RESULTS: Twenty-two eligible TKI-exposed patients with CML were identified. The median follow-up was 6.0 years (range: 2.2-14.3). All pericardial (n = 3) or pleural (n = 3) effusion outcomes occurred in patients treated with TKIs during the data-capture period. Other outcomes included hypertension (n = 2), ectopy on electrocardiogram (n = 2), and gastrointestinal bleed (n = 1). All outcomes were graded as mild to moderate: some resulted in a temporary discontinuation of TKI, but none led to a change in TKI. No differences were noted in outcome incidence by type of TKI exposure. CONCLUSIONS: TKIs have substantially improved prognosis for subsets of childhood leukemia, but there are limited long-term data to inform exposure-based risk for late-onset complications and screening. Our results suggest that TKI-exposed survivors may be at risk for long-term outcomes that extend well into survivorship.

Signal-to-Noise Analysis Can Inform the Likelihood That Incidentally Identified Variants in Sarcomeric Genes Are Associated with Pediatric Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and can predispose individuals to sudden death. Most pediatric HCM patients host a known pathogenic variant in a sarcomeric gene. With the increase in exome sequencing (ES) in clinical settings, incidental variants in HCM-associated genes are being identified more frequently. Diagnostic interpretation of incidental variants is crucial to enhance clinical patient management. We sought to use amino acid-level signal-to-noise (S:N) analysis to establish pathogenic hotspots in sarcomeric HCM-associated genes as well as to refine the 2015 American College of Medical Genetics (ACMG) criteria to predict incidental variant pathogenicity. Methods and Results: Incidental variants in HCM genes (MYBPC3, MYH7, MYL2, MYL3, ACTC1, TPM1, TNNT2, TNNI3, and TNNC1) were obtained from a clinical ES referral database (Baylor Genetics) and compared to rare population variants (gnomAD) and variants from HCM literature cohort studies. A subset of the ES cohort was clinically evaluated at Texas Children's Hospital. We compared the frequency of ES and HCM variants at specific amino acid locations in coding regions to rare variants (MAF < 0.0001) in gnomAD. S:N ratios were calculated at the gene- and amino acid-level to identify pathogenic hotspots. ES cohort variants were re-classified using ACMG criteria with S:N analysis as a correlate for PM1 criteria, which reduced the burden of variants of uncertain significance. In the clinical validation cohort, the majority of probands with cardiomyopathy or family history hosted likely pathogenic or pathogenic variants. Conclusions: Incidental variants in HCM-associated genes were common among clinical ES referrals, although the majority were not disease-associated. Leveraging amino acid-level S:N as a clinical tool may improve the diagnostic discriminatory ability of ACMG criteria by identifying pathogenic hotspots.

Ripple mapping: A precise tool for atrioventricular nodal reentrant tachycardia ablation.

INTRODUCTION: Ablation for atrioventricular nodal reentrant tachycardia (AVNRT) classically utilizes evaluation of signal morphology within the anatomic region of the slow pathway (SP), which involves subjectivity. Ripple mapping (RM; CARTO-3© Biosense Webster Inc) displays each electrogram at its three-dimensional coordinate as a bar changing in length according to its voltage-time relationship. This allows prolonged, low-amplitude signals to be displayed in their entirety, helping identify propagation in low-voltage areas. We set out to evaluate the ability of RM to locate the anatomic site of the SP and assess its use in guiding ablation for AVNRT. METHODS: Patients ≤18 years with AVNRT in the EP laboratory between 2017 and 2021 were evaluated. RM was performed to define region of SP conduction in patients from 2019 to 2021, whereas standard electro-anatomical mapping was used from 2017 to 2019. All ablations were performed using cryotherapy. Demographics, outcomes, and analysis of variance in number of test lesions until success was compared between groups. RESULTS: A total of 115 patients underwent AVRNT ablation during the study; 46 patients were in the RM group and 69 were in the control group. There were no demographic differences between groups. All procedures, in both groups, were acutely successful. In RM group, 89% of first successful lesions were within 4 mm of the predicted site. There was significantly reduced variability in number of test lesions until success in the RM group (p = .01). CONCLUSION: RM is a novel technique that can help identify SP location, allowing for successful ablation of AVNRT with decreased variability.