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Pathogenic and likely pathogenic variants in the TECRL gene are known to be associated with recessive catecholaminergic polymorphic ventricular tachycardia 3, which can include prolonged QT intervals (MIM#614021). We report a case of cardiac arrest in a previously healthy adolescent male in the community. The patient was found to have a novel maternally inherited likely pathogenic variant in TECRL (c.915T>G [p.Tyr305Ter]) and an additional 19-kb duplication encompassing multiple exons of TECRL (chr4:65165944-65185287, dup [4q13.1]) not identified in the mother. Genetic results were revealed via rapid whole-genome sequencing, which allowed appropriate treatment and prognostication.

Smartwatches provide health tracking in various ways and there has been a recent rise in reporting cardiac arrhythmias. While original studies focused on atrial fibrillation, fewer reports have been made on other arrhythmias especially in pregnancy. We report a pregnant patient who presented at 34 weeks' gestation with palpitations. An ECG recorded through her Apple Watch showed ventricular tachycardia. Hospital ECG confirmed monomorphic ventricular tachycardia likely caused by increased sympathetic tone from the gravid state. She was admitted to the cardiac intensive care unit for close monitoring with intravenous anti-arrhythmic agents; however, the rhythm persisted. She underwent a caesarean delivery and the arrhythmia resolved post partum. She later underwent a catheter ablation, after which she discontinued all anti-arrhythmic medications with no recurrence. This case highlights the importance of requesting relevant digital health information, if available, from patients in our modern era. Controlled clinical studies are needed to validate such practices.

Echocardiography is recommended as a first-line diagnostic tool in patients with premature ventricular contractions (PVCs). However, standard echocardiography is not always able to identify early signs of myocardial dysfunction and cardiac magnetic resonance (CMR) may offer additional information. Since CMR has lower accessibility and higher cost compared to echocardiography, we wanted to evaluate how additional echocardiographic parameters, not included in routine examinations, perform compared to CMR in detecting signs of cardiomyopathy in PVC patients with normal findings at a standard echocardiogram. We compared CMR findings and results from an extended echocardiographic examination in thirty-nine patients who had a high PVC burden. The additional echocardiographic parameters were global longitudinal strain, mechanical dispersion, ventricular–arterial coupling, integrated backscatter and left atrial activation time. Eleven patients had pathological findings at CMR. The additional echocardiographic parameters did not significantly differ between patients with or without CMR findings. However, several patients with normal CMR findings showed signs of ventricular dysfunction when evaluated with the additional echocardiographic parameters, which suggests that these could possibly offer supplementary information in the assessment of PVC patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.

Echocardiography is recommended as a first-line diagnostic tool in patients with premature ventricular contractions (PVCs). However, standard echocardiography is not always able to identify early signs of myocardial dysfunction and cardiac magnetic resonance (CMR) may offer additional information. Since CMR has lower accessibility and higher cost compared to echocardiography, we wanted to evaluate how additional echocardiographic parameters, not included in routine examinations, perform compared to CMR in detecting signs of cardiomyopathy in PVC patients with normal findings at a standard echocardiogram. We compared CMR findings and results from an extended echocardiographic examination in thirty-nine patients who had a high PVC burden. The additional echocardiographic parameters were global longitudinal strain, mechanical dispersion, ventricular–arterial coupling, integrated backscatter and left atrial activation time. Eleven patients had pathological findings at CMR. The additional echocardiographic parameters did not significantly differ between patients with or without CMR findings. However, several patients with normal CMR findings showed signs of ventricular dysfunction when evaluated with the additional echocardiographic parameters, which suggests that these could possibly offer supplementary information in the assessment of PVC patients.

Objective We aimed to analyze somatic growth of patients after total cavopulmonary connection (TCPC) as well as to identify factors influencing postoperative catch-up growth. Methods A total of 309 patients undergoing TCPC at 4 years old or less between 1994 and 2021 were included. Weight for age z-score (WAZ) and height for age-z-score (HAZ) at TCPC and at postoperative time between 1 and 3 years were calculated. Factors influencing somatic growth were analyzed. Results Most frequent diagnosis and initial palliation were hypoplastic left heart syndrome (HLHS) (34%) and the Norwood procedure (51%), respectively. Median age and weight at TCPC were 2.0 (IQR: 1.7–2.5) years and 11.3 (10.5–12.7) kg, respectively. Median 519 days after TCPC, a significant increase in WAZ (−0.4 to −0.2, p < 0.001) was observed, but not in HAZ (−0.6 to −0.6, p = 0.38). Older age at TCPC (p < 0.001, odds ratio [OR]: 2.6) and HLHS (p = 0.007, OR: 2.2) were risks for low WAZ after TCPC. Older age at TCPC (p = 0.009, OR: 1.9) and previous Norwood procedure (p = 0.021, OR: 2.0) were risks for low HAZ after TCPC. Previous bidirectional cavopulmonary shunt (BCPS) was a protective factor for both WAZ (p = 0.012, OR: 0.06) and HAZ (p = 0.028, OR: 0.30) at TCPC. Conclusion In patients undergoing TCPC at the age of 4 years or less, a significant catch-up growth was observed in WAZ after TCPC, but not in HAZ. Previous BCPS resulted to be a protective factor for a better somatic development at TCPC. HLHSs undergoing Norwood were considered as risks for somatic development after TCPC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Differentiating wide complex tachycardias (WCTs) into ventricular tachycardia (VT) and supraventricular wide tachycardia via 12-lead ECG interpretation is a crucial but difficult task. Automated algorithms show promise as alternatives to manual ECG interpretation, but direct comparison of their diagnostic performance has not been undertaken. METHODS: Two electrophysiologists applied 3 manual WCT differentiation approaches (ie, Brugada, Vereckei aVR, and VT score). Simultaneously, computerized data from paired WCT and baseline ECGs were processed by 5 automated WCT differentiation algorithms (WCT Formula, WCT Formula II, VT Prediction Model, Solo Model, and Paired Model). The diagnostic performance of automated algorithms was compared with manual ECG interpretation approaches. RESULTS: A total of 212 WCTs (111 VT and 101 supraventricular wide tachycardia) from 104 patients were analyzed. WCT Formula demonstrated superior accuracy (85.8%) and specificity (87.1%) compared with Brugada (75.2% and 57.4%, respectively) and Vereckei aVR (65.3% and 36.4%, respectively). WCT Formula II achieved higher accuracy (89.6%) and specificity (85.1%) against Brugada and Vereckei aVR. Performance metrics of the WCT Formula (accuracy 85.8%, sensitivity 84.7%, and specificity 87.1%) and WCT Formula II (accuracy 89.8%, sensitivity 89.6%, and specificity 85.1%) were similar to the VT score (accuracy 84.4%, sensitivity 93.8%, and specificity 74.2%). Paired Model was superior to Brugada in accuracy (89.6% versus 75.2%), specificity (97.0% versus 57.4%), and F1 score (0.89 versus 0.80). Paired Model surpassed Vereckei aVR in accuracy (89.6% versus 65.3%), specificity (97.0% versus 75.2%), and F1 score (0.89 versus 0.74). Paired Model demonstrated similar accuracy (89.6% versus 84.4%), inferior sensitivity (79.3% versus 93.8%), but superior specificity (97.0% versus 74.2%) to the VT score. Solo Model and VT Prediction Model accuracy (82.5% and 77.4%, respectively) was superior to the Vereckei aVR (65.3%) but similar to Brugada (75.2%) and the VT score (84.4%). CONCLUSIONS: Automated WCT differentiation algorithms demonstrated favorable diagnostic performance compared with traditional manual ECG interpretation approaches. [ABSTRACT FROM AUTHOR]

BACKGROUND: During pulsed field ablation (PFA), relationships between ablation parameters (contact force [CF], number of burst pulses, impedance decrease, and electrode temperature) and lesion size in beating hearts have not been well validated. METHODS: A 7.5F-catheter with a 3.5-mm ablation electrode and CF sensor (ThermoCool SmartTouch SF-Dual-Energy, Biosense Webster, Inc, Irwindale, CA) was connected to a PFA system (TRUPULSE2, Biosense Webster, Inc). In 11 closedchest swine, biphasic PFA current was delivered between the ablation electrode and the skin patch at 219 sites in left ventricle and right ventricle using 12, 18, and 24 burst pulses with 4 different levels of CF: (1) low (n=57; CF, 4--15g; median, 10g); (2) moderate (n=60; CF, 16--30g; median, 22.5g); (3) high (n=68; CF, 32--65g; median, 40g); and (4) no electrode contact (n=34), 2 mm away from the endocardium. Swine were euthanized 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. RESULTS: All PFA lesions with electrode-myocardium contact were well demarcated with triphenyl tetrazolium chloride staining, demonstrating (1) pale central zone (contraction band necrosis with minimal coagulation necrosis), (2) dark brown zone (contraction band necrosis with hemorrhage), and (3) hyperstained red zone by triphenyl tetrazolium chloride (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). Lesion depth increased significantly with increasing CF and the number of PFA burst pulses. An exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlated lesion depth with high accuracy: R=0.809, P<0.0001, ±1.0-mm accuracy in 128 of 163 (79%) lesions, and ±1.5-mm accuracy in 153 of 163 (94%) lesions. Impedance decrease and electrode temperature were poor predictors of lesion size. There were no detectable lesions resulting from ablation without electrode contact. CONCLUSIONS: Acute PFA ventricular lesions demonstrate irreversible and reversible lesion boundaries. Electrode-tissue contact is required for effective lesion formation. Lesion depth increases significantly with increasing CF and PFA burst pulses. A new exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlates lesion depth with high accuracy. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the PARTITA trial (Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator?), antitachycardia pacing (ATP) predicted the occurrence of implantable cardioverter defibrillator (ICD) shocks. Catheter ablation of ventricular tachycardia after the first shock reduced the risk of death or worsening heart failure. A threshold of ATPs that might warrant an ablation procedure before ICD shocks is unknown. Our aim was to identify a threshold of ATPs and clinical features that predict the occurrence of shocks and cardiovascular events. METHODS: We analyzed data from 517 patients in phase A of the PARTITA study. We used classification and regression tree analysis to develop and test a risk stratification model based on arrhythmia patterns and clinical data to predict ICD shocks. Secondary end points were worsening heart failure and cardiovascular hospitalization. RESULTS: Classification and regression tree classified patients into 6 leaves by increasing shock probability. Patients treated with ≥5 ATPs in 6 months (active arrhythmia pattern) had the highest risk of ICD shocks (93% and 86%, training and testing samples, respectively). Patients without ATPs had the lowest (1% and 2%). Other predictors included left ventricle ejection fraction<35%, age of <60 years, and obesity. Survival analysis revealed a higher risk of worsening heart failure (hazard ratio, 5.45 [95% CI, 1.62-18.4]; P=0.006) and cardiovascular hospitalization (hazard ratio, 7.29 [95% CI, 3.66-14.5]; P<0.001) for patients with an active arrhythmia pattern compared with those without ATPs. CONCLUSIONS: Patients with an active arrhythmia pattern (≥5 ATPs in 6 months) are associated with an increased risk of ICD shocks, as well as heart failure hospitalization and cardiovascular hospitalization. These data suggest that additional treatments may be helpful to this high-risk group as a preventive strategy to reduce the incidence of major events. Further prospective randomized trials are needed to confirm the benefits of early ventricular tachycardia ablation in this setting. [ABSTRACT FROM AUTHOR]

BACKGROUND: Endocardial catheter-based pulsed field ablation (PFA) of the ventricular myocardium is promising. However, little is known about PFA's ability to target intracavitary structures, epicardium, and ways to achieve transmural lesions across thick ventricular tissue. METHODS: A lattice-tip catheter was used to deliver biphasic monopolar PFA to swine ventricles under general anesthesia, with electroanatomical mapping, fluoroscopy and intracardiac echocardiography guidance. We conducted experiments to assess the feasibility and safety of repetitive monopolar PFA applications to ablate (1) intracavitary papillary muscles and moderator bands, (2) epicardial targets, and (3) bipolar PFA for midmyocardial targets in the interventricular septum and left ventricular free wall. RESULTS: (1) Papillary muscles (n=13) were successfully ablated and then evaluated at 2, 7, and 21 days. Nine lesions with stable contact measured 18.3±2.4 mm long, 15.3±1.5 mm wide, and 5.8±1.0 mm deep at 2 days. Chronic lesions demonstrated preserved chordae without mitral regurgitation. Two targeted moderator bands were transmurally ablated without structural disruption. (2) Transatrial saline/carbon dioxide assisted epicardial access was obtained successfully and epicardial monopolar lesions had a mean length, width, and depth of 30.4±4.2, 23.5±4.1, and 9.1±1.9 mm, respectively. (3) Bipolar PFA lesions were delivered across the septum (n=11) and the left ventricular free wall (n=7). Twelve completed bipolar lesions had a mean length, width, and depth of 29.6±5.5, 21.0±7.3, and 14.3±4.7 mm, respectively. Chronically, these lesions demonstrated uniform fibrotic changes without tissue disruption. Bipolar lesions were significantly deeper than the monopolar epicardial lesions. CONCLUSIONS: This in vivo evaluation demonstrates that PFA can successfully ablate intracavitary structures and create deep epicardial lesions and transmural left ventricular lesions. [ABSTRACT FROM AUTHOR]

In-hospital electrocardiographic (ECG) monitors are typically configured to alarm for premature ventricular complexes (PVCs) due to the potential association of PVCs with ventricular tachycardia (VT). However, no contemporary hospital-based studies have examined the association of PVCs with VT. Hence, the benefit of PVC monitoring in hospitalized patients is largely unknown. This secondary analysis used a large PVC alarm data set to determine whether PVCs identified during continuous ECG monitoring were associated with VT, in-hospital cardiac arrest (IHCA), and/or death in a cohort of adult intensive care unit patients. Six PVC types were examined (i.e., isolated, bigeminy, trigeminy, couplets, R-on-T, and run PVCs) and were compared between patients with and without VT, IHCA, and/or death. Of 445 patients, 48 (10.8%) had VT; 11 (2.5%) had IHCA; and 49 (11%) died. Isolated and run PVC counts were higher in the VT group (p = 0.03 both), but group differences were not seen for the other four PVC types. The regression models showed no significant associations between any of the six PVC types and VT or death, although confidence intervals were wide. Due to the small number of cases, we were unable to test for associations between PVCs and IHCA. Our findings suggest that we should question the clinical relevance of activating PVC alarms as a forewarning of VT, and more work should be done with larger sample sizes. A more precise characterization of clinically relevant PVCs that might be associated with VT is warranted.

BackgroundFalse ventricular tachycardia (VT) alarms are common during in-hospital electrocardiographic (ECG) monitoring. Prior research shows that the majority of false VT can be attributed to algorithm deficiencies.PurposeThe purpose of this study was: (1) to describe the creation of a VT database annotated by ECG experts and (2) to determine true vs. false VT using a new VT algorithm created by our group.MethodsThe VT algorithm was processed in 5320 consecutive ICU patients with 572,574 h of ECG and physiologic monitoring. A search algorithm identified potential VT, defined as: heart rate >100 beats/min, QRSs > 120 ms, and change in QRS morphology in >6 consecutive beats compared to the preceding native rhythm. Seven ECG channels, SpO2 , and arterial blood pressure waveforms were processed and loaded into a web-based annotation software program. Five PhD-prepared nurse scientists performed the annotations.ResultsOf the 5320 ICU patients, 858 (16.13%) had 22,325 VTs. After three levels of iterative annotations, a total of 11,970 (53.62%) were adjudicated as true, 6485 (29.05%) as false, and 3870 (17.33%) were unresolved. The unresolved VTs were concentrated in 17 patients (1.98%). Of the 3870 unresolved VTs, 85.7% (n = 3281) were confounded by ventricular paced rhythm, 10.8% (n = 414) by underlying BBB, and 3.5% (n = 133) had a combination of both.ConclusionsThe database described here represents the single largest human-annotated database to date. The database includes consecutive ICU patients, with true, false, and challenging VTs (unresolved) and could serve as a gold standard database to develop and test new VT algorithms.

BackgroundA large proportion of genetic risk remains unexplained for structural heart disease involving the interventricular septum (IVS) including hypertrophic cardiomyopathy and ventricular septal defects. This study sought to develop a reproducible proxy of IVS structure from standard medical imaging, discover novel genetic determinants of IVS structure, and relate these loci to diseases of the IVS, hypertrophic cardiomyopathy, and ventricular septal defect.MethodsWe estimated the cross-sectional area of the IVS from the 4-chamber view of cardiac magnetic resonance imaging in 32 219 individuals from the UK Biobank which was used as the basis of genome wide association studies and Mendelian randomization.ResultsMeasures of IVS cross-sectional area at diastole were a strong proxy for the 3-dimensional volume of the IVS (Pearson r=0.814, P=0.004), and correlated with anthropometric measures, blood pressure, and diagnostic codes related to cardiovascular physiology. Seven loci with clear genomic consequence and relevance to cardiovascular biology were uncovered by genome wide association studies, most notably a single nucleotide polymorphism in an intron of CDKN1A (rs2376620; β, 7.7 mm2 [95% CI, 5.8-11.0]; P=6.0×10-10), and a common inversion incorporating KANSL1 predicted to disrupt local chromatin structure (β, 8.4 mm2 [95% CI, 6.3-10.9]; P=4.2×10-14). Mendelian randomization suggested that inheritance of larger IVS cross-sectional area at diastole was strongly associated with hypertrophic cardiomyopathy risk (pIVW=4.6×10-10) while inheritance of smaller IVS cross-sectional area at diastole was associated with risk for ventricular septal defect (pIVW=0.007).ConclusionsAutomated estimates of cross-sectional area of the IVS supports discovery of novel loci related to cardiac development and Mendelian disease. Inheritance of genetic liability for either small or large IVS, appears to confer risk for ventricular septal defect or hypertrophic cardiomyopathy, respectively. These data suggest that a proportion of risk for structural and congenital heart disease can be localized to the common genetic determinants of size and shape of cardiovascular anatomy.

Stroke is one of the leading causes of death and disability in adults. It can present itself in many different ways beginning with focal neurological symptoms and ending with sudden cardiac arrest. Stroke predisposes to ventricular arrhythmias due to prolongation of the QT interval. This problem mainly affects patients with additional risk factors that affect QT interval prolongation. The following case report presents the story of a 68-year-old patient with diabetes mellitus, hypertension, heart failure and rheumatoid arthritis taking chronic chloroquine diagnosed in the ED and subsequently admitted to the Cardiac Intensive Care Clinic for out-of-hospital ventricular fibrillation cardiac arrest in the course of recurrent ventricular tachyarrhythmias, who was diagnosed with ischaemic stroke. Coordinated management is presented to achieve a stable outcome. [ABSTRACT FROM AUTHOR]

Introduction: Despite advancements in implantable cardioverter‐defibrillator (ICD) technology, sudden cardiac death (SCD) remains a persistent public health concern. Chagas disease (ChD), prevalent in Brazil, is associated with increased ventricular tachycardia (VT) and ventricular fibrillation (VF) events and SCD compared to other cardiomyopathies. Methods: This retrospective observational study included patients who received ICDs between October 2007 and December 2018. The study aims to assess whether mortality and VT/VF events decreased in patients who received ICDs during different time periods (2007–2010, 2011–2014, and 2015–2018). Additionally, it seeks to compare the prognosis of ChD patients with non‐ChD patients. Time periods were chosen based on the establishment of the Arrhythmia Service in 2011. The primary outcome was overall mortality, assessed across the entire sample and the three periods. Secondary outcomes included VT/VF events and the combined outcome of death or VT/VF. Results: Of the 885 patients included, 31% had ChD. Among them, 28% died, 14% had VT/VF events, and 37% experienced death and/or VT/VF. Analysis revealed that period 3 (2015–2018) was associated with better death‐free survival (p =.007). ChD was the only variable associated with a higher rate of VT/VF events (p <.001) and the combined outcome (p =.009). Conclusion: Mortality and combined outcome rates decreased gradually for ICD patients during the periods 2011–2014 and 2015–2018 compared to the initial period (2007–2010). ChD was associated with higher VT/VF events in ICD patients, only in the first two periods. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Idiopathic giant cell myocarditis (IGCM) is an uncommon and frequently fatal type of myocarditis. It primarily affects young individuals and has the potential to result in heart failure and life-threatening arrhythmias. IGCM seems to be dependent on activation of CD4-positive T lymphocytes and can show improvement with treatment aimed at reducing T-cell function. We present a case of a 65-year-old patient who presented with features of acute heart failure refractory to guideline-directed medical therapy (GDMT), due to IGCM. A review of the natural history and treatment of IGCM is also presented. Case Report: A 65-year-old woman with multiple comorbidities was admitted to our hospital for ventricular tachycardia in the setting of progressive non-ischemic heart failure, unresponsive to GDMT. This led to further investigation, including an endomyocardial biopsy, which revealed inflammatory infiltration, with multinucleated giant cells and lymphocytes in the absence of granuloma formation, prompting a diagnosis of IGCM. An implantable cardioverter-defibrillator (ICD) was placed for secondary prevention of sudden cardiac death and the patient was initiated on combined immunosuppressive therapy. Owing to numerous comorbidities, she was determined to be unsuitable for a heart transplant. Unfortunately, she eventually died from complications secondary to the disease. Conclusions: IGCM remains a challenging clinical diagnosis with a poor long-term outcome without heart transplantation. This case highlights the importance of considering atypical causes of heart failure in patients who do not respond to conventional therapies. Early recognition and appropriate management, involving medical and interventional approaches, are crucial in improving outcomes for patients with IGCM. [ABSTRACT FROM AUTHOR]

The incidence of atrial fibrillation (AF) is significantly higher in patients with pacemakers than in the general population, which could be due to patient characteristics and the diagnostic tool of the pacemaker in detecting atrial high-rate episodes and subclinical AF, but also to the pacemaker itself providing AF-promoting conditions. It is well known that high ventricular pacemaker burden increases the likelihood of AF occurrence. However, the sites of atrial and ventricular pacing may also influence the risk for AF. The conventional sites for atrial and ventricular pacing are in the right atrial appendage and in the right ventricular apex. However, growing evidence suggests that alternative pacing sites may be superior for the prevention of AF. Bachmann bundle pacing, for example, promotes interatrial excitation conduction, resulting in atrial synchronicity and a shorter total atrial activation time, which may be preventive for the occurrence of AF. Moreover, in recent years, new ventricular pacing sites have come into focus with His bundle and left bundle branch pacing. In addition to the hemodynamic and electrophysiological cardiac benefits, these new options may also offer benefits in the prevention of AF. This review provides an overview of pacing-induced AF mechanisms and the association with different pacing sites, as well as approaches for prevention of pacing-induced AF, highlighting different sites and modes of atrial pacing and the newer sites of ventricular pacing.

BACKGROUND: The accuracy of noninvasive arrhythmia source localization using a forward-solution computational mapping system has not yet been evaluated in blinded, multicenter analysis. This study tested the hypothesis that a computational mapping system incorporating a comprehensive arrhythmia simulation library would provide accurate localization of the site-of-origin for atrial and ventricular arrhythmias and pacing using 12-lead ECG data when compared with the gold standard of invasive electrophysiology study and ablation. METHODS: The VMAP study (Vectorcardiographic Mapping of Arrhythmogenic Probability) was a blinded, multicenter evaluation with final data analysis performed by an independent core laboratory. Eligible episodes included atrial and ventricular: tachycardia, fibrillation, pacing, premature atrial and ventricular complexes, and orthodromic atrioventricular reentrant tachycardia. Mapping system results were compared with the gold standard site of successful ablation or pacing during electrophysiology study and ablation. Mapping time was assessed from time-stamped logs. Prespecified performance goals were used for statistical comparisons. RESULTS: A total of 255 episodes from 225 patients were enrolled from 4 centers. Regional accuracy for ventricular tachycardia and premature ventricular complexes in patients without significant structural heart disease (n=75, primary end point) was 98.7% (95% CI, 96.0%-100%; P

AimsCardiomyopathy patients are prone to ventricular arrhythmias (VA) and sudden cardiac death. Current therapies to prevent VA include radiofrequency ablation to destroy slowly conducting pathways of viable myocardium which support re-entry. Here, we tested the reverse concept, namely that boosting local tissue viability in zones of slow conduction might eliminate slow conduction and suppress VA in ischaemic cardiomyopathy.Methods and resultsExosomes are extracellular vesicles laden with bioactive cargo. Exosomes secreted by cardiosphere-derived cells (CDCEXO) reduce scar and improve heart function after intramyocardial delivery. In a VA-prone porcine model of ischaemic cardiomyopathy, we injected CDCEXO or vehicle into zones of delayed conduction defined by electroanatomic mapping. Up to 1-month post-injection, CDCEXO, but not the vehicle, decreased myocardial scar, suppressed slowly conducting electrical pathways, and inhibited VA induction by programmed electrical stimulation. In silico reconstruction of electrical activity based on magnetic resonance images accurately reproduced the suppression of VA inducibility by CDCEXO. Strong anti-fibrotic effects of CDCEXO, evident histologically and by proteomic analysis from pig hearts, were confirmed in a co-culture assay of cardiomyocytes and fibroblasts.ConclusionBiological substrate modification by exosome injection may be worth developing as a non-destructive alternative to conventional ablation for the prevention of recurrent ventricular tachyarrhythmias.

Introduction. Sustained monomorphic ventricular tachycardia (VT) -- SMVT is a rare, underdiagnosed pathology with a very poor prognosis. Along with ventricular fibrillation, SMVT is responsible for nearly all of the arrhythmic sudden cardiac deaths (SCD). The most common cause of VT is ischemic heart disease, but there are many other reasons, among which are arrhythmogenic right ventricular cardiomyopathy (ARVD) and myocardial bridging phenomenon. Treatment options include a hybrid approach consisting of antiarrhythmic drugs, catheter ablation, and implantable cardioverter defibrillators (ICD). Case report. We present a case of a 46-year-old man, a military officer, who experienced chest pain, palpitations, and nausea during regular physical activity at home. Due to the symptoms described, he was examined immediately and diagnosed with SMVT. Shortly after the diagnosis, he lost consciousness and was successfully resuscitated. A complete non-invasive and invasive cardiology examination was performed. It revealed that the patient had stable coronary disease and a muscle bridge on the left anterior descending artery. An ARVD was suspected after transthoracic echocardiography and heart magnetic resonance imaging. Genetic testing for ARVD was negative, but according to the Heart Rhythm Society expert consensus criteria, we had enough for a definitive diagnosis. The patient was hospitalized for ten days and treated with drugs without recurring VT or other disorders. We implanted an implantable loop recorder before the discharge and monitored the heart rhythm for one year. During a three-year follow-up, all of his electrocardiographic findings presented sinus rhythm without heart rhythm disorders. Conclusion. Sudden SMVT is the most common cause of SCD. It is of inestimable importance to carry out a detailed examination and determine the immediate cause of the arrhythmia and the right therapy, which, for these patients, is a life-saving form of treatment. Therapy includes medications, electrophysiology or ICD, or a combination of these treatment approaches. [ABSTRACT FROM AUTHOR]

Background/Aim. Patients who were treated with primary percutaneous coronary intervention (pPCI) and survived ventricular tachycardia (VT) and ventricular fibrillation (VF) in the first 48 hrs after ST-elevation myocardial infarction (STEMI) had, in most investigations, a similar long-term prognosis of the outcome, compared to those patients who did not have VT and VF during the first 48 hrs after STEMI. The aim of the study was to determine the association of myocardial infarction markers: creatine kinase-MB fraction (CK-MB), heart failure marker -- B-type natriuretic peptide (BNP), and systemic inflammation factor -- Creactive protein (CRP) with early VT and VF onset, in relation to patient mortality during the first six months after STEMI. Methods. The retrospective study included 971 patients with STEMI treated with pPCI for ten years. VF and sustained VT (sVT) were detected outside of the hospital and during the first 48 hrs of hospitalization. Results. During t he first 48 hrs from admission, 108 (11.1%) patients had life-threatening arrhythmias, of which 75 (69.4%) had VF, and 33 (30.6%) had sVT and were treated with direct current -- DC shock and intravenous amiodarone. Intrahospital mortality was significantly higher in patients with VF/sVT in the first 48 hrs compared to patients without VF/sVT (14.8% vs. 5.7%, p = 0.001). BNP level had higher accuracy in the prediction of six-month death than the maximum blood level of CRP in patients without VF/sVT after 48 hrs. However, in patients with early-onset malignant arrhythmias, BNP showed a lower level of accuracy in predicting the six-month mortality, as did the CRP values, which had almost the same level of accuracy. Admission glycemia had a much lower predictive value in both groups of patients compared t o BNP and CRP [ 0.705 (0.628-0.781), p < 0.001 and 0.662 (0.521-0.803), p = 0.046, respectively]. In either of the groups, maximum CK-MB levels were not significant in predicting the six-month all-cause mortality. Conclusion. Our study indicates that STEMI patients with early onset of VF and sVT, treated with pPCI, with a high BNP level, have a statistically significantly higher mortality rate compared to patients with a lower BNP level. [ABSTRACT FROM AUTHOR]

AbstractBackgroundClinical descriptionConclusionCNS ganglioneuroblastoma in an extremely rare embryonal tumour, specifically in the pediatric population. Bad prognosis is documented due to aggressiveness and absence of protocolized treatment at the moment.We present the case of a 5-year-old boy who presented with sudden loss of consciousness. CT scan was performed showing a large posterior fossa lesion with several intraventricular focal lesions, suggesting metastases, the largest one located inside the III ventricle. The patient underwent a posterior fossa resection of the lesion and a subtotal resection of the III ventricle lesion, with adjuvant chemotherapy. The evolution was poor and the patient finally died 3 months after diagnosis.Ganglioneuroblastoma is extremely likely to recur quickly and extensively. There is little knowledge about treatment options but is documented that gross total resection followed by adjuvant radiotherapy and chemotherapy is the best management in these patients. [ABSTRACT FROM AUTHOR]

Store-operated calcium entry (SOCE) in cardiomyocytes may be involved in cardiac remodeling, but the underlying mechanisms remain elusive. We hypothesized that SOCE may increase nuclear calcium, which alters gene expression via calcium/calmodulin-dependent enzyme signaling, and elucidated the underlying cellular mechanisms. An experimental protocol was established in isolated adult rat cardiomyocytes to elicit SOCE by re-addition of calcium following complete depletion of sarcoplasmic reticulum (SR) calcium and to quantify SOCE in relation to the electrically stimulated calcium transient (CaT) measured in the same cell before SR depletion. Using confocal imaging, calcium changes were recorded simultaneously in the cytosol and in the nucleus of the cell. In ventricular myocytes, SOCE was observed in the cytosol and nucleus amounting to ≈15% and ≈25% of the respective CaT. There was a linear correlation between the SOCE-mediated calcium increase in the cytosol and nucleus. Inhibitors of TRPC or Orai channels reduced SOCE by ≈33–67%, whereas detubulation did not. In atrial myocytes, SOCE with similar characteristics was observed in the cytosol and nucleus. However, the SOCE amplitudes in atrial myocytes were ≈two-fold larger than in ventricular myocytes, and this was associated with ≈1.4- to 3.6-fold larger expression of putative SOCE proteins (TRPC1, 3, 6, and STIM1) in atrial tissue. The results indicated that SOCE in atrial and ventricular myocytes is able to cause robust calcium increases in the nucleus and that both TRPC and Orai channels may contribute to SOCE in adult cardiomyocytes. [ABSTRACT FROM AUTHOR]

Ventricular tachycardia (VT) is an important type of arrhythmia with a risk of sudden death. Although implanted cardiac defibrillation and radiofrequency ablation are used together with medical treatments for VT, the treatment options are limited in cases that do not respond to them. Stereotactic ablative body radiotherapy (SABR) applied to VT substrates in resistant cases is an emerging treatment with positive results. Such clinical results have increased the interest in this subject. However, the ideal treatment device and method have not yet been described for this therapy, which is generally applied at a single fraction using various devices and methods. Herein, treatment planning was conducted for a total of 8 patients (11 VT substrates) using the Varian TrueBeam EDGE and TomoTherapy Radixact devices at a single center, and the results were compared dosimetrically. The Wilcoxon-signed rank test was used for the statistical analysis, and mean values were expressed as medians and interquartile ranges (IQRs). In the volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) plans, the plan coverages and conformity indexes were similar; meanwhile, the homogeneity indexes were 0.10 (IQR = 0.05) and 0.07 (IQR = 0.05), respectively, and were significantly better in the HT plan (p = 0.02). The gradient indexes were 3.18 (IQR = 0.8) and 5.33 (IQR = 3.68) in the VMAT and HT plans, respectively, and were significantly better in the VMAT plan. For the organs at risk, similar doses were observed. The maximum doses for the stomach and esophagus and the mean doses for the left lung and both lungs were significantly lower in the VMAT plan. Similarly, the maximum and mean doses for the cardiac substructures and great vessels were significantly lower in the VMAT plan. More homogeneous plans were obtained in HT, while a faster dose reduction and lower critical organ dose were observed in VMAT. Reasonable myocardial SABR plans could be obtained with both techniques. The effects of the dosimetric differences on the clinical outcomes should be evaluated in prospective clinical studies. [ABSTRACT FROM AUTHOR]

We present a case of anatomic repair of dextro-transposition of the great arteries (d-TGA) with ventricular septal defect (VSD) in a 55-year-old man who presented with acute heart failure. This case highlights the importance of multimodal imaging and multidisciplinary involvement in developing a comprehensive surgical and medical plan for adults with congenital heart disease. We think this is the oldest reported patient undergoing anatomic surgical repair of d-TGA with VSD.

ObjectivesThe goal of this study was to evaluate whether intermittent VNS reduces electrical heterogeneities and arrhythmia inducibility during sympathoexcitation.BackgroundSympathoexcitation increases the risk of ventricular tachyarrhythmias (VT). Vagal nerve stimulation (VNS) has been antiarrhythmic in the setting of ischemia-driven arrhythmias, but it is unclear if it can overcome the electrophysiological effects of sympathoexcitation in the setting of chronic myocardial infarction (MI).MethodsIn Yorkshire pigs after chronic MI, a sternotomy was performed, a 56-electrode sock was placed over the ventricles (n = 17), and a basket catheter was positioned in the left ventricle (n = 6). Continuous unipolar electrograms from sock and basket arrays were obtained to analyze activation recovery interval (ARI), a surrogate of action potential duration. Bipolar voltage mapping was performed to define scar, border zone, or viable myocardium. Hemodynamic and electrical parameters and VT inducibility were evaluated during sympathoexcitation with bilateral stellate ganglia stimulation (BSS) and during combined BSS with intermittent VNS.ResultsDuring BSS, global epicardial ARIs shortened from 384 ± 59 milliseconds to 297 ± 63 milliseconds and endocardial ARIs from 359 ± 36 milliseconds to 318 ± 40 milliseconds. Dispersion in ARIs increased in all regions, with the greatest increase observed in scar and border zone regions. VNS mitigated the effects of BSS on border zone ARIs (from -18.3% ± 6.3% to -2.1% ± 14.7%) and ARI dispersion (from 104 ms2 [1 to 1,108 ms2] to -108 ms2 [IQR: -588 to 30 ms2]). VNS reduced VT inducibility during sympathoexcitation (from 75%-40%; P < 0.05).ConclusionsAfter chronic MI, VNS overcomes the detrimental effects of sympathoexcitation by reducing electrophysiological heterogeneities exacerbated by sympathetic stimulation, decreasing VT inducibility.

BackgroundRight ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT's unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT.MethodsWe conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics.ResultsWe found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions (P=0.003), whereas acetylcholine (100 μM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions (P=0.034) and partially reversed action potential duration at 80% repolarization shortening (P=0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium (P=0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT.ConclusionsHuman RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium.

ObjectivesTo evaluate sex differences in demographic and clinical characteristics, treatments and outcomes for patients with diagnosed obstructive hypertrophic cardiomyopathy (oHCM) in the USA.SettingRetrospective observational study of administrative claims data from MarketScan Commercial Claims and Encounters Database from IBM Watson Health.ParticipantsOf the 28 million covered employees and family members in MarketScan, 9306 patients with oHCM were included in this analysis.Main outcome measuresoHCM-related outcomes included heart failure, atrial fibrillation, ventricular tachycardia/ fibrillation, sudden cardiac death, septal myectomy, alcohol septal ablation (ASA) and heart transplant.ResultsAmong 9306 patients with oHCM, the majority were male (60.5%, p

[Figure: see text].

The need to improve access to health services for the transgender community has become evident, especially concerning cardiovascular risk, which is higher compared to the general population. Surgical procedures and hormone therapies are common in this population to affirm gender identity, but they pose challenges as they are associated with disruptions in lipid metabolism, body fat concentration, and insulin resistance. Additionally, there is an increased risk of adverse cardiovascular events such as venous thromboembolism, stroke, and myocardial infarction. The influence of sex hormones on the electrophysiological properties of the heart has been studied, highlighting gender differences that may predispose the transgender population to cardiac arrhythmias. Exogenous hormone therapy, for both transgender women and men, can affect the QT interval and increase the risk of arrhythmias, including atrial fibrillation. Although the incidence of arrhythmias in the transgender population is not entirely clear, evidence suggests the need for careful cardiovascular monitoring and consideration of risk factors before initiating hormone therapies. [ABSTRACT FROM AUTHOR]

Employing animal models to study heart failure (HF) has become indispensable to discover and test novel therapies, but their translatability remains challenging. Although cytoskeletal alterations are linked to HF, the tubulin signature of common experimental models has been incompletely defined. Here, we assessed the tubulin signature in a large set of human cardiac samples and myocardium of animal models with cardiac remodeling caused by pressure overload, myocardial infarction or a gene defect. We studied levels of total, acetylated, and detyrosinated α-tubulin and desmin in cardiac tissue from hypertrophic (HCM) and dilated cardiomyopathy (DCM) patients with an idiopathic (n = 7), ischemic (n = 7) or genetic origin (n = 59), and in a pressure-overload concentric hypertrophic pig model (n = 32), pigs with a myocardial infarction (n = 28), mature pigs (n = 6), and mice (n = 15) carrying the HCM-associated MYBPC32373insG mutation. In the human samples, detyrosinated α-tubulin was increased 4-fold in end-stage HCM and 14-fold in pediatric DCM patients. Acetylated α-tubulin was increased twofold in ischemic patients. Across different animal models, the tubulin signature remained mostly unaltered. Only mature pigs were characterized by a 0.5-fold decrease in levels of total, acetylated, and detyrosinated α-tubulin. Moreover, we showed increased desmin levels in biopsies from NYHA class II HCM patients (2.5-fold) and the pressure-overload pig model (0.2–0.3-fold). Together, our data suggest that desmin levels increase early on in concentric hypertrophy and that animal models only partially recapitulate the proliferated and modified tubulin signature observed clinically. Our data warrant careful consideration when studying maladaptive responses to changes in the tubulin content in animal models. [ABSTRACT FROM AUTHOR]

Background: Holter electrocardiographic monitoring is a cornerstone of diagnostic testing for arrhythmogenic cardiomyopathy (ACM) in Boxer dogs, but physical activity during monitoring is not controlled. In humans, exercise testing (ExT) can identify latent tachyarrhythmias associated with cardiomyopathy, and exercise increases serum cardiac troponin‐I concentrations ([hs‐cTnI]). These effects have not yet been investigated in Boxer dogs. Hypothesis/Objectives: Subjecting Boxer dogs to brief, moderate‐intensity ExT can identify changes in Holter recordings and [hs‐cTnI] compared to baseline results. Animals: Thirty overtly healthy, client‐owned Boxer dogs. Methods: Prospective interventional study. Dogs underwent baseline diagnostic testing including 24‐hour Holter monitoring and [hs‐cTnI], followed by brief ExT (accompanied, brisk stair‐climbing and ‐descending for <5 minutes). Results: Eleven dogs (37%) had >100 premature ventricular complexes (PVCs)/24 hours at baseline (3), ExT (3), or both (5). After ExT, these dogs had more PVCs/24 hours and greater increases in [hs‐cTnI] compared to those with ≤100 PVCs/24 hours. Dogs with the striatin mutation had more PVCs/24 hours and a greater increase in [hs‐cTnI] after ExT than did dogs without the striatin mutation. Conclusions and Clinical Importance: Exercise testing may improve the binary classification of Boxer dogs with or without ACM by increasing the number of PVCs and [hs‐cTnI] in affected dogs to a greater degree than in unaffected dogs. This effect also is associated with presence or absence of the striatin mutation. Exercise should be a controlled variable when screening Boxer dogs for ACM. [ABSTRACT FROM AUTHOR]

Torsades de Pointes (TdP) is a potentially lethal ventricular tachydysrhythmia. Prolonged heartrate corrected QT interval (QTc) predicts TdP; however, with poor specificity. We performed this study to identify other predictors of TdP among patients with prolonged QTc. We performed a retrospective case control study with 2:1 matching at an urban academic hospital. We searched our hospital electrocardiogram (ECG) database for tracings with heartrate ≤ 60, QTc ≥ 500, and QRS < 120, followed by a natural language search for electronic records with "Torsades," "polymorphic VT," or similar to identify TdP cases from 2005 to 19. We identified controls from a similar ECG database search matching for QTc, heartrate, age, and sex. We compared cardiologic and historical factors, medications, laboratory values, and ECG measurements including ectopy using univariate statistics. For those cases with saved telemetry strips that included preceding beats or TdP onset, we compared ectopy and TdP onset characteristics between the ECG and telemetry strips using mixed linear modeling. Seventy-five cases including 50 with telemetry strips and 150 controls were included. Historical, pharmacologic, laboratory, and cardiologic testing results were similar between cases and controls. The proportion of telemetry tracings with premature ventricular contractions (PVC's) preceding TdP was 0.78 compared to 0.16 for case ECG's (difference 0.62(95%CI 0.44–0.75)) and 0.10 for control ECGs (difference 0.68(95%CI 0.56–0.80)). Average telemetry heartrate was 72 and QTc 549 immediately preceding TdP, similar to the ECG values. Clinical factors don't differentiate patients with long QTc who develop TdP, however, an increase in PVC's in patients with prolonged QTc may usefully predict imminent TdP. [Display omitted] • History or meds don't differ between long QTc patients who do or don't suffer TdP. • Serum chemistries don't differ between long QTc patients who do or don't suffer TdP. • Increased ventricular ectopy commonly precedes TdP. • Increased ventricular ectopy and its characteristics could be used to predict TdP TdP = Torsades de Pointes. [ABSTRACT FROM AUTHOR]

Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD." All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations.

PurposePrior studies reporting efficacy of radiofrequency catheter ablation for complex ventricular ectopy in mitral valve prolapse (MVP) are limited by selective inclusion of bileaflet MVP, papillary muscle only ablation, or short-term follow-up. We sought to evaluate the long-term incidence of hemodynamically significant ventricular tachycardia (VT) or fibrillation (VF) in patients with MVP after initial ablation.MethodsWe studied consecutive patients with MVP undergoing ablation for complex ventricular ectopy between 2013 and 2017 at our institution. Of 580 patients with MVP, we included 15 (2.6%, 10 women; mean age 50 ± 14 years, 53% bileaflet) with complex ventricular ectopy treated with initial ablation.ResultsOver a median follow-up of 3406 (1875-6551) days or 9 years, 5 of 15 (33%) patients developed hemodynamically significant VT/VF after their initial ablation and underwent placement of an implantable cardioverter defibrillator (ICD). Three of 5 also underwent repeat ablations. Sustained VT was inducible prior to index ablation in all 5 who developed VT/VF, compared to none of the 10 patients who did not develop VT/VF after index ablation (p = 0.002). Complex ventricular ectopy at index ablation was multifocal in all 5 patients who underwent repeat intervention versus 4 of 10 patients (40%) who did not (p = 0.04). All 3 patients with subsequent VT/VF who underwent repeat ablation had a new clinically dominant focus of ventricular arrhythmia and 3 of the patients with ICD had appropriate VT/VF therapies.ConclusionsIn the long term, a subset of MVP patients treated with ablation for ventricular arrhythmias, all with multifocal ectopy on initial EP study, develop hemodynamically significant VT/VF. Our findings suggest the progressive nature of ventricular arrhythmias in patients with MVP and multifocal ectopy.

BackgroundBilateral cardiac sympathetic denervation (BCSD) is a surgical treatment for refractory ventricular arrhythmias. Although the procedure has shown efficacy at reducing cardiac arrhythmias, its impact on mental health is unknown. In the current study we examined associations between the BCSD procedure and mental health.Methods10 ventricular arrhythmia patients undergoing BCSD completed assessments of anxiety, depression, and posttraumatic stress symptoms at pre- and post-BCSD time points. Wilcoxon signed rank and Mann-Whitney U tests were used to examine differences in mental health symptoms in the pre- and post-BSCD states. Point biserial correlations were used to explore associations between BCSD response and mental health symptoms.ResultsA significant reduction of anxiety symptoms was observed from pre- to post-BCSD. At the post-BCSD assessment, participants who successfully responded to the BCSD procedure exhibited lower anxiety symptoms compared to non-responders. However, no significant relationships were identified for depressive or PTSD symptoms.ConclusionThe BCSD procedure is associated with reduced anxiety shortly after successful treatment for refractory ventricular arrhythmias in a small sample. Longitudinal surveillance of mental health symptoms after BCSD may be warranted to monitor the impact of this procedure on mental health.

Cardiac sarcoidosis (CS) is known to be associated with ventricular tachycardia (VT); however, most investigations to date have focused on patients with known extra-cardiac sarcoidosis. The presence of CS is typically evaluated using 18F-fluorodeoxyglucose (18F-FDG) uptake on cardiac positron emission tomography (PET) or late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). In this study, we sought to determine the prevalence of primary CS and the relationship between myocardial 18F-FDG uptake and LGE in patients with VT without known sarcoidosis. We retrospectively identified 67 patients without known sarcoidosis or active ischemic heart disease (i.e. significant ischemic disease that had not been previously revascularized) referred for both CMR and PET for evaluation of VT. Standard cine- and LGE- CMR and cardiac PET protocols were used. Myocardial LGE was defined as signal intensity > 5 SDs above the mean signal intensity of normal myocardium. Cardiac PET images were considered positive if there was focal myocardial 18F-FDG uptake having greater activity than the left ventricular blood pool. 45 patients (67%) had LGE, while only 4 (6%) had myocardial FDG uptake. Nine percent of patients with LGE had FDG-uptake while none without LGE did, and 10% of the cohort had indeterminate FDG uptake presumably from poor dietary preparation. Of those with both FDG uptake and LGE, 3/4 ultimately received a clinical diagnosis of CS. 4.5% of patients without previously known sarcoidosis or active ischemic heart disease presenting with VT have newly diagnosed CS. Detection of CS can be increased using a CMR first approach followed by cardiac PET for patients with non-ischemic LGE.

Background Sarcoidosis is a granulomatous disease usually affecting the lungs, although cardiac morbidity may be common. The risk of these outcomes and the characteristics that predict them remain largely unknown. This study investigates the epidemiology of heart failure, atrioventricular block, and ventricular tachycardia among patients with and without sarcoidosis. Methods and Results We identified California residents aged ≥21 years using the Office of Statewide Health Planning and Development ambulatory surgery, emergency, or inpatient databases from 2005 to 2015. The risk of sarcoidosis on incident heart failure, atrioventricular block, and ventricular tachycardia were each determined. Linkage to the Social Security Death Index was used to ascertain overall mortality. Among 22 527 964 California residents, 19 762 patients with sarcoidosis (0.09%) were identified. Sarcoidosis was the strongest predictor of heart failure (hazard ratio [HR], 11.2; 95% CI, 10.7-11.7), atrioventricular block (HR, 117.7; 95% CI, 103.3-134.0), and ventricular tachycardia (HR, 26.1; 95% CI, 24.2-28.1) identified among all risk factors. The presence of any cardiac involvement best predicted each outcome. Approximately 22% (95% CI, 18%-26%) of the relationship between sarcoidosis and increased mortality was explained by the presence of at least 1 of these cardiovascular outcomes. Conclusions The magnitude of risk associated with sarcoidosis as a predictor of heart failure, atrioventricular block, and ventricular tachycardia, exceeds all established risk factors. Surveillance for and anticipation of these outcomes among patients with sarcoidosis is indicated, and consideration of a sarcoidosis diagnosis may be prudent among patients with heart failure, atrioventricular block, or ventricular tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal cardiac channelopathy characterized by episodes of ventricular tachycardia (VT) during exercise or in stressful situations. As the peripartum period creates a stressful environment, we describe our approach of this rare condition in a very common situation, child birth.

The article focuses on the management of recurrent electrical storms in an 82-year-old patient with end-stage heart failure and ischaemic cardiomyopathy. Topics include the use of catheter ablation for left ventricular substrate modification and pulmonary vein isolation, the role of mechanical circulatory support with an Impella device during the procedure, and the challenge of managing electrical storms triggered by ventricular arrhythmias and atrial fibrillation.

RATIONALE: Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside. OBJECTIVE: To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes. METHODS AND RESULTS: We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10-fold. Support vector machines and convolutional neural networks were trained to 2 end points: (1) sustained VT/VF or (2) mortality at 3 years. Support vector machines provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each end point. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI, 0.76-1.00) and 0.91 for mortality (95% CI, 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained support vector machine revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium-calcium exchanger as predominant phenotypes for VT/VF. CONCLUSIONS: Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.

Background Cardiac sympathetic denervation (CSD) has been used as a bailout strategy for refractory ventricular tachycardia (VT). Risk of VT recurrence in patients with scar-related monomorphic VT referred for CSD and the extent to which CSD can modify this risk is unknown. We aimed to quantify arrhythmia recurrence risk and impact of CSD in this population. Methods and Results Adjusted competing risk time to event models were developed to adjust for risk of VT recurrence and sustained VT/implantable cardioverter-defibrillator shocks after VT ablation based on patient comorbidities at the time of VT ablation. Adjusted VT and implantable cardioverter-defibrillator shock recurrence rates were estimated for the subgroup who subsequently required CSD after ablation. The expected adjusted recurrence rates were then compared with the observed rates after CSD. Data from 381 patients with scar-mediated monomorphic VT who underwent VT ablation were analyzed, excluding patients with polymorphic VT. Sixty eight patients underwent CSD for recurrent VT. CSD reduced the expected adjusted VT recurrence rate by 36% (expected rate of 5.61 versus observed rate of 3.58 per 100 person-months, P=0.01) and the sustained VT/implantable cardioverter-defibrillator shock rates by 34% (expected rate of 4.34 versus observed 2.85 per 100 person-months, P=0.03). The median number of sustained VT/implantable cardioverter-defibrillator shocks in the year before versus the year after CSD was reduced by 90% (10 versus 1, P

Sudden death is the most common mode of mortality in patients with heart failure and preserved ejection fraction (HFpEF). Ventricular arrhythmias (VA) have been suspected as the etiology but the supporting evidence in patients with HFpEF is scarce. We sought to investigate VA prevalence, and to determine if VA are associated with prolonged repolarization, in patients with HFpEF. In a retrospective case-control study design, Cedars-Sinai patients who underwent prolonged ambulatory electrocardiographic monitoring (Zio Patch) between 2016 and 2018 were screened for a clinical diagnosis of HFpEF. Patients with normal diastolic and systolic function who underwent Zio Patch monitoring were also reviewed as controls. Multivariable logistic regression was used to compare the prevalence of rhythm disturbances in patients with and without HFpEF. Ventricular tachycardia (VT) was more prevalent in patients with HFpEF (37% vs. 16% in controls, p = 0.001). Most episodes were non-sustained except for one case of sustained VT in a patient with HFpEF. Covariate-adjusted logistic regression including HFpEF diagnosis, age, sex, body mass index, and the presence of comorbidities revealed that only HFpEF was associated with increased risk of VT (relative risk 2.86, p = 0.023). Subgroup-analyses revealed an association between increased QTc interval and risk of VT (460 ± 38 ms in HFpEF patients with VT vs. 445 ± 28 ms in HFpEF patients without VT, p = 0.03). Non-sustained VT was more prevalent in patients with HFpEF compared to patients without HFpEF, and QTc interval prolongation was associated with VT in HFpEF.

Mitochondrial diseases are rare, often go undiagnosed and can lead to devastating cascades of multisystem organ dysfunction. This report of a young woman with hearing loss and gestational diabetes illustrates a novel presentation of a cardiomyopathy caused by a previously described mutation in a mitochondrial gene, MT-TL1. She initially had biventricular heart dysfunction and ventricular arrhythmia that ultimately recovered with beta blockade and time. She continues to participate in sport without decline. It is important to keep mitochondrial diseases in the differential diagnosis and understand the testing and management strategies in order to provide the best patient care.

Mutations in the calcium-binding protein calsequestrin cause the highly lethal familial arrhythmia catecholaminergic polymorphic ventricular tachycardia (CPVT). In vivo, calsequestrin multimerizes into filaments, but there is not yet an atomic-resolution structure of a calsequestrin filament. We report a crystal structure of a human cardiac calsequestrin filament with supporting mutational analysis and in vitro filamentation assays. We identify and characterize a new disease-associated calsequestrin mutation, S173I, that is located at the filament-forming interface, and further show that a previously reported dominant disease mutation, K180R, maps to the same surface. Both mutations disrupt filamentation, suggesting that disease pathology is due to defects in multimer formation. An ytterbium-derivatized structure pinpoints multiple credible calcium sites at filament-forming interfaces, explaining the atomic basis of calsequestrin filamentation in the presence of calcium. Our study thus provides a unifying molecular mechanism through which dominant-acting calsequestrin mutations provoke lethal arrhythmias.

A case study describes a German Shepherd Dog (GSD) presented for abdominal CT evaluation of a suspected intrahepatic portosystemic shunt, with recent serum biochemistry abnormalities including hypoglycemia, decreased BUN and creatinine, hypoproteinemia, hypoalbuminemia and hypocholesterolemia. Anesthesia induction was briefly delayed due to ventricular bigeminy noted during preoxygenation, but despite the arrhythmia, the patient showed normal mentation and adequate pulse quality.

Summary: Accelerated idioventricular rhythms (AIVR) are increasingly diagnosed in horses, particularly in those with underlying systemic disease. Recognition of these abnormal rhythms is important but specific treatment is often not necessary unless the rhythms become haemodynamically relevant, with AIVR often resolving as the systemic disease improves. The goals of treatment, when indicated, include improving cardiac output, decreasing systemic and myocardial inflammation (if present) and controlling the ventricular rate and rhythm. Identification of any persistent myocardial damage or arrhythmia burden will be important for the prognosis and risk assessment of these patients in the longer term. [ABSTRACT FROM AUTHOR]

BACKGROUND: Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among patients with an implantable cardioverter-defibrillator (ICD). METHODS: The study population comprised 3895 ICD recipients in the United States enrolled in primary prevention ICD trials. Outcome measures included ventricular tachyarrhythmia (VTA), atrial tachyarrhythmia (ATA), ICD therapies, VTA burden (using Andersen-Gill recurrent event analysis), death, and the predicted benefit of the ICD. All events were adjudicated blindly. Outcomes were compared between self-reported Black patients versus White patients with cardiomyopathy (ischemic and NICM). RESULTS: Black patients were more likely to be female (35% versus 22%) and younger (57±12 versus 62±12 years) with a higher frequency of comorbidities. In NICM, Black patients had a higher rate of first VTA, fast VTA, ATA, and appropriate and inappropriate ICD therapy (VTA ≥170 bpm, 32% versus 20%; VTA ≥200 bpm, 22% versus 14%; ATA, 25% versus 12%; appropriate therapy, 30% versus 20%; and inappropriate therapy, 25% versus 11%; P <0.001 for all). Multivariable analysis showed that Black patients with NICM experienced a higher risk of all types of arrhythmia or ICD therapy (VTA ≥170 bpm, hazard ratio [HR] 1.71; VTA ≥200 bpm, HR 1.58; ATA, HR 1.87; appropriate therapy, HR 1.62; inappropriate therapy, HR 1.86; P ≤0.01 for all), higher burden of tachyarrhythmias or therapies (VTA, HR 1.84; appropriate therapy, HR 1.84; P <0.001 for both), and a higher risk of death (HR 1.92; P =0.014). In contrast, in ischemic cardiomyopathy, the risk of all types of tachyarrhythmia, ICD therapy, or death was similar between Black patients and White patients. Both Black patients and White patients derived a significant and similar benefit from ICD implantation. CONCLUSIONS: Among patients with NICM with an ICD for primary prevention, Black patients compared with White patients had a high risk and burden of VTA, ATA, and ICD therapies with a lower survival rate. Nevertheless, the overall benefit of the ICD was maintained and was similar to that of White patients. [ABSTRACT FROM AUTHOR]