Abstract Background Although electrolyte disturbances may affect cardiac action potential, little is known about the association between serum magnesium and corrected QT (QTc) interval as well as ...clinical outcomes. Methods A consecutive 8498 patients admitted to the Mayo Clinic Hospital—Rochester cardiac care unit (CCU) from January 1, 2004 through December 31, 2013 with 2 or more documented serum magnesium levels, were studied to test the hypothesis that serum magnesium levels are associated with in-hospital mortality, sudden cardiac death, and QTc interval. Results Patients were 67 ± 15 years; 62.2% were male. The primary diagnoses for CCU admissions were acute myocardial infarction (50.7%) and acute decompensated heart failure (42.5%), respectively. Patients with higher magnesium levels were older, more likely male, and had lower glomerular filtration rates. After multivariate analyses adjusted for clinical characteristics including kidney disease and serum potassium, admission serum magnesium levels were not associated with QTc interval or sudden cardiac death. However, the admission magnesium levels ≥2.4 mg/dL were independently associated with an increase in mortality when compared with the reference level (2.0 to <2.2 mg/dL), having an adjusted odds ratio of 1.80 and a 95% confidence interval of 1.25-2.59. The sensitivity analysis examining the association between postadmission magnesium and analysis that excluded patients with kidney failure and those with abnormal serum potassium yielded similar results. Conclusion This retrospective study unexpectedly observed no association between serum magnesium levels and QTc interval or sudden cardiac death. However, serum magnesium ≥2.4 mg/dL was an independent predictor of increased hospital morality among CCU patients.
Reentrant ventricular arrhythmias are a major cause of sudden death in patients with structural heart disease. Current treatments focus on electrically homogenizing regions of scar contributing to ...ventricular arrhythmia with ablation or altering conductive properties using antiarrhythmic drugs. The high conductivity of carbon nanotubes may allow restoration of conduction in regions where impaired electrical conduction results in functional abnormalities. We propose a new concept for arrhythmia treatment using a stretchable, flexible biopatch with conductive properties to attempt to restore conduction across regions in which activation is disrupted.
Carbon nanotube patches composed of nanofibrillated cellulose/single-walled carbon nanotube ink 3-dimensionally printed in conductive patterns onto bacterial nanocellulose were developed and evaluated for conductivity, flexibility, and mechanical properties. The patches were applied on 6 canines to epicardium before and after surgical disruption. Electroanatomic mapping was performed on normal epicardium, then repeated over surgically disrupted epicardium, and then finally with the patch applied passively.
We developed a 3-dimensional printable carbon nanotube ink complexed on bacterial nanocellulose that was (1) expressable through 3-dimensional printer nozzles, (2) electrically conductive, (3) flexible, and (4) stretchable. Six canines underwent thoracotomy, and, during epicardial ventricular pacing, mapping was performed. We demonstrated disruption of conduction after surgical incision in all 6 canines based on activation mapping. The patch resulted in restored conduction based on mapping and assessment of conduction direction and velocities in all canines.
We have demonstrated 3-dimensional custom-printed electrically conductive carbon nanotube patches can be surgically manipulated to improve cardiac conduction when passively applied to surgically disrupted epicardial myocardium in canines.
Atrial fibrillation (AF) ablation is an increasingly utilized rhythm control strategy that can damage adjacent structures in the mediastinum including the esophagus. Atrioesophageal fistulas and ...esophagopericardial fistulas are life-threatening complications that are thought to progress from early esophageal mucosal injury (EI). Endoscopic ultrasound (EUS) has been proposed as a superior method than EGD to survey EI and damage to deeper structures. We aim to evaluate the safety of EUS in categorizing post-ablation EI and quantify EUS-detected lesions and their correlation with injury severity and clinical course.
234 consecutive patients between 2006-2020 who underwent AF ablation followed by EUS for the purpose of EI screening were retrospectively reviewed. Kansas City Classification (KCC) was used to classify EI (Type 1, Type 2a/b, Type 3a/b).
EUS identified pleural effusions (31.6%) of patients, mediastinal adventitia changes (22.2%), mediastinal lymphadenopathy (14.1%), pulmonary vein changes (10.6%), and esophageal wall changes (7.7%). EGD revealed 175 (75%) patients without and 59 (25%) with EI. Patients with Type 2a/b EI and no EI were compared with multivariate logistic regression, and the presence of esophageal wall abnormality on EUS with OR 72.85 (95% CI 13.9-380.7), female sex with OR 3.97 (95% CI 1.3-12.3), and number of energy deliveries with OR 1.01 (95% CI 1.003-1.03), were associated with the presence EI type 2a or 2b. Pre-ablation PPI use was not associated with decreased risk of EI.
EUS safely assesses mediastinal damage after ablation for atrial fibrillation and may excel over EGD in evaluating mucosal lesions of uncertain significance, with reduced risk of gas embolization in the setting of a full thickness injury (entero-vascular fistula). We propose an EUS-first guided approach to post-AF ablation examination, followed by EGD if it is safe to do so.
Introduction
Although prior studies indicate that a QTc > 500 ms on a single baseline 12‐lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT ...syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS.
Methods
We performed a retrospective analysis of 433 patients with LQTS evaluated, risk‐stratified, and undergoing active guideline‐based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF‐terminating ICD shock, and sudden cardiac death (SCD).
Results
During the median follow‐up of 5.5 years (interquartile range IQR = 3–9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c‐statistic = 0.93–0.95). Patients in the high‐risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%–81%) when compared to patients in both medium‐risk (93%–97%) and low‐risk (98%–99%) groups.
Conclusions
The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12‐lead ECGs are at the highest risk of BCE while on guideline‐directed medical therapy.
Dofetilide is an effective antiarrhythmic medication for rhythm control in atrial fibrillation, but carries a significant risk of pro-arrhythmia and requires meticulous dosing and monitoring. The ...cornerstone of this monitoring, measurement of the QT/QTc interval, is an imperfect surrogate for plasma concentration, efficacy, and risk of pro-arrhythmic potential.
The aim of our study was to test the application of a deep learning approach (using a convolutional neural network) to assess morphological changes on the surface ECG (beyond the QT interval) in relation to dofetilide plasma concentrations.
We obtained publically available serial ECGs and plasma drug concentrations from 42 healthy subjects who received dofetilide or placebo in a placebo-controlled cross-over randomized controlled clinical trial. Three replicate 10-s ECGs were extracted at predefined time-points with simultaneous measurement of dofetilide plasma concentration We developed a deep learning algorithm to predict dofetilide plasma concentration in 30 subjects and then tested the model in the remaining 12 subjects. We compared the deep leaning approach to a linear model based only on QTc.
Fourty two healthy subjects (21 females, 21 males) were studied with a mean age of 26.9 ± 5.5 years. A linear model of the QTc correlated reasonably well with dofetilide drug levels (r = 0.64). The best correlation to dofetilide level was achieved with the deep learning model (r = 0.85).
This proof of concept study suggests that artificial intelligence (deep learning/neural network) applied to the surface ECG is superior to analysis of the QT interval alone in predicting plasma dofetilide concentration.
Background
Though infrequent, incomplete left atrial appendage closure (LAAC) may result from residual leaks. Percutaneous closure has been described though data is limited.
Methods
We compiled a ...registry from four centers of patients undergoing percutaneous closure of residual leaks following LAAC via surgical means or with the Watchman device. Leak severity was classified as none (no leak), mild (1–2 mm), moderate (3–4 mm), or severe (≥5 mm). Procedural and clinical success was defined as the elimination of leak or mild residual leak at the conclusion of the procedure or follow‐up, respectively.
Results
Of 72 (age 72.2 ± 9.2 years; 67% male) patients, 53 had undergone prior LAAC using the Watchman device and 19 patients surgical LAAC. Mean CHADS2‐VA2Sc score was 4.0 ± 1.8. The median leak size was 5 mm, range: 2–13). A total of 13 received Amplatzer Vascular Plug‐II, 18 received Amplatzer Duct Occluder‐II and 40 patients received coils. One underwent closure using a 21 mm‐Watchman. Procedural success was 94%. Zero surgical and nine Watchman patients (13%) had a residual leak at procedural‐end (five mild, three moderate, and one severe)—only one patient had no reduction in leak size. Overall leak size reduction was 94%. Two (3%) had intraoperative pericardial effusion. There were no device embolizations, device‐related thrombi, or procedural deaths. Clinical success was maintained at 94%. Two had cerebrovascular accidents—at 2 days (transient ischemic attack) and 10 months postprocedure. Two had major bleeding outside the 30‐day periprocedural window.
Conclusion
Percutaneous closure of residual leaks following left atrial appendage closure is feasible and associated with good outcomes. The procedural risk appears to be satisfactory.
Background
Incidental mobile thrombi are commonly found on endovascular leads of cardiac implantable electronic devices (CIEDs). Transseptal puncture for catheter ablation of arrhythmia poses a risk ...for paradoxical embolism. We examined risk of ischemic stroke, transient ischemic attack (TIA), or systemic embolism after transseptal ablation in patients with and without CIEDs.
Methods and Results
Using a national administrative claims database, 31 720 patients who underwent a transseptal catheter ablation between January 2004 and September 2014 were identified. Two propensity‐matched cohorts were created by matching demographic variables, administrative variables, Charlson Comorbidity Index, CHA2DS2‐Vasc score, and year and indication for ablation (5533 and 11 300 patients with and without CIEDs). Incidence rates and Cox proportional hazards models were used to estimate risk of ischemic stroke, TIA, or systemic embolism for patients with and without CIEDs. Impact of oral anticoagulation (OAC) use on the endpoint was examined. Over a mean follow‐up of 2.1 years, the incidence of the combined endpoint was 1.9 per 100 person‐years in patients with CIEDs and 1.5 per 100 person‐years in patients without CIEDs (P=0.03). Among patients not on OAC, presence of a cardiac device was associated with an increased risk (hazard ratio HR, 1.71 1.24–2.35; P<0.01), whereas there was no association noted among patients treated with OAC (HR, 0.98 0.75–1.28).
Conclusion
CIEDs are associated with an increased risk of stroke, TIA, or systemic embolism after transseptal ablation, but this risk is attenuated with postablation OAC use. Role of anticoagulation post‐transseptal ablation in patients with CIED warrants further investigation.
The application of brief high voltage electrical pulses to tissue can lead to an irreversible or reversible electroporation effect in a cell-specific manner. In the management of ventricular ...arrhythmias, the ability to target different tissue types, specifically cardiac conduction tissue (His-Purkinje System) vs. cardiac myocardium would be advantageous. We hypothesize that pulsed electric fields (PEFs) can be applied safely to the beating heart through a catheter-based approach, and we tested whether the superficial Purkinje cells can be targeted with PEFs without injury to underlying myocardial tissue.
In an acute (n = 5) and chronic canine model (n = 6), detailed electroanatomical mapping of the left ventricle identified electrical signals from myocardial and overlying Purkinje tissue. Electroporation was effected via percutaneous catheter-based Intracardiac bipolar current delivery in the anesthetized animal. Repeat Intracardiac electrical mapping of the heart was performed at acute and chronic time points; followed by histological analysis to assess effects.
PEF demonstrated an acute dose-dependent functional effect on Purkinje, with titration of pulse duration and/or voltage associated with successful acute Purkinje damage. Electrical conduction in the insulated bundle of His (n = 2) and anterior fascicle bundle (n = 2), was not affected. At 30 days repeat cardiac mapping demonstrated resilient, normal electrical conduction throughout the targeted area with no significant change in myocardial amplitude (pre 5.9 ± 1.8 mV, 30 days 5.4 ± 1.2 mV, p = 0.92). Histopathological analysis confirmed acute Purkinje fiber targeting, with chronic studies showing normal Purkinje fibers, with minimal subendocardial myocardial fibrosis.
PEF provides a novel, safe method for non-thermal acute modulation of the Purkinje fibers without significant injury to the underlying myocardium. Future optimization of this energy delivery is required to optimize conditions so that selective electroporation can be utilized in humans the treatment of cardiac disease.
Right ventricular systolic dysfunction (RVD) often coexists with various cardiopulmonary diseases. However, the association between RVD and risk of sudden cardiac death (SCD) has not been well ...studied. This study examined the risk of SCD associated with RVD in patients with heterogeneous underlying cardiac diseases.
The Mayo Clinic cardiac care unit database included 5463 consecutive patients with complete echocardiographic evaluation to assess right ventricular systolic function and RVD severity. Prospective surveillance follow-up was obtained for all patients. SCD was adjudicated when a malignant ventricular arrhythmia was documented as the primary rhythm leading to death.
The prevalence of mild RVD and moderate-severe RVD was 14.9% and 17.1%, respectively. Patients with RVD were more likely to have a history of congestive heart failure, cardiac arrest, pulmonary disease, and lower baseline left ventricular ejection fraction compared with those with normal right ventricular systolic function. During a median follow-up of 14 months, the incidence of SCD was highest in patients with moderate-severe RVD (7.4% versus 4.4% in mild RVD versus 1.6% in normal right ventricular function;
<0.001). After adjustment for baseline characteristics, mild RVD (adjusted hazard ratio, 1.57;
=0.046) and moderate-severe RVD (adjusted hazard ratio, 1.91;
=0.006) were independently associated with an increased risk of SCD. Moderate-severe RVD remained an independent predictor of SCD for patients with left ventricular ejection fraction >35% without or with preexisting implantable cardioverter-defibrillator (adjusted hazard ratio, 4.12;
=0.003 and adjusted hazard ratio, 5.04;
<0.001, respectively).
Presence of RVD in patients with a history of preexisting cardiac disease is an independent predictor of SCD irrespective of left ventricular ejection fraction.
Background
Pulmonary vein isolation (PVI) with autonomic modulation may be more successful than PVI alone for atrial fibrillation (AF) ablation and may be signaled by changes in sinus rhythm heart ...rate (HR) post ablation. We sought to determine if a change in sinus rhythm HR predicted AF recurrence post PVI.
Methods
Patients who underwent AF ablation from 2000 to 2011 were included if sinus rhythm was noted on ECG within 90 days pre and 7 days post ablation. Basic ECG interval and HR changes were analyzed and outcomes determined.
Results
A total of 1152 patients were identified (74.3% male, mean age 57 ± 11 years). Mean AF duration was 5.2 ± 5.3 years. Paroxysmal AF was noted in 712 (61.8%) of the patients. Mean EF was 61% ± 6%. Sinus rhythm HR was 61 ± 11 pre‐ablation and 76 ± 13 bpm post‐ablation (27% ± 24% increase, p < .001). The ability of relative HR change post‐ablation to predict AF recurrence was borderline (hazard ratio 0.65 0.41–1.01, p = .067). With patients separated into quartiles based on the relative HR change, the upper quartile with the largest relative increase in HR had a significantly lower rate of AF recurrence compared to the lowest quartile following multi variable modeling (p = .038). There were significant changes in PR (171 ± 28 to 167 ± 30 ms) and QTc (424 ± 25 to 434 ± 29 ms) intervals (both p < .001) but these were not predictive of outcome.
Conclusion
Relative changes in HR post AF ablation correlates with AF recurrence. Further prospective studies are needed to confirm this relationship.
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