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Purpose Catheter ablation has become a mainstay therapy for atrial fibrillation (AF) with rapid innovation over the past decade. Variability in ablation techniques may impact efficiency, safety, and efficacy; and the ideal strategy is unknown. Real-world evidence assessing the impact of procedural variations across multiple operators may provide insight into these questions. The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal (PAF) and Persistent (PsAF) Atrial Fibrillation registry (Real-AF) is a multicenter prospective registry that will enroll patients at high volume centers, including academic institutions and private practices, with operators performing ablations primarily with low fluoroscopy when possible. The study will also evaluate the contribution of advent in technologies and workflows to real-world clinical outcomes. Methods Patients presenting at participating centers are screened for enrollment. Data are collected at the time of procedure, 10–12 weeks, and 12 months post procedure and include patient and detailed procedural characteristics, with short and long-term outcomes. Arrhythmia recurrences are monitored through standard of care practice which includes continuous rhythm monitoring at 6 and 12 months, event monitors as needed for routine care or symptoms suggestive of recurrence, EKG performed at every visit, and interrogation of implanted device or ILR when applicable. Results Enrollment began in January 2018 with a single site. Additional sites began enrollment in October 2019. Through May 2021, 1,243 patients underwent 1,269 procedures at 13 institutions. Our goal is to enroll 4000 patients. Discussion Real-AF’s multiple data sources and detailed procedural information, emphasis on high volume operators, inclusion of low fluoroscopy operators, and use of rigorous standardized follow-up methodology allow systematic documentation of clinical outcomes associated with changes in ablation workflow and technologies over time. Timely data sharing may enable real-time quality improvements in patient care and delivery. Trial registration Clinicaltrials.gov: NCT04088071 (registration date: September 12, 2019) Supplementary Information The online version contains supplementary material available at 10.1007/s10840-021-01031-w.

Background Cardiac implantable electronic device (CIED) implantation is increasingly performed worldwide with improving safety. Outpatient CIED implantation has similar complication rates compared to those implants which are hospitalized. Here, we analyze patient preferences on discharge timing after CIED implantation. Objective To identify and understand the factors contributing to patient preferences towards same-day or next-day discharge after CIED implantation. Methods One hundred and two patients undergoing new CIED implants were included in the study at two separate hospitals in CT (CT group) and FL (FL group) from 2018-2019. A 7-question survey was administered to the patients after the procedure. Survey responses and demographic data were statistically analyzed. Results Seventy-four percent of CT group and 58% of the FL group responded with a 10 score (0-10) that they were ready to be discharged home the same day (p=0.09). Both groups reported a low number of patients feeling safer by having a remote monitor provided at the time of discharge (44% CT group, 28% FL group; p=0.123). The mean distance of patients living from the hospital in CT group (21.6 miles) was significantly lower than that for the FL group (35.5 miles); p=0.01. Hypertension (86% vs 52%; p=0.0002) and Diabetes mellitus (44% vs 21%; p=0.013) were more prevalent in the FL group compared to the CT group. Conclusion Despite the influence of local practices, the majority of patients preferred same-day discharge after CIED implantation. Improved patient education regarding the ability of remote monitors to provide real-time response to acute events is needed.

Introduction: Atrial fibrillation increases the risk of stroke 5-fold. The efficacy of endocardial catheter ablation (CA) for drug - refractory persistent and longstanding persistent AF (PsAF) is limited and has led to the development of minimally invasive hybrid epicardial/endocardial ablation technique (hybrid Convergent) to achieve a comprehensive lesion set with durable transmural lesions. The CONVERGE IDE randomized controlled trial prospectively evaluated the effectiveness of Convergent ablation compared to CA for the treatment of PsAF. Methods: PsAF patients, >18 to Results: One hundred fifty-three patients (102 Convergent, 51 CA) with similar baseline characteristics were treated. Body mass index (mean 33.7, range 19.1- 50.1) and years since PsAF diagnosis (mean 4.4 years, range 0.5 - 26.0 years) were high; 42.5% (65/153) patients had longstanding persistent AF. In the Convergent arm, 4 major adverse events (3.9%, 4/102) were reported through the first 7 days and additional 4 events (3.9%) from days 8 - 30. The safety rates were lower than the performance goal of 12%. Rates of freedom from atrial arrythmia stratified by AAD use are included in Table1. Irrespective of the criteria, the hybrid Convergent procedure demonstrated significantly higher treatment success compared to CA (RR 1.28 - 1.67, p Conclusion: The hybrid Convergent procedure combining epicardial and endocardial ablation is safe and has superior effectiveness as compared to the endocardial catheter ablation for the treatment of PsAF, irrespective of AAD use.

Background: The limited effectiveness of endocardial catheter ablation (CA) for persistent and long-standing persistent atrial fibrillation (AF) treatment led to the development of a minimally invasive epicardial/endocardial ablation approach (Hybrid Convergent) to achieve a more comprehensive lesion set with durable transmural lesions. The multicenter randomized controlled CONVERGE trial (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent AF) evaluated the safety of Hybrid Convergent and compared its effectiveness to CA for persistent and long-standing persistent AF treatment. Methods: One-hundred fifty-three patients were randomized 2:1 to Hybrid Convergent versus CA. Primary effectiveness was freedom from AF/atrial flutter/atrial tachycardia absent new/increased dosage of previously failed/intolerant class I/III antiarrhythmic drugs through 12 months. Primary safety was major adverse events through 30 days. CONVERGE permitted left atrium size up to 6 cm and imposed no limits on AF duration, making it the only ablation trial to substantially include long-standing persistent–AF, that is, 42% patients with long-standing persistent–AF. Results: Of 149 evaluable patients at 12 months, primary effectiveness was achieved in 67.7% (67/99) patients with Hybrid Convergent and 50.0% (25/50) with CA ( P =0.036) on/off previously failed antiarrhythmic drugs and in 53.5% (53/99) versus 32.0% (16/50; P =0.0128) respectively off antiarrhythmic drugs. At 18 months using 7-day Holter, 74.0% (53/72) Hybrid Convergent and 55% (23/42) CA patients experienced ≥90% AF burden reduction. A total of 2.9% (3/102) patients had primary safety events within 7 days, and 4.9% (5/102) between 8 and 30 days postprocedure. No deaths, cardiac perforations, or atrioesophageal fistulas occurred. All but one primary safety event resolved. Conclusions: The Hybrid Convergent procedure has superior effectiveness compared to the CA for the treatment of persistent and long-standing persistent atrial fibrillation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01984346.

Introduction: Catecholamines are known to affect cardiac repolarization, and provocation with either isoproterenol or epinephrine has been proposed as a tool for uncovering latent repolarization abnormalities. This study systematically compares the effects of isoproterenol and epinephrine infusions on QT interval (QT), T waves and U waves in normal subjects. Methods and Results: Twenty-four normal subjects (29 ± 8 years) were evaluated during graded infusions of up to 0.30 μg/kg/minute epinephrine and 5.0 μg/minute isoproterenol. Heart rates at peak doses were 81 ± 13 bpm at 0.28 ± 0.04 μg/kg/minute epinephrine and 104 ± 5 bpm at 2.4 μg/minute isoproterenol. The longest absolute QT increase was 4 ± 5 msec above baseline during isoproterenol (P < 0.001) and 12 ± 23 msec during epinephrine (P = 0.07), while the longest corrected QT interval (QTc) increase was 67 ± 28 msec (P < 0.0001) and 79 ± 40 msec (P < 0.0001) above baseline during isoproterenol and epinephrine, respectively (P = 0.12 for difference). There was a 2-fold increase in U-wave amplitude during each intervention (P < 0.001). The specificity of paradoxical QT prolongation (≥30 msec at 0.05 μg/kg/minute or ≥35 msec at 0.10 μg/kg/minute epinephrine) and an increase in QTc ≥600 msec at any dose epinephrine were 100%. However, the specificity of other proposed criteria that utilized QTc measurement (≥30 msec at 0.10 μg/kg/minute or ≥65 msec at any dose) was poor whether all leads or only lead II were assessed. Conclusion: Both epinephrine and isoproterenol are associated with QTc prolongation and amplification of the U wave in normal subjects. The specificity of proposed criteria for epinephrine provocation in diagnosis of the long-QT syndrome is variable; however, paradoxical QT prolongation at low-dose epinephrine or a QTc ≥600 msec is highly specific.

Mechanical unloading during left ventricular assist device (LVAD) support may lead to cardiac recovery. Predictors of recovery, however, have not been identified. We aimed to evaluate the time course and durability of echocardiographic, electrocardiographic (ECG), histologic, and neurohormonal changes that occur with LVAD support and to screen for non-invasive markers of cardiac recovery.LVAD patients underwent monthly testing, including echocardiographic, ECG, and serum B-type natriuretic peptide (BNP) measurement. Paired myocardial tissue samples from implant and explant were also analyzed.Thirty-six LVAD patients were prospectively followed for an average of 101 +/- 99 days. Left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD) significantly improved at 30 days compared with pre-LVAD (19% +/- 6.6% vs 33% +/- 8.1%, 7.1 +/- 1.2 cm vs 4.9 +/- 1.0 cm, respectively; both p0.001), with no improvement thereafter. At 30 days, QRS duration and QTc interval were significantly decreased from pre-LVAD (both p0.05). There was a marked reduction in BNP, myocyte size, and collagen deposition with LVAD support (all p0.01). In screening for markers of recovery, the decrease in QTc was inversely related to LVEDD at 60 days. Changes in QRS and myocyte diameter also correlated with the improvement in LVEF at 30 days. No patients had sufficient recovery for device explantation.We demonstrate echocardiographic, ECG, histologic, and neurohormonal improvement during LVAD support. Cardiac recovery peaked by 60 days, and there was a trend toward progressive improvement in QRS duration with ongoing support. We report the association of ECG changes with echocardiographic and histologic improvements. Future prospective studies may yield important markers of recovery.

Prolonged repolarization time, an important contributor to the pathogenesis of ventricular arrhythmias, is usually identified by a long QT interval (QT) on the ECG but is frequently confounded by the presence of a U wave. The physiological basis and clinical relevance of the U wave is unresolved. To better understand the relationship between the T and U waves, this study examined their behavior during nonresting autonomic conditions. Twenty-five healthy subjects were evaluated during sympathomimetic infusion with isoproterenol and vagal inhibition with atropine. As heart rate (HR) increased in response to isoproterenol, the QU interval (QU) decreased by an eightfold greater extent than QT. Furthermore, a marked increase in U wave amplitude and decrease in T wave amplitude were observed with T and U wave fusion at higher HRs. During atropine, QU decreased by only a threefold greater extent than QT, T and U wave amplitudes were affected only minimally, and T-U wave fusion was not observed. These results demonstrate that sympathomimetic stimulation causes striking alterations in the timing and amplitude of U waves that differ from effects on the T wave. These effects are not observed during vagal inhibition. Thus, the U wave represents a component of cardiac repolarization that is electrocardiographically and physiologically distinct from the T wave with a unique response to sympathomimetic stimulation.

ObjectivesWe sought to determine whether the relationship between heart rate (HR) and QT interval (QT) differs as HR increases in response to exercise, atropine and isoproterenol.BackgroundAutonomic nervous system influences on repolarization are poorly understood and may complicate the interpretation of QT measurements.MethodsTwenty-five normal subjects sequentially underwent graded-intensity bicycle exercise, atropine injection and isoproterenol infusion. Serial 12-lead electrocardiograms were recorded at steady state during each condition and analyzed using interactive computer software. The HR-QT data were modeled linearly and the slopes (quantifying QT adaptation to HR) as well as the QT intervals at 100 beats/min for each intervention were compared by repeated-measures analysis of variance.ResultsAs HR increased, QT was longer for isoproterenol in comparison to exercise or atropine, which were similar. The HR-QT slope (ms/beats/min) was less steep for isoproterenol (−0.83 ± 0.53) than for atropine (−1.45 ± 0.21) or exercise (−1.37 ± 0.23) (p < 0.0001). In comparison to men, women had more negative HR-QT slopes during all interventions. At 100 beats/min, the QT was 364 ms during isoproterenol, which was significantly longer than that during exercise (330 ms) or atropine (339 ms) (p < 0.0001). Isoproterenol produced a dose-dependent increase in U-wave amplitude that was not observed during exercise or atropine.ConclusionsIn comparison to exercise and atropine, isoproterenol is associated with much less QT shortening for a given increase in HR and, therefore, greater absolute QT intervals. Our findings demonstrate that autonomic conditions directly affect the ventricular myocardium of healthy subjects, causing differences in QT that are independent of HR.

The proarrhythmic effects of cocaine may be mediated in part by its effects on cardiac repolarization properties. This study evaluated the acute effects of smoking cocaine 25 mg on the electrocardiograms of 14 habitual cocaine users during a 12-minute observation period. After cocaine administration, heart rate increased by a mean of 22 beats/min (p

Atrial Arrhythmias After Surgical AF ablation. Introduction: Typical and atypical atrial flutters (AFLs) and atrial tachycardias (ATs) have been reported in patients with prior surgical atrial fibrillation ablation. The underlying mechanisms for this group of atrial tachyarrhythmias have not been well characterized and the efficacy of catheter ablation in their treatment is unknown. Methods and Results: Twenty patients (6 females) with a surface ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation underwent 26 electrophysiology studies. Patients manifesting sustained, organized, and beat-by-beat reproducible atrial electrical activity underwent complete right and left atrial catheter mapping and catheter ablation. One patient had no inducible tachyarrhythmia, while 5 patients had nonmappable arrhythmias. Nineteen of the 31 potentially mappable atrial tachyarrhythmias were completely characterized in 14 patients. The underlying mechanisms were macro-reentrant left AFL (n = 9), focal left AT (n = 3), typical right AFL (n = 6), and atypical right AFL (n = 1). Of the 19 completely characterized atrial arrhythmias, catheter ablation was performed for 18, and the procedure was successful for 13 of these. After a mean follow-up of 15 ± 10 months, 15 of 20 patients (75%) were in sinus rhythm including 10 of 13 patients (77%) with AT/flutter ablation. Ten patients, including 6 following ablation, were maintaining sinus rhythm without antiarrhythmic medications. Conclusions: Patients with an ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation may have multiple tachycardia mechanisms with the right or left atrium as the site of origin. Many of these rhythms may resolve with further maturation of surgical atrial fibrillation ablation (SAFA) lesions or be treatable with antiarrhythmic medication. However, persistent tachyarrhythmias can often be treated successfully with catheter mapping and ablation.

Maintenance of a reduced body weight is accompanied by decreased energy expenditure that is due largely to increased skeletal muscle work efficiency. In addition, decreased sympathetic nervous system tone and circulating concentrations of leptin, thyroxine, and triiodothyronine act coordinately to favor weight regain. These “weight-reduced” phenotypes are similar to those of leptin-deficient humans and rodents. We examined metabolic, autonomic, and neuroendocrine phenotypes in 10 inpatient subjects (5 males, 5 females [3 never-obese, 7 obese]) under 3 sets of experimental conditions: (a) maintaining usual weight by ingesting a liquid formula diet; (b) maintaining a 10% reduced weight by ingesting a liquid formula diet; and (c) receiving twice-daily subcutaneous doses of leptin sufficient to restore 8 am circulating leptin concentrations to pre–weight-loss levels and remaining on the same liquid formula diet required to maintain a 10% reduced weight. During leptin administration, energy expenditure, skeletal muscle work efficiency, sympathetic nervous system tone, and circulating concentrations of thyroxine and triiodothyronine returned to pre–weight-loss levels. These responses suggest that the weight-reduced state may be regarded as a condition of relative leptin insufficiency. Prevention of weight regain might be achievable by strategies relevant to reversing this leptin-insufficient state.

A 48-year-old man with a history of idiopathic dilated cardiomyopathy, Class 3 symptoms of congestive heart failure, and left bundle-branch block with QRS duration of 164 ms was referred for revision of his implantable cardioverter-defibrillator to a biventricular pacing device. At the time of initial cardioverter-defibrillator implantation at an outside hospital, a coronary sinus (CS) lead was not placed because of …

The etiology of U waves on the electrocardiogram is uncertain. We previously found that U waves could be amplified by isoproterenol infusion. Whether other autonomic interventions modify U-wave amplitude is unknown. Twenty-five healthy subjects underwent graded infusions of esmolol and phenylephrine. Heart rate, T-wave amplitude, U-wave amplitude, and QT and QU intervals were measured using interactive computerized electrocardiogram software. Heart rate decreased with both interventions (P < .001), though to a greater degree with phenylephrine. U-wave amplitude increased by 16.3% during phenylephrine (P < .001) but decreased by 14.5% during esmolol (P < .001). The change in U-wave amplitude was strongly dose-dependent for both phenylephrine (P < .001) and esmolol (P < .001). T-wave amplitude increased with phenylephrine (597-692 μV, P < .001) but decreased with esmolol (632-568 μV, P < .001). QT and QU intervals increased with both interventions (P < .001). We conclude that sympathetic and parasympathetic activities are important determinants of U-wave timing and amplitude.

ObjectivesIn a retrospective study, we sought to evaluate the effect of left ventricular assist device (LVAD) therapy on ventricular tachyarrhythmias in patients with advanced congestive heart failure.BackgroundDespite the increasing use of LVAD as a bridge to cardiac transplantation, our knowledge regarding its effect on ventricular arrhythmias is currently limited to small series. Little is known about the prevalence, predictors, and clinical consequences of ventricular arrhythmias in LVAD recipients.MethodsWe reviewed the pre- and post-LVAD course of the last 100 consecutive adult patients to receive a HeartMate LVAD (Thoratec Laboratories Corp., Pleasanton, California) at our institution. All ventricular arrhythmias sustained for at least 30 s or requiring defibrillation were analyzed. All documented pre- and post-LVAD sustained ventricular arrhythmias were classified either as monomorphic ventricular tachycardia (MVT) or polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF).ResultsOur population had an average age of 51 years, had predominately ischemic cardiomyopathy (63%), and a mean left ventricular ejection fraction of 20 ± 10%. New-onset MVT was observed in 18 patients who did not have MVT before LVAD placement. After LVAD, new-onset MVT was 4.5 times more likely than elimination of previously present MVT (p = 0.001), whereas the effect of LVAD on incidence of PVT/VF was not significant. In a multivariate Cox proportional hazards regression analysis, serum electrolyte abnormality was an independent predictor of post-LVAD ventricular arrhythmias. Preoperative MVT did not predict postoperative MVT.ConclusionsAfter LVAD placement, there is a significant rise in the incidence of de novo MVT. By contrast, the incidence of PVT/VF was unaffected by LVAD placement.

In light of the significant morbidity and mortality from atrial fibrillation (AF), there has been significant interest in the development of percutaneous catheter ablation procedures for the suppression of AF. Given the success of the surgical Maze procedure, initial catheter-based approaches involved creation of linear atrial lesions. Success rates were low and utility was limited by a high complication rate and long procedural times. The recent discovery that AF is often initiated by atrial ectopic beats has resulted in therapies designed to target the ectopic sources, particularly those within the pulmonary veins. Experience and technological advances have improved the efficacy and safety of such procedures. This article will review catheter ablation procedures for the maintenance of sinus rhythm in patients with AF.

Clinically important supraventricular arrhythmias are occasionally encountered in patients following cardiac transplantation and the use of catheter ablation as a treatment has been reported. The following three cases are described: (1) atrial flutter, including electroanatomic mapping of the donor and recipient components of the right atrium, (2) a mid-septal accessory pathway, and (3) atrioventricular nodal reentrant tachycardia (AVNRT). A Medline database search was performed and articles addressing catheter ablation following cardiac transplantation were reviewed. The efficacy of RFA for treating various arrhythmia mechanisms was evaluated based on a summary of published case reports.

A 60-year-old man presented to the emergency department with multiple episodes of palpitations, dyspnea, diaphoresis, and lightheadedness. One episode was associated with a syncopal event 1 week before admission. His symptoms recurred during hospitalization, at which time telemetry documented a narrow complex tachycardia at 160 bpm accompanied by hypotension. During the next 24 hours, he developed sinus tachycardia and hypotension followed by normal sinus rhythm and hypertension, which alternated in a cyclic pattern with a periodicity of ≈8 minutes (Figure …

R-R interval variability (RR variability) is increasingly being used as an index of autonomic activity. High-frequency (HF) power reflects vagal modulation of the sinus node. Since vagal modulation occurs at the respiratory frequency, some investigators have suggested that HF power cannot be interpreted unless the breathing rate is controlled. We hypothesized that HF power during spontaneous breathing would not differ significantly from HF power during metronome-guided breathing. We measured HF power during spontaneous breathing in 20 healthy subjects and 19 patients with heart disease. Each subject's spontaneous breathing rate was determined, and the calculation of HF power was repeated with a metronome set to his or her average spontaneous breathing rate. There was no significant difference between the logarithm of HF power measured during spontaneous and metronome-guided breathing [4.88 ± 0.29 vs. 5.29 ± 0.30 ln(ms2), P = 0.32] in the group as a whole and when patients and healthy subjects were examined separately. We did observe a small (9.9%) decrease in HF power with increasing metronome-guided breathing rates (from 9 to 20 breaths/min). These data indicate that HF power during spontaneous and metronome-guided breathing differs at most by very small amounts. This variability is several logarithmic units less than the wide discrepancies observed between healthy subjects and cardiac patients with a heterogeneous group of cardiovascular disorders. In addition, HF power is relatively constant across the range of typical breathing rates. These data indicate that there is no need to control breathing rate to interpret HF power when RR variability (and specifically HF power) is used to identify high-risk cardiac patients.

Neurogenic stunned myocardium (NSM), a syndrome of reversible left ventricular dysfunction best described after subarachnoid hemorrhage, has not been associated with peripheral neuropathy. We describe a woman with Guillain-Barre syndrome in whom a syndrome compatible with NSM developed in the setting of a physiologically documented increase in sympathetic cardiovascular tone. This case supports the presumed unifying role of excessive sympathetic nervous system activation in the pathogenesis of NSM.