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BACKGROUND: A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot. METHODS: Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation. RESULTS: A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%–44%] at baseline to 42% [32%–50%] at early follow-up (P <0.001) and remained improved from baseline thereafter (P ≤0.002). The QRS duration decreased from 180 [160–205] ms at baseline to 152 [133–182] ms at early follow-up (P <0.001) and remained decreased at intermediate and late follow-up (P ≤0.001). Patients with upgraded CRT had consistent improvement in left ventricular ejection fraction and QRS duration at each time point (P ≤0.004). Patients had a significantly improved New York Heart Association functional class after CRT implantation at each time point compared with baseline (P ≤0.002). The transplant-free survival rates at 3, 5, and 8 years after CRT implantation were 85%, 79%, and 73%. CONCLUSIONS: In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population. [ABSTRACT FROM AUTHOR]

Background: Premature ventricular contractions originating in the left ventricle outflow tract represent a significant subgroup of patients referred for catheter ablation. Mechanical artifacts from aortic valve leaflet motion may be observed during mapping, although the incidence and characteristics have not been reported.Methods and Results: Twenty-eight consecutive patients with left ventricle outflow tract premature ventricular contraction were included. Electric signals recorded on the ablation catheter not coincident with atrial or ventricular depolarization were analyzed on the recording system. Correlation with invasive hemodynamic aortic pressure tracings was performed. Additionally, 4 patients with mechanical aortic valves, who underwent scar-related ventricular tachycardia ablation, were analyzed to correlate the timing of the observed artifacts with native aortic valves. Aortic valve artifact was observed while mapping within the coronary cusps in 11 patients (39%; 73% men; age, 41±25 years; left ventricular ejection fraction 49±16%) with high incidence from the left coronary cusp. This artifact was consistently observed with timing coincident with the terminal portion of the T wave. The average interval between the end of the T wave and the aortic valve artifact was 19±37 ms. The duration of the aortic valve artifact was 39±8 ms with amplitude of 0.12±0.07 mV (range, 0.06-0.36 mV).Conclusions: In patients referred for left ventricle outflow tract premature ventricular contraction ablation, an aortic valve closure artifact is observed in up to one third of cases during mapping within the aortic cusps. The timing of this artifact correlates with invasive hemodynamics and mechanical aortic valve artifacts. Recognition of this physiological phenomenon is useful when assigning near-field activation. [ABSTRACT FROM AUTHOR]

Background: Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach.Methods and Results: In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli (P<0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response (P<0.05 versus short CI), particularly on convergent neurons (P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic input (P<0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs.Conclusions: Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: The occurrence of ventricular tachyarrhythmias seems to follow circadian, daily, and seasonal distributions. Our aim is to identify potential temporal patterns of electrical storm (ES), in which a cluster of ventricular tachycardias or ventricular fibrillation, negatively affects short- and long-term survival.Methods and Results: The TEMPEST study (Circannual Pattern and Temperature-Related Incidence of Electrical Storm) is a patient-level, pooled analysis of previously published data sets. Study selection criteria included diagnosis of ES, absence of acute coronary syndrome as the arrhythmic trigger, and ≥10 patients included. At the end of the selection and collection processes, 5 centers had the data set from their article pooled into the present registry. Temperature data and sunrise and sunset hours were retrieved from Weather Underground, the largest weather database available online. Total sample included 246 patients presenting with ES (221 men; age: 65±9 years). Each ES episode included a median of 7 ventricular tachycardia/ventricular fibrillation episodes. Fifty-nine percent of patients experienced ES during daytime hours (P<0.001). The prevalence of ES was significantly higher during workdays, with Saturdays and Sundays registering the lowest rates of ES (10.4% and 7.2%, respectively, versus 16.5% daily mean from Monday to Friday; P<0.001). ES occurrence was significantly associated with increased monthly temperature range when compared with the month before (P=0.003).Conclusions: ES incidence is not homogenous over time but seems to have a clustered pattern, with a higher incidence during daytime hours and working days. ES is associated with an increase in monthly temperature variation.Clinical Trial Registration: https://www.crd.york.ac.uk. Unique identifier: CRD42013003744. [ABSTRACT FROM AUTHOR]

Background: The effects of varying the wavefront of activation on ventricular scar characterization has not been systematically assessed.Methods and Results: Patients referred for ablation of scar-related ventricular tachycardia underwent voltage maps during a minimum of 2 wavefronts of activation. The bipolar and unipolar low-voltage areas were compared, and direct electrogram analysis was performed in regions where discrepancies were seen. Concordance between wavefronts was measured by calculating percentage of overlap between maps. Sixty endocardial voltage maps (360±147 points) were performed in 29 patients during 2 distinct wavefronts, with 3 wavefronts in 7 patients. With median bipolar and unipolar low-voltage areas of 37 and 116 cm(2), respectively, 22% and 14% variability in median scar area was observed with a different activation wavefront. Concordance between wavefronts was lower in patients with mixed scar compared to those with dense scar (52% [interquartile range, 29%-70%] versus 84% [interquartile range, 71%-87%]), with septal scars exhibiting the lowest concordance [(27% (interquartile range, 21%-56%)]. Among 16 critical sites for ventricular tachycardia, 3 (18%) were in a discordant region of scar, with one of the wavefronts showing voltage >1.5 mV.Conclusions: Significant differences in bipolar and unipolar low-voltage characterization of scar were observed with different ventricular activation wavefronts, particularly in septal locations and in patients without dense scar. In patients with a paucity of dense, low-voltage regions identified during substrate mapping, an alternate activation wavefront may increase the sensitivity to detect arrhythmogenic substrate and critical sites for ventricular tachycardia. [ABSTRACT FROM AUTHOR]

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST. [ABSTRACT FROM AUTHOR]

Background: It is not known whether the most delayed late potentials are functionally most specific for scar-related ventricular tachycardia (VT) circuits.Methods and Results: Isochronal late activation maps were constructed to display ventricular activation during sinus rhythm over 8 isochrones. Analysis was performed at successful VT termination sites and prospectively tested. Thirty-three patients with 47 scar-related VTs where a critical site was demonstrated by termination of VT during ablation were retrospectively analyzed. In those who underwent mapping of multiple surfaces, 90% of critical sites were on the surface that contained the latest late potential. However, only 11% of critical sites were localized to the latest isochrone (87.5%-100%) of ventricular activation. The median percentage of latest activation at critical sites was 78% at a distance from the latest isochrone of 18 mm. Sites critical to reentry were harbored in regions with slow conduction velocity, where 3 isochrones were present within a 1-cm radius. Ten consecutive patients underwent ablation prospectively guided by isochronal late activation maps, targeting concentric isochrones outside of the latest isochrone. Elimination of the targeted VT was achieved in 90%. Termination of VT was achieved in 6 patients at a mean ventricular activation percentage of 78%, with only 1 requiring ablation in the latest isochrone.Conclusions: Late potentials identified in the latest isochrone of activation during sinus rhythm are infrequently correlated with successful ablation sites for VT. The targeting of slow conduction regions propagating into the latest zone of activation may be a novel and promising strategy for substrate modification. [ABSTRACT FROM AUTHOR]

Background: T-peak to T-end interval (Tp-e) is an independent marker of sudden cardiac death. Modulation of Tp-e by sympathetic nerve activation and circulating norepinephrine is not well understood. The purpose of this study was to characterize endocardial and epicardial dispersion of repolarization (DOR) and its effects on Tp-e with sympathetic activation.Methods and Results: In Yorkshire pigs (n=13), a sternotomy was performed and the heart and bilateral stellate ganglia were exposed. A 56-electrode sock and 64-electrode basket catheter were placed around the epicardium and in the left ventricle (LV), respectively. Activation recovery interval, DOR, defined as variance in repolarization time, and Tp-e were assessed before and after left, right, and bilateral stellate ganglia stimulation and norepinephrine infusion. LV endocardial and epicardial activation recovery intervals significantly decreased, and LV endocardial and epicardial DOR increased during sympathetic nerve stimulation. There were no LV epicardial versus endocardial differences in activation recovery interval during sympathetic stimulation, and regional endocardial activation recovery interval patterns were similar to the epicardium. Tp-e prolonged during left (from 40.4±2.2 ms to 92.4±12.4 ms; P<0.01), right (from 47.7±2.6 ms to 80.7±11.5 ms; P<0.01), and bilateral (from 47.5±2.8 ms to 78.1±9.8 ms; P<0.01) stellate stimulation and strongly correlated with whole heart DOR during stimulation (P<0.001, R=0.86). Of note, norepinephrine infusion did not increase DOR or Tp-e.Conclusions: Regional patterns of LV endocardial sympathetic innervation are similar to that of LV epicardium. Tp-e correlated with whole heart DOR during sympathetic nerve activation. Circulating norepinephrine did not affect DOR or Tp-e. [ABSTRACT FROM AUTHOR]

Background: Data on relative safety, efficacy, and role of different percutaneous left ventricular assist devices for hemodynamic support during the ventricular tachycardia (VT) ablation procedure are limited.Methods and Results: We performed a multicenter, observational study from a prospective registry including all consecutive patients (N=66) undergoing VT ablation with a percutaneous left ventricular assist devices in 6 centers in the United States. Patients with intra-aortic balloon pump (IABP group; N=22) were compared with patients with either an Impella or a TandemHeart device (non-IABP group; N=44). There were no significant differences in the baseline characteristics between both the groups. In non-IABP group (1) more patients could undergo entrainment/activation mapping (82% versus 59%; P=0.046), (2) more number of unstable VTs could be mapped and ablated per patient (1.05±0.78 versus 0.32±0.48; P<0.001), (3) more number of VTs could be terminated by ablation (1.59±1.0 versus 0.91±0.81; P=0.007), and (4) fewer VTs were terminated with rescue shocks (1.9±2.2 versus 3.0±1.5; P=0.049) when compared with IABP group. Complications of the procedure trended to be more in the non-IABP group when compared with those in the IABP group (32% versus 14%; P=0.143). Intermediate term outcomes (mortality and VT recurrence) during 12±5-month follow-up were not different between both groups. Left ventricular ejection fraction ≤15% was a strong and independent predictor of in-hospital mortality (53% versus 4%; P<0.001).Conclusions: Impella and TandemHeart use in VT ablation facilitates extensive activation mapping of several unstable VTs and requires fewer rescue shocks during the procedure when compared with using IABP. [ABSTRACT FROM AUTHOR]

Background: The extent to which channels within scar are interconnected is not known. The objective of the study was to evaluate the impact of local ablation of late potentials (LPs) on adjacent and remote areas of slow conduction with simultaneous multipolar mapping.Methods and Results: Analysis was performed on consecutive patients referred for ablation of scar-mediated ventricular tachycardia with double ventricular access. Ablation was performed targeting the earliest of LPs visualized on the multipolar catheter, and the impact on later LPs was recorded. In 21 patients, a multipolar catheter placed within scar visualized spatially distinct LPs. Among 39 radiofrequency applications, ablation at earlier LPs had an effect on neighboring and remote LPs in 31 (80%), with delay in 8 (21%), partial elimination in 9 (23%), and complete elimination in 14 (36%). The mean distance where an ablation impact was detected was 17.6±14.7 mm (range, 2-50 mm). Among all patients, 9.7±7.8 radiofrequency applications were delivered to homogenize the targeted scar region with a mean number of 23±12 LPs targeted.Conclusions: Ablation can eliminate neighboring and remote areas of slow conduction, suggesting that channels within scar are frequently interconnected. This is the first mechanistic demonstration to show that ablation can modify electrical activity in regions of scar outside of the known radius of an radiofrequency lesion. The targeting of relatively earlier LPs can expedite scar homogenization without the need for extensive ablation of all LPs. [ABSTRACT FROM AUTHOR]

Background: Right 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.Methods: We 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.Results: We 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.Conclusions: Human 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. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation for ventricular tachycardia is an established therapy. Use of chemical agents for scar homogenization represents an alternative approach. The purpose of this study was to characterize the efficacy of collagenase (CLG) application on epicardial ventricular scar homogenization.Methods and Results: Myocardial infarcts were created in Yorkshire pigs (n=6) by intracoronary microsphere injection. After 46.6±4.3 days, CLG type 2, type 4, and purified CLG were applied in vitro (n=1) to myocardial tissue blocks containing normal myocardium, border zone, and dense scar. Histopathologic studies were performed to identify the optimal CLG subtype. In vivo high-density electroanatomic mapping of the epicardium was also performed, and border zone and dense scar surface area and late potentials were quantified before and after CLG-4 application (n=5). Of the CLG subtypes tested in vitro, CLG-4 provided the best scar modification and least damage to normal myocardium. During in vivo testing, CLG-4 application decreased border zone area (21.3±14.3 to 17.1±11.1 mm(2), P=0.043) and increased dense scar area (9.1±10.3 to 22.0±20.6 mm(2), P=0.043). The total scar area before and after CLG application was 30.4±23.4 and 39.2±29.5 mm(2), respectively (P=0.08). Late potentials were reduced by CLG-4 application (28.8±21.8 to 13.8±13.1, P=0.043). During CLG-4 application (50.0±15.5 minutes), systolic blood pressure and heart rate were not significantly changed (68.0±7.7 versus 61.8±5.3 mmHg, P=0.08; 77.4±7.3 versus 78.8±6.0 beats per minute, P=0.50, respectively).Conclusions: Ventricular epicardial scar homogenization by CLG-4 application is feasible and effective. This represents the first report on bioenzymatic ablation of arrhythmogenic tissue as an alternative strategy for lesion formation. [ABSTRACT FROM AUTHOR]

Background: The foundation for successful arrhythmia ablation is the mapping of electric propagation to identify underlying mechanisms. In atrial fibrillation (AF), however, mapping is difficult so that ablation has often targeted electrogram features, with mixed results. We hypothesized that wide field-of-view (panoramic) mapping of both atria would identify causal mechanisms for AF and allow interpretation of local electrogram features, including complex fractionated atrial electrograms (CFAE).Methods and Results: Contact mapping was performed using biatrial multipolar catheters in 36 AF subjects (29 persistent). Stable AF rotors (spiral waves) or focal sources were seen in 35 of 36 cases and targeted for ablation (focal impulse and rotor modulation) before pulmonary vein isolation. In 31 of 36 subjects (86.1%), AF acutely terminated (n=20; 16 to sinus rhythm) or organized (n=11; 19±8% slowing) with 2.5 minutes focal impulse and rotor modulation (interquartile range, 1.0-3.1) at one source, defined as the primary source. Subjects exhibited 2.1±1.0 concurrent AF sources of which the primary, by phase mapping, precessed in limited areas (persistent 2.5±1.7 versus paroxysmal 1.7±0.5 cm(2); P=0.30). Notably, source regions showed mixed electrogram amplitudes and CFAE grades that did not differ from surrounding atrium (P=NS). AF sources were not consistently surrounded by CFAE (P=0.67).Conclusions: Stable rotors and focal sources for human AF were revealed by contact panoramic mapping (focal impulse and rotor modulation mapping), but not by electrogram footprints. AF sources precessed within areas of ≈2 cm(2), with diverse voltage characteristics poorly correlated with CFAE. Most CFAE sites lie remote from AF sources and are not suitable targets for catheter ablation of AF. [ABSTRACT FROM AUTHOR]

The article presents information on the utility of the pericardial space in the electrophysiology laboratory. It informs that the space is used for the mapping and catheter ablation of ventricular tachycardia (VT). It further informs that this surface has now become the future in the case of catheter ablation and therapeutics.

The article discusses a study that determined whether cardiac pathology is associated with remodeling of the stellate ganglia in humans. It observes that intramyocardial nerve sprouting after myocardial infarction is associated with ventricular arrythmias. The article also indicates that neuronal hypertrophy within left stellate ganglia is associated with chronic cardiomyopathy in humans and finds ganglionic and myocardial nerve sprouting and nerve density were not significantly different.

The article presents a study that hypothesized the role of recurrent ventricular tachycardia in improving scar substrates with multiple exit sites (MES) identified during pace-mapping. The study conducted high-density mapping in all subjects to delineate scar. Pace-mapping reveals the specificity of electrograms that exhibit MES and pace-mapped induction for sites critical to reentry.

The article discusses a multicenter study of the difference in the long-term (LT) freedom from ventricular arrhythmias in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) who are undergoing ventricular tachycardia ablation by using either endocardial-alone ablation (EAA) or endo-epicardial ablation (EEA). The researchers found that an EEA approach offers higher LT arrhythmia survival than the EAA strategy.

Sudden cardiac death (SCD), the unexpected death due to acquired or genetic cardiovascular disease, follows distinct 24-hour patterns in occurrence. These 24-hour patterns likely reflect daily changes in arrhythmogenic triggers and the myocardial substrate caused by day/night rhythms in behavior, the environment, and endogenous circadian mechanisms. To better address fundamental questions regarding the circadian mechanisms, the National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death. We present a 2-part report of findings from this workshop. Part 1 summarizes the workshop and serves to identify research gaps and opportunities in the areas of basic and translational research. Among the gaps was the lack of standardization in animal studies for reporting environmental conditions (eg, timing of experiments relative to the light dark cycle or animal housing temperatures) that can impair rigor and reproducibility. Workshop participants also pointed to uncertainty regarding the importance of maintaining normal circadian rhythmic synchrony and the potential pathological impact of desynchrony on SCD risk. One related question raised was whether circadian mechanisms can be targeted to reduce SCD risk. Finally, the experts underscored the need for studies aimed at determining the physiological importance of circadian clocks in the many different cell types important to normal heart function and SCD. Addressing these gaps could lead to new therapeutic approaches/molecular targets that can mitigate the risk of SCD not only at certain times but over the entire 24-hour period. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) is the sudden, unexpected death due to abrupt loss of heart function secondary to cardiovascular disease. In certain populations living with cardiovascular disease, SCD follows a distinct 24-hour pattern in occurrence, suggesting day/night rhythms in behavior, the environment, and endogenous circadian rhythms result in daily spans of increased vulnerability. The National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death to identify fundamental questions regarding the role of the circadian rhythms in SCD. Part 2 summarizes research gaps and opportunities in the areas of population and clinical research identified in the workshop. Established research supports a complex interaction between circadian rhythms and physiological responses that increase the risk for SCD. Moreover, these physiological responses themselves are influenced by several biological variables, including the type of cardiovascular disease, sex, age, and genetics, as well as environmental factors. The emergence of new noninvasive biotechnological tools that continuously measure key cardiovascular variables, as well as the identification of biomarkers to assess circadian rhythms, hold promise for generating large-scale human data sets that will delineate which subsets of individuals are most vulnerable to SCD. Additionally, these data will improve our understanding of how people who suffer from circadian disruptions develop cardiovascular diseases that increase the risk for SCD. Emerging strategies to identify new biomarkers that can quantify circadian health (eg, environmental, behavioral, and internal misalignment) may lead to new interventions and therapeutic targets to prevent the progression of cardiovascular diseases that cause SCD. [ABSTRACT FROM AUTHOR]

The authors reflect on a study on the efficacy of catheter ablation of idiopathic ventricular tachycardia (VTs). They describe approaches to idiopathic VTs such as stepwise mapping of the outflow tracts, coronary arteries and veins and percutaneous epicardial mapping and ablation. Determinants for the two approaches include the proximity of coronary arteries, pre-and postablation coronary angiography and phrenic nerve capture testing. The authors affirm safety of ablation within the coronary venous system with option for percutaneous epicardial mapping.

Background: Recurrence of ventricular tachycardia (VT) after ablation in patients with previous myocardial infarction is associated with adverse prognosis. However, the impact of the timing of VT recurrence on outcomes is unclear.Methods and Results: We analyzed data from a multicenter collaborative database of patients who underwent catheter ablation for infarct-related VT. Multivariable Cox regression analyses investigated the effect of the timing of VT recurrence on the composite outcome of death or heart transplantation using VT recurrence as a time-varying covariate. A total of 1412 patients were included (92% men; age: 66.7±10.7 years), and 605 patients (42.8%) had a recurrence after median 116 days (188 [31.1%] within 1 month, 239 [39.5%] between 1 and 12 months, and 178 [29.4%] after 12 months). At median follow-up of 670 days, 375 patients (26.6%) experienced death or heart transplantation. The median time from recurrence to death or heart transplantation was 65 and 198.5 days in patients with recurrence ≤30 days and >30 days post ablation, respectively. The adjusted hazard ratio (95% confidence interval) for the effect of VT recurrence occurring immediately post ablation on death or heart transplantation was 3.45 (2.33-5.11) in reference to no recurrence. However, the magnitude of this effect decreased statistically significantly (P<0.001) as recurrence occurred later in the follow-up period. The respective risk estimates for VT recurrence at 30 days, 6 months, 1 year, and 2 years were 3.36 (2.29-4.93), 2.94 (2.09-4.14), 2.50 (1.85-3.37), and 1.81 (1.37-2.40).Conclusions: VT recurrence post ablation is associated with a mortality risk that is highest soon after the ablation and decreases gradually thereafter. [ABSTRACT FROM AUTHOR]

Competing Interests: Disclosures None.

[Figure: see text].

Background: Several distinct risk factors for arrhythmia recurrence and mortality following ventricular tachycardia (VT) ablation have been described. The effect of concurrent risk factors has not been assessed so far; thus, it is not yet possible to estimate these risks for a patient with several comorbidities. The aim of the study was to identify specific risk groups for mortality and VT recurrence using the Survival Tree (ST) analysis method., Methods: In 1251 patients 16 demographic, clinical and procedure-related variables were evaluated as potential prognostic factors using ST analysis using a recursive partitioning algorithm that searches for relationships among variables. Survival time and time to VT recurrence in groups derived from ST analysis were compared by a log-rank test. A random forest analysis was then run to extract a variable importance index and internally validate the ST models., Results: Left ventricular ejection fraction, implantable cardioverter defibrillator/cardiac resynchronization device, previous ablation were, in hierarchical order, identified by ST analysis as best predictors of VT recurrence, while left ventricular ejection fraction, previous ablation, Electrical storm were identified as best predictors of mortality. Three groups with significantly different survival rates were identified. Among the high-risk group, 65.0% patients were survived and 52.1% patients were free from VT recurrence; within the medium- and low-risk groups, 84.0% and 97.2% patients survived, 72.4% and 88.4% were free from VT recurrence, respectively., Conclusions: Our study is the first to derive and validate a decisional model that provides estimates of VT recurrence and mortality with an effective classification tree. Preprocedure risk stratification could help optimize periprocedural and postprocedural care.

Background: Successful ventricular tachycardia (VT) ablation is associated with improved survival in patients with heart failure. However, the safety and efficacy of VT ablation in the elderly, a population with higher competing nonsudden death risk and comorbidities, have not been well defined., Methods and Results: The International Ventricular Tachycardia Center Collaborative Study Group registry of 2061 patients who underwent VT ablation at 12 international centers was analyzed. Kaplan-Meier analysis was used to estimate survival of patients ≥70 years with and without VT recurrence. Of the 2049 patients who met inclusion criteria, 681 (33%) patients were ≥70 years of age (mean age, 75±4 years). Among these, 92% were men, 71% had ischemic VT, and 42% had VT storm at presentation. Mean (±SD) left ventricular ejection fraction was 30±11%. Compared with patients <70 years, patients ≥70 years had higher in-hospital (4.4% versus 2.3%; P =0.01) and 1-year mortality (15% versus 11%; P =0.002) but a similar incidence of VT recurrence at 1 year (26% versus 25%; P =0.74) and time to VT recurrence (280 versus 289 days; P =0.20). Absence of VT recurrence during follow-up was strongly associated with improved survival in patients ≥70 years., Conclusion: VT ablation in the elderly is feasible and reasonably safe with a modestly higher in-hospital and 1-year mortality, with similar rates of VT recurrence at 1 year compared with younger patients. Successful VT ablation, that is, lack of VT recurrence, is strongly associated with improved survival even in this elderly subgroup., (© 2017 American Heart Association, Inc.)

Background: Ventricular tachycardia (VT) radiofrequency ablation has been associated with reduced VT recurrence and mortality, although it is typically not considered among New York Heart Association class IV (NYHA IV) heart failure patients. We compared characteristics and VT radiofrequency ablation outcomes of those with and without NYHA IV in the International VT Ablation Center Collaboration., Methods and Results: NYHA II-IV patients undergoing VT radiofrequency ablation at 12 international centers were included. Clinical variables, VT recurrence, and mortality were analyzed by NYHA IV status using Kaplan-Meier analysis and Cox proportional hazard models. There were significant differences between NYHA IV (n=111) and NYHA II and III (n=1254) patients: NYHA IV had lower left ventricular ejection fraction; more had diabetes mellitus, kidney disease, cardiac resynchronization implantable cardioverter-defibrillator, and VT storm despite greater antiarrhythmic drug use (P<0.01). NYHA IV subjects required more hemodynamic support, were inducible for more and slower VTs, and were less likely to undergo final programmed stimulation. There was no significant difference in acute complications. In-hospital deaths, recurrent VT, and 1-year mortality were higher in the NYHA IV group, in the context of greater baseline comorbidities. Importantly, NYHA IV patients without recurrent VT had similar survival compared with NYHA II and III patients with recurrent VT (68% versus 73%). Early VT recurrence (≤30 days) was significantly associated with mortality, especially in NYHA IV patients., Conclusions: Despite greater baseline comorbidities, VT radiofrequency ablation can be safely performed among NYHA IV patients. Early VT recurrence is significantly associated with subsequent mortality regardless of NYHA status. Elimination of recurrent VT in NYHA IV patients may reduce mortality to a level comparable to NYHA II and III with arrhythmia recurrence., (© 2017 American Heart Association, Inc.)

Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy, and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem, and higher centers), which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes to hours), and long term (days to years). This important neurovisceral/autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death. Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extracardiac neural remodeling has also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provide a rational mechanistic basis for the development of neuraxial therapies for preventing sudden cardiac death and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention., (© 2015 American Heart Association, Inc.)

Background: New approaches to ablation of atrial fibrillation (AF) include focal impulse and rotor modulation (FIRM) mapping, and initial results reported with this technique have been favorable. We sought to independently evaluate the approach by analyzing quantitative characteristics of atrial electrograms used to identify rotors and describe acute procedural outcomes of FIRM-guided ablation., Methods and Results: All FIRM-guided ablation procedures (n=24; 50% paroxysmal) at University of California, Los Angeles Medical Center were included for analysis. During AF, unipolar atrial electrograms collected from a 64-pole basket catheter were used to construct phase maps and identify putative AF sources. These sites were targeted for ablation, in conjunction with pulmonary vein isolation in most patients (n=19; 79%). All patients had rotors identified (mean, 2.3±0.9 per patient; 72% in left atrium). Prespecified acute procedural end point was achieved in 12 of 24 (50%) patients: AF termination (n=1), organization (n=3), or >10% slowing of AF cycle length (n=8). Basket electrodes were within 1 cm of 54% of left atrial surface area, and a mean of 31 electrodes per patient showed interpretable atrial electrograms. Offline analysis revealed no differences between rotor and distant sites in dominant frequency or Shannon entropy. Electroanatomic mapping showed no rotational activation at FIRM-identified rotor sites in 23 of 24 patients (96%)., Conclusions: FIRM-identified rotor sites did not exhibit quantitative atrial electrogram characteristics expected from rotors and did not differ quantitatively from surrounding tissue. Catheter ablation at these sites, in conjunction with pulmonary vein isolation, resulted in AF termination or organization in a minority of patients (4/24; 17%). Further validation of this approach is necessary., (© 2015 American Heart Association, Inc.)

Background: Reducing sympathetic output to the heart from the neuraxis can protect against ventricular arrhythmias. The purpose of this study was to assess the value of thoracic epidural anesthesia (TEA) and left cardiac sympathetic denervation (LCSD) in the management of ventricular arrhythmias in patients with structural heart disease., Methods and Results: Clinical data of 14 patients (25 to 75 years old, mean+/-SD of 54.2+/-16.6 years; 13 men) who underwent TEA, LCSD, or both to control ventricular tachycardia (VT) refractory to medical therapy and catheter ablation were reviewed. Twelve patients were in VT storm, and 2 experienced recurrent VT despite maximal medical therapy and catheter ablation procedures. The total number of therapies per patient before either procedure ranged from 5 to 202 (median of 24; 25th and 75th percentile, 5 and 56). Eight patients underwent TEA, and 9 underwent LCSD (3 patients had both procedures). No major procedural complications occurred. After initiation of TEA, 6 patients had a large (> or =80%) decrease in VT burden. After LCSD, 3 patients had no further VT, 2 had recurrent VT that either resolved within 24 hours or responded to catheter ablation, and 4 continued to have recurrent VT. Nine of 14 patients survived to hospital discharge (2 TEA alone, 3 TEA/LCSD combined, and 4 LCSD alone), 1 of the TEA alone patients underwent an urgent cardiac transplantation., Conclusions: Initiation of TEA and LCSD in patients with refractory VT was associated with a subsequent decrease in arrhythmia burden in 6 (75%) of 8 patients (68% confidence interval 51% to 91%) and 5 (56%) of 9 patients (68% confidence interval 34% to 75%), respectively. These data suggest that TEA and LCSD may be effective additions to the management of refractory ventricular arrhythmias in structural heart disease when other treatment modalities have failed or may serve as a bridge to more definitive therapy.

Background: Monitoring tissue oxygenation (StO(2)) by visible light spectroscopy (VLS) can identify tissue ischemia, but its feasibility for detecting myocardial ischemia is not known. We hypothesized that VLS can reliably detect changes in myocardial StO(2) in pigs subjected to acute regional or global myocardial ischemia., Methods: In 11 pigs, regional myocardial ischemia was created by ligation of left anterior descending artery (LAD). Myocardial StO(2) was determined from the ischemic and nonischemic left ventricular (LV) regions and compared to coronary venous saturations. Myocardial function was assessed by echocardiography. In six pigs, LV-StO(2) was measured during cardiopulmonary bypass (CPB), after cardioplegic cardiac arrest, and during CPB with inadequate myocardial protection. Additionally, right ventricular (RV)- and LV-StO(2) were assessed during acute RV pressure overload from pulmonary artery (PA) banding., Results: StO(2) baselines in pigs undergoing LAD occlusion were similar in the ischemic and nonischemic myocardium (70% +/- 8% vs 74% +/- 5%). After LAD ligation, StO(2) rapidly declined (30 s: 59% +/- 8%; 1 min:50 +/- 9; 5 min:42% +/- 4%; P < 0.05) in the ischemic myocardium. Decreases in StO(2) correlated with coronary venous saturations (r = 0.88) and were associated with myocardial dysfunction. In pigs undergoing CPB, LV-StO(2) remained unchanged with initiation of CPB or after cardioplegic cardiac arrest, but LV ischemia was detected by StO(2) after aortic cross-clamp without adequate myocardial protection. Similarly, PA banding resulted in a profound decrease of RV-StO(2) from 69% +/- 6% to 52% +/- 7% (P < 0.05) with recovery after PA release., Conclusions: VLS is a reliable method of detecting alterations in myocardial StO(2) and can be a useful monitor for rapid identification of myocardial ischemia.

Background: The upper limit of vulnerability (ULV) correlates with the defibrillation threshold and can be determined with 1 episode of ventricular fibrillation (VF). To automate the ULV in an implantable cardioverter-defibrillator (ICD), the most vulnerable intervals must be identified from an ICD electrogram rather than the latest-peaking surface T wave (Tpeak). We hypothesized that the recovery time (TR), defined as the maximum derivative (dV/dt) of the T wave of the shock electrogram, correlates with the most vulnerable intervals., Methods and Results: We determined ULV, defibrillation threshold, and the most vulnerable intervals in 25 patients at ICD implantation. The ULV was the weakest T-wave shock that did not induce VF. The most vulnerable intervals were the ones associated with the strongest shocks that induced VF. Telemetered shock electrograms were stored on digital tape and differentiated offline to measure TR. Tpeak and TR were highly correlated (Tpeak-TR=-2+/-11 ms; rho=0.80, P<0.001). At least 1 most vulnerable interval timed between -20 ms and +20 ms relative to Tpeak in all patients and between -40 ms and +20 ms relative to TR in 96% of patients., Conclusions: The recovery time of shock electrograms provides accurate information about global repolarization. TR closely approximates Tpeak. The ULV method may be automated in an ICD by timing T-wave shocks relative to TR.