Negative Electrophysiological Study Research Articles

Safety of electrophysiological study in atrioventricular block risk stratification in new-onset persistent left bundle brunch block following transcathether aortic valve implantation

Abstract Background A significant percentage of patients develops a persistent complete left bundle branch block (LBBB) following TAVI. Electrophysiological (EP) study could be useful to stratify the risk of atrioventricular block (AVB) in these patients, guiding the need of follow-up and the indication of definite pacemaker. Purpose The primary objective of the study was describing the incidence of bradyarrhythmic events in the 30-day follow-up of patients with new-onset LBBB: AV block with ECG long-term monitoring system (Nuubo) in patients with negative EP study, and ≥ 5 % of ventricular stimulation in patients with positive EP study and pacemaker implantation. Methodology Observational prospective study of consecutive patients without previous permanent pacemaker implantation where transfemoral TAVI was implanted between 2021 and 2023. In case new-onset complete LBBB was present after TAVI, an EP study was performed. EP study was considered positive when His-Ventricule interval was more than 70ms, or after procainamide infusion at 10mg/kg, more than 100ms or more than double the basal HV interval. In case EP was positive, a permanent pacemaker was implanted. In case EP was negative, a 30-day follow-up with ECG long-term monitoring system (Nuubo) was performed. Results In this cohort, 266 patients without pacemaker following TAVI were included. Persistent new-onset left bundle branch block was present in 10,15% of patients (n=27). EP study was positive in 29.62% of patients (n=8), following a definite pacemaker implantation. During follow-up, only one patient (12.5%) was dependent of ventricular stimulation. The group with negative EP study (n=19) were monitored with a 30-day ECG long-term monitoring system (Nuubo). No bradyarrhythmic events were registered in this group. Conclusions Approximately one tenth of patients develop persistent new-onset LBBB after TAVI. Events were seldom in both study groups. Positive EP study patients were dependent of ventricular stimulation in 12.5% of cases, and there was no bradyarrhythmic event registered in EP negative group. EP study could be a safe tool to stratify AVB risk in new-onset LBBB following TAVI.

HV interval cutoff should be different in women and men with syncope and bundle branch block

Abstract Background Determining the optimal HV interval cutoff for predicting the need for pacemaker (PM) implantation has been a recent focus of research. Current ESC guidelines recommend HV > 70 msec based on initial studies; however, new data suggest that a cutoff of >60 msec could appropriately identify patients at high risk for requiring PM implantation. While previous studies have indicated that women with bundle branch block (BBB) have a lower risk of AV block (AVB), gender differences in the optimal cutoff for considering a positive EPS have not been thoroughly investigated. Methods This cohort study included consecutive patients with unexplained syncope and BBB, enrolled from January 2010 to October 2021, with a median follow-up time of 3 years. Patients underwent a stepwise workup protocol involving an electrophysiological study (EPS) and long-term follow-up with an implantable cardiac monitor (ICM). Results Of the 503 patients in the study, 185 (38%) were women. The median age was 78 years (IQR 71-83), the median LVEF was 58% (IQR 50-62), and 110 (22%) had ischemic heart disease. The ECG showed LBBB in 194 (39%) patients and RBBB in 287 (57%). Among these, 177 (35%) also had left anterior hemiblock. The median HV interval was 60 msec (IQR 52-73), and EPS was diagnostic in 252 (50%) patients, with the majority (221, 44%) for AVB. In 91 patients with initially negative EPS, a diagnosis was made during follow-up with an ICM, and in 35, AVB was documented. In patients with negative EPS, an HV interval >60 msec was associated with an increased risk of AVB during follow-up (HR 2.5, 95% CI 1.6-4). However, significant gender differences were found. The risk of AVB was 2.5 times higher in men (95% CI 1-6) (Figure 1). Furthermore, sensitivity, specificity, PPV, and NPV for the cutoff of 60 msec were 47%/84%/51%/82% in men and 21%/78%/21%/78% in women. The AUC to predict AVB was 0.72 (95% CI 0.6-0.8) in men and 0.51 (95% CI 0.4-0.6) in women (Figure 2). Conclusions In patients with initially negative EPS, an HV interval >60 msec was associated with a higher risk of AVB during follow-up; however, significant gender differences were observed in diagnostic accuracy. In women, a cutoff of HV interval >60 msec presented poor diagnostic accuracy compared to men. Moreover, the HV interval did not adequately predict the development of AVB in women with a basal HV interval <70 msec, suggesting it may not be suitable for considering PM implantation in female patients.FIGURE 1FIGURE 2

Arrhythmia detection using an implantable loop recorder after a negative electrophysiology study in Brugada syndrome: Observations from a multicenter international registry

BackgroundRisk stratification in Brugada syndrome (BrS) remains controversial. In this respect, the role of the electrophysiology study (EPS) has been a subject of debate. In some centers, it is common practice to use an implantable loop recorder (ILR) after a negative EPS to help in risk stratification. However, the diagnostic value of this approach has never been specifically addressed. ObjectiveThe aim of this study was to describe the baseline characteristics and the main findings of a diagnostic workup strategy with an ILR after a negative EPS in BrS. MethodsWe conducted a retrospective international registry including patients with BrS and negative EPS (ie, noninducible ventricular tachycardia or ventricular fibrillation) before ILR monitoring. ResultsThe study included 65 patients from 8 referral hospitals in The Netherlands, Spain, and the United Kingdom (mean age, 39 ± 16 years; 72% male). The main indication for ILR monitoring was unexplained syncope/presyncope (66.2%). During a median follow-up of 39.0 months (Q1 25.0–Q3 47.6 months), 18 patients (27.7%) experienced 21 arrhythmic events (AEs). None of the patients died during follow-up. Bradyarrhythmias were the most common finding (47.6%), followed by atrial tachyarrhythmias (38.1%). Only 3 patients presented with ventricular arrhythmias. AEs were considered incidental in 12 patients (66.7%). In 11 patients (61.1%), AEs led to specific changes in treatment. ConclusionThe use of ILR after a negative EPS in BrS is a safe strategy that reflected the high negative predictive value of EPS for ventricular arrhythmia in this syndrome. In addition, it allowed the detection of AEs in a significant proportion of patients, with therapeutic implications in most of them.

Asymptomatic Brugada patients: long-term prognosis from a large prospective study

Abstract Background One of the greatest challenges concerning the Brugada syndrome is how to stratify and manage asymptomatic patients, who represent the majority of patients with Brugada ECG pattern (BrECG). Purpose Aim of our study was to evaluate the long-term prognosis of a large population of asymptomatic Brugada patients. Methods One thousand one hundred and forty-nine asymptomatic Brugada patients were collected. Patients were treated as follows: in the 539 subjects with spontaneous type 1 BrECG documented on basal ECG or at 12-lead 24-hour Holter monitoring (12L-Holter) an electrophysiological study (EPS) was proposed and ICD implantation was proposed on the basis of the EPS results; in the 610 subjects with drug-induced-only type 1, clinical follow-up with multiple ECGs and 12L-Holter was suggested to search for spontaneous type 1 BrECG. Results Over a median follow-up of 6 (4-9) years there were 17 arrhythmic events (1.5%). Sixteen events occurred in the 539 patients with spontaneous type 1 (3%; 0.4% person-years) and only 1 in the 610 patients with drug-induced type 1 BrECG (0.16%; 0.03% person-years, p 0.001). Patients with spontaneous type 1 had a 15-time higher risk of arrhythmic events than patients with drug- induced type 1 BrECG. Patients with spontaneous type 1 BrECG and positive EPS had a 3-time higher risk of arrhythmic events than patients with negative EPS (6.8% vs 1.6%, p 0.035). An ICD was implanted in 163 patients: 8 (5%) received an appropriate intervention, while 23% experienced device-related complications, including 1 death. Conclusions Asymptomatic patients with spontaneous type 1 BrECG have an event rate of 3% at a median follow-up of 6 years. In this group, EPS represents a useful risk stratification procedure, as a positive EPS identifies patients with a 3-time higher event rate as compared to subjects with negative EPS. A negative EPS identifies a population at low although not zero-risk. Asymptomatic patients with drug-induced only Brugada ECG pattern are a group at very low arrhythmic risk. ICD implantation is burdened by a high incidence of complications, therefore alternative therapeutic strategies are needed.

Asymptomatic Patients With Brugada ECG Pattern: Long-Term Prognosis From a Large Prospective Study.

Brugada syndrome poses significant challenges in terms of risk stratification and management, particularly for asymptomatic patients who comprise the majority of individuals exhibiting Brugada ECG pattern (BrECG). The aim of this study was to evaluate the long-term prognosis of a large cohort of asymptomatic patients with BrECG. Asymptomatic patients with BrECG (1149) were consecutively collected from 2 Italian centers and followed-up at least annually for 2 to 22 years. For the 539 asymptomatic patients (men, 433 [80%]; mean age, 46±13 years) with spontaneous type 1 documented on baseline ECG (87%) or 12-lead 24-hour Holter monitoring (13%), an electrophysiologic study (EPS) was proposed; for the 610 patients with drug-induced-only type 1 (men, 420 [69%]; mean age, 44±14 years), multiple ECGs and 12-lead Holter were advised in order to detect the occurrence of a spontaneous type-1 BrECG. Arrhythmic events were defined as sudden death or documented ventricular fibrillation or tachycardia. Median follow-up was 6 (4-9) years. Seventeen (1.5%) arrhythmic events occurred in the overall asymptomatic population (corresponding to an event-rate of 0.2% per year), including 16 of 539 (0.4% per year) in patients with spontaneous type-1 BrECG and 1 of 610 in those with drug-induced type-1 BrECG (0.03% per year; P<0.001). EPS was performed in 339 (63%) patients with spontaneous type-1 BrECG. Patients with spontaneous type-1 BrECG and positive EPS had significantly higher event rates than patients with negative EPS (7 of 103 [0.7% per year] versus 4 of 236 [0.2% per year]; P=0.025). Among 200 patients who declined EPS, 5 events (0.4% per year) occurred. There was 1 device-related death. The entire population of asymptomatic patients with BrECG exhibits a relatively low event rate per year, which is important in view of the long life expectancy of these young patients. The presence of spontaneous type-1 BrECG associated with positive EPS identifies a subgroup at higher risk. Asymptomatic patients with drug-induced-only BrECG have a minimal arrhythmic risk, but ongoing follow-up with 12-lead Holter monitoring is recommended to detect the appearance of spontaneous type-1 BrECG pattern.

820 VARIABLE EXPRESSIVITY OF SCN5A MUTATION IN A FAMILY WITH CARDIAC DYSFUNCTION AND SUSPECTED BRUGADA SYNDROME

Abstract Background Inherited arrhythmogenic diseases (IADs) represent a group of life-threatening genetic cardiomyopathies that predispose young individuals to sudden cardiac death (SCD), often in the absence of structural cardiac alterations. Some IADs share mutations in genes encoding for surface membrane ion channels, and the gene for the alpha subunit of the voltage-dependent channel Nav1.5 (SCN5A) is among the ones mostly involved. Brugada syndrome represents one of the possible spectrum deriving from SCN5A gene mutations, and it is characterized by “loss-of-function” genetic alterations. Interestingly, both loss-of and gain-of-function mutations have been associated with familial dilated cardiomyopathy (DCM). Materials and Methods In the context of an Italian Ministry of Health-funded research project devoted to identify genetic isolates of IADs in the Calabria region, we found a family affected by different cardiovascular manifestations including cardiac dysfunction, ventricular tachyarrhythmias, atrioventricular block and suspected Brugada syndrome pattern in first-degree relatives in association with a newly identified SCN5A mutation. Results The proband came to our attention with a diagnosis of DCM, echocardiographic assessment of reduced left ventricular ejection fraction (EF) to 38%, high occurrence of premature ventricular complexes (PVCs) and first-degree atrioventricular block (PR = 240ms) at electrocardiogram. In spite of negative electrophysiologic study, he underwent implantable cardioverter defibrillator implantation (ICD), hypothesizing lamin A/C mutation; genetic analysis turned out negative for lamin A/C and CACNA1C, while a SCN5A gene mutation (c.4554 G&amp;lt;T p.Gln1518His) was detected. Proband's sons and his brother underwent clinical evaluations as well as genetic testing: the second son's ECG showed first-degree AV block (PR = 220ms), QTc interval 426ms, and coved type ST-segment elevation of 1.5mm, in the context of normal cardiac function; the remaining male (see Figure 1) was asymptomatic, while the daughter had a hypokinetic non-dilated cardiomyopathy. The proband's brother had first-degree AV block and very frequent monomorphic ventricular couplets. Conclusions These phenotypic differences in first degree-relatives, can be explained by the concept of variable expressivity of genes, according to which individuals carrying the same mutation can have different clinical features. Therefore, the search for genetic mutations assumes a preponderant role for stratifying the risk of SCN5A-related diseases and to adopt appropriate diagnostic and therapeutic strategies.

663 OCCURRENCE OF VENTRICULAR AND SUPRAVENTRICULAR ARRHYTHMIAS IN BRUGADA SYNDROME: RESULTS OF A TERTIARY REFERRAL CENTER EXPERIENCE

Abstract Brugada Syndrome (BrS) is one of the most common channelopathies and is related to an increased risk of ventricular arrhythmias. Current guidelines recommend the implantation of a Cardiac Defibrillator (ICD) in those patients that have a diagnostic ECG pattern and a history of aborted cardiac arrest. Nevertheless, management of asymptomatic patients, who are the majority, remains controversial as their risk stratification is often based on the results of an inductive Electrophysiologic Study (EPS) the predictive accuracy of which is debated. Furthermore, BrS has also been associated to an increased risk of supraventricular tachy- and bradyarrhythmias. Aim to describe the occurrence of ventricular and supraventricular arrhythmias in BrS patients that receive an implantable cardiac monitoring device following an EPS study Methods we retrospectively identified all BrS patients followed at our tertiary referral centre that were candidate to an EPS. Patient were candidate to EPS if: (1) they had a spontaneous diagnostic Brugada pattern at ECG and (2) they had no history of previous ventricular arrhythmias or high-risk syncope. Those patients that tested positive for induction of a sustained ventricular arrhythmia at EPS received an ICD; those that tested negative received an ILR. During the follow-up visits, implantable devices were interrogated for the occurrence of ventricular and supraventricular arrhythmias. Results We identified 87 patients matching the inclusion criteria. Of these, 31 (35.7%) received an ICD for a positive EPS while the remaining 56 (64.3%) received an ILR. Over a mean follow-up period of 34 months (IQR 5-45, 249 patient-year), only one patient in the EPS positive group experienced a ventricular arrhythmia effectively treated by the ICD (0.3 events per patient-year) compared to zero patients in the EPS negative group (100% NPV, 3.2% PPV). Notably, implanted devices allowed for the detection of supraventricular arrhythmias in 12 out of the 87 patients (14%): 5 were cases of symptomatic sinus bradycardia, with an indication to permanent pacing in two of them, and 7 were cases of atrial tachycardia/fibrillation. Discussion in our registry, consistently with previous literature, ventricular arrhythmias in BrS patients are rare and a negative EPS identifies with high accuracy those that are at low risk for this event. Conversely, a positive EPS may overestimate the risk of these patients resulting, according to current practice, in frequent implantations of ICD that will never be required for defibrillation. Although the patient-year observation period of the presented cohort is sizeable, our results should be furtherly validated on multi-center cohorts with even longer follow-up periods. Nonetheless, our results support the idea that risk stratification tools other than EPS are probably needed to properly identify the minority of BrS patients that will experience a ventricular arrhythmia throughout their life. In addition, we report a considerable number of supraventricular arrhythmias recorded by the implanted cardiac monitoring devices in our population. This is consistent with the knowledge of BrS patients being at increased risk of sinoatrial node dysfunction and atrial fibrillation and may elicit a more widespread and methodical screening for these events.

Arrhythmia detection using insertable cardiac monitors after a negative electrophysiology study in Brugada syndrome: observations from a multicenter Spanish registry

Abstract Background/Introduction Risk stratification in Brugada syndrome (BrS) remains controversial. In this respect, the role of electrophysiology study (EPS) has been subject of debate. It is common practice in some centers to implant an insertable cardiac monitor (ICM) after a negative EPS, especially in the presence of unexplained symptoms. However, the diagnostic value of this approach has never been specifically addressed. Purpose We aimed to describe the baseline characteristics and the main findings of a diagnostic work-up strategy using an insertable cardiac monitor (ICM) after a negative EPS in patients with BrS. Methods We retrospectively evaluated data from a multicenter registry including 56 BrS patients from 7 referral hospitals who received an ICM to help risk stratification. Only patients with a negative EPS (ie, non-inducible VT/VF) prior to ICM implantation were considered for this analysis. EPS protocols differed across hospitals (see Figure 1) Results A total of 26 patients from 5 different hospitals were studied. Mean age was 33.0±12.8 and 77% were male. Spontaneous type 1 pattern was present in 12 patients (46%). Positive genotype was found in 10 (38%) and family history of sudden cardiac death was present in 11 (42%). Previous symptoms were syncope/presyncope in 15 patients (58%) and palpitations in 3 patients (12%). The rest of the patients (30%) were asymptomatic. After a median follow-up of 33.4 months (IQR 16.5 and 43.1 months), none of the patients presented ventricular arrhythmias. ICM allowed the detection of other arrhythmias in 5 patients (19%), which led to specific therapeutic actions in all but 2 of them (see Table 1). ICM-detected arrhythmias correlated with previously reported symptoms only in one of the patients. Conclusion The results of this exploratory analysis support the notion that EPS in BrS has a high negative predictive value for risk stratification. ICM implantation after a negative EPS may allow the detection of incidental arrhythmias during follow-up. Despite the apparent low correlation of these findings with previously reported symptoms, this strategy may lead to important treatment decisions in a significant proportion of patients. Funding Acknowledgement Type of funding sources: None.

564 Controversial role of intracardiac eletrophysiology study in Brugada syndrome: analysis of a single-centre retrospective cohort study

Abstract Aims According to European guidelines, aborted sudden cardiac death (SCD) in Brugada syndrome (BrS) is regarded as a I class recommendation for secondary prevention implantable cardioverter defibrillator (ICD). However, the risk stratification of BrS patients for primary prevention ICD still represents a clinical conundrum. Although intracardiac electrophysiology (EP) study proved useful for the selection of high-risk patients in this setting. Therefore, aim of this study was to assess all clinical and EP variables associated with the induction of VA at EP study and the rate of appropriate/inappropriate ICD interventions and/or clinical SCD events in these patients occurring at follow-up. Methods and results From 2001 to 2021, all EP studies performed in symptomatic/asymptomatic patients (46 ± 14 years, M 88%) with/without family history of SCD spontaneous/drug-induced type I pattern (TIP) on ECG and no spontaneous ventricular arrhythmias were retrospectively considered at our study centre. Clinical variables, BrS pattern, EP study data (including right ventricular site and type of stimulation protocol), and ICD interventions (DC-shocks or Anti-Tachycardia Pacing events, ATP) and/or SCD events occurring at follow-up were all evaluated. EP study was deemed positive for any polymorphic VA induced during programmed ventricular stimulation; non-sustained episodes included. ICD was routinely implanted in all patients with a positive EP study. Follow-up data were detected by the collection of medical and home-monitoring recordings at study-site level. Follow-up data were available in 50 patients (9 ± 6 years on average). Patients were generally young with few cardiovascular comorbidities. SCD history was known in 21 (42%) with a significant number of asymptomatic patients (48%). Br patterns were equally distributed in the investigated population (spontaneous and drug-induced TIP in 52% and 48%, respectively) and AF history was fairly common (16%). In the study population, EP study tested positive in 30 patients (60%): spontaneous TIP (P = 0.0518), few extrastimuli during programmed ventricular stimulation (P = 0.0015), and right ventricular stimulation at the apical site (P ≤ 0.0001) were the only variables to be clearly associated with a positive EP study in the appraised patients. At follow-up, appropriate ICD shocks were documented in 4 out of 30 implanted patients (13%) at generally 5 ± 7 years from EP study evaluation. Although three ICD interventions (75%) occurred in patients with spontaneous TIP, one patient with drug-induced TIP pattern and positive EP study referred to Emergency Department for unrelenting VT storm after roughly 13 years from ICD implantation. Inappropriate ICD interventions for fast rate AF were detected in 10% of cases. Finally, no SCD events were documented at follow up in patients with a negative EP study. Conclusions In a retrospective analysis, EP study proved useful in the risk stratification of SCD in BrS patients. A few ventricular extrastimuli delivered at the right ventricular apex seem sufficient to prompt the induction of life-threatening VA in high-risk BrS patients during EP study. Moreover, in this setting, a negative EP study seems protective against the development of VA/SCD events at follow-up. However, not only is spontaneous TIP associated with an increased risk of arrhythmic death, but a drug-induced TIP, generally regarded as a low-risk condition, might also be associated with a long-term hazard of SCD in these patients.

The role of electrophysiology study in risk stratification of cardiac sarcoidosis patients: Meta-analyses and systemic review

BackgroundThe utility of an electrophysiologic study (EPS) in the risk stratification of cardiac sarcoidosis (CS) patients is not clear. We conducted a systemic review and meta-analysis to evaluate the utility of EPS in the risk stratification of CS patients. MethodsWe searched PubMed, Embase, and Scopus databases from their inception to 12/4/2020 with search terms “Cardiac sarcoidosis” And “Electrophysiological studies OR ablation”. The first and second authors reviewed all the studies. We extracted the data of positive and negative EPS, and outcomes defined as ventricular arrhythmias, implantable cardioverter defibrillator therapy, death, left ventricular assist device placement, or heart transplantation. Risk of bias assessment was done by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Subgroup analysis of patients with left ventricular ejection fraction (LVEF) >35%, and probable CS, no prior ventricular tachycardia (VT) and LVEF >35% were performed. ResultsWe found 544 articles after removing duplicates. A total of 52 full articles were reviewed, and eight studies were included in the meta-analysis. The pooled sensitivity and specificity (95% confidence interval) of EPS in predicting clinical outcomes were 0.70 (0.51–0.85) and 0.93 (0.85–0.97), respectively. Subgroup analysis of patients with LVEF >35% resulted in pooled sensitivity of 0.63 (0.29–0.88) and pooled specificity of 0.97 (0.92–0.99), and subgroup analysis of patients with probable CS, no prior VT, and LVEF >35% resulted in pooled sensitivity of 0.71 (0.33–0.93) and pooled specificity of 0.96 (0.88–0.99) in predicting adverse clinical outcomes. ConclusionsEPS is an effective risk stratification tool in patients with CS across all subgroups with high sensitivity and specificity.

Abstract 9169: A Non-Invasive Virtual Heart Approach Predicts Reentrant Ventricular Arrythmia (VA) Circuits in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): A Proof-of-Concept Study

Introduction: ARVC is a leading inherited cause of VA in young adults. Progressive and extensive structural and electrical remodeling in the right ventricle (RV) serves as a complex substrate for reentrant VA circuits in ARVC. Non-invasive prediction of ARVC reentrant VA circuits could provide a thorough pre-ablation evaluation of the arrhythmogenic substrate and identify specific region(s) to target during the ablation procedure. Here we developed a non-invasive personalized virtual heart approach that accurately predicts reentrant VA circuits in ARVC patients. Methods: As a proof-of-concept retrospective study, we constructed 3D computational models of ARVC patients’ hearts from LGE-CMR scans with observed RV hyperenhancements representing arrhythmogenic substrates (Fig A). 3 patients were included in this study: patient 1 (P1) had clinical VA and inducibility in electrophysiologic study (EPS); patient 2 (P2) had negative EPS despite previous evidence of VA; patient 3 had no VA. We generated a computational model for each heart incorporating personalized diffuse and dense (scar) fibrosis distribution. ARVC-specific ionic and conduction properties were represented in different regions. The VA inducibility of each model was assessed by rapid pacing from 9 RV sites. Results: For all cases, model outcomes correlated with clinical observations. In P1 model, VA was induced from the inferior basal region, as observed in EPS. Reentrant wavefronts occurred endocardially near the patient’s scar region, matching the EPS (Fig C1). Clinical ablation at this location terminated VA. In P2, VA was induced by pacing from the inferior lateral wall, a pacing location not part of the EPS protocol; reentry occurred on the basal lateral wall (Fig C2), a common location for VA circuits in ARVC. No VA was induced in P3. Conclusions: The novel ARVC virtual heart approach accurately predicts reentrant VA circuits and can potentially become a tool in assisting ablation in ARVC patients.

Heterogeneity of right ventricular refractory period: a novel prognostic predictor in type-1 Brugada

Abstract Funding Acknowledgements Type of funding sources: None. Risk stratification in Brugada syndrome (BrS) is needed especially for the choice of an Implantable Cardiac Defibrillator (ICD). To date the predictive value of either clinical or conventional electrophysiological indexes in type 1 electrocardiographic pattern BrS is rather low. We aimed to evaluate the eventual prognostic significance of refractoriness heterogeneity of right ventricular outflow tract, an emergent relevant pathophysiological substrate, at electrophysiological study (EPS) in patients with BrS. From 5 centers 348 patients were retrospectively selected (age 44 ± 15 years, males 68%). Eighty-five (24%) patients had an ICD. EPS was proposed in patients with spontaneous type-1 ECG pattern regardless of symptoms, or in patients with drug-induced type-1 ECG pattern with symptoms (n = 174). The difference in the refractory period between the right ventricular outflow tract and the apex (ΔRPRVOT-apex) at EPS was evaluated as a prognostic factor. The optimal ΔRPRVOT-apex cutpoint for prognosis prediction was calculated through a P-spline hazard ratio analysis. Thus, ΔRPRVOT-apex was compared through different statistical analyses to other other clinical or conventional electrophysiological prognostic indexes previosly described in literature. During a 36-month median follow-up (range 6-228) 3 SCD and 10 appropriate ICD shocks (aborted SCD, aSCD) occurred. Fifty patients (29%) had a positive EPS (induction of sustained ventricular tachycardia, VT, or ventricular fibrillation, VF, during the procedure). At multivariable logistic analysis, only ΔRPRVOT-apex and late potentials remained independent predictors of a positive EPS. At Cox Proportional Hazard analysis, family history of SCD, history of syncope, VT/VF inducibility and a ΔRPRVOT-apex &amp;gt;60 ms were all univariate predictors of SCD/aSCD. At bivariate analysis, a ΔRPRVOT-apex &amp;gt;60 ms remained an independent predictor of SCD/aSCD even when adjusted the other univariate predictors. At C-Statistic analysis, the strongest predictive model was the one using ΔRPRVOT-apex &amp;gt;60 ms as covariate with a C-statistics (95% CI) of 0.72 (0.51-0.93). At Kaplan-Meyer curves, ΔRPRVOT-apex &amp;gt;60 ms was confirmed a strong predictor of SCD/aSCD and another very interesting observation was possible: patients with positive EPS, but a ΔRPRVOT-apex &amp;lt; 60 ms, had a similar risk to SCD/aSCD compared to patients with a negative EPS, while those with a positive EPS and a ΔRPRVOT-apex &amp;gt; 60 ms were found to be at a higher risk of events. Refractory period heterogeneity of the right ventricle defined as ΔRPRVOT-apex &amp;gt; 60 ms at EPS is a strong and independent predictor of SCD/aSCD in patients with BrS, beyond VT/VF inducibility at EPS and common clinical predictors. Abstract Figure.

Sudden cardiac death risk stratification in patients with a preserved or mildly reduced ejection fraction: role of cardiac magnetic resonance and electrophysiological study

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Patients presenting with syncope of suspected arrhythmogenic origin or symptomatic documented non sustained ventricular tachycardia (NSVT) may represent a population with higher risk for sudden cardiac death (SCD). However today there are still no defined criteria to stratify the risk of SCD in this population. PURPOSE To assess the prognostic value of magnetic resonance (MRI) and electrophysiological study (EPS) in the risk stratification for SCD of patients with a preserved or mildly-reduced ejection fraction (EF) that may benefit from implantable cardiac defibrillator (ICD) therapy. METHODS We selected ischemic and non-ischemic patients with a preserved or mildly-reduced ejection fraction who came to our attention either after a probably arrhythmogenic syncopal event or a documented NSVT between 12/2018 and 09/2020. Patients with other ICD indications following current guideline-criteria were excluded (id est Brugada syndrome, Long QT and hypertrophic cardiomyopathy). All patients underwent an echocardiography, a coronary angiography, and an MRI with gadolinium, those among them with a positive LGE also underwent an induction EPS. Non inducible patients were followed-up clinically or with an implantable event-recorder, while inducible patients received an ICD. RESULTS In our observational study seventeen patients with preserved or only mildly-reduced EF were enrolled (13 males and 5 females; mean age 68 years). Among these patients, nine were identified with an underlying myocardial scar with positive Late-Gadolinium-Enhancement (LGE) in MRI. Based on the clinical orientation and the MRI LGE pattern patients were divided in ischemic group (5 patients) and non-ischemic group (4 patients). All 9 patients underwent an induction EPS. Three of them, 2 with non-ischemic and 1 with an ischemic pattern, demonstrated a reproducible inducibility of a sustained ventricular tachycardia or ventricular fibrillation and were implanted with an ICD. During our follow-up two of the three patients had an adequate shock within a year from the ICD implantation. Among the 6 patients with negative induction EPS there were no clinical events in the follow up, except one death for unknown causes. CONCLUSION Our preliminary results demonstrated that in patients with ischemic or non ischemic cardiopathy with preserved or mildly reduced EF, a positive MRI LGE pattern and the inducibility of ventricular arrhythmias during induction EPS identify a population at higher risk for clinical recurrence of ventricular arryhthmic events. Further investigation is needed to validate this combined diagnostic strategy as new SCD prevention tool.

Sex Differences in Electrophysiology, Ventricular Tachyarrhythmia, Cardiac Arrest and Sudden Cardiac Death Following Acute Myocardial Infarction

Women experience less appropriate implantable cardioverter-defibrillator (ICD) interventions and are underrepresented in randomised ICD trials. Sex-differences in inducible and spontaneous ventricular tachycardia/fibrillation (VT/VF), cardiac arrest and sudden cardiac death (SCD) early post-myocardial infarction (MI) require further study. Consecutive ST-elevation MI patients with left ventricular ejection fraction (LVEF)≤40% underwent electrophysiology study (EPS) to target early prevention of SCD. An ICD was implanted for a positive (inducible monomorphic VT) but not a negative (no arrhythmia or inducible VF) EPS. The combined primary endpoint of VT/VF (spontaneous or ICD-treated), cardiac arrest or SCD was assessed using competing risk survival analysis in women versus men with adjustment for confounders. Logistic regression was used to determine independent predictors of inducible VT at EPS. A total of 403 patients (16.9% female) underwent EPS. Women were significantly older than men but with similar LVEF (31.5 ± 6.3 versus 31.6 ± 6.4%, p = 0.91). Electrophysiology study was positive for inducible VT in 22.1% and 33.4% (p = 0.066) and an ICD implanted in 25.0% and 33.4% (p = 0.356) of women versus men. Appropriate ICD activations (VT/VF) occurred in 5.9% of women and 36.6% of men (p = 0.012). The adjusted cumulative primary endpoint incidence was significantly lower in women than men (1.6% versus 26.5%, p = 0.03). Female sex was not an independent predictor of inducible VT at EPS (HR 0.63, 95% CI 0.33-1.23, p = 0.178). Women with early post-MI cardiomyopathy had lower VT/VF, cardiac arrest and SCD, compared to men. In ICD recipients the rate of appropriate activations was six-fold less in women compared to men.

Etiology and Outcomes of Syncope in Patients With Structural HeartDisease and Negative Electrophysiology Study.

This study sought to determine the cause of recurrent syncope and clinical outcomes by using the head-uptilt test (HUTT) and an insertable loop recorder (ILR) in patients with structural heart disease (SHD) and negative electrophysiology study (EPS) results. Patients with syncope and SHD with negative EPS findings have a low risk of sudden cardiac arrest. Nevertheless, the cause of recurrent syncope and the outcomes in these patients are not well characterized. This prospective study evaluated syncope patients with SHD and negative EPS results by using HUTT (with sublingual nitroglycerine [NTG] provocation as needed) and ILR. A total of 41 SHD patients (27 patients [66%] had coronary arterial disease, and 14 patients [34.15%] had dilated cardiomyopathy with mean EF of 42 ± 4.8% [range 30% to 49%]) were included. HUTT findings were positive in 25 patients (61%) in group A and negative in 16 patients (39%) in group B. An ILR was implanted in 21 of 25 group A patients (84%) and in 12 of 16 group B patients (75%), and they were followed for 15 ± 8 months. During follow-up, 17 of 21 patients (81%) in group A and 5 of 12 patients (41.7%) in group B had ILR evidence consistent with reflex syncope. One group B patient had documented atrioventricular block and underwent pacemaker implantation. There were no malignant ventricular arrhythmias or deaths on follow-up. Reflex syncope is the most common cause of syncope and accounts for approximately 60% of cases in patients with SHD, negative EPS results, left ventricular systolic dysfunction with left ventricular EF >30%, and not in heart failure.

Electrophysiology study for risk stratification in patients with cardiac sarcoidosis and abnormal cardiac imaging

BackgroundAbnormalities on cardiac imaging (cardiac magnetic resonance imaging [CMR] or positron emission tomography [PET]), left ventricular ejection fraction (LVEF), and electrophysiology study (EPS) all predict ventricular arrhythmias (VA) in patients with cardiac sarcoidosis (CS). We sought to assess the utility of EPS in patients with CS and abnormal cardiac imaging, focusing on those with LVEF >35%. MethodsWe identified all patients treated at our institution from 2000 to 2017 who: 1.) had probable or definite CS; 2.) had either late gadolinium enhancement (LGE) on CMR or abnormal 18-flourodeoxyglucose (FDG) uptake on PET, and 3.) had undergone EPS. The primary endpoint was VA during follow up. ResultsTwenty five patients were included, of whom 10 (40%) had positive EPS. During a mean follow-up of 4.8 +/− 3.4 years, 11 (44%) patients had VA. The positive predictive value (PPV) of EPS for VA was 100% and the negative predictive value (NPV) of EPS for VA was 93%. Among 12 patients with LVEF >35% and no prior VA, the PPV of EPS for VA was 100% and the NPV of EPS for VA was 90%. ConclusionEPS may help with risk stratification in patients with CS and abnormal imaging, especially those without conventional indications for ICD placement. Among patients with LVEF >35% and no history of prior VA, a negative EPS has good positive and negative predictive value for future VA events.

Pooled Analysis of Risk Stratification of Spontaneous Type 1 Brugada ECG: Focus on the Influence of Gender and EPS.

Aims: Risk stratification of patients with Brugada syndrome (BrS) is vital for accurate prognosis and therapeutic decisions. Spontaneous Type 1 ST segment elevation is generally considered to be an independent risk factor for arrhythmic events. Other risk factors include gender, syncope, sudden cardiac arrest (SCA), and positive electrophysiological study (EPS). However, the further risk stratification of spontaneous type 1 combined with the other risk factors remains unclear. The present study pooled data from 4 large trials aiming to systematically evaluate the risk of spontaneous Type-1 ECG when combined with one or more of these other recognized risk factors.Methods: We searched for related studies published from November 2, 2002 to February 10, 2018 in PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Databases. The pooled data were evaluated combining each risk factor with the presence of a spontaneous Type-1 ECG. All analyses were performed using Review Manager, version 5.0.12.Results: Four eligible studies involving 1,338 patients (85% males, mean age: 48.1 ± 18.1 years) were enrolled. Spontaneous Type-1 ECG was associated with higher risk for ventricular tachycardia/fibrillation (VT/VF) than cases with non-Type 1 ECG in males (odds ratio: 95% CI: 1.84–5.17; P < 0.0001), but not in females (P = 0.29). Among spontaneous Type-1 cases with syncope or with positive EPS, the difference was not statistically significant (P = 0.06 and 0.07, respectively). Patients with Type-1 ECGs and positive EPS were at higher risk than those with negative EPS (95% CI: 1.10–5.04; P = 0.03). Pooled analysis showed an association of Spontaneous Type-1 ECG, Type-1 ECGs combined with male, and Type-1 ECGs combined with positive EPS between increased risk of arrhythmic events.Conclusion: Our results indicate that in BrS patients, a spontaneous Type-1 ECG is an independent risk factor for SCD in males, but not in females. A spontaneous Type-1 BrS is associated with a worse prognosis when combined with positive EPS

Gender Differences in Electrophysiology, Ventricular Tachyarrhythmia, Cardiac Arrest and Sudden Cardiac Death Following Acute Myocardial Infarction

Introduction: Women experience less appropriate implantable cardioverter-defibrillator (ICD) interventions and are underrepresented in primary prevention ICD trials. Gender differences in inducible and spontaneous ventricular tachycardia/fibrillation (VT/VF), cardiac arrest and sudden cardiac death (SCD) early post-myocardial infarction (MI) require further study. Methods and Results: Consecutive ST-elevation MI patients with left ventricular ejection fraction (LVEF) ≤40% underwent electrophysiology study (EPS) to target early prevention of SCD (n = 403, 16.9% female). An ICD was implanted for a positive (inducible monomorphic VT) but not a negative (no arrhythmia or inducible VF) EPS. The combined primary endpoint of VT/VF (spontaneous or ICD-treated), cardiac arrest or SCD was assessed using competing risk survival analysis in women versus men with adjustment for confounders. Logistic regression was used to determine independent predictors of inducible VT at EPS. Women were significantly older than men but with similar mean LVEF (31.5 ± 6.3 versus 31.6 ± 6.4%, P = 0.91). EPS was positive for inducible VT in 22.1% and 33.4% (P = 0.066) and an ICD implanted in 25.0% and 33.4% (P = 0.356) of women versus men. Appropriate ICD activations (VT/VF) occurred in 5.9% and 36.6% of women versus men (P = 0.012). The adjusted cumulative primary endpoint incidence was significantly lower in women than men (1.6% versus 26.5%, P = 0.03). Female gender was not an independent predictor of inducible VT at EPS (HR 0.63, 95% CI 0.33–1.23, P = 0.178). Conclusion: Women with early post-MI cardiomyopathy had significantly lower VT/VF, cardiac arrest and SCD, compared to men. In ICD recipients the rate of appropriate activations was 6-fold less in women compared to men.

Syncope, conduction disturbance, and negative electrophysiological test: Predictive factors and risk score to predict pacemaker implantation during follow-up

Patients with syncope and bundle branch block (BBB) are at risk for atrioventricular block (AVB). Electrophysiological study (EPS) can help in identifying patients at higher risk for AVB, but the false-negative rate is remarkable. Few data on the predictors of the need for pacemaker implantation during follow-up have been reported. The purpose of this study was to analyze the rate of patients who need pacemaker implantation after negative EPS and predictive factors. A single-center prospective study of 159 consecutive patients (73.9 ± 12.1 years; male 64.9%) with syncope and BBB (January 2012-December 2016) and negative EPS was conducted. An implantable loop recorder was implanted. After 27.9 ± 10.8 months of follow-up, 39 patients (24.8%) underwent pacemaker implantation because of bradyarrhythmia. In the univariate analysis, bifascicular (right BBB + left fascicular block) block, bifascicular block + long PR interval, conduction disturbance different from isolated right BBB, HV ≥60 ms, and HV≥70 ms after class I drug challenge were predictors of pacemaker implantation. In the multivariate analysis, only bifascicular block (hazard ratio 2.5; 95% confidence interval 1.4-4.8; P = .04) andHV interval ≥60 ms (hazard ratio 3.5; 95% confidence interval 1.8-6.2; P <.001) were statistically significant. A risk score according to the multivariate model identified 3 levels of pacemaker implantation rate (13.5%, 32.7%, and 66.7%; P <.001). No death or severe trauma related to bradyarrhythmia occurred. The strategy of an implantable loop recorder in patients with syncope and BBB is safe after negative EPS, but some patients might need pacemaker implantation during follow-up. A risk score based on HV ≥60 ms and bifascicular block can be useful in identifying patients at risk for advanced AVB after negative EPS.

Flecainide Versus Procainamide in Electrophysiological Study in Patients With Syncope and Wide QRS Duration.

This study sought to compare the differences between procainamide and flecainide to stress the His-Purkinje system during electrophysiological study (EPS) in patients with syncope and bundle branch block (BBB). Patients with syncope and BBB are at risk of developing atrioventricular block. EPS is recommended including class I drug challenge to unmask His-Purkinje disease in cases with baseline normal His-ventricular interval. There is little data on differences between different class I drugs. This was a prospective study of all consecutive patients undergoing EPS for syncope and BBB at a single center (January 1, 2012 to June 30, 2017). Of those patients with negative baseline EPS, 2 cohorts were compared: groupA (historical cohort: procainamide) and group B (flecainide). During the study, 271 patients (age 73.9 ± 12.1 years, 64.9% male, QRS duration: 139.4 ± 13.9 ms) underwent EPS. In 166, baseline EPS was negative and class I drug challenge was performed (90 procainamide, 76 flecainide). The final value and percentage increase in the His-ventricular interval (76 ± 16 ms vs. 64 ± 10 ms and 22.5 ± 6.2% vs. 11.8 ± 5.3%; p< 0.001) and diagnostic yield (14.5% vs. 7.8%, p= 0.04) were higher with flecainide. No differences were found in baseline characteristics. During follow-up (25.8 ± 6.3 months), 39 patients (24.8%) with negative EPS (19.2% with flecainide vs. 30.1% with procainamide: relative risk: 5.1; 95% confidence interval: 2.6 to 10.2; p< 0. 001) received a pacemaker. Flecainide has a higher diagnostic yield than does procainamide in patients with BBB, syncope, and negative baseline EPS due to a greater increase of the His-ventricular interval. Additionally, there is a lesser need for pacemaker implantation in patients in whom the class I drug test using flecainide was negative.