Programmed Ventricular Stimulation Research Articles

Programmed Ventricular Stimulation: Risk Stratification and Guiding Antiarrhythmic Therapies.

Electrophysiologic testing with programmed ventricular stimulation (PVS) has been utilized to induce ventricular tachycardia (VT), thereby improving risk stratification for patients with ischemic and nonischemic cardiomyopathies and determining the effectiveness of antiarrhythmic therapies, especially catheter ablation. A variety of procedural aspects can be modified during PVS in order to alter the sensitivity and specificity of the test including the addition of multiple baseline pacing cycle lengths, extrastimuli, and pacing locations. The definition of a positive result is also critically important, which has varied from exclusively sustained monomorphic VT (>30 seconds) to any ventricular arrhythmia regardless of morphology. In this review, we discuss the history of PVS and evaluate its role in sudden cardiac death risk stratification in a variety of patient populations. We propose an approach to future investigations that will capitalize on the unique ability to vary the sensitivity and specificity of this test. We then discuss the application of PVS during and following catheter ablation. The strategies that have been utilized to improve the efficacy of intraprocedural PVS are highlighted during a discussion of the limitations of this probabilistic strategy. The role of noninvasive programmed stimulation is also reviewed in predicting recurrent VT and informing management decisions including repeat ablations, modifications in antiarrhythmic drugs, and implantable cardioverter-defibrillator programming. Based on the available evidence and guidelines, we propose an approach to future investigations that will allow clinicians to optimize the use of PVS for risk stratification and assessment of therapeutic efficacy.

Endocardial repolarization dispersion in BrS: A novel automatic algorithm for mapping activation recovery interval.

Repolarization dispersion in the right ventricular outflow tract (RVOT) contributes to the type-1 electrocardiographic (ECG) phenotype of Brugada syndrome (BrS), while data on the significance and feasibility of mapping repolarization dispersion in BrS patients are scarce. Moreover, the role of endocardial repolarization dispersion in BrS is poorly investigated. We aimed to assess endocardial repolarization patterns through an automated calculation of activation recovery interval (ARI) estimated on unipolar electrograms (UEGs) in spontaneous type-1 BrS patients and controls; we also investigated the relation between ARI and right ventricle activation time (RVAT), and T-wave peak-to-end interval (Tpe) in BrS patients. Patients underwent endocardial high-density electroanatomical mapping (HDEAM); BrS showing an overt type-1 ECG were defined asOType1, while those without (latent type-1 ECGandLType1) received ajmaline infusion. BrS patients only underwent programmed ventricular stimulation (PVS). Data were elaborated to obtain ARI corrected with the Bazett formula (ARIc), while RVAT was derived from activation maps. 39 BrS subjects (24 OType1 and 15 LTtype1) and 4 controls were enrolled. OType1 and post-ajmaline LType1 showed longer mean ARIc than controls (306 ± 27.3 ms and 333.3 ± 16.3 ms vs. 281.7 ± 10.3 ms, p = .05 and p < .001, respectively). Ajmaline induced a significant prolongation of ARIc compared to pre-ajmaline LTtype1 (333.3 ± 16.3 vs. 303.4 ± 20.7 ms, p < .001) and OType1 (306 ± 27.3 ms, p < .001). In patients with type-1 ECG (OTtype1 and post-ajmaline LType1) ARIc correlated with RVAT (r = .34, p = .04) and Tpec (r = .60, p < .001), especially in OType1 subjects (r = .55, p = .008 and r = .65 p < .001, respectively). ARIc mapping demonstrates increased endocardial repolarization dispersion in RVOT in BrS. Endocardial ARIc positively correlates with RVAT and Tpec, especially in OType1.

Ventricular tachycardia ablation after myocardial infarction guided by cardiac magnetic resonance/multidetector computed tomography image integration

Abstract INTRODUCTION The persistent challenge of ventricular tachycardia (VT) ablation lies in the elevated morbidity and mortality due to the underlying disease progression and the complexity of the arrhythmogenic substrate. As imaging methods are evolving, substrate-based VT ablation is moving closer to the realm of precision medicine. CASE PRESENTATION A 52-year-old patient with a history of hypertension, type II diabetes mellitus, hyperlipidemia, and stage IIIB chronic kidney disease was referred to our hospital for sustained monomorphic VT. Upon admission, the patient was hemodynamically stable. Laboratory results indicated mild anemia, moderate renal dysfunction, and normal myocardial enzymes. ECG during sinus rhythm showed widespread repolarization abnormalities in the apical and postero-lateral leads. Echocardiography revealed mild left ventricular dysfunction and coronary angiography confirmed significant lesions in multiple coronary arteries that were treated with drug-eluting stents (DES). Cardiac MRI showed relatively limited areas of old myocardial infarctions in the left circumflex artery and left anterior descending artery territories, therefore we decided to perform VT ablation. We used a Carto 3 Biosense Webster electro-anatomical mapping system (EAM) guided by fusion imaging (cardiac MRI and multidetector computed tomography - MDCT) with the aid of ADAS 3D software. The voltage map created during sinus rhythm, was concordant with the lesions identified on LGE-CMR. Radiofrequency (RF) catheter ablation targeted abnormal signals from the EAM, which were identified based on conduction channels (CCs) from the fusion imaging. There was complete VT non-inducibility at programmed ventricular stimulation (PVS). At the 3-month follow-up, echocardiography showed a slight improvement in LVEF and repeated PVS proved persistent ventricular arrhythmia non-inducibility. CONCLUSION Substrate-based VT ablation in structural heart disease has greatly improved by high-resolution substrate imaging with detailed anatomy, allowing successful personalized treatment. There is room for further improvement in the near future with the contribution of artificial intelligence, possibly with a more targeted and automated VT ablation.

[Development and clinical value of programmed ventricular stimulation in coronary artery disease and dilated cardiomyopathy].

Programmed ventricular stimulation (PVS), aclinical tool introduced in the early 1980s, aims to prove the electrical vulnerability of the heart and, independent of spontaneous arrhythmia variability, to trigger arrhythmias under controlled conditions. Aspecific response is the inducibility of monomorphic sustained ventricular tachycardia. This depends on the underlying heart disease, e.g., only for coronary artery disease but not for nonischemic diseases. The value of pharmacologic arrhythmia control as serial electrical testing is uncertain. Up to now there seems to be no prognostic value of PVS concerning sudden cardiac death. PVS is used as atool to monitor the results of ventricular tachycardia (VT)-catheter ablation in patients who were primarily inducible.

Assessment of repolarization dispersion by using endocardial unipolar electrograms in patients with brugada syndrome and spontaneous coved-type electrocardiographic pattern

Abstract Background Coved-type electrocardiographic (ECG) pattern of patients with Brugada syndrome (BrS) is secondary to action potential lengthening in the right ventricular outflow tract (RVOT) epicardium. This may be approximated by activation-recovery interval (ARI), a marker of local repolarization dispersion. Purpose Our aim was to examine epicardial repolarization dispersion by ARI in the RVOT in patients with BrS and its correlation with conduction slowing and Tpeak-Tend (Tpe) interval, a marker of altered repolarization on surface ECG previously associated with a higher arrhythmic risk in this setting. Methods 24 patients with coved-type BrS phenotype underwent an invasive electrophysiological evaluation with endocardial high-density 3D mapping and programmed ventricular stimulation (PVS). Mapping data was exported and converted into MatLab format using OpenEP. Paraview was used to select a region of interest (ROI) specifically comprising of sub-pulmonary RVOT and RV free wall. ARI was calculated for each point of the ROI using a semi-automated algorithm with the Wyatt method and corrected with the Bazett formula (ARIc). The values were then interpolated to create ARI maps. For each patient, we calculated the value of ARIc at 75% of the distribution (ARIcQ3) and mean ARI for the values in the interval above ARIcQ3 (meanARIcQ3); ARIcQ3 points were also used to create maps. Activation maps were used to determine right ventricular activation time (RVAT). Tpe intervals were calculated with the tangent method on V1, V2 and V3 of 20 low-noise sinus beats recorded during the procedure, and then corrected with the Bazzett formula. Results Out of 24 patients, 6 had inducible VT/ VF during PVS (PVS+) while 18 did not (PVS-). Average ARI, ARIc, ARIcQ3, and meanARIcQ3 were 291.4 ± 22.1 ms; 306.0 ± 27.3 ms; 335.1 ± 28.3 ms; 353.1 ± 30.3 ms, respectively. Average Tpe was 75.0 ± 7.3 ms, with a mean corrected Tpe of 79.0 ± 10 ms. Mean RVAT was 111.9 ± 30.7 ms. Zones with ARIcQ3 were all located into the anterior and subpulmonary RVOT. We found a correlation between ARIcQ3 and mean corrected Tpe (R=0.58, p=0.003), and between meanARIcQ3 and mean corrected Tpe (R=0.65, p&amp;lt;0.001). A good correlation was also found between ARIcQ3 and RVAT (R=0.5441, p=0.009), and meanARIcQ3 and RVAT (R=0.49, p=0.02). No significant differences were found between PVS+ and PVS- patients. Conclusions Our results show the presence of zones with long ARI within RVOT of BrS with type-1 phenotype, indicating marked local repolarization dispersion. Longer ARIs correlate with altered repolarization on surface ECG and with prolongation of local activation time. ARI mapping can help identify repolarization dispersion and should be evaluated in the setting of a multi-parametric risk assessment in BrS with spontaneous coved-type ECG.

Predicting ventricular arrhythmia inducibility in ajmaline-induced brugada type I pattern: validation of the dST-Tiso interval

Abstract Background The dST-Tiso is the interval between the onset of the coved ST-segment elevation and its termination at the isoelectric line in V1 and V2 electrocardiographic (ECG) leads during manifest Brugada (BrS) type I pattern. A dST-Tiso &amp;gt;300 ms was proposed as a predictor of ventricular arrythmia (VA) inducibility in patients with ajmaline-induced pattern. Purpose The aim of this study was to validate this criterion in an independent data set. Methods Consecutive patients with a BrS type I ECG pattern found after ajmaline administration underwent programmed ventricular stimulation (PVS). dST-Tiso was measured in all patients and tested as a predictor of positive VA inducibility. Results In our institution, a total of 128 patients (median age 43 years, 59% male) with drug-induced BrS Type I ECG pattern underwent PVS between January 2021 and December 2022. Thirty-two patients (25.0%) had VA inducibility that required defibrillation. Compared to non-inducible subjects, those with positive PVS were more frequently male (81% vs 51%, p=0.003), had longer PQ (165 vs. 160 ms, p=0.016) and dST-Tiso (310 vs 230 ms, p&amp;lt;0.001) intervals, and shorter QT interval (412 vs. 420 ms, p=0.022). The figure shows the distribution of dST-Tiso intervals for patients with not inducible and inducible VA. As a continuous variable, dST-Tiso confirmed significant association with VA inducibility with an adjusted odds ratio of 1.02 (95% CI 1.01-1.03, p&amp;lt;0.001) for each 1 ms increase in duration. A dST-Tiso interval &amp;gt;300 ms yielded a sensitivity of 75%, a specificity of 86%, positive and negative predictive values of 69% and 91%, respectively. Conclusion The validation of the estimation model based on the dST-Tiso interval &amp;gt;300 ms confirmed its high accuracy in predicting VA inducibility in drug-induced BrS type I pattern. This simple ECG marker might be related to the extent of the electrical substrate of the disease.Distribution of dST-Tiso intervals

Non-revascularized chronic total occlusions impact on substrate and post-ablation results in drug-refractory electrical storm.

There is limited data concerning the effect of non-revascularized chronic total occlusions (NR-CTOs) after VT ablation. This study sought to evaluate the impact of NR-CTOs after ablation for electrical storm (ES). Post-hoc retrospective analysis of data regarding 64 consecutive post-myocardial infarction patients (out of which 12 patients with NR-CTOs and 52 without NR-CTOs) undergoing substrate ablation for ES with an available median follow-up of 37.53 (7.25-64.65) months. Ablation result was assessed by inducibility of sustained monomorphic VT (SMVT) during final programmed ventricular stimulation (PVS). The primary endpoints were all-cause mortality and VT/VF recurrences after ablation, respectively, stratified by the presence of NR-CTOs. The secondary endpoint was to assess the predictive effect of NR-CTOs on all-cause mortality and VT/VF recurrences in relation to other relevant prognostic factors. At baseline, the presence of NR-CTOs was associated with higher bipolar BZ-to-total scar ratio (72.4% ± 17.9% vs. 52% ± 37.7%, p = 0.022) and more failure to eliminate the clinical VT (25% (3) vs. 0% (0), p < 0.001). During follow-up, overall all-cause mortality and recurrences were more frequent in the NR-CTO subgroup (75% (9) vs. 19.2% (10), log rank p = 0.003 and 58.3% vs. 23.1% (12), log rank p = 0.042 respectively). After adjusting for end-procedural residual SMVT inducibility, NR-CTOs predicted death during follow-up (HR 3.380, p = 0.009) however not recurrence (HR 1.986, p = 0.154). NR-CTO patients treated by RFCA for drug-refractory ES demonstrated a higher ratio of BZ-to-total-scar area. In this analysis, NR-CTO was associated with worse acute procedural results and may as well impact long-term outcomes which should be further assessed in larger patient populations.

Risk assessment of post-myocardial infarction patients with preserved ejection fraction using 45-min short resting Holter electrocardiographic recordings.

Risk stratification for sudden cardiac death in post-myocardial infarction (post-MI) patients remains a challenging task. Several electrocardiographic noninvasive risk factors (NIRFs) have been associated with adverse outcomes and were used to refine risk assessment. This study aimed to evaluate the performance of NIRFs extracted from 45-min short resting Holter ECG recordings (SHR), in predicting ventricular tachycardia inducibility with programmed ventricular stimulation (PVS) in post-MI patients with preserved left ventricular ejection fraction (LVEF). We studied 99 post-MI ischemia-free patients (mean age: 60.5 ± 9.5 years, 86.9% men) with LVEF ≥40%, at least 40 days after revascularization. All the patients underwent PVS and a high-resolution SHR. The following parameters were evaluated: mean heart rate, ventricular arrhythmias (premature ventricular complexes, couplets, tachycardias), QTc duration, heart rate variability (HRV), deceleration capacity, heart rate turbulence, late potentials, and T-wave alternans. PVS was positive in 24 patients (24.2%). HRV, assessed by the standard deviation of normal-to-normal R-R intervals (SDNN), was significantly decreased in the positive PVS group (42 ms vs. 51 ms, p = .039). SDNN values <50 ms were also associated with PVS inducibility (OR 3.081, p = .032 in univariate analysis, and 4.588, p = .013 in multivariate analysis). No significant differences were identified for the other NIRFs. The presence of diabetes, history of ST-elevation MI (STEMI) and LVEF <50% were also important predictors of positive PVS. HRV assessed from SHR, combined with other noninvasive clinical and echocardiographic variables (diabetes, STEMI history, LVEF), can provide an initial, practical, and rapid screening tool for arrhythmic risk assessment in post-MI patients with preserved LVEF.

Electrophysiological study prior to planned pulmonary valve replacement in patients with repaired tetralogy of Fallot.

Ventricular arrhythmias (VAs) are the most common cause of death in patients with repaired Tetralogy of Fallot (rTOF). However, risk stratifying remains challenging. We examined outcomes following programmed ventricular stimulation (PVS) with or without subsequent ablation in patients with rTOF planned for pulmonary valve replacement (PVR). We included all consecutive patients with rTOF referred to our institution from 2010 to 2018 aged ≥18 years for PVR. Right ventricular (RV) voltage maps were acquired and PVS was performed from two different sites at baseline, and if non-inducible under isoproterenol. Catheter and/or surgical ablation was performed when patients were inducible or when slow conduction was present in anatomical isthmuses (AIs). Postablation PVS was undertaken to guide implantable cardioverter-defibrillator (ICD) implantation. Seventy-seven patients (36.2 ± 14.3 years old, 71% male) were included. Eighteen were inducible. In 28 patients (17 inducible, 11 non-inducible but with slow conduction) ablation was performed. Five had catheter ablation, surgical cryoablation in 9, both techniques in 14. ICDs were implanted in five patients. During a follow-up of 74 ± 40 months, no sudden cardiac death occurred. Three patients experienced sustained VAs, all were inducible during the initial EP study. Two of them had an ICD (low ejection fraction for one and important risk factor for arrhythmia for the second). No VAs were reported in the non-inducible group (p < .001). Preoperative EPS can help identifying patients with rTOF at risk for VAs, providing an opportunity for targeted ablation and may improve decision-making regarding ICD implantation.

A novel workflow for advanced mapping of repolarization dispersion from endocardial unipolar electrograms in patients with coved-type brugada syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Accentuation of the action potential notch in the epicardium causes the prolongation of the epicardial action potentials in the right ventricular outflow tract (RVOT) and is the basis for arrhythmogenesis in patients affected by Brugada syndrome (BrS). Activation-recovery interval (ARI) approximates the action potential duration and may be used to study repolarization dispersion in BrS. Purpose Our aim was to investigate repolarization dispersion within the RVOT in spontaneous coved-type ECG BrS patients and in controls, evaluating also the relation between repolarization dispersion and conduction abnormalities to better define the electro-anatomical substrate of the disease. Methods BrS probands (n=13) and control subjects (n=4) underwent endocardial mapping of RV with the CARTO 3 system. BrS patients were also studied with programmed ventricular stimulation (PVS). Data was exported from the CARTO system and converted into MatLab format using OpenEP. A specific region of interest (ROI) including the sub-pulmonary RVOT and entire RV free wall was then selected using Paraview. With an automated algorithm, we measured ARI and ARIc (corrected using the "Bazett formula") for each point of the ROI, which were then interpolated to obtain ARI maps. We also acquired right ventricular activation time (RVAT) and maps for the assessment of slow conduction zones. By dividing RVAT color scale in 5 ms steps (isoSteps), isochronal activation areas were identified in the ROI. Results Out of the 13 BrS subjects, 4 had VT or VF inducible during PVS (PVS+) while 9 did not (PVS-). One patient had appropriate ICD shocks during follow-up. BrS patients had higher mean ARI and ARIc compared to controls (288.5±22.2 vs 251.5±8.4 ms, p&amp;lt;0.001; 312.0±30.4 vs 281.8±10.3 ms, p=0.023). ARI was found to be higher in PVS+ than in PVS- patients (294.8±27.1 vs 285.8±20.1 ms, p=0.5), as well as ARIc (327.7±49.9 vs 304.6±16.4 ms, p=0.49) although these differences were not significant. BrS patients showed a longer RVAT (106.0±21.4 vs 74.5±5.5 ms, p=0.003), and increased zones of crowding, as expressed by isochronal steps (13.85±2.94 vs 9.25±1.26, p=0.01). Notably, a strong correlation was found between ARIc and RVAT (Pearson R coefficient = 0.83, p&amp;lt;0.05), independently from the results of PVS (PVS+ R=0.99, p=0.01; PVS- R=0.83, p=0.06). Conclusions We introduced a novel workflow for the electrical substrate characterisation of subjects with BrS phenotype. Our preliminary data show the presence of repolarization dispersion along with conduction slowing in the RVOT of BrS patients compared to controls. In our population, repolarization dispersion and impairment of RVOT conduction were strongly related especially in inducible BrS patients.

Non-revascularized chronic total occlusion is associated with worse outcomes in post-MI drug-refractory electrical storm patients treated by catheter ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Outcomes in post-myocardial infarction (MI) patients which are referred for catheter ablation (CA) for drug-refractory electrical storm (ES) are influenced both by patient characteristics and procedural results. Previous data has shown higher risk for the first incident ES episode in the presence of non-revascularized chronic total occlusions (nCTOs). However, the prognostic effect of nCTOs in post-ES ablation patients is relatively unknown. Purpose We evaluated the impact of the presence of nCTO on all-cause mortality and sustained VT recurrence rate after CA for ES in post-MI patients. Methods In this single centre retrospective longitudinal study, we included consecutive post-MI patients referred for CA for drug-refractory ES. The median follow-up interval was 34.36 (7.25-63.65) months. CA outcome was defined by the absence or presence of residual sustained monomorphic VT at end-procedural programmed ventricular stimulation (PVS). Coronary angiography was performed prior to ablation in all patients. Results Sixty-four patients were included (85.9% (n = 55) males, age 62.64 ± 11.13 years). The mean left ventricular ejection fraction (LVEF) was 31.41 ± 10.99. There were 18.8% (n = 12) patients with nCTOs. Residual sustained monomorphic VT inducibility was documented in 28.1% (n = 18) cases. There were 29.7% (n = 19) deaths and sustained VT recurrences, respectively, during the monitored interval. Nine out of twelve (75%) nCTO patients died during follow-up. The presence of a nCTO induced a borderline significant higher risk of sustained VT recurrence during follow-up (HR 2.527, CI.95% 0.992 – 6.435, p = 0.052) in univariable Cox regression. In addition to age and residual sustained monomorphic VT at PVS, a multivariable Cox regression model identified the presence of nCTO as an independent predictor for all-cause mortality (HR 3.194, CI 95% 1.212-8.420, p = 0.019) (Figure 1). Conclusion(s) The presence of a nCTO in post-MI patients may be associated with higher all-cause mortality and sustained VT recurrences after ablation for drug-refractory electrical storm.

Invasive risk stratification and implantable loop recorders in brugada syndrome: a single centre experience

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Risk stratification in Brugada syndrome (BrS) is challenging. Cardiogenic syncope, family history of sudden cardiac death and ECG markers are useful variables in determining patient risk. Invasive risk stratification is sometimes needed in those with an intermediate risk phenotype. Implantable loop recorders (ILR) may be considered in those patients with no inducible ventricular arrythmias during programmed ventricular stimulation (PVS). Objective The aim of this study was to retrospectively evaluate the outcome of BrS patients referred for PVS and ILR implantation. Methodology Demographic, clinical and follow-up data of BrS patients seen in clinic were retrospectively analysed from hospital databases. A p vale of &amp;lt;0.05 was considered significant. Results 129 patients have been diagnosed with BrS since launching the inherited arrhythmia clinic service (53.5% males). 15 (high risk patients) had an ICD (n=13, 10.1%) or PM (n=2, 1.6%) implanted because of a hospital cardiac arrest, ventricular arrhythmias, high grade AV Block or cardiogenic syncope. 26 (20.2%) were placed in the intermediate risk category, (65.4% males). Patients were offered an electrophysiology study (EPS/PVS) or an ILR depending on the clinical indication (Figure 1). Most were male (65.4%), with a mean age of 41.8±17.7 years at the time of risk stratification. 6 had a likely or definite pathogenic mutation (n=5 19.2% SCN5A, n=1 3.8% MYBPC3). This group had a median Shanghai score of 4.0±0.9. Gender (p=0.429), age (p=0.246), genotype (p=0.273) and shanghai score (p=0.746) did not differ between strategies. Most (n=12, 9.3%) were offered an EPS/PVS from the offset. Ventricular arrhythmias were induced in 1 (8.3%), an ICD was then implanted. The rest were implanted with an ILR on the day. Patients not offered an EPS (n=14, 10.9%) were initially implanted with an ILR because of insufficient grounds to proceed with an EP study. Patients with an ILR (n=25, 19.4%) were followed up for a median 39 ± 21 months. ILR monitoring identified actionable events in 3 (12.0%) patients. One (4.0%) needed a pacemaker for sick sinus syndrome. Two (8.0%) recorded non-sustained ventricular arrhythmias. Both were subjected to an EPS/PVS, one needed an ICD. None of the patients who had an EPS initially had any significant events during follow up. Conclusion ILR implantation has a role in risk stratifying intermediate risk patients who do not fulfil criteria for EPS referral. This may also be considered in intermediate risk patients who are not keen on an invasive risk assessment with EPS.

A rapid wide complex tachycardia

A 25-year-old woman presented with frequent bursts of palpitations and shortness of breath experienced while running in preparation for a marathon in 2 days. She experienced rapid palpitations without dizziness or syncope. Upon arrival in the emergency department, her baseline electrocardiogram (ECG) showed sinus bradycardia with right axis deviation (Figure 1A ) and later a symptomatic wide QRS complex tachycardia (Figure 1B). Spontaneous premature ventricular complexes (PVCs) matching the ventricular tachycardia (VT) morphology occurred with a coupling interval of 380–400 ms. She denied prior palpitations or significant medical problems. Her family history was unremarkable. The presenting ECG shows sinus bradycardia at 43 beats/min with right axis deviation. The PR interval is normal at 172 ms with normal QRS and QT intervals. The subsequent wide complex tachycardia has a rate of 248 beats/min with an atypical right bundle branch block (RBBB) and right superior axis and QRS duration 160 ms. The tachycardia has a transition from a monophasic R wave in lead V3 to a QS complex in lead V4. The tachycardia recurred despite oral metoprolol, diltiazem infusion, sotalol, intravenous procainamide, and cardioversion. Cardiac magnetic resonance imaging revealed normal biventricular systolic function without late gadolinium enhancement. The patient underwent an electrophysiology study. There was no inducible supraventricular tachycardia (SVT). The wide complex tachycardia spontaneously occurred and exhibited atrial-ventricular dissociation consistent with VT. Activation mapping identified a focal origin of the VT with the earliest site of activation at the base of the posteromedial papillary muscle with a bipolar electrogram that preceded the QRS complex by 30 ms and QS unipolar electrogram (Online Supplemental Figure 1). Pace mapping produced a 12/12 pace-map match at the site of earliest activation. Open-irrigated radiofrequency catheter ablation was performed in the power-controlled mode at 40 W at this site. After successful ablation, the VT could not be induced with right ventricular and left ventricular programmed stimulation with triple extrastimuli with or without isoproterenol infusion. In this young patent with no evidence of structural heart disease, the differential diagnosis for the wide complex tachycardia includes SVT with RBBB aberrancy, mitral annular left VT, left posterior fascicle VT, or left ventricular posteromedial papillary muscle VT. For this tachycardia, there is clear evidence of atrial-ventricular association; this is inconsistent with atrioventricular reentrant tachycardia or atrial tachycardia. In addition, for RBBB aberrancy, lead V1 typically has an RsRʹ or rSrʹ configuration, which is inconsistent with the V1 RRʹ morphology in this case. The monophasic R wave in lead avR and QS pattern in lead V6 exclude SVT with aberrancy. Once diagnosing the arrhythmia as VT, thoughts turn to identifying the site of origin for this VT. A’Aref et al1A’Aref S.J. Ip J.E. Markowitz S.M. et al.Differential of papillary muscle from fascicular and mitral annular ventricular arrhythmias in patients with and without structural heart disease.Circ Arrhythm Electrophysiol. 2015; 8: 616-624Crossref Scopus (60) Google Scholar used an algorithm analyzing the axis of the tachycardia and subsequently the QRS morphology in leads V5 and V1 for differentiation of fascicular, mitral annular, and papillary muscle VT/PVCs. This VT has (1) an RBBB superior axis morphology with a QRS duration of 160 ms and is missing both (2) an R > S in lead V5 and (3) an r < Rʹ in lead V1—all consistent with a posteromedial papillary muscle VT. The “RR” morphology in lead V1 for this VT is 1 of 3 morphologies that has been shown to have a 93% sensitivity and 98% specificity for posteromedial papillary muscle VT.2Briceno D.F. Santangeli P. Frankel D.S. et al.QRS morphology in lead V1 for the rapid localization of idiopathic ventricular arrhythmias originating from the left ventricular papillary muscles: a novel electrocardiographic criterion.Heart Rhythm. 2020; 17: 1711-1718Abstract Full Text Full Text PDF Scopus (5) Google Scholar Papillary muscle VTs (QRS duration 150 ± 15 ms) are typically wider than fascicular VTs (121 ± 11 ms).1A’Aref S.J. Ip J.E. Markowitz S.M. et al.Differential of papillary muscle from fascicular and mitral annular ventricular arrhythmias in patients with and without structural heart disease.Circ Arrhythm Electrophysiol. 2015; 8: 616-624Crossref Scopus (60) Google Scholar Fascicular VTs also have a small q wave in leads I and avL reflecting left to right septal depolarization via the fascicular system in contrast to the monophasic R wave or an Rs complex in lead I for papillary muscle VT.3Enriquez A. Supple G.E. Marchlinski F.E. Garcia F.C. How to map and ablate papillary muscle ventricular arrhythmias.Heart Rhythm. 2017; 14: 1721-1728Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Papillary muscle VTs in the absence of structural heart disease are typically sensitive to catecholamines, noninducible with programmed stimulation, and unable to be entrained, consistent with a mechanism of triggered activity or abnormal automaticity. In a canine model, the junctional cells located at the Purkinje–ventricular myocardium junction have been shown to exhibit triggered activity that can be suppressed with verapamil, consistent with the clinical manifestation of papillary muscle VT.4Li Z.Y. Wang Y.H. Maldonado C. Kupersmith J. Role of junctional zone cells between Purkinje fibers and ventricular muscle in arrhythmogenesis.Cardiovasc Res. 1994; 28: 1277-1284Crossref PubMed Scopus (21) Google Scholar Left ventricular papillary muscles are a well-known source of ventricular arrhythmias (VAs) in patients with and without structural heart disease. These VAs can manifest as PVCs, nonsustained VT, sustained VT, and PVC triggers for ventricular fibrillation. The site of origin for these arrhythmias can be mapped to the base, body, or apex of the papillary muscles. The dynamic motion of the papillary muscles can create challenges with achieving adequate catheter stability for successful ablation. Contact force sensing catheters and detailed anatomic maps of the papillary muscles created with intracardiac echocardiography have been shown to increase the rate of successful ablation of papillary muscle VA with acute and long-term success rates of 95% and 91%, respectively.5Lin A.N. Shirai Y. Liang J.J. et al.Strategies for catheter ablation of left ventricular papillary muscle arrhythmias: an institutional experience.JACC Clin Electrophysiol. 2020; 6: 1381-1392Crossref Scopus (11) Google Scholar The differential diagnosis for RBBB wide complex tachycardias in patients with no evidence of structural heart disease include SVT with RBBB aberrancy, antidromic atrioventricular reentrant tachycardia using a left-sided accessory pathway, mitral annular VT, papillary muscle VT, and fascicular VT. Application of diagnostic ECG criteria can allow an individual to successfully differentiate SVT from VT as well as to identify the site of the origin of the VT.

Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Study.

A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.

Prediction of programmed ventricular stimulation inducibility using machine learning in post-myocardial infarction patients at risk for sudden cardiac arrest with preserved ejection fraction ≥40%

Abstract Introduction Sudden cardiac death (SCD) in post myocardial infarction (post-MI) patients with a relatively preserved left ventricular ejection fraction (LVEF ≥40%) has 1% annual incidence. In the PRESERVE-EF study, we used a two-step SCD risk stratification approach to detect patients with a relatively preserved left ventricular ejection fraction ≥40% at risk for major arrhythmic events. Seven noninvasive risk factors (NIRFs) were extracted from ambulatory electrocardiography. Patients with at least one NIRF present were referred for invasive programmed ventricular stimulation (PVS). Inducible patients received an ICD. Purpose The present study examines the performance of machine learning technology for the prediction of the inducible patients in PRESERVE-EF study. Methods After first step screening with NIRFs, 152 out of 575 patients underwent PVS and 41 of them were inducible. For the present analysis, data from these 152 patients were analysed. We used machine learning of NIRFs to predict these inducible high risk patients. We selected as classification method the Nearest Neighbour (NN) algorithm, after experimentation with several classifiers. NN classifies each subject according to the class of the N nearest neighbours. For each subject, we created a vector with the following 7 features: SAECG Late Potentials, Ventricular Premature beats ≥30/hour, Non-sustained Ventricular Tachycardia ≥1 episode (s)/24 hours, Fredericia corrected QT interval ≥45 0ms, SDNN/HRV ≤75 ms, T Wave Alternans ≥65 μV, Combined Deceleration capacity (DC) ≤4.5 ms and Heart Rate Turbulence Onset (To) ≥0% and Heart Rate Turbulence Slope (Ts) ≤2.5 ms. Results The achieved accuracy reached up to 72.2% when N was set to 7. We had totally 144 samples, 41 of which were inducible high risk patients. Results were similar for other values of N. To ensure independence of train and test sets, we employed 10-fold cross validation. Conclusions Inducible on PVS patients in PRESERVE-EF study were predicted with machine learning classification of NIRFs. Funding Acknowledgement Type of funding sources: None.

Monomorphic VT Non-Inducibility after Electrical Storm Ablation Reduces Mortality and Recurrences.

Background: Electrical storm (ES) is defined by clustering episodes of ventricular tachycardia (VT) and is associated with severe long-term outcomes. We sought to evaluate the prognostic impact of radiofrequency catheter ablation (RFCA) in ES as assessed by aggressive programmed ventricular stimulation (PVS). Methods: Single-center retrospective longitudinal study with 82 consecutive ES patients referred for RFCA with a median follow-up (IQR 25–75%) of 45.43 months (15–69.86). All-cause mortality and VT recurrences were assessed in relation to RFCA outcomes defined by 4-extrastimuli PVS: Class 1—no ventricular arrhythmia; Class 2—no sustained monomorphic VTs (mVT) inducible, but non-sustained mVTs, polymorphic VTs, or VF inducible; Class 3—clinical VT non-inducible, other sustained mVTs inducible; and Class 4—clinical VT inducible. Results: Class 1, Class 2, Class 3, and Class 4 were achieved in 56.1%, 13.4%, 23.2%, and 7.4% of cases, respectively. The combined outcome of Class 1 + Class 2 (no sustained monomorphic VT inducible) led to improved survival (log-rank p < 0.001) and reduced VT recurrence (log-rank p < 0.001). Residual monomorphic VT inducibility (HR 6.262 (95% CI: 2.165–18.108, p = 0.001), NYHA IV heart failure symptoms (HR 20.519 (95% CI: 1.623–259.345), p = 0.02)), and age (HR 1.009 (95% CI: 1.041–1.160), p = 0.001)) independently predicted death during follow-up. LVEF was not predictive of death (HR 1.003 (95% CI: 0.946–1.063) or recurrences (HR 0.988 (95% CI: 0.955–1.021)). Conclusions: Non-inducibility for sustained mVTs after aggressive PVS post-RFCA leads to improved survival in ES, independently of LVEF.

Programmed ventricular stimulation for predicting arrhythmic events in patients with myocardial infarction: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular ejection fraction (LVEF) is at present the main parameter used to guide the implantation of cardioverter-defibrillators (ICD) in patients with ischaemic cardiomyopathy. However, LVEF alone is a poor predictor of ventricular arrhythmias (VA) and sudden cardiac death (SCD). The majority of ICDs implanted for the primary prevention of SCD never deliver appropriate therapies, while being an expensive therapy and being potentially iatrogenic. Therefore, insertion of ICDs based solely on LVEF is not efficient and calls for an improvement in the risk-stratification of post-myocardial infarction patients. Inducibility of ventricular arrhythmias with programmed ventricular stimulation (PVS) has been used in the past to assess the risk of malignant arrhythmias. However, its current role in clinical practice is unknown. Purpose The aim of this meta-analysis was to study the role of PVS to predict future arrhythmic events in patients with previous myocardial infarction. Methods We performed a systematic review and a random-effect meta-analysis of studies reporting VAs –defined as SCD, sudden cardiac arrest, sustained monomorphic ventricular tachycardia (SMVT) or appropriate ICD therapies– after PVS in patients with ischaemic heart disease. Whenever possible, we used inducibility of SMVT as the positive response to PVS. Otherwise, we used the definition pre-specified in the corresponding study. The primary outcome was to estimate the positive and negative predictive value (PPV and NPV, respectively) of PVS. Subgroup analyses were performed according to the PVS timing (&amp;lt;1 or ≥1 month after infarction), definition of a positive PVS, use of ICD, or study era (before or after 2000). We searched in MEDLINE, EMBASE and Cochrane Library electronic databases up to November 2021. Results Thirty studies were included with a total of 8253 patients (mean age 58.5 years, mean LVEF 38.8%). A total of 909 arrhythmic events occurred after a mean follow-up of 24.5 months. Overall, 23% (95% confidence interval [CI] 18-29%) of subjects had inducible arrhythmias with PVS. Inducibility was associated with a higher risk of subsequent VAs (odds ratio 6.26, 95% CI 3.97-9.89, p&amp;lt;0.001). The pooled NPV was 95%, (95% CI 93-96%, p&amp;lt;0.001) and the PPV was 25% (95% CI 20-31%, p&amp;lt;0.001). There was significant heterogeneity between studies (I2 78% for the odds ratio, 96% for the NPV and 68% for the PPV). There were no statistically significant differences in any of the values according to the pre-specified subgroups. Meta-regression showed a reduction of the NPV with longer follow-up (B coefficient –0.033; p=0.012). Conclusion PVS has a high NPV (95%) and could be useful to rule out subjects at low risk of arrhythmic events. However, it decreases with longer follow-ups and, thus, the arrhythmic risk may need to be reassessed.

Programmed ventricular stimulation for risk stratification in patients with myocardial scarring and an ejection fraction above or equal to 40%

Abstract Funding Acknowledgements Type of funding sources: None. Background Sudden cardiac death (SCD) is one of the leading causes of death, particularly among patients with myocardial scars. Implantable cardioverter defibrillators (ICD) are recommended in patients with a left ventricular ejection fraction (LVEF) ≤ 35%. Another recognised indication is the induction of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) during programmed ventricular stimulation (PVS) in post-myocardial infarction patients with non-sustained VT and a LVEF between 35% and 40%. However, no recommendation exists to guide the use of prophylactic ICD implantation in patients with less altered LVEF, even though they represent the majority of SCDs. Purpose We aimed to evaluate the prognostic value of PVS in patients with myocardial scars and a relatively preserved LVEF (≥ 40%). Methods Patients with evidence of a chronic myocardial scar and a LVEF ≥ 40%, who underwent PVS at two hospital centers were considered for inclusion. Ischemic and non-ischemic myocardial scars were included. The primary endpoint was the occurrence of a Major Arrhythmic Event (MAE), namely SCD, clinical VT/ventricular fibrillation, or appropriate ICD therapy. Results 134 patients were included (mean age 62.4 ± 12.5 years, LVEF 54.7 ± 8.6 %). Indication for PVS was mostly non-sustained VT and/or syncope (84%). Post-myocardial infarction patients represented about half of the cases (53%). Inducibility during PVS was observed in 17 patients (13%). There was a nonsignificant trend towards higher inducibility rates in ischemic versus nonischemic scars (17% and 8%, respectively; p-value = 0.1). Of these patients, 15 received an ICD (88%). Over a mean follow-up of 49 (±42) months, a MAE occurred in 7 patients (41.2%) with positive PVS, versus 4 patients (3.4%) with negative PVS. MAE-free survival at 10 years was 91% and 43% in PVS-negative and PVS-positive patients, respectively (p-value &amp;lt; 0.001). One SCD occurred in a PVS-positive patient who denied prophylactic ICD implantation. Inducibility during PVS provided a 64% sensitivity and a 97% negative predictive value (PV) to predict the occurrence of MAE (specificity 92%, positive PV 41%). Conclusion PVS is a useful tool to discriminate patients with myocardial scars and LVEF ≥ 40% at increased arrhythmic risk. Effective utilisation of ICD may be anticipated in case of positive PVS, while non-inducible patients are at lower MAE risk.

Endocardial ablation of ventricular tachycardia ablation in arrhythmogenic right ventricular cardiomyopathy aiming epicardial late potential abolition

Abstract Funding Acknowledgements Type of funding sources: None. Background Catheter ablation is frequently needed to treat ventricular tachycardia (VT) in ARVC patients. Ablation aiming non-inducibility (NI) and late potential (LP) abolition has been shown to be effective1. Simultaneous endo-epicardial mapping demonstrate epicardial involvement in most VT2. However epicardial fat and vicinity of coronary artery may prevent effective epicardial ablation. Aims (a) evaluate endocardial-only ablation guided by epicardial late-potential recording (EA-ELP) to achieve LP abolition (LPA) and NI; (b) measure ablation-index(AI) values allowing epicardial LP suppression by endocardial ablation, as a surrogate for transmurality. Methods From 2019 to 2021 the authors (XW, EG) evaluated EA-ELP in ARVC patients patient referred for ablation. Our ablation protocol was previously described3. Endo and epicardial voltage mapping of the right ventricle (RV) were performed in sinus rhythm using 0.5-1.5 mV threshlods for endocardial scar and 0.5-1 mV for the epicardial. All LP were manually tagged. Programmed ventricular stimulation (PVS) was performed till S4 from the RV apex and other sites, all inducible tolerated VT were mapped. Endocardial ablation was performed with an irrigated tip catheter positioned in front of epi-LP recorded by a multi-electrode catheter aiming to eliminate or delay epi-LP as a surrogate for transmurality. For each lesion fulfilling the «transmurality criteria», the AI values were recorded. Remap was performed to validate LPA and NI was tested. Patient follow-up (FU) rely on telemonitoring in ICD-carriers and holter/exercise test for the others. Results 11 patients were enrolled (9M/2F, mean age 45 years), 9 for VT recurrence (3 redo) and 2 for de novo VT. The median ICD therapy before ablation was 5/patient (mean 1.7). The clinical VT originated from the RV outflow tract (RVOT) in 5 patients, peritricuspid (PT) in 2, RV free wall (RFW) in 4. Substrate were more extended in the epicardium compared to the endocardium: epi-LP and scar surfaces were 42.5 cm2/118 cm2 versus 24.5 cm2/25.5 cm2 for the endocardium. In one patient, additional epicardial lesion was necessary to achieve LPA. The mean ablation duration was 3377 s. Remap showed LPA in all patients and PVS was negative in all (not tested in one due to hemodynamic instability). One patient presented retrosternal hematoma after ablation with spontaneous favorable outcome. Endocardial AI values allowing epi-LP abolition were 595 for the inferior wall, 625 in the RVOT, 604 for PT and 639 for RFW. During a mean FU of 12 months (median 16.5 mths), only one patient had VT recurrence. Conclusion Based on this case-series, EA-ELP appeared as a safe and effective method to treat VT in ARVC. EA-ELP ablation allowed VT suppression in 91 % of patients after an mean FU of 12 mths. The RV endocardial AI needed to suppress epi-LP ranged was between 595-639 and could be used as surrogate for transmurality in ARVC.

The prevalence of concealed Brugada Syndrome in patients with paroxysmal atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Brugada Syndrome (BS) is an inherited rhythm-disorder with risk of sudden-cardiac-death defined by a specific ST-segment elevation pattern in precordial ECG-leads either spontaneous or provoked by Na-channel-blocker-drug-provocation-test with Ajmaline and/or higher-precordial-intercostal-space (HICS)-ECGs. Scarce data denote that the prevalence of atrial fibrillation (AF) is higher in BS and most of the antiarrhythmic-drugs used in AF are contraindicated in BS. Purpose Our aim was to elucidate the frequency of BS in paroxysmal-AF (PAF) patients without heart-disease and reveal possible clinical/genetic relations. Methods Adult patients with an history of PAF less than 55-years-old were prospectively and consecutively evaluated with resting and HICS-ECGs, cardiac-examination and routine Ajmaline-drug-provocation-test (if not contraindicated). After the exclusion of subjects with any cardiac-disease, anti-arrhythmic-use, bundle-branch-blocks, pre-excitations and ventricular hypertrophies; 96 subjects ([mean±SD] age, 37.3±18, [range]18-55 years) were enrolled in the study (male n [%overall]:55 [57.2%]). All ECGs were interpreted manually by two experienced cardiologists for BS and Brugada-type-ECG-patterns (BTEPs). In 32 patients SCNA5A genetic tests were done (n: 15 BS(+) 17 BS(-) patients). In BS(+) patients, electrophysiological-study (EPS) with programmed-ventricular-stimulation (PVS) was also done and compared with the EPS parameters of BS(-) PAF patients that undergone AF-catheter-ablation-strategy (n: 30). Results Overall frequency of concealed-BS was 22,9% (n: 22 [male n: 14]). No spontaneous type-1 BTEP was found with HICS-ECGs and all BS diagnosis were Ajmaline-induced. The clinical characteristics of PAF patients with and without BS and statistical findings are presented in Table-1 and Figure-1. BS(+) patients were predominantly male, younger, slimmer, significantly more suffering from situational syncopal episodes and revealing more BTEPs by baseline HICS-ECGs. The SCN5A-mutation positivity was non-significant between BS(+) and (-) PAF patients (p= 0,80). Baseline heart-rates were lower and PR-intervals, P-wave-duration and Sinus-node-recovery-times were significantly higher in BS(+) patients. Only one BS(+) PAF patient with an history of syncope developed VF with 2 extra-beats in PVS and received an ICD. Conclusions Concealed-BS is found to be highly prevalent in middle-aged-subjects and especially males with PAF without an apparent cardiac-disorder. Knowing this considerably lethal condition might protect a vulnerable sub-group of patients from the deleterious effects of antiarrhythmics and risk stratification might confer an increased risk. Non-invasive/invasive indices regarding the delayed conduction features in atrial electrophysiological characteristics of BS(+) patients and a higher vagal state might be suggested as one of the probable mechanisms underlying the higher prevalence of AF in BS.