Predicting ventricular arrhythmia inducibility in ajmaline-induced Brugada type I pattern: Validation of the dST-Tiso interval.

INTRODUCTION: The dST-Tiso is a newly proposed electrocardiographic (ECG) marker during Brugada (BrS) type I pattern, that predicts the likelihood of ventricular arrhythmia (VA) inducibility in patients with ajmaline-induced pattern. The objective of this study was to validate the effectiveness of this criterion using an independent data set. METHODS: Consecutive patients exhibiting a BrS type I ECG pattern following ajmaline administration underwent programmed ventricular stimulation (PVS). dST-Tiso interval was measured in all patients and tested as a predictor for positive VA inducibility. RESULTS: Among 128 patients (median age 43 years, 59% male) with drug-induced BrS type I ECG pattern who underwent PVS, 32 (25.0%) had VA inducibility that required defibrillation. Compared to noninducible subjects, those with positive PVS were more commonly 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 < 0.001) intervals, and shorter QT interval (412 vs. 420 ms, p = 0.022). When treated as a continuous variable, dST-Tiso confirmed significant association with VA inducibility, with an adjusted odds ratio of 1.02 (95% confidence interval: 1.01-1.03, p < 0.001) for each 1 ms increase in duration. A dST-Tiso interval >300 ms yielded a sensitivity of 75%, a specificity of 86%, and positive and negative predictive values of 69% and 91%, respectively. CONCLUSION: The validation of the model based on the dST-Tiso interval >300 ms confirmed its high accuracy in predicting VA inducibility in drug-induced BrS type I pattern. This straightforward ECG marker might be linked to the extent of the electrical substrate of the disease.

Prognostic value of noninvasive programmed stimulation in primary prevention implantable cardioverter-defibrillator recipients.

Background: Implantable cardioverter-defibrillator (ICD) offers an opportunity to study inducibility of ventricular tachycardia (VT) or ventricular fibrillation (VF) by performing noninvasive programmed ventricular stimulation (NIPS). Whether NIPS can predict future arrhythmic events or mortality in patients with primary prevention ICD, has not yet been examined. Methods: From the NIPS-ICD study (ClinicalTrials ID: NCT02373306) 41 consecutive patients (34 males, age 64 ± 11 years, 76% ischemic cardiomyopathy [ICM]) had ICD for primary prevention indication. Patients underwent NIPS using a standardized protocol of up to three premature extrastimuli at 600, 500 and 400 ms drive cycle lengths. NIPS was classified as positive if sustained VT or VF was induced. The study endpoint was occurrence of sustained VT/VF during the follow-up. Results: At baseline NIPS, VT/VF was induced in 8 (20%) ICM patients. During the 5-year follow-up, the VT/VF occurred in 7 (17%) patients, all with ICM. The difference between NIPS-inducible versus NIPS-noninducible patients regarding VT/VF occurrence did not meet statistical significance (38% vs. 12%, log rank test p = .11). After a 5-year follow-up, the mortality rate was significantly higher in patients who had VT/VF induced at NIPS versus no VT/VF at NIPS (38% vs. 12%, p = .043). The occurrence of a composite endpoint consisting of VT/VF recurrence or death in patients with ICM was also most frequent in the NIPS-inducible group (75% vs. 35%, p = .037). Conclusions: Inducibility of VT/VF during NIPS in ICM patients with primary prevention ICD is associated with higher mortality and higher incidence of composite endpoint consisting of death or VT/VF during a long-term observation.

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.

Scar architecture affects the electrophysiological characteristics of induced ventricular arrhythmias in hypertrophic cardiomyopathy.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) detects myocardial scarring, a risk factor for ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy (HCM). The LGE-CMR distinguishes core, borderzone (BZ) fibrosis, and BZ channels, crucial components of re-entry circuits. We studied how scar architecture affects inducibility and electrophysiological traits of VA in HCM. METHODS AND RESULTS: We correlated scar composition with programmed ventricular stimulation-inducible VA features using LGE intensity maps. Thirty consecutive patients were enrolled. Thirteen (43%) were non-inducible, 6 (20%) had inducible non-sustained, and 11 (37%) had inducible sustained mono (MMVT)- or polymorphic VT/VF (PVT/VF). Of 17 induced VA, 13 (76%) were MMVT that either ended spontaneously, persisted as sustained monomorphic, or degenerated into PVT/VF. Twenty-seven patients (90%) had LGE. Of these, 17 (57%) had non-sustained or sustained inducible VA. Scar mass significantly increased (P = 0.002) from non-inducible to inducible non-sustained and sustained VA patients in both the BZ and core components. Borderzone channels were found in 23%, 67%, and 91% of non-inducible, inducible non-sustained, and inducible sustained VA patients (P = 0.003). All 13 patients induced with MMVT or monomorphic-initiated PVT/VF had LGE. The origin of 10/13 of these VTs matched scar location, with 8/10 of these LGE regions showing BZ channels. During follow-up (20 months, interquartile range: 7-37), one patient with BZ channels and inducible PVT had an ICD shock for VF. CONCLUSION: Scar architecture determines inducibility and electrophysiological traits of VA in HCM. Larger studies should explore the role of complex LGE patterns in refining risk assessment in HCM patients.

[Development and clinical value of programmed ventricular stimulation in coronary artery disease and dilated cardiomyopathy]. / Entwicklung und Bedeutung der programmierten Ventrikelstimulation bei der koronaren Herzerkrankung und dilatativen Kardiomyopathie.

Programmed ventricular stimulation (PVS), a clinical 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. A specific 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 a tool to monitor the results of ventricular tachycardia (VT)-catheter ablation in patients who were primarily inducible.

Ventricular arrhythmia inducibility in porcine infarct model after stereotactic body radiation therapy.

BACKGROUND: Ventricular arrhythmia (VA) is the primary mechanism of sudden death in patients with structural heart disease. Cardiac stereotactic body radiation therapy (SBRT) delivered to the scar in the left ventricle significantly reduces the burden of VA. OBJECTIVE: The goal of this study was to investigate the impact of SBRT on scar morphology and VA inducibility in a porcine infarct model. METHODS: Myocardial infarction (MI) was created in 10 Yorkshire pigs involving the left anterior descending artery territory. Cardiac positron emission tomography and computed tomography were performed for targeted SBRT. Alternative pigs received SBRT at 25 Gy in a single fraction. The terminal experiment included endocardial mapping, programmed ventricular stimulation, and tissue harvesting. RESULTS: Of the 10 pigs infarcted, 2 died prematurely after MI and 8 (4 MI and 4 MI+SBRT) survived. Mean time from MI to SBRT was 48 ± 12 days, and mean time from SBRT to harvest was 32 ± 12 days. Scar was localized on intracardiac mapping in all pigs, and the scar was denser in the MI+SBRT compared with the MI-only group (33% ± 20% vs 14% ± 11%; P = .07). All 4 MI pigs had inducible VA during programmed stimulation, whereas only 1 of 4 pigs had inducible VA in the MI+SBRT arm (100% vs 25%; P = .07). No myocardial fibrosis was seen in the remote areas in either group. CONCLUSION: SBRT reduced VA inducibility in pigs with scarring after MI. Endocardial mapping revealed denser scar in pigs receiving SBRT compared with those that did not, suggesting that SBRT suppresses VA inducibility through better scar homogenization.

Long-term clinical outcomes of patients with drug-induced type 1 Brugada electrocardiographic pattern: A nationwide cohort registry study.

BACKGROUND: There are limited real-world data on the extended prognosis of patients with drug-induced type 1 Brugada electrocardiogram (ECG). OBJECTIVE: We assessed the clinical outcomes and predictors of life-threatening arrhythmias in patients with drug-induced type 1 Brugada ECG. METHODS: This multicenter retrospective study, conducted at 21 Italian and Swiss hospitals from July 1997 to May 2021, included consecutive patients with drug-induced type 1 ECG. The primary outcome, a composite of appropriate ICD therapies and sudden cardiac death, was assessed along with the clinical predictors of these events. RESULTS: A total of 606 patients (mean age 49.7 ± 14.7 years; 423 [69.8%] men) were followed for a median of 60.3 months (interquartile range 23.0-122.4 months). Nineteen patients (3.1%) experienced life-threatening arrhythmias, with a median annual event rate of 0.5% over 5 years and 0.25% over 10 years. The SCN5A mutation was the only predictor of the primary outcome (hazard ratio 4.54; P = .002), whereas a trend was observed for unexplained syncope (hazard ratio 3.85; P = .05). In patients who were asymptomatic at presentation, the median annual rate of life-threatening arrhythmias is 0.24% over 5 years and increases to 1.2% if they have inducible ventricular fibrillation during programmed ventricular stimulation. CONCLUSION: In patients with drug-induced type 1 Brugada ECG, the annual risk of life-threatening arrhythmias is low, with the SCN5A mutation as the only independent predictor. Unexplained syncope correlated with worse clinical outcomes. Ventricular fibrillation inducibility at programmed ventricular stimulation significantly increases the median annual rate of life-threatening arrhythmias from 0.24% to 1.2% over 5 years.

Long-term outcomes of patients with ventricular arrhythmias and negative programmed ventricular stimulation followed with implantable loop recorders: Impact of delayed-enhancement cardiac magnetic resonance imaging.

BACKGROUND: Programed ventricular stimulation (PVS) is a risk stratification tool in patients at risk for adverse arrhythmia outcomes. Patients with negative PVS may yet be at risk for adverse arrhythmia-related events, particularly in the presence of symptomatic ventricular arrhythmias (VA). OBJECTIVE: To investigate the long-term outcomes of real-world patients with symptomatic VA without indication for device therapy and negative PVS, and to examine the role of cardiac scaring on arrhythmia recurrence. METHODS: Patients with symptomatic VA, and late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR), and negative PVS testing were included. All patients underwent placement of implantable cardiac monitors (ICM). Survival analysis was performed to investigate the impact of LGE-CMR findings on survival free from adverse arrhythmic events. RESULTS: Seventy-eight patients were included (age 60 ± 14 years, women n = 36 (46%), ejection fraction 57 ± 9%, cardiomyopathy n = 26 (33%), mitral valve prolapse [MVP] n = 9 (12%), positive LGE-CMR scar n = 49 (62%), history of syncope n = 23 (29%)) including patients with primarily premature ventricular contractions (n = 21) or nonsustained VA (n = 57). Patients were followed for 1.6 ± 1.5 years during which 14 patients (18%) experienced VA requiring treatment (n = 14) or syncope due to bradycardia (n = 2). Four/9 patients (44%) with MVP experienced VA (n = 3) or syncope (n = 1). Baseline characteristics between those with and without adverse events were similar (p > 0.05); however, the presence of cardiac scar on LGE-CMR was independently associated with an increased risk of adverse events (hazard ratio: 5.6 95% confidence interval: [1.2-27], p = 0.03, log-rank p = 0.03). CONCLUSIONS: In a real-world cohort with long-term follow-up, adverse arrhythmic outcomes occurred in 18% of patients with symptomatic VA despite negative PVS, and this risk was significantly greater in patients with positive DE-CMR scar. Long term-monitoring, including the use of ICM, may be appropriate in these patients.

Increased in vivo perpetuation of whole-heart ventricular arrhythmia in heterozygous Na+/Ca2+ exchanger knockout mice.

Aims: Na+/Ca2+ exchanger (NCX) upregulation in cardiac diseases like heart failure promotes as an independent proarrhythmic factor early and delayed afterdepolarizations (EADs/DADs) on the single cell level. Consequently, NCX inhibition protects against EADs and DADs in isolated cardiomyocytes. We here investigate, whether these promising cellular in vitro findings likewise apply to an in vivo setup. Methods/Results: Programmed ventricular stimulation (PVS) and isoproterenol were applied to a murine heterozygous NCX-knockout model (KO) to investigate ventricular arrhythmia initiation and perpetuation compared to wild-type (WT). KO displayed a reduced susceptibility towards isoproterenol-induced premature ventricular complexes. During PVS, initiation of single or double ectopic beats was similar between KO and WT. But strikingly, perpetuation of ventricular tachycardia (VT) was significantly increased in KO (animals with VT - KO: 82 %; WT: 47 %; p = 0.0122 / median number of VTs - KO: 4.5 (1.0, 6.25); WT: 0.0 (0.0, 4.0); p = 0.0039). The median VT duration was prolonged in KO (in s; KO: 0.38 (0.19, 0.96); WT: 0.0 (0.0, 0.60); p = 0.0239). The ventricular refractory period (VRP) was shortened in KO (in ms; KO: 15.1 ± 0.7; WT: 18.7 ± 0.7; p = 0.0013). Conclusions: Not the initiation, but the perpetuation of provoked whole-heart in vivo ventricular arrhythmia was increased in KO. As a potential mechanism, we found a significantly reduced VRP, which may promote perpetuation of reentrant ventricular arrhythmia. On a translational perspective, the antiarrhythmic concept of therapeutic NCX inhibition seems to be ambivalent by protecting from initiating afterdepolarizations but favoring arrhythmia perpetuation in vivo at least in a murine model.

Long-term outcome of ventricular tachycardia ablation in patients who did not undergo programmed electrical stimulation after ablation.

BACKGROUND: Ventricular arrhythmia inducibility is one of the ideal endpoints of ventricular tachycardia (VT) ablation. However, it may be challenging to implement programmed electrical stimulation (PES) at the end of the procedure under several circumstances. The long-term outcome of patients who did not undergo PES after VT ablation remains largely unknown. PURPOSE: To investigate the details and long-term outcome of VT ablation in patients who did not undergo PES at the end of the ablation procedure. METHODS: Among 183 VT ablation procedures in patients with structural heart disease who underwent VT ablation using an irrigated catheter, we enrolled those who did not undergo PES after VT ablation. VT ablation strategy involved targeting clinical VT plus pacemap-guided substrate ablation if inducible. When VT was not inducible, substrate-based ablation was performed. The primary endpoint was VT recurrence. RESULTS: In 58 procedures, post-ablation VT inducibility was not assessed. The causes were non-inducibility of sustained VT before ablation (27/58, 46.6%), long procedure time (27.6%, mean 392 min), complications (10.3%), intolerant hemodynamic state (10.3%), and inaccessible or unsafe target (6.9%). With regard to the primary endpoint, 23 recurrences (39.7%) were observed during a mean follow-up period of 2.5 years. Patients with non-inducibility before ablation showed less VT recurrences (4/27, 14.8%) during follow-up than patients with other causes of untested PES after ablation (19/31, 61.2%) (Log-rank < 0.001). CONCLUSIONS: VT recurrence was not observed in approximately 60% of the patients who did not undergo PES at the end of the ablation procedure. PES after VT ablation may be not needed among patients with pre-ablation non-inducibility.

Ventricular arrhythmias after fibroma resection: Are patients still at risk?

BACKGROUND: Ventricular fibromas frequently present with life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) in children. The long-term risk of sustained ventricular arrhythmias after surgical resection is unknown. OBJECTIVES: The aims of this study were to quantify the VT/VF risk after surgical resection and to examine the results of early (during index surgical hospitalization) and late (≥3 months after surgery) postoperative ventricular stimulation (V-stim) studies. METHODS: We performed a retrospective cohort study of all patients with ventricular fibromas who underwent surgical resection at our institution (2000-2020). The primary outcome was defined as recurrent VT/VF ≥3 months after index surgical resection. RESULTS: Forty-six patients with a median age at surgery of 2 years (range 0.3-18.9 years) formed our study cohort. Indications for surgery included cardiac arrest in 11 (24%), sustained VT in 16 (35%), premature ventricular contractions/nonsustained VT in 10 (22%), and hemodynamic abnormalities in 9 (20%). Of the 11 patients who presented with cardiac arrest, 4 underwent pre-resection implantable cardioverter-defibrillator (ICD) implantation, all of which were explanted at the time of surgery. An early postoperative V-stim study was performed in 26 (57%) patients, and all were negative for inducible VT/VF. Of the 13 late postoperative V-stim studies, 3 were positive: 2 underwent ICD implantation and 1 was initiated on amiodarone and underwent loop recorder implantation. At the time of last follow-up (median 1.5 years; range 0.3-16.5 years), 45 (98%) were free of clinical VT/VF and no patient with an ICD has received an appropriate shock. CONCLUSION: Surgical resection of ventricular fibromas significantly reduces the risk of life-threatening arrhythmias in children; however, a small number of patients remain vulnerable.

The Prognostic Role of Programmed Ventricular Stimulation in the Risk Stratification of Sudden Cardiac Death.

Sudden cardiac death (SCD) is one of the leading causes of cardiovascular death in general population. SCD primary prevention requires the correct selection of patients at increased risk who may benefit from implantable cardioverter-defibrillator (ICD). Despite several non-invasive arrhythmic risk indexes are available, their ability to stratify the SCD risk among asymptomatic patients with cardiac disease at increased arrhythmic risk is debated. The programmed ventricular stimulation (PVS) is an invasive approach historically used for SCD risk stratification in patients with acquired or inherited cardiac disease and is currently included in international guidelines. Aim of this review is to summarize all available data about the role of PVS for the SCD risk stratification in different clinical settings.

Arrhythmic CArdiac DEath in MYotonic dystrophy type 1 patients (ACADEMY 1) study: the predictive role of programmed ventricular stimulation.

AIMS: Myotonic dystrophy type 1 (DM1) predisposes to the development of life-threatening arrhythmias and sudden cardiac death. Our study aimed to evaluate the prognostic value of programmed ventricular stimulation (PVS) in DM1 patients with conduction system disease. METHODS AND RESULTS: Arrhythmic CArdiac DEath in MYotonic dystrophy type 1 patients (ACADEMY 1) is a double-arm non-randomized interventional prospective study. Myotonic dystrophy type 1 patients with permanent cardiac pacing indication were eligible for the inclusion. The study population underwent to pacemaker (PM) or implantable cardioverter-defibrillator (ICD) implantation according to the inducibility of ventricular tachyarrhythmias at PVS. Primary endpoint of the study was a composite of appropriate ICD therapy and cardiac arrhythmic death. The secondary study endpoint was all-cause mortality. Seventy-two adult-onset DM1 patients (51 ± 12 years; 39 male) were enrolled in the study. A ventricular tachyarrhythmia was induced in 25 patients (34.7%) at PVS (PVS+) who underwent dual chambers ICD implantation. The remaining 47 patients (65.3%) without inducible ventricular tachyarrhythmia (PVS-) were treated with dual-chamber PM. During an average observation period of 44.7 ± 10.2 months, nine patients (12.5%) met the primary endpoint, four in the ICD group (16%) and five (10.6%) in the PM group. Thirteen patients died (18.5%), 2 in the ICD group (8%) and 11 in PM group (23.4%). The Kaplan-Meier analysis did not show a significantly different risk of both primary and secondary endpoint event rates between the two groups. CONCLUSIONS: The inducibility of ventricular tachyarrhythmias has shown a limited value in the arrhythmic risk stratification among DM1 patients.

Subcutaneous ICD Implantation and Catheter Ablation: A Step-Planned Approach for Ventricular Tachycardia Management in ARVC.

Secondary prevention of sudden cardiac death in the young patient with arrhythmogenic right ventricular cardiomyopathy and hemodynamically tolerated ventricular tachycardia is still a challenging field. We present a combined approach, including subcutaneous implantable cardioverter-defibrillator (ICD) and catheter ablation, as a promising treatment to prevent both ventricular tachycardia recurrences and ICD shocks. (Level of Difficulty: Intermediate.).

Case report: Lamin A/C gene mutation in patient with drug-induced type 1 Brugada syndrome at high arrhythmic risk.

We report the case of drug-induced type 1 Brugada syndrome at high arrhythmic risk associated with Lamin A/C gene mutation.

Sudden Cardiac Death Prevention in Patients with Ischemic Heart Disease-Beyond the Ejection Fraction.

Sudden cardiac death (SCD) in patients with ischemic heart disease remains a leading cause of death. Prediction of who is at risk is based on the left ventricular ejection fraction (EF). However, the majority of victims of SCD have a normal EF, and the majority of patients implanted with an implantable cardioverter- defibrillator based on their EF are never treated by their device. Several parameters could allow better prediction of SCD. Several signs on the ECG and Periodic Repolarization Dynamics have been associated with increased risk. Elevated serum biomarkers such as pro-B type natriuretic peptides and serum soluble suppression of tumorigenicity 2 protein (sST2) are predictive of SCD. On the echocardiogram, global longitudinal strain, speckle tracking and relative wall thickness have been implicated. Programmed ventricular stimulation studies and cardiac magnetic resonance are promising modalities that could be further investigated. In conclusion, the EF is an imperfect tool for predicting SCD. Using the modalities reviewed, a model could be created for better prediction of patients at risk.

The value of cardiac magnetic resonance imaging and programmed ventricular stimulation in patients with ventricular noncompaction and ventricular arrhythmias.

INTRODUCTION: Left ventricular noncompaction (LVNC) is associated with ventricular arrhythmias (VA) including premature ventricular complexes, and ventricular tachycardia (VT). The value of imaging with delayed enhancement cardiac magnetic resonance (DE-CMR) and programmed ventricular stimulation (PVS) for risk stratification in patients with VA and LVNC is unknown. The purpose of this study was to determine whether DE-CMR and PVS are beneficial for risk stratification and whether CMR helps to identify VA target sites. METHODS AND RESULTS: Consecutive patients with LVNC undergoing ablation for VAs were included, all patients had preprocedure DE-CMR. A total of 23 patients (7 women, 46 ± 14 years, ejection fraction 35 ± 14) were included and followed for 2.9 ± 2.2 years. DE-CMR scar was present in 12/23 patients (52%). PVS was performed in 20/23 patients, 8/10 patients (80%) with scar were inducible for VT compared to 0/10 (0%) patients without scar (p < .001). VA target sites in patients with scarring were located adjacent to areas of scarring in all but 1 patient and ablation was successful in 15/23 patients (65%). Patients with scar had worse survival free of VT than those without scar (log rank p = .01) and patients with inducible VT had worse survival free of VT than those who were noninducible (log rank p < .001). CONCLUSIONS: The presence of CMR defined scar in patients with LVNC was associated with inducible VT and worse outcomes. Inducibility for VT was associated with VT recurrence. Furthermore, CMR is beneficial in localizing the arrhythmogenic substrate in LVNC and therefore can aid in procedural planning.