Non-Invasive Programmed Stimulation (NIPS) to Guide the Subsequent VT Therapeutic Strategies

The Value of Late Non-Invasive Programmed Stimulation (NIPS) in the Setting of Ventricular Tachycardia (VT) Ablation to Guide the Subsequent VT Therapeutic Strategies: a Prospective Randomized Multicenter Study

The aim of this study is to define the importance of non-invasive programmed stimulation (NIPS) in risk stratification of ventricular tachycardia (VT) recurrence after catheter ablation and to determine the optimal treatment strategy. The primary objective is to establish whether a new VT ablation based on NIPS inducibility will reduce the risk of VT recurrence compared to antiarrhythmic drug therapy.

Study Overview

• Status: Recruiting
• Conditions: Ventricular Tachycardia (VT)
• Intervention / Treatment: Drug: Antiarrhythmic Drug Therapy (amiodarone, sotalol, or mexiletine); Procedure: Re-Do ventricular tachycardia ablation

Detailed Description

The value of non-invasive programmed ventricular stimulation (NIPS) in the setting of ablation of ventricular tachycardia (VT) in patients with structural heart disease has been the object of studies in the last decade.

The technique is based on the feature, uniformly available in the Implantable Cardioverter-Defibrillator (ICD), to perform a complete programmed stimulation study from the apex of the right ventricle to assess the inducibility of ventricular tachycardia, similar to what is routinely performed during an invasive electrophysiology procedure. Data from our group indicate that 26% of patients who were non-inducible (apparent success) at the end of the ablation session become re-inducible to ventricular tachycardia at "late" NIPS (day 6). This finding, possibly related to partial recovery of conduction within the treated area, had prognostic significance, as it was associated with a 6-fold increased risk of VT recurrence at follow-up.

Recently Muser et al. reported similar findings (45/216 -21% of patients had clinical VT induced) with "late" NIPS performed on day 3. However, within this group of patients, the VT recurrence rate was significantly lower in those who had undergone, based on this finding, a re-do VT ablation as compared to those treated conservatively (rec in 1/11 of the Re-do ablation group, 9% vs. 24/34 in the conservative treatment group, 71%, p<0.01).

These data, however, originated from a retrospective observational analysis, where the indication of ablation was based on empirical physician preference.

No prospective randomized data compare the conservative attitude versus performing a new ablation in subjects who did not obtain a stable result after the first one. Therefore, this randomized multicenter clinical study aims to evaluate whether the repetition (Re-Do) of VT ablation process is superior to conservative medical therapy for reducing VT recurrences on post-procedural NIPS.

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrea Radinovic, MD; Phone Number: +39 0226436316; Email: radinovic.andrea@hsr.it
• Study Contact Backup: Name: Anna Montagna, PhD; Phone Number: +39 0226437489; Email: montagna.anna@hsr.it

Study Locations

• Italy
  • Italy
    • Milan, Italy, Italy, 20132
      • Recruiting
      • San Raffaele Hospital, Arrhythmology and Electrophysiology unit
      • Contact: Paolo Della Bella, MD; Phone Number: +39 0226436247; Email: dellabella.paolo@hsr.it
      • Contact: Andrea Radinovic, MD; Email: radinovic.andrea@hsr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with an implanted ICD (all brands)
• Patients who underwent a successful (non-inducibility of any VT) Ventricular Tachycardia Ablation procedure, the "index procedure", supported by EnSite Precision or CARTO 3D mapping systems for the following etiologies: previous MI, myocarditis, ARVD, IDCM.
• Induction of monomorphic VT at NIPS 3-7days after a successful index procedure
• Age 18 years or more
• Able to provide an informed consent to participate to the study and available to respect the assessments described in the protocol.

Exclusion Criteria:

• Inducible VT after index procedure
• Contraindication to anticoagulants
• Presence of thrombi
• Presence of Mitral and Aortic prosthetic valve
• Recent (<3 months) myocardial infarction or unstable angina or Coronary Artery Bypass
• Pregnant or nursing
• Ventricular Tachycardia caused by reversible pathology
• < 1 Year life expectancy according to the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; AAD therapy	Drug: Antiarrhythmic Drug Therapy (amiodarone, sotalol, or mexiletine); The patients with a positive NIPS already on antiarrhythmic drugs (AAD) before the index procedure will re-start the original antiarrhythmic therapy. Patients who were not on AAD will start a new drug at the operator's discretion (amiodarone, sotalol, or mexiletine) according to clinical practice.
Experimental: Group 2; Re-Do ablation procedure	Procedure: Re-Do ventricular tachycardia ablation; 1. Programmed ventricular stimulation (PVS); 2. Mapping during Sinus Rhythm (SR) or right ventricular pacing in pacing dependent patients; 3. Late Potentials identification; 4. VT(s) induction with diastolic pathway mapping when possible; 5. Catheter Ablation in SR or, at the operator's discretion, in VT if tolerated by the patient; 6. If VT is not inducible or the diastolic pathway is not mappable, a substrate ablation approach will be performed. 7. PVS is repeatedly attempting to reinduce VT after completing; 8. Endpoint: non-inducibility of any VT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VT recurrence free survival rate	Compare the efficacy on the reduction of VT recurrence of a NIPS-based Re-Do VT ablation versus antiarrhythmic drug therapy	12 months after the procedure

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of ICD shocks	Procedural, periprocedural, 6 and 12 months after procedure
Proportion of patients with VT storm	Procedural, periprocedural, 6 and 12 months after procedure
Rate of subsequent hospitalization for VT recurrence/HF.	Procedural, periprocedural, 6 and 12 months after procedure
Cardiac mortality	Procedural, periprocedural, 6 and 12 months after procedure

Collaborators and Investigators

• Sponsor: IRCCS Ospedale San Raffaele

Publications and helpful links

General Publications

• Della Bella P, Peretto G, Paglino G, Bisceglia C, Radinovic A, Sala S, Baratto F, Limite LR, Cireddu M, Marzi A, D'Angelo G, Vergara P, Gulletta S, Mazzone P, Frontera A. Bipolar radiofrequency ablation for ventricular tachycardias originating from the interventricular septum: Safety and efficacy in a pilot cohort study. Heart Rhythm. 2020 Dec;17(12):2111-2118. doi: 10.1016/j.hrthm.2020.06.025. Epub 2020 Jun 26.
• Oloriz T, Baratto F, Trevisi N, Barbaro M, Bisceglia C, D'Angelo G, Yamase M, Paglino G, Radinovic A, Della Bella P. Defining the Outcome of Ventricular Tachycardia Ablation: Timing and Value of Programmed Ventricular Stimulation. Circ Arrhythm Electrophysiol. 2018 Mar;11(3):e005602. doi: 10.1161/CIRCEP.117.005602.
• Irie T, Yu R, Bradfield JS, Vaseghi M, Buch EF, Ajijola O, Macias C, Fujimura O, Mandapati R, Boyle NG, Shivkumar K, Tung R. Relationship between sinus rhythm late activation zones and critical sites for scar-related ventricular tachycardia: systematic analysis of isochronal late activation mapping. Circ Arrhythm Electrophysiol. 2015 Apr;8(2):390-9. doi: 10.1161/CIRCEP.114.002637. Epub 2015 Mar 4.
• Muser D, Hayashi T, Castro SA, Supple GE, Schaller RD, Santangeli P, Arkles J, Kumareswaran R, Nazarian S, Deo R, Lin D, Dixit S, Epstein AE, Callans DJ, Marchlinski FE, Frankel DS. Noninvasive Programmed Ventricular Stimulation-Guided Management Following Ventricular Tachycardia Ablation. JACC Clin Electrophysiol. 2019 Jun;5(6):719-727. doi: 10.1016/j.jacep.2019.03.007. Epub 2019 May 1.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 21, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): November 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Ventricular Tachycardia, VT, Non-Invasive Programmed Stimulation, NIPS, ICD, Implantable Cardioverter Defibrillator
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Tachycardia; Pathological Conditions, Signs and Symptoms; Tachycardia, Ventricular; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Phenols; Benzene Derivatives; Alcohols; Amino Alcohols; Ethanolamines; Propylamines; Phenyl Ethers; Benzofurans; Amiodarone; Sotalol; Mexiletine
• Other Study ID Numbers: NIPS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No