HEAL-IST IDE Trial

Hybrid Epicardial and Endocardial Sinus Node Sparing Ablation Therapy for Inappropriate Sinus Tachycardia

Inappropriate Sinus Tachycardia (IST) is a prevalent and debilitating condition in otherwise healthy younger patients, resulting in significant loss of quality of life, lacking effective treatment options or systematic clinical evidence to support a therapy. The primary objective of this clinical trial is to evaluate the safety and effectiveness of a hybrid sinus node sparing ablation procedure for the treatment of symptomatic drug refractory or drug intolerant IST.

Study Overview

• Status: Active, not recruiting
• Conditions: Inappropriate Sinus Tachycardia
• Intervention / Treatment: Device: AtriCure ISOLATOR Synergy Surgical Ablation System

• Study Type: Interventional
• Enrollment (Estimated): 142
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • UZ Brussels
• Italy
  • Milan, Italy
    • San Raffaele Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam University Medical Center
  • Maastricht, Netherlands
    • Maastricht University Medical Center
• Poland
  • Warsaw, Poland
    • Central Clinic Hospital
• United Kingdom
  • Sheffield, United Kingdom, S5 7AU
    • Northern General Hospital
• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • St. Bernard
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health
    • Redwood City, California, United States, 94063
      • Stanford University
    • Redwood City, California, United States, 94062
      • Sequoia Hospital
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Saint Vincent's Medical Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33143
      • Baptist Health
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
    • Tampa, Florida, United States, 33607
      • St. Joseph's Hospital / Baycare Health System
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Kansas City Cardiac Arrhythmia Research LLC
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cincinnati, Ohio, United States, 45202
      • TriHealth, Inc.
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Cardiac Arrhythmia Research Foundation
  • Utah
    • Salt Lake City, Utah, United States, 84111
      • Intermountain Healthcare
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 75 years at time of enrollment consent
2. Subject has a diagnosis of IST
3. Documentation of refractoriness (intolerance or failure) of a drug (e.g., rate control drugs such as beta-blockers/calcium channel blockers, ivabradine), and/or AADs
4. Subject is willing and able to provide written informed consent

Exclusion Criteria:

1. Subjects on whom cardiac surgery or single lung ventilation cannot be performed
2. Subjects with indication for or existing ICDs/Pacemakers
3. Presence of channelopathies
4. Previous cardio-thoracic surgery
5. Left Ventricular Ejection Fraction (LVEF) < 50%
6. Body Mass Index (BMI) ≥ 35
7. Presence of supraventricular or ventricular tachycardia
8. Presence of Postural Orthostatic Sinus Tachycardia (POTS)
9. Presence of congenital heart disease
10. History suggestive of secondary cause of tachycardia such as pheochromocytoma, anemia, thyrotoxicosis, chronic fever of unknown origin, COPD, long-term bronchodilators use, severe asthma or carcinoid syndrome
11. Subjects who have had a previous catheter ablation in the right atrium for IST or other disorders
12. Life expectancy < 24 months
13. Pregnant or planning to become pregnant during trial
14. Subjects with substance abuse
15. Subjects with previous weight loss surgery
16. Subject is unwilling and/or unable to return for scheduled follow-up visits
17. Current participation in another clinical investigation of a medical device or a drug, or recent participation in such a trial that may interfere with trial results
18. Not competent to legally represent him or herself (e.g., requires a guardian or caretaker as a legal representative) and;
19. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hybrid sinus node sparing ablation procedure; Hybrid sinus node sparing ablation procedure using the ISOLATOR Synergy Surgical Ablation System	Device: AtriCure ISOLATOR Synergy Surgical Ablation System; Hybrid sinus node sparing ablation procedure using the ISOLATOR Synergy Surgical Ablation System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Effectiveness Endpoint	Freedom from IST at 12-months. Freedom from IST is defined as mean heart rate of ≤ 90bpm or at least a 15% reduction in mean heart rate as compared to baseline, in the absence of new or higher dosage of previously failed medications.	12-months Post Procedure
Primary Safety Endpoint	Incidence of device or procedure-related major adverse events (MAEs) for subjects undergoing the hybrid sinus node sparing ablation procedure from the index procedure through 30-days post procedure	30-days Post Procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-Minute Walk Test	Change in 6-Minute Walk Test (6-MWT) from baseline compared to 6-, 12- and 24-months post-procedure	24-months Post Procedure
Borg dyspnea score	Change in Borg dyspnea severity of breathlessness and fatigue score from baseline compared to 6-, 12- and 24-months post-procedure. Borg dyspnea score will be assessed at each of the 6-MWT.	24-months Post Procedure
Self-Rating Anxiety Scale	Change from baseline in psychological evaluation compared to 6-, 12- and 24-months post-procedure utilizing the Self-Rating Anxiety Scale (SAS)	24-months Post Procedure
IST symptom reduction	IST symptom reduction at baseline to 6-, 12- and 24-months post-procedure	24-months Post Procedure
QoL - SF-12	Change in QoL based on a Short Form Survey (SF-12) domain and component scores at baseline compared to 6-, 12- and 24-months post-procedure	24-months Post Procedure
Mean heart rate	Change in mean heart rate at 6-, 12- and 24-months post-procedure compared to baseline, using 7-day continuous monitoring	24-months Post Procedure
Reduction in mean heart rate in the absence of rate control drugs	Freedom from IST or at least 15% reduction in mean heart rate at 12- and 24-months compared to baseline, in the absence of rate control drugs (beta-blockers/calcium channel blockers, ivabradine) and/or AADs	24-months Post Procedure
Reduction in mean heart rate regardless of rate control drugs	Freedom from IST or at least a 15% reduction in mean heart rate at 12- and 24-months compared to baseline, regardless of rate control drugs (beta-blockers/calcium channel blockers, ivabradine) and/or AADs	24-months Post Procedure
Device or procedure related Serious Adverse Events	Device or procedure related Serious Adverse Events (SAEs) through 12-months	12-months Post Procedure
Improved heart rate variability - 7-day monitor	Improved heart rate variability for subjects using 7-day continuous monitoring	12-months Post Procedure
Improved heart rate variability - Implantable loop recorder	Improved heart rate variability and activity levels for subjects with implantable loop recorders (ILRs)	12-months Post Procedure
Health Economics	Health Economics: ER visits and readmissions	24-months Post Procedure

Collaborators and Investigators

• Sponsor: AtriCure, Inc.
• Investigators: Principal Investigator: Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute; Principal Investigator: Mark La Meir, MD, Universitair Ziekenhuis Brussel; Principal Investigator: Carlo de Asmundis, MD, Universitair Ziekenhuis Brussel; Principal Investigator: Thomas Beaver, MD, University of Florida

Publications and helpful links

General Publications

• Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J, Chen PS, Chen SA, Chung MK, Nielsen JC, Curtis AB, Davies DW, Day JD, d'Avila A, de Groot NMSN, Di Biase L, Duytschaever M, Edgerton JR, Ellenbogen KA, Ellinor PT, Ernst S, Fenelon G, Gerstenfeld EP, Haines DE, Haissaguerre M, Helm RH, Hylek E, Jackman WM, Jalife J, Kalman JM, Kautzner J, Kottkamp H, Kuck KH, Kumagai K, Lee R, Lewalter T, Lindsay BD, Macle L, Mansour M, Marchlinski FE, Michaud GF, Nakagawa H, Natale A, Nattel S, Okumura K, Packer D, Pokushalov E, Reynolds MR, Sanders P, Scanavacca M, Schilling R, Tondo C, Tsao HM, Verma A, Wilber DJ, Yamane T. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017 Oct;14(10):e275-e444. doi: 10.1016/j.hrthm.2017.05.012. Epub 2017 May 12. No abstract available.
• Sheldon RS, Grubb BP 2nd, Olshansky B, Shen WK, Calkins H, Brignole M, Raj SR, Krahn AD, Morillo CA, Stewart JM, Sutton R, Sandroni P, Friday KJ, Hachul DT, Cohen MI, Lau DH, Mayuga KA, Moak JP, Sandhu RK, Kanjwal K. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015 Jun;12(6):e41-63. doi: 10.1016/j.hrthm.2015.03.029. Epub 2015 May 14. No abstract available.
• Olshansky B, Sullivan RM. Inappropriate sinus tachycardia. Europace. 2019 Feb 1;21(2):194-207. doi: 10.1093/europace/euy128.
• Pellegrini CN, Scheinman MM. Epidemiology and definition of inappropriate sinus tachycardia. J Interv Card Electrophysiol. 2016 Jun;46(1):29-32. doi: 10.1007/s10840-015-0039-8. Epub 2015 Aug 27.
• Khiabani AJ, Greenberg JW, Hansalia VH, Schuessler RB, Melby SJ, Damiano RJ Jr. Late Outcomes of Surgical Ablation for Inappropriate Sinus Tachycardia. Ann Thorac Surg. 2019 Oct;108(4):1162-1168. doi: 10.1016/j.athoracsur.2019.03.103. Epub 2019 May 8.
• de Asmundis C, Chierchia GB, Sieira J, Stroker E, Umbrain V, Poelaert J, Brugada P, La Meir M. Sinus Node Sparing Novel Hybrid Approach for Treatment of Inappropriate Sinus Tachycardia/Postural Orthostatic Sinus Tachycardia With New Electrophysiological Finding. Am J Cardiol. 2019 Jul 15;124(2):224-232. doi: 10.1016/j.amjcard.2019.04.019. Epub 2019 Apr 23.
• Nwazue VC, Paranjape SY, Black BK, Biaggioni I, Diedrich A, Dupont WD, Robertson D, Raj SR. Postural tachycardia syndrome and inappropriate sinus tachycardia: role of autonomic modulation and sinus node automaticity. J Am Heart Assoc. 2014 Apr 10;3(2):e000700. doi: 10.1161/JAHA.113.000700.
• Masumoto A, Takemoto M, Mito T, Tanaka A, Kawano Y, Kumeda H, Kang H, Matsuo A, Hida S, Okazaki T, Tayama KI, Yoshitake K, Kosuga K. Inappropriate Sinus Tachycardia Diagnosed and Treated as Depression Successfully Treated by Radiofrequency Catheter Ablation. Intern Med. 2017;56(5):523-526. doi: 10.2169/internalmedicine.56.7579. Epub 2017 Mar 1.
• Yasin OZ, Vaidya VR, Chacko SR, Asirvatham SJ. Inappropriate Sinus Tachycardia: Current Challenges and Future Directions. J Innov Card Rhythm Manag. 2018 Jul 15;9(7):3239-3243. doi: 10.19102/icrm.2018.090706. eCollection 2018 Jul. No abstract available.
• Cappato R, Castelvecchio S, Ricci C, Bianco E, Vitali-Serdoz L, Gnecchi-Ruscone T, Pittalis M, De Ambroggi L, Baruscotti M, Gaeta M, Furlanello F, Di Francesco D, Lupo PP. Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double-blind, crossover evaluation. J Am Coll Cardiol. 2012 Oct 9;60(15):1323-9. doi: 10.1016/j.jacc.2012.06.031. Epub 2012 Sep 12.
• Kreisel D, Bailey M, Lindsay BD, Damiano RJ Jr. A minimally invasive surgical treatment for inappropriate sinus tachycardia. J Thorac Cardiovasc Surg. 2005 Aug;130(2):598-9. doi: 10.1016/j.jtcvs.2004.12.026. No abstract available.
• de Asmundis C, Chierchia GB, Lakkireddy D, Romeya A, Okum E, Gandhi G, Sieira J, Vloka M, Jones SD, Shah H, Winner M, Patel D, Whalen SP, Beaty EH, Kincaid EH, Lee A, Brodt C, Taylor BJ, Colombowala I, Romano M, Morady F, Stroker E, Overeinder I, Bala G, Van Meeteren J, Krauthammer Y, Koerber S, Shults C, Thomaides A, Badhwar N, Gopinathannair R, Shah A, Tummala R, Bello D, Hoff S, Almorad A, Frazier K, Brugada P, La Meir M. Sinus node sparing novel hybrid approach for treatment of inappropriate sinus tachycardia/postural sinus tachycardia: multicenter experience. J Interv Card Electrophysiol. 2022 Apr;63(3):531-544. doi: 10.1007/s10840-021-01044-5. Epub 2021 Aug 23.
• C. De Asmundis et al, "Thoracoscopic Ablation of Inappropriate Sinus Tachycardia and Postural Orthostatic Tachycardia Syndrome." Hands-On-Ablation, The Expert's Approach, Third Edition.
• Lakkireddy D, Garg J, DeAsmundis C, LaMeier M, Romeya A, Vanmeetren J, Park P, Tummala R, Koerber S, Vasamreddy C, Shah A, Shivamurthy P, Frazier K, Awasthi Y, Chierchia GB, Atkins D, Bommana S, Di Biase L, Al-Ahmad A, Natale A, Gopinathannair R. Sinus Node Sparing Hybrid Thoracoscopic Ablation Outcomes in Patients with Inappropriate Sinus Tachycardia (SUSRUTA-IST) Registry. Heart Rhythm. 2022 Jan;19(1):30-38. doi: 10.1016/j.hrthm.2021.07.010. Epub 2021 Jul 30.
• Broglio KR, Connor JT, Berry SM. Not too big, not too small: a goldilocks approach to sample size selection. J Biopharm Stat. 2014;24(3):685-705. doi: 10.1080/10543406.2014.888569.

Helpful Links

• Hybrid epicardial and endocardial sinus node-sparing ablation therapy for inappropriate sinus tachycardia: Rationale and design of the multicenter HEAL-IST IDE trial

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: March 4, 2022
• First Submitted That Met QC Criteria: March 4, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Tachycardia, Supraventricular; Tachycardia; Tachycardia, Sinus
• Other Study ID Numbers: CP-2021-04

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: Yes