Protocol

INTRODUCTION

Patients who are young and sporty at the time of implantation of an implantable cardioverter defibrillator (ICD), justifiably inquire about the risks involved with continuation of sportive activities after the device implantation.¹ Available data suggests that continuation of sports with an implanted ICD is generally safe. The Multinational ICD Sports Safety Registry showed that after a median follow-up of 44 months, there were no events of death or shock-related physical injury among 440 athletes who continued organized, competitive, or high-risk sports after ICD implantation.^2,3 A European sub-study demonstrated that the risk of definite or probable lead malfunction is <10% at years among patients who continued competitive or recreative sports after ICD implantation.⁴ Finally, sport activity, other than perhaps intense weight lifting, has not been linked to an increased risk of ICD lead fracture.⁵ All these data, however, relate exclusively to patients implanted with standard, transvenous ICD systems (TV-ICD).

Nowadays, young ICD-candidates, the patient subgroup more likely to engage in sport activities, are likely to request an S-ICD system. This is because S-ICD systems evade most of the long-term complications of intravenous leads. However, the long path of the subcutaneous electrode, from beyond the latissimus-dorsi muscle (where the S-ICD is commonly implanted) through subcutaneous tissue in the lateral and anterior chest wall, could (at least in theory) increase risk for electrodes fracture or far field noise detection during strenuous sport. Furthermore, sports with static and dynamic components involving chest and shoulder muscles, like weight lifting or swimming, and even sports that are traditionally considered safe for patients with heart disease and/or implanted TV-ICD, like golf, could impose risk for patients with S-ICD because of the proximity of the active muscles to the site of S-ICD and electrode implantation.

Recent data suggest that the risk of inappropriate shocks from newer generation S-ICD systems is very low.⁶ In fact, a recent study suggests that the risk of receiving an inappropriate shock from an S-ICD is as low as that for patients with imlanted TV-ICD, even when the latter have optimal programming.^7,8 However, these recent studies did not specify the degree of sportive activities performed by S-ICD recipients.

Clearly, data on the impact of athletic activities on the short-term and the long-term safety of S-ICD systems is urgently needed. This is particularly true because physicians may disfavor the selection of an S-ICD system for a young patient who intends to continue sport activities or may advice against performance of sports with little data to support such recommendations. We therefore propose a multicenter observational study designed specifically to collect data on the safety of sport activities in patients with implanted S-ICD systems.

STUDY DESIGN

Non-interventional, observational, multicenter study with prospective follow-up. Newly-implanted, and those with prior S-ICD implantation, can enroll.

Patient recruitment from two sources:

Recruitment via physicians. Physicians taking care of patients with implanted S-ICD screen and recruit patients who fulfil the inclusion criteria (see below) and provide informed consent. For enrolled patients, physicians provide coded (anonymous) demographic data, clinical data and information on sportive activities at the time of enrollment. Follow-up data is collected periodically on clinical data, sports participation and adverse events (See below).
Direct patient recruitment: Patients with an implanted S-ICD are approached via existing Patients’ Groups in the social media (like: The “Living with the S-ICD” group in Facebook (https://www.facebook.com/groups/livingwithSICD/). Patients are also reached via their treating physicians and are invited to participate in the screening process. Finally, patients can enroll directly through the central site.

Those who fulfil the inclusion criteria and provide informed consent are enrolled. The Informed Consent provided by the patient includes: A) Permission to approach the clinical electrophysiologist taking direct care of the him/her and his/her implanted device. B) Authorization (by the patient and his/her physician) to get access to the online data on device function and arrhythmia/noise detection that are transmitted weekly by the patient’s device via the Latitude System for home-monitoring.

The study population will consist of patients with an implanted S-ICD as their first implanted device, who continue to exercise regularly and actively participate in competitive or recreational sports with a sport-intensity above a predefined level (see below).

Incidence of primary and secondary endpoints during follow-up (see below) will be compared with two reference study-populations:

1) Young patients actively participating in sports who have an implanted TV-ICD. Data shared by The Multinational Sports ICD Trial.^2-5

2) Non-athletic patients in the S-ICD arm of ATLAS (a study comparing S-ICD with TV-ICD in non-athletes).⁹

Of note: Comparisons with both studies will be at the original data level for all studies.

Estimate number of participants: 450 patients with implanted S-ICD who continue to exercise after implantation. Number of participants is not defined by risk-estimation but reproduces the number of patients who participated in the ICD Sports Safety Registry of athletes with TV-ICD.²

Inclusions Criteria. All the following inclusion criteria are mandatory for inclusion:

Patient (male or female) is <80 years of age.
Patient has an implanted, new-generation, S-ICD [Boston Scientific EMBLEM, Generations 2 (model A209), 3 (A219) or newer].
Patient has a functioning LATITUDE™ Home-Monitoring-System at home, knows how to use it and sends weekly reports via the home-monitoring system.
Patient actively participates in sport activities above a predefined level of exercise (see below).
Patient understands that, at present, there is virtually no data on the safety of sport participation for patients with implanted S-ICD system, particularly regarding potential damage caused by sport activities to the S-ICD system, including the subcutaneous electrode.
Patient understands that the level of sport activity, type of sport and frequency of exercise activities are entirely at his/her own discretion and responsibility.
Patient understands that The Sport S-ICD Study investigator neither encourage nor discourage performance of any given sport.
Patient understands that The Sport S-ICD Study is not liable for- and does assume any responsibility for any damages caused by sport participation to the implanted system or the health of patients participating in the study.
Patient is willing to provide informed consent to participate in the Sport S-ICD

Informed consent includes agreement to provide all the following information:

Clinical data (age, gender, clinical diagnosis, indication for S-ICD implantation, arrhythmic events since S-ICD implantation, adverse events since S-ICD implantation)
Type and level of exercise and sport participation at the time of inclusion and during follow-up.
Information concerning endpoint events during follow-up.
Direct access to the patients’ LATITUDE™ Home-Monitoring-System data, both at the time of inclusion and all weekly reports during the follow-up period, until the study ends or the informed consent is revoked. Access to the personal LATITUDE™ Home-Monitoring-System data is in addition to the access by the primary treating physician and only for purpose of data collection for the study. Consent from the patient AND for the primary treating physician (monitoring the patient’s LATITUDE data) are required. Once the study ends, participating patients will be notified that the Study Investigators are no longer monitoring his/her LATITUDE Home-Monitoring-System.

Exclusion Criteria

Subjects with an inability to communicate well with the investigators.
Subjects who are non-cooperative or unwilling to sign consent form.
Evidence suggestive of malfunction of the implanted S-ICD system (like abnormal impedance or detected noise) at the time of screening.

Definitions of type and level of exercise.

According to the 2020 ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Disease,¹⁰ competitive athletes exercise ≥6 hours/week and recreational athletes exercise ≥4 hours/week. For the present study, the minimal level of exercise required for inclusion is:
- The equivalent of recreational sports, that is, an average exercise time of ≥4 hours/week.
- Exercise of ≥2 hours/week if the exercise involves any of the following:
2A) Forceful and/or repetitive movements of the pectoral girdle (example weight lifting, “pushup,” “pullover” or pullup” exercises).
2B) Repetitive single-arm movements (like tennis or Ping-Pong) in left-handed patients (that is, repetitive arm movements in the arm ipsilateral to the site of S-ICD implantation.
2C) Contact sports that involve substantial risk of collision, including sports like soccer or football and sports like judo or wrestling.

Primary Endpoints

- Arrhythmia related primary endpoints:
1A) Tachyarrhythmia-related death or externally resuscitated cardiac arrest due to S-ICD shock failure, incessant ventricular arrhythmia, or post-shock pulseless electrical activity.

1B) Injury requiring hospitalization, due to shock or syncopal arrhythmia.

1C) Unexpected sudden death without arrhythmia documentation due to absence of device interrogation.
1. S-ICD system related primary endpoint:
2A) Lead fracture leading to lead/device replacement

2B) Lead fracture/malfunction leading to S-ICD inactivation.

Secondary Endpoints:

Arrhythmia related secondary endpoints:

1A) Number of appropriate shocks (for ventricular tachyarrhythmia) and their relation to sport activity.

1B) Number of inappropriate shocks (for supraventricular tachyarrhythmia) and their relation to sport activity.

1C) Multiple shocks within one appropriate episode (i.e., failure of first maximum-energy shock or recurrent arrhythmia), electrical storm (>3 event in 24 h) or recurrent inappropriate shocks.

1C) Moderate injury (requiring emergency room visit) associated with a shock.

S-ICD related secondary endpoints:

2A) Inappropriate shock due to noise (and its relation to sport) leading to device reprogramming.*

2B) Noise detected that does not lead to inappropriate shock but leads to device reprogramming.*

*If the inappropriate shock leads to S-ICD system (device/lead) replacement, this is a Primary Endpoint.

3. Clinical secondary endpoint.

Interruption or cessation of sports for reasons other than ICD shocks or ICD related complications.

References

1. Heidbuchel H, Arbelo E, D’Ascenzi F, et al. Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part 2: ventricular arrhythmias, channelopathies, and implantable defibrillators. Europace 2021;23:147-8.
2. Lampert R, Olshansky B, Heidbuchel H, et al. Safety of sports for athletes with implantable cardioverter-defibrillators: results of a prospective, multinational registry. Circulation 2013;127:2021-30.
3. Lampert R, Olshansky B, Heidbuchel H, et al. Safety of Sports for Athletes With Implantable Cardioverter-Defibrillators: Long-Term Results of a Prospective Multinational Registry. Circulation 2017;135:2310-2.
4. Heidbuchel H, Willems R, Jordaens L, et al. Intensive recreational athletes in the prospective multinational ICD Sports Safety Registry: Results from the European cohort. Eur J Prev Cardiol 2019;26:764-75.
5. Link MS, Sullivan RM, Olshansky B, et al. Implantable Cardioverter Defibrillator Lead Survival in Athletic Patients. Circ Arrhythm Electrophysiol 2021;14:e009344.
6. Knops RE, van der Stuijt W, Smeding L. Subcutaneous or Transvenous Defibrillator Therapy. Reply. N Engl J Med 2021;384:678-9.
7. Gold MR, Lambiase PD, El-Chami MF, et al. Primary Results From the Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction (UNTOUCHED) Trial. Circulation 2021;143:7-17.
8. Al-Khatib SM, Kusumoto FM. Be-All End-All Real-World Evidence on the Subcutaneous ICD. Circulation 2021;143:18-20.
9. Mondesert B, Bashir J, Philippon F, et al. Rationale and design of the randomized prospective ATLAS study: Avoid Transvenous Leads in Appropriate Subjects. Am Heart J 2019;207:1-9.
10. Pelliccia A, Sharma S, Gati S, et al. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021;42:17-96.