Bridging Implantable Cardioverter-Defibrillator Patients Undergoing Radiotherapy with a Wearable Cardioverter-Defibrillator

Introduction

Chest radiation therapy (RT) for cancer treatment in patients with an implantable cardioverter defibrillator (ICD) can be prob- lematic and cause transitory malfunction or permanent damage to the device. Although limited data exist, the most common re- ported malfunctions to ICDs are resets errors, especially during high energies that may cause secondary neutron production [1,2]. Oversensing due to electromagnetic interference could cause pacing inhibition or inappropriate detections and shocks. Manufacturer recommendations regarding safe doses vary from no safe dose (Boston Scientific and BIOTRONIK) to five Gy (Medtronic) depending on the device.

If the implantable cardioverter defibrillator (ICD) cannot be safely relocated or properly shielded from the radiation therapy necessary for the treatment, then it may be necessary to turn off certain aspects (i.e. tachy-therapy) of the device or to tempo- rarily remove the device leaving the patient without protection and exposed to high risk of complications. How to protect the high-risk patient from sudden cardiac death (SCD) during this time is unclear. Unless the patient is pacemaker dependent, the wearable cardioverter defibrillator (WCD) may be considered as bridging therapy in patients requiring temporary removal of an infected implanted defibrillator by the American and European Guidelines [3,4]. We hypothesize that the wearable cardiovert- er defibrillator may be a safe and reliable tool to keep the pa- tient temporarily protected from potentially lethal ventricular tachy-arrhythmias during the weeks/months of RT. This would allow the patient to receive the proper dose of radiation while still being protected. Once RT is finished, then the ICD can be re-implanted/ re-activated and functionality restored. We are only aware of one small case study that specifically utilized the wearable cardioverter defibrillator for this purpose [5]. The pri- mary objective of this study was to examine a larger cohort of patients to evaluate the utility of the WCD for protecting these patients during this time.

Methods

Study Sample

The study sample was comprised of two retrospectively collected cohorts (University of Padova and the Zoll Life Vest (Pittsburgh, PA, USA) database). De-identified data from patients retrieved from a database maintained by ZOLL. All patients consented to the data collection. Only patients with complete follow-up data, having an implanted ICD, and prescribed, with a wearable car- dioverter defibrillator for bridging therapy while treated with RT from November 2016- January 2021 were included.

The data collected for analysis included baseline demographics (age and sex), ICD 9/10 code indication for the WCD, length of WCD wear, malignancy type, cardiac history, reasons for wear- able cardioverter defibrillator termination, ventricular arrhyth- mias during wearable cardioverter defibrillator use, outcomes and compliance with device use. For each patient the average daily use calculated at the end of device use. The first day, last day and days where device use was less than 15 minutes exclud- ed from the average daily use. All-cause mortality data during wearable cardioverter defibrillator use obtained by review of records.

The Wearable Cardioverter Defibrillator (WCD)

LifeVest® (ZOLL Medical Corporation, Pittsburgh, PA) Pitts- burgh, PA) has three non-adhesive defibrillator electrodes and four non-adhesive sensing electrodes. A chest garment holds the defibrillation and sensing electrodes in proper position against the skin. Sensing electrodes positioned circumferentially around the chest. Defibrillation electrodes positioned for apical-posteri- or defibrillation. The electrodes are connected to a monitor unit that is worn in a holster around the waist or over the shoulder. The monitor collects ECG data continuously from the sensing electrodes. If the device senses a ventricular tachycardia or ven- tricular fibrillation, the patient alerted first with tactile vibration, followed by an escalating audible alarm and a voice warning to bystanders of an impending shock [6]. A conscious patient can prevent a shock by simultaneously pressing two response but- tons located on the monitor within 25 seconds of VT detection by the device. If there is no response, as is the case for uncon- scious patients, the device releases gel through the defibrillator electrodes and delivers an electrical shock (75 to 150 joules) in an attempt to restore sinus rhythm. The Wearable Cardioverter Defibrillator system transmits ECG signals and event history to the manufacturer’s webserver. Shock delivery time is typically <60 seconds from the onset of tachycardia and the device can deliver up to 5 shocks per event if the arrhythmia is not ter- minated with the first shock [7-9]. The Wearable Cardioverter Defibrillator, including its arrhythmia detection algorithm have been described elsewhere in detail [10].

Statistical Analysis

Data analyzed using Microsoft Excel. Descriptive statistics pre- sented as mean with one standard deviation (SD) and range for continuous variables, and frequency and percent for categorical variables. When appropriate, medians and quartiles used to de- scribe the data. Tests of hypotheses were 2-sided, with signifi- cance declared for a p-value < 0.05. All arrhythmias occurring within 24 hours of index arrhythmia considered one episode for analysis. Device-declared arrhythmias were adjudicated and confirmed by Dr. Leoni.

Results

Eighty patients meeting criteria with implantable cardioverter defibrillator inactivation/removal during radiation therapy for cancer who prescribed the Wearable Cardioverter Defibrillator identified. Seventy-six patients were from the US, and four were from the site in Padova, Italy Table 1. The median age of this population was 69 years with a range of 33-88 years. Females comprised 56% of the population. Implantable Cardioverter De- fibrillator (ICD) management strategy included removing the implantable cardioverter defibrillator in 66 (82.5%), or turn- ing off therapy in the remaining 14 (17.5%). Seven of the latter group had back-up pacing for bradycardia left on.

Table 1: Description of the Patient Population Treated with Wearable Cardioverter Defibrillator (WCD) (N=80)

SD: Standard Deviation; CAD: Coronary Artery Disease; ICM: Ischemic Cardiomyopathy; CHF: Congestive Heart Failure; HTN: Hypertension; WCD: Wearable Cardioverter Defibrillator; VF: Ventricular Fibrillation; VT: Ventricular Tachycardia; NSVT: Non-Sustained Ventricular Tachycardia; AF: Atrial Fibrillation; AFL: Atrial Flutter; SVT: Supra Ventricular Tachycardia

*Not mutually exclusive

Cancer History

The most common type of cancer amongst the patient popula- tion was breast cancer (n=35, 44%), followed by lung cancer (n=26, 33%). Nine additional patients (11%) had more than one cancer documented, including breast, lung, bladder, cervical, leukemia, and prostate. All had a current cancer diagnosis and were undergoing radiation therapy at the time of wearable car- dioverter defibrillator prescription.

Past Medical History (Non-Cardiac)

Serious medical co-morbidities (excluding cardiac) included: 47 patients (58.8%) had hypertension, 18 patients (22.5%) had di- abetes mellitus, 48 patients (60%) had dyslipidemia, 9 patients (11.3%) had peripheral vascular disease, 5 patients (6.3%) had chronic kidney disease, 7 patients (8.8%) with obstructive sleep apnea, and 18 patients (22.5%) with chronic obstructive pulmo- nary disease.

Cardiac History (Before Wearable Cardioverter Defibrilla- tor Use)

In addition to having a previously implanted defibrillator, 43 pa- tients (53.8%) had a history of coronary artery disease (CAD) and 47 (58.8%) had a history of heart failure (HF). Arrhythmias prior to WCD use including ventricular fibrillation (VF) or ventricu- lar tachycardia (VT) in 31 (38.8%), atrial fibrillation/flutter in 22 (27.5%), and supraventricular tachycardia in 5 (6.3%). A history of sudden cardiac arrest was present in 11 patients (13.8%).

Radiation Therapy

In the four patients from the Padova site, two of them received 2 Gy per session for a total of 30 sessions and 60 Gy, the other two underwent a more aggressive protocol with 60 Gy in 8 sessions which means 7.5 Gy per session. The type of energy used was photon beam energy of 6 MV or 10 MV with an estimated ICD dose of < 3%. Deidentified data from US patients did not include details on the type or dose of RT received.

Wearable Cardioverter Defibrillator Use and Events

The wearable cardioverter defibrillator prescribed for protection against life-threatening ventricular arrhythmias (VA) in these patients while undergoing RT for cancer, during which time their ICDs were not active. Days of Wearable Cardioverter De- fibrillator use analyzed for all patients resulting in a median of 57 days worn with a range of 2 to 364 days. The median daily use time was 22.2 hours with a range of 8.5 to 24 hours per day.

During wearable cardioverter defibrillator use, 3 appropriate shocks were delivered to one patient (Male, 66 years old, lung cancer, history of coronary artery disease and VT/VF) during sustained ventricular tachy- arrhythmias. Successful defibrilla- tion shocks were delivered on two separate days, both for VF. The second VF episode required two shocks to convert to si- nus rhythm. The patient survived and was re-implanted with an ICD. There were also 20 inappropriate shocks delivered to one patient due to ECG artifact caused by cardiopulmonary resusci-tation (CPR) given during asystole. The patient did not survive. Other non-shocked arrhythmias that were recorded by the wear- able cardioverter defibrillator included non-sustained VT (9, 15 and 16 seconds duration, of 33, 42 and 42, beats, respectively) in three patients, episodes of fast supra-ventricular tachyarrhyth- mia’s/atrial fibrillation in 14 patients that were recorded by the wearable cardioverter defibrillator, and four patients with asys- tole, none of whom survived. None of the patients with asysto- le had back-up pacing left in place. Arrhythmic events during wearable cardioverter defibrillator use were not correlated with any specific cancer type as shown in Table 2.

Table 2: Arrhythmic Events during Wearable Cardioverter Defibrillator Use by Cancer Location

VF: Ventricular Fibrillation; VT: Ventricular Tachycardia; NSVT: Non-Sustained Ventricular Tachycardia; SVT: Supra Ventricular Tachycardia; AF: Atrial Fibrillation; AFL: Atrial Flutter

Outcomes

The majority of patients (n = 57, 71%) ended wearable cardio- verter defibrillator use as planned or with the implantable car- dioverter defibrillator replaced. Eleven patients (14%) ended wearable cardioverter defibrillator use for unknown/other rea- sons, and seven patients (9%) ended use for non-compliance or comfort reasons. During the study period 5 deaths were reported (mortality rate of 6.3%) in patients with lung (3) and breast can- cer (2), including the patient that was shocked due to CPR arti- fact. Deaths occurred 3, 28, 33, 116, and 134 days from the start of wearable cardioverter defibrillator use. Four of five (80%) had asystole as the terminal ECG rhythm recorded by the WCD. The fifth reportedly died from heart failure while not wearing the wearable cardioverter defibrillator.

Discussion

With heart disease and cancer being the top two causes of death in the Unites States, it is not surprising that these two conditions often overlap. Radiation therapy (RT) is used in approximately fifty percent of adults with cancer [11]. While improved RT tech- nology and techniques have improved the safety and reduced off-target effects to vital organs such as the heart and lungs, the cardiac devices themselves may be at risk of damage, especially ICDs and in the presence of higher beam energies [12,13]. Many variables will dictate what types of precautions should be taken to protect the device and the patient, and several expert consen- sus statements and society guidelines have been written on the topic [1,2,13]. Occasionally, depending on the risk to the device, the best decision may be to deactivate or remove the defibrillator to prevent damage and potential harm to the patient, but there is little guidance on how to protect the patient during this high-risk time [14].

This study observed whether the wearable cardioverter defibril- lator (WCD) might be useful in managing SCD risk during ra- diotherapy when the existing implantable defibrillator has been deactivated or removed. There is little guidance on how to man- age these high-risk patients. The WCD is capable of continuous ECG monitoring and treatment until the decision regarding the ICD can be made. Although the wearable cardioverter defibril- lator has not been tested on a patient during a RT session, it can be removed prior to the RT and then put back on immediately afterwards. A patient with previous ventricular arrhythmias (VA) or having high anxiety and stress may be at even higher risk of having an event during the RT session. Such high-risk patients should have continuous heart rate and/or rhythm monitoring and access to an external defibrillator in case of emergency during the live RT session [11]. In patients that are pacemaker depen- dent, we recommend use of an external or temporary pacemaker.

Several unique observations from this retrospective cohort study are worth noting, including:

1. Patients with active cancer undergoing RT were compliant with WCD use (median 22 hrs/day over 57 days),

2. The WCD bridged the time until the ICD could be safely replaced in a majority of patients,

3. The WCD successfully aborted SCD during VF in a patient on two separate days,

4. Worsening disease and Brady-asystole rhythms, led to death in 6.4%, and

5. Patients had a high prevalence of atrial arrhythmias (17.5%) that were fast enough to be captured by the WCD algorithm. Heart rate alerts from the ZOLL Patient Management Net- work could be used to alert the healthcare provider to such tachyarrhythmia.

In our clinic, implantable cardioverter-defibrillator patients are, by definition, at high risk of sudden cardiac death and thus we follow a protocol to assure the best possible protection for the patient. In the cases presented here, it was necessary to deacti- vate the device in order to ensure adequate RT while avoiding risk of implantable cardioverter-defibrillator malfunction.

In particular, we followed this protocol:

• Verified the non-pacing-dependence

• Verified the integrity of the implanted ICD system before starting RT

• Assessed the arrhythmic burden

• Inactivated the ventricular anti-tachycardia therapy, main- taining back up pacing at 40 bpm

• Programmed, or provided if not already active, the telemed- icine function of the ICD with daily transmissions to verify system integrity

• At the same time, activated the WCD with its telemedicine function, and performed training for the patient and his or her family

• The patient continued to be monitored remotely through both devices for two weeks after the end of RT, then an in-clinic follow-up was performed to verify the integrity of the implanted system and, if confirmed, the ICD was reacti- vated and the WCD removed.

This approach seems to be in line with the most recent indica- tions that also emerged from the EHRA consensus on prevention and management of interference due to medical procedures in patients with cardiac implantable electronic devices [2].

Abbreviations

CAD: Coronary Artery Disease

CPR: Cardiopulmonary Resuscitation

HF: Heart Failure

ICD: Implantable Cardioverter-Defibrillator

ICM: Ischemic Cardiomyopathy

SVT: Supra Ventricular Tachycardia

RT: Radiation Therapy

SCD: Sudden Cardiac Death

CHF: Congestive Heart Failure

VA: Ventricular Arrhythmias

VF: Ventricular Fibrillation

WCD: Wearable Cardioverter-Defibrillator

Conclusions

Many patients will undergo cancer remission or recovery after appropriate treatment, and the WCD may be a reasonable option to protect ICD explanted or deactivated patients during radio- therapy. The WCD can bridge until the ICD replaced, if desired, or re-activated in most patients. Under these circumstances, pa- tients that are pacemaker dependent should have back-up pacing in place. Considering our positive experience and other recent literature data in which modern cardiac implantable electronic devices very rarely need to be preventively explanted or re-lo- cated to a contralateral pectoral position, we consider a safe ap- proach the temporary deactivation of ICD combined with the use of WCD.

Study Limitations

This study has the established limitations of a retrospective anal- ysis derived from a registry database. Several data of particular interest were not recorded or recorded inconsistently, including ICD data such as device specifics, pacemaker dependency and the primary reason for implantation. Evidence of pacing was not available in patients with pacing function left on. Finally, as the registry does not include data following the end of WCD use, long-term data is unavailable.

Conflict of Interest: Nicole Bianco is an employee of ZOLL.

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