STandardized Ultra-conservative Or Physician-directed ICD Programming for SHOCK Reduction Among Patients on Continuous Flow LVAD Support: a Randomized Controlled Trial (STOP SHOCK LVAD Study)
Phase: NA
Conditions: Heart Failure, Systolic, Left Ventricular Assist Device, ICD
Sponsor: The Cleveland Clinic

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-STandardized ultra-conservative Or Physician-directed ICD programming for SHOCK reduction among 
patients on continuous flow LVAD support: a randomized controlled trial (STOP SHOCK LVAD study) 
 
Study Design 
Randomized unblinded clinical trial 
 
Planned Number of Patients 
280 patients; 140 per treatment arm 
 
Randomization Method 
 REDCap 
Treatment Arms 
A) Ultraconservative ICD programming for maximal shock 
avoidance (see table at end of protocol) 
 
B) Physician Discretion 
 
Primary Endpoints 
Any ICD shock 
Mortality 
Syncope 
 
Secondary Endpoints 
Time to first ICD shock  
Time to first ICD shock for VT/VF  
Quality of Life  questionnaire 
Hospitalizations; including HF and ventricular arrhythmia  
 
Inclusion Criteria 
- 
>18 years of age 
- 
Pre-existing ICD 
 
Exclusion Criteria 
- 
Non-functional ICD system 
- 
Uncontrolled ventricular arrhythmias ≤7 days of enrollment 
(defined as VT/VF >30 seconds and/or causing 
hemodynamic instability and/or symptoms or pre-syncope 
or syncope) 
 
Follow-up schedule 
Routine post-LVAD care; no additional study visits 
 
Remote ICD monitoring encouraged 
 
Study Duration 
2 years 
 
 
 

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INTRODUCTION  
The proposed study will evaluate the utilization of an ultra-conservative programming strategy to 
reduce shocks for ventricular arrhythmias (VA) in heart failure (HF) patients with an implantable 
cardioverter-defibrillator (ICD) and a continuous-flow (CF) left ventricular assist device (LVAD). The 
survival benefit of ICDs with VA detections and therapies enabled has been established in HF patients 
with reduced ejection fraction (EF) without LVAD, as well as HF patients with older-generation, pulsatile-
flow (PF) LVADs. However, newer studies do not demonstrate the same benefit of VA tachy-therapy in 
patients with current-generation CF LVAD devices, potentially due to better hemodynamic tolerability of 
VA. In addition, ICD shocks are known to worsen clinical outcomes while causing patients psychosocial 
harm. Recent studies have applied extended-detection programming to successfully reduce ICD shocks 
in non-LVAD HF patients. However, shock reduction strategies have not been previously evaluated in 
LVAD patients in an adequately-powered, randomized clinical trial. This study will prospectively 
randomize HF patients with pre-existing ICDs to programming at the discretion of their EP provider 
versus “ultra-conservative” ICD programming, in which a single ventricular fibrillation (VF) zone will be 
programmed using the maximum rate cutoff allowable across all ICD manufacturers (250 beats per 
minute [bpm]), as well as the manufacturer-specific maximum detection intervals. In the ultra-
conservative arm, a monitor-only zone will be programmed at 150 bpm. The primary endpoint will be 
the percentage of patients receiving an ICD shock at 2-year follow-up with planned interim analyses at 6 
months and 1 year. Secondary endpoints include time to first ICD shock, time to first VT/VF shock, and 
Quality Life questionnaires. Data collected will include mortality, syncope, LVAD-related hospitalizations 
(including HF, VA), and the percentage of patients receiving inappropriate ICD shocks at 2-year follow-
up. The study hypothesis is that the standardized application of ultra-conservative ICD programming will 
reduce shocks and improve quality of life without an increase in mortality, syncope, or hospitalizations 
compared to physician discretion programming in CF LVAD patients.  
 
Study Rationale  
The current International Society for Heart and Lung Transplantation (ISHLT) guidelines provide a class I 
recommendation for tachy-therapy re-activation in patients with ICDs undergoing LVAD implantation 
[1]. However, these guidelines reflect a survival benefit observed in cohorts comprised primarily of 
older-generation PF LVADs [2, 3].  While the overall VA prevalence in the LVAD population exceeds 50% 
[4-6] with VA usually occurring >200 beats per minute [7], VA are generally well-tolerated both 
hemodynamically and symptomatically. Observed LVAD flows do decrease during sustained VA [8, 9], 
but there are multiple case reports of LVAD patients remaining awake and asymptomatic despite hours 
of ventricular fibrillation [10-12] and a large case series reported no deaths and rare syncope due to VA 
in CF LVAD patients [7]. Contrary to guidelines, contemporary evaluations restricted to CF LVADs show 
no clear ICD survival benefit in single center studies [7, 13] nor a large, pooled meta-analysis [14]. In 
fact, propensity-matched analyses of CF LVAD patients in the INTERMACS [15] and UNOS [16] registries 
have demonstrated increased mortality and more hospitalizations among patients with an active ICD 
and treated VA.   
 
It is unclear in the CF LVAD population whether ICD shocks themselves are harmful or rather identify a 
higher-acuity patient subgroup. In the general HF population, however, shocks have consistently been 
associated with worse outcomes [17-21]. Shock reduction programming resulted in reduced mortality in 
the MADIT-RIT trial [22], suggesting shocks may be directly harmful and not only a marker of substrate 

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severity. In addition, repeated ICD shocks have been clearly linked to psychological harm [23-26] in the 
form of post-traumatic stress disorder (PTSD).   
 
Despite signals towards physical and psychological harm, the predominant U.S. practice pattern is to 
maintain active ICD tachy-therapy in CF LVAD patients. In a nationwide single-vendor study, 93% of 
LVAD patients retained active ICDs. While only 5% were re-programed in a strategy aimed to minimize 
shocks, >50% were programmed in a manner more likely to deliver tachy-therapy than in a non-LVAD, 
primary prevention HF population [Kiehl HFSA 2017]. This discordance triggered a small, single-center 
study that prospectively evaluated multiple-zone ultra-conservative ICD programming in CF LVAD 
patients [27]. While no reduction in shocks was observed, there was also no signal towards clinical harm. 
Nevertheless, by programming multiple zones for ventricular tachycardia (VT) and VF, detection rates 
and intervals were not fully maximized. The authors concluded that a prospective trial of a monitor-only 
programming strategy was needed, however this remains impossible due to vendor-locked 
programming restrictions. The proposed study aims to evaluate the most “ultra-conservative” VA tachy-
therapy currently programmable in CF LVAD patients. 
OBJECTIVES AND ENDPOINTS 
To evaluate the utilization of an “ultra-conservative,” single-zone programming strategy for  
ICD tachy-therapies in CF LVAD patients as compared to a passive strategy of standard programming (at 
the discretion of the provider).  The study hypothesis is that an ultra-conservative strategy will result in a 
reduction in shocks and an improvement in quality of life without increasing adverse outcomes including 
death, hospitalization, and syncope among patients on CF LVAD support. 
 
Sample Size  
 
The projected sample size is 280 enrolled subjects, 140 randomized to each programming arm. Prior 
observed ICD shock rates in similar CF LVAD + ICD cohorts were 21% over 11 month follow-up in a study 
by Richardson et al [27] and 13% over 15 month follow-up in the aforementioned internal study 
currently under review by Kiehl et al. We thus projected an annual ICD shock incidence of 17% (the 
mean of the prior 2 studies). Thus, in order to detect a 15% absolute risk reduction in shocks over 2-year 
follow-up with 80% power and two-tailed α=0.05, 280 patients are needed. 
 
Statistical Plan 
 
At the end of study enrollment, baseline characteristics will be compared with potential covariates of 
interest able to later be balanced either via multi-variable regression or propensity analysis if needed. 
For continuous outcomes, linear regression will be utilized, for categorical outcomes, logistic regression 
will be utilized, and for time to event outcomes, Cox regression will be utilized.  
 
Study Population 
 
Patients will be eligible for study enrollment and randomization if adult (>18 years old) with a pre-
existing, active ICD prior to CF LVAD implantation. Possible study enrollment will be discussed with 
eligible patients by their treating medical teams and the dedicated study research coordinator during 

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their index LVAD hospitalization. Consent and randomization will occur either at the time of index 
hospitalization discharge or during the first post-discharge LVAD/ICD clinic visit, whichever comes first. 
 
Inclusion:  
- 
>18 years of age 
- 
Pre-existing ICD 
 
Exclusion:  
- 
Non-functional ICD system 
- 
Uncontrolled ventricular arrhythmias ≤7 days of enrollment (defined as VT/VF >30 seconds 
and/or causing hemodynamic instability and/or symptoms or pre-syncope or syncope) 
 
Of note, the need for anti-arrhythmic (AAT) drug therapy and/or catheter ablation is not an exclusion 
criteria, with treatment of VA per treatment team discretion and non-protocol driven. Ventricular 
ectopy and/or palpitations associated with non-sustained VT also do not serve as an exclusion criteria. 
 
Enrollment and Informed Consent 
The multi-disciplinary study investigators include physicians and nurse practitioners in 
electrophysiology, HF, and cardiothoracic surgery.  The LVAD nurse practitioners, HF physicians, and 
surgical team will identify eligible patients and hold a preliminary discussion with patients about the 
study.  A research coordinator will then verify eligibility, obtain informed consent, complete 
randomization, direct the device clinic on assigned programming changes (if any), and coordinate 
research follow-up visits to coincide with clinical LVAD visits for data collection on ICD therapies, 
symptomatology, HF hospitalizations, and death/transplantation.  
 
All subjects who complete the informed consent process, sign and date the informed consent 
form are considered enrolled in the Stop Shock LVAD study. Subjects enrolled in this 
investigation must be followed 
per protocol. 
 
Randomization  
Randomization to ultra-conservative versus standard programming will occur at the time of study 
enrollment using REDCap.  Radomization will be a 1:1 ratio. Neither the patient nor treatment team are 
blinded to the randomization or programming assignment. ICD re-programming will occur in the device 
clinic or patient hospital room as per the current routine care pathway. 
 
ICD Programing 
 
There were will be no study-related diagnostic tests, treatments, or follow-up visits beyond routine post 
LVAD care. The ICD re-programming will be performed during the routine pre-discharge ICD check 
during the LVAD implant hospitalization or at routine LVAD clinic follow-up ≤ 30 days.  For patients 
experiencing sustained VA below the VT zone in the ultra-conservative pathway, a symptom-driven care 
pathway will be implemented involving same-day cardioversion with the associated routine care.  In the 
physician-discretion arm, ICD shocks delivered for VA routinely result in emergency department visits 
and hospitalizations, which fall under usual care covered by private and public payers. 

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Data for Supplemental Protocol Document 
Ultra-conservative Programming by Vendor  
Manufacturer 
Monitor 
Zone 
VT Zone 
Detection 
VT Zone  
Therapy 
VF Zone Detection 
VF Zone Therapy 
Abbott 
Rate: 150 
bpm 
Off 
Off 
Rate: 250 bpm  
100 intervals (25s) to 
detection 
ATP x1 (prior to 
charge) 
36J, 40J x5 
Biotronik 
Rate: 150 
bpm 
Off 
Off 
Rate: 250 bpm 
30/40 intervals (10 s) to 
detection 
ATP x 1 (prior to 
charge) 
***J 
Boston 
Scientific  
Rate: 150 
bpm 
Off 
Off 
Rate: 250 bpm 
15s to detection 
ATP x1 (quick 
convert) 
41J x8 
Medtronic  
Rate: 150 
bpm 
Off 
Off 
Rate: 250 bpm  
120/160 intervals (40s) to 
detection 
ATP x1 (prior to 
charge)  
35J x6 
 
Proposed care pathway ICD re-programming if a) asymptomatic shock in standard programming arm; or 
b) symptoms prompting external cardioversion in ultra-conservative programming am 
 
Manufacturer 
Monitor 
Zone 
VT Zone Detection 
VT Zone  
Therapy 
VF Zone Detection 
VF Zone 
Therapy 
Abbott 
Rate: 150 
bpm 
Rate: 10 bpm below 
clinical VT 
100 intervals to 
detection 
ATP x 30 
(20-pulse 
burst) 
Rate: 250 bpm  
100 intervals (25s) to 
detection 
ATP x1 
(prior to 
charge) 
36J, 40J x5 
Biotronik 
Rate: 150 
bpm 
Rate: 10 bpm below 
clinical VT 
32 intervals to 
detection 
ATP x 20 
(10-pulse 
burst) 
Rate: 250 bpm 
30/40 intervals (10 s) to 
detection 
ATP x 1 
(prior to 
charge) 
40J x6 
Boston 
Scientific  
Rate: 150 
bpm 
Rate: 10 bpm below 
clinical VT 
30s to detection 
ATP x 60 
(30-pulse 
burst)  
Rate: 250 bpm 
15s to detection 
ATP x1 
(quick 
convert) 
41J x8 
Medtronic  
Rate: 150 
bpm 
Rate: 10 bpm below 
clinical VT 
130 intervals to 
detection 
ATP x 10  
(15-pulse 
burst) 
Rate: 250 bpm  
120/160 intervals (40s) 
to detection 
ATP x1 
(prior to 
charge)  
35J x6 
 

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Follow Up 
 
 
Screening 
Enrollment 
1 mo 3  mo 6 mo 9 mo 12 mo 15 mo 18 mo 21 mo 
24 mo 
History, 
demographics, 
cardiac test results 
x 
 
 
 
 
 
 
 
 
 
Informed Consent x 
 
 
 
 
 
 
 
 
 
Randomization 
x 
 
 
 
 
 
 
 
 
 
Office Visit 
x 
 
x 
x 
 
x 
 
x 
 
x 
Research Visit *, 
including 
assessment for 
AE/SAE/QOL 
 
x 
 
 
x 
 
x 
 
x 
 
Device 
interrogation/data 
(may be remote) 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
*Can be completed in-office, by phone, medical record review and from the Interagency Registry of 
Mechanically Assisted Circulatory Support/NIH registry. 
 
All visits follow the schedule of routine LVAD follow up. 
 
Withdrawal 
All subjects enrolled in the clinical study, including those withdrawn from the clinical study 
or lost to follow-up, shall be accounted for and documented. 
 
Data Monitoring 
 
The principal investigator will be responsible for ensuring the study is being carried out per protocol and 
the associated data documented and submitted for analysis.  Adverse events will be reviewed by the 
Principle Investigator.  
 
  
 
 
 
 

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