The AngelMed Guardian^® System in the Detection of Coronary Artery Occlusion: Current Perspectives

Figures & data

Figure 1 AngelMed Guardian^® system device design and components.

Figure 2 Implantable medical device (IMD) and external medical device (EXD).

Table 1 AngelMed Guardian^® System Alarm Types

Alert Type	Qualifying Event Category	IMD Function	EXD Function	Data Storage
High Priority Alarms
Emergency alerts (Patient calls 911 for prompt arrival at a medical facility	3 successive 10-second electrogram segments with each segment at least six out of eight beats with ST shifts that exceed the detection threshold while the heart rate is within normal range	Vibrates	Beeps in a synchronized 3-2-3-2 pattern, and flashes a red light	24 hrs before alarm through 8 hrs after alarm
Low Priority Alarms
See Doctor alerts	(a) Abnormal heart rates (Tachycardia and bradycardia) (b) Persistent irregular rhythms (c) Loss of signal (Lead detachment/low battery/general malfunction)	Vibrates	Beeps once after each 7 second interval, and flashes a yellow light	24 hrs before alarm and at time of alarm
None	Save data in the See Doctor manner but do not alert the patient	N/A	N/A	24 hrs before alarm and at time of alarm
Ignore	Neither save the data nor alert the patient	N/A	N/A	N/A

Table 2 Evidence Generating Studies for the AngelMed Guardian^® System

Study	Authors	Study Population	Study Design	Primary Endpoint	Secondary Endpoint	Results
Proof of Concept Study^Citation15	Fischell T.A. et al	n = 17 vessels, 14 patients that underwent balloon occlusion of an epicardial artery	Case series	Feasibility of intracardiac electrogram recording for the detection of ST-segment shift during balloon occlusion in the setting of PTCA	N/A	Mean ST-segment shift of 36.4%, relative to the QRS amplitude with intracardiac lead, within 2 min of balloon occlusion vs. 10.1% for surface lead; p = 0.00011
Magnitude and Duration of Intracardiac ST-Segment Changes for Confirmed Clinical Events: First in-man Experience^Citation71	Gibson C.M. et al	n = 76 high risk patients with coronary artery disease	Case series	Size and duration of the intracardiac ST-segment changes for true positive emergency alarms (EAs) corresponding to clinically relevant recurrent ischemic events confirmed by conventional tests (EKG, cardiac enzymes and angiographic vessel occlusion)	N/A	For a total of 21 EAs detected by intracardiac RV lead, size and duration of the ST-shift% changes did not correspond to the severity of the events as measured using conventional tests. (a) For positive EAs, mean ST-shift% was −22.4% with a mean duration of 56 mins (b) For negative EAs, mean ST-shift% was 22.6% with a mean duration of 78 mins (c) Mean ischemia detection threshold were −15.9% and 17.5%; p<0.01, indicating asymmetrical distribution of normal daily ST-shift%
First-in-Man Study of the Guardian System (Cardiosaver)^Citation72	Hopenfeld B et al	n = 20 patients with (1) ischemia on an exercise stress test; (2) stenosis of a coronary artery on angiogram; or (3) clinical indication for stenting and/or angioplasty	Phase I clinical feasibility study (Brazil)	Performance testing of Guardian system in detecting intracardiac ST shifts resulting from subendocardial and transmural ischemia	N/A	Successful demonstration of proof-of-concept with improvements in device design and ischemia detection algorithm
US Investigational Device Exemption Safety Study of the Guardian System (DETECT)^Citation72	Hopenfeld B et al	n = 17 patients who were survivors of a prior ACS event or bypass with additional risk factors	Phase I clinical feasibility study (USA)	(1) Reliability of the Guardian system’s “Autopick function” to identify ischemia detection thresholds tailored to individual’s 24 hr ST segment variability (rest and exercise) (2) Safety of Guardian system	N/A	(a) At rest, average ST segment shift across all patients was within 5% (ST segment shift % = (Current ST deviation – ST deviation of 24 hr baseline/R-wave height of a 24 hr baseline) x 100 (b) Post-exercise stress test, average ST shift% was −40% (c) ST shift % variation showed that 90% of fluctuations were < 6% indicating noise-free, stable function
ALERTS Trial^Citation65	Gibson C.M. et al	n = 907 patients at high-risk of MI due to acute coronary syndrome or bypass surgery	Bayesian adaptive, phase III prospective, randomized, multicenter trial	Efficacy: Composite of cardiac or unexplained death, new Q-wave MI, and time-to-door for a confirmed occlusive event at a medical facility >2 hrs Safety: Fraction of subjects free from system or device related complications >90%	(1) Individual components of primary end point (2) Superior false positive rate (FPR) for Guardian alerting (3) Ability to detect silent MIs (4) Timely presentation to a medical facility due to Guardian alerting in STEMI, NSTEMI and ACS patients (5) Ability to detect other clinically relevant conditions for timely presentation to a medical facility	(a) Primary efficacy endpoint not met (met with use of a dual-baseline for EKG) (b) Guardian system significantly reduced detection to arrival time at a medical facility (51 mins in alarms activated versus 30.6 hrs in alarms deactivated; Pr >0.999) (c) Met primary safety endpoint with 96.7%complication-free rate, Pr >0.9999 (d) FPR in alarms activated was 0.164 vs 0.678 in alarms deactivated; p<0.001 for non-inferiority (e) In treatment group (alarms activated), median symptom-to-door times for ACS, all MIs and STEMI were 1.04 h, 1.0 h and 0.75 h, respectively (f) Guardian system detected 108 other clinically relevant events (atrial fibrillation, anemia, bradycardia, bundle branch block, hypokalemia, tachycardia, transient heart block)

Figure 3 Timeline for the clinical studies of the AngelMed Guardian^® system.

Table 3 Device-Related Complications of the AngelMed Guardian^® System in the ALERTS Trial

Complication	Number of Events/Total Subjects	Percentage (%)
Cardiac perforation	2/907	0.22
Erosion	3/907	0.33
Infection	11/907	1.21
Lead misplacement	4/907	0.44
Device defect	2/907	0.22
Lead malfunction	1/907	0.11
Signal loss secondary to dislodgement or malfunction of the lead	2/907	0.22
Pain at or near implantation site	5/907	0.55
Visible bump at site of implantation	1/907	0.11
Total	30/907	3.3 (96.7% complication-free rate)

Fischell TA, Fischell DR, Fischell RE, et al. Potential of an intracardiac electrogram for the rapid detection of coronary artery occlusion. Cardiovasc Revasc Med. 2005;6:14–20. doi:10.1016/j.carrev.2005.05.002

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