Download navigate x4 - clinical summary

CLINICAL SUMMARY
NAVIGATE X4 STUDY
(with the ACUITY™ X4 lead family)
CAUTION: Federal (US) law
restricts this device to sale by
or on the order of a physician
trained or experienced in
device implant and follow-up
procedures.
TABLE OF CONTENTS
STUDY DESIGN........................................................................................................................................ 1
METHODS................................................................................................................................................. 1
Subject Selection................................................................................................................................. 1
Inclusion and Exclusion Criteria.......................................................................................................... 1
ACUITY X4 Endpoints......................................................................................................................... 2
Safety Endpoint............................................................................................................................ 2
Effectiveness Endpoints............................................................................................................... 2
RESULTS.................................................................................................................................................. 3
Subject Demographics ....................................................................................................................... 4
Study Endpoint Results....................................................................................................................... 7
ACUITY X4 Primary Effectiveness Endpoint 1............................................................................. 9
Data Analysis............................................................................................................................... 9
ACUITY X4 Primary Effectiveness Endpoint 2............................................................................11
ACUITY X4 Secondary Effectiveness Endpoint 1...................................................................... 13
ACUITY X4 Secondary Effectiveness Endpoint 2...................................................................... 16
Utility of ACUITY X4 Leads................................................................................................................ 19
Lead Measurements in Programmed Configurations throughout Follow-up..................................... 20
Pacing Capture Threshold Measurements in Programmed Configurations throughout
Follow-up.................................................................................................................................... 20
Sensed Amplitude Measurements in Programmed Configurations throughout Follow-up......... 22
Pacing Impedance Measurements in Programmed Configurations throughout Follow-up........ 24
Programmed Cathode at 3 Months............................................................................................ 26
ACUITY X4 Lead Placement Times........................................................................................... 32
ACUITY X4 Lead Location......................................................................................................... 33
ADVERSE EVENTS SUMMARY............................................................................................................. 34
DEATH SUMMARY................................................................................................................................. 39
CONCLUSIONS...................................................................................................................................... 39
The following is a trademark of Boston Scientific or its affiliates: ACUITY.
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
STUDY DESIGN
1
CLINICAL STUDY — SUMMARY OF NAVIGATE X4 CLINICAL STUDY
The NAVIGATE X4 Clinical Study was designed to collect data to establish the safety, performance and
effectiveness of the ACUITY™ X4 quadripolar coronary venous leads.
STUDY DESIGN
The NAVIGATE X4 Clinical Study is a prospective, non-randomized, multi-center, single-arm, clinical study.
All study sites are in the United States. Data points were collected at Enrollment, Implant/ Attempted Implant,
Follow-up at 3-72 hours, 3- and 6 months post implant procedure to study the Safety and Effectiveness
Endpoints, with additional follow up required at 1, 2, 3, 4, and 5 years post-implant for long-term follow up.
METHODS
Subject Selection
The study enrolled patient with an approved Class I/IIa indication for a cardiac resynchronization- defibrillator
(CRT-D) who were intended to be implanted with the ACUITY X4 quadripolar lead and a Boston Scientific CRT-D
as their initial (de novo) CRT-D system implant. Only patients who met all of the inclusion criteria and none of the
exclusion criteria, were enrolled.
Inclusion and Exclusion Criteria
Inclusion Criteria
• Subjects indicated for a CRT-D that fulfill one of the following 5 criteria:
1. Subject with LVEF less than or equal to 35%, sinus rhythm, LBBB with a QRS duration greater than or
equal to 150 ms, and a NYHA class II, III or ambulatory IV symptoms on GDMT1
2. Subject with LVEF less than or equal to 35%, sinus rhythm, LBBB with a QRS duration 120 to 149 ms,
and NYHA class II, III, or ambulatory IV symptoms on GDMT
3. Subject with LVEF less than or equal to 35%, sinus rhythm, a non-LBBB pattern with a QRS duration
greater than or equal to 150 ms, and NYHA class III/ ambulatory class IV symptoms on GDMT
4. Subject with atrial fibrillation and LVEF less than or equal to 35% on GDMT if a) the subject
requires ventricular pacing or otherwise meets CRT criteria [listed here] and b) AV nodal ablation or
pharmacological rate control will allow near 100% ventricular pacing with CRT
5. Subject on GDMT who have LVEF less than or equal to 35% and are undergoing new device placement
with anticipated requirement for significant (>40%) ventricular pacing
• Subject is intended to receive the ACUITY X4 LV lead and RELIANCE 4-FRONT RV lead (optional in Study
Phase 1) and BSC CRT-D with quad header as their initial (de novo) cardiac implants
• Subject is willing and capable of providing informed consent (which can include the use of a legally authorized
representative (LAR) for documentation of informed consent) and participating in all testing associated with
this investigation at an approved center and at the intervals defined by this protocol
• Subject is age 18 or above, or of legal age to give informed consent specific to state and national law
Exclusion Criteria
• Subject has a known or suspected sensitivity to dexamethasone acetate (DXA)
• Subject has a mechanical tricuspid heart valve
1 GDMT = Guideline-directed medical therapy (formerly known as optimal pharmaceutical therapy (OPT)), represents optimal medical
therapy as defined by ACCF/ AHA guideline-recommended therapies (primarily Class I)
2
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
METHODS
NOTE: This is a contraindication for the RELIANCE 4-FRONT lead. Therefore, it was included in the
NAVIGATE X4 Study for the purpose of the implant of that lead, and is not related to the implant of the
ACUITY X4 lead.
• Subject is enrolled in any other concurrent study, with the exception of local mandatory governmental
registries and observational studies/registries2 that are not in conflict and do not affect the following:
• Schedule of procedures for the Study (i.e. should not cause additional or missed visits);
• Study outcome (i.e. involve medications that could affect the heart rate of the subject);
• Conduct of the Study per GCP/ ISO 14155:2011/ 21 CFR 812, local regulations
• Subject is currently on the active heart transplant list
• Subject has a documented life expectancy of less than twelve months
• Women of childbearing potential who are or might be pregnant at the time of study enrollment or CRT-D
System implant (method of assessment upon physician’s discretion)
• Subjects currently requiring chronic dialysis
ACUITY X4 Endpoints
The long and short spiral ACUITY X4 leads serve as cohort 1 and the straight ACUITY X4 leads are cohort 2 in
the study endpoints.
Safety Endpoint
Primary Safety Endpoint: Lead-related Complication-free Rate from Implant through Six Months Post-Implant.
Cohorts 1 and 2 were evaluated separately for this endpoint.
Lead-related complications associated with attempted ACUITY X4 lead implants count toward the safety
endpoint. Lead-related adverse events that are not a complication are counted as a complication if intravenous
(IV) drug therapy is necessary to treat the event. IV drug therapy that occurs concomitant but unrelated to the
lead-related adverse event is not counted as a lead-related complication. Complications involving an ACUITY
X4 lead that occur as a result of a procedure unrelated to that ACUITY X4 lead do not count toward the safety
endpoints. Two examples of this scenario are 1) an ACUITY X4 lead dislodgement resulting from a repositioning
of an RA and/or RV lead and 2) an ACUITY X4 lead dislodgement resulting from a CABG procedure.
Effectiveness Endpoints
The following endpoints were evaluated to establish effectiveness of the ACUITY X4 lead.
• Primary Effectiveness Endpoint 1: Pacing Capture Threshold in the Programmed Configuration. This
endpoint was evaluated at 3 months post-implant. X4 Cohorts 1 and 2 will be analyzed together. For this
endpoint, responders will be defined as subjects with PCT ≤ 2.5 V in the programmed configuration. The
hypothesis for this endpoint is that the 3 month responder rate will be greater than 75%.
• Primary Effectiveness Endpoint 2: Pacing Capture Threshold in the Proximal Zone (electrode E2, E3,
or E4) for the ACUITY X4 primary cohort. This endpoint was evaluated at 3 months post-implant. For this
endpoint, responders will be defined as patients with PCT ≤ 2.5 V in the best proximal zone at 3 months
post-implant. For this endpoint “best” will be defined as the electrode with the lowest PCT without PNS. The
hypothesis for this endpoint is that the 3 month responder rate will be greater than 75%.
• Secondary Effectiveness Endpoint 1: Sensed Amplitude in the programmed configuration. This endpoint
was evaluated at 3 months post-implant. The hypothesis for this endpoint is that the 3 month mean R-wave
amplitude will be greater than 3.0mV.
2 Sponsors of such studies/registries should be informed and Boston Scientific must be informed by the investigator about the parallel
conduct of these projects in the subject and of the project’s basic nature. The decision if a desired mandatory governmental registry or
observational study/ registry is in conflict with this exclusion criterion is up to the enrolling investigator.
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
3
• Secondary Effectiveness Endpoint 2: Pacing impedance in the programmed configuration. This endpoint
was evaluated at 3 months post-implant. The hypothesis for this endpoint is that the mean LV lead impedance
is greater than 300Ω.
RESULTS
Results included in this NAVIGATE X4 study summary were collected through July 17, 2015. If a follow-up visit
was missed, the subject remained eligible to contribute data at subsequent follow-up visits. A summary of the
subject disposition is shown in Figure 1 on page 3.
Figure 1. Subject Disposition
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CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Subject Demographics
A total of 791 subjects were enrolled at 88 centers in the study. See Table 1 on page 4 for a summary of the
subject demographics. Overall, the average age of the subjects at implant was 68.3 ± 10.9 years, with an overall
gender ratio of 66.4% males to 33.6% females.
NOTE: Intent and partial attempt subjects did not contribute to a lead cohort, therefore the N for Cohort 1
added to the N for Cohort 2 does not equal the N for All Patients
Table 1. PMA Population Subject Demographics
Characteristic
Age at Implant (years)
Gender [N (%)]
Race [N (%)]
NYHA Class [N (%)]
LVEF (%)
QRS Duration (ms)
Height (cm)
Weight (kg)
Systolic Blood Pressure
(mm Hg)
Measurement
Cohort 1
Cohort 2
ACUITY X4
ACUITY X4
Spiral
Straight
(N=536)
(N=228)
All Patients
(N=791)
N
536
228
791
Mean ± SD
68.2 ± 11.0
68.9 ± 10.5
68.3 ± 10.9
Range
25.0 - 89.0
27.0 - 89.0
25.0 - 89.0
Male
352 (65.7%)
155 (68.0%)
525 (66.4%)
Female
184 (34.3%)
73 (32.0%)
266 (33.6%)
White
433 (84.2%)
188 (85.5%)
640 (84.4%)
Black
74 (14.4%)
25 (11.4%)
103 (13.6%)
Asian
5 (1.0%)
4 (1.8%)
10 (1.3%)
Pacific
0 (0%)
1 (0.5%)
1 (0.1%)
Other
2 (0.4%)
2 (0.9%)
4 (0.5%)
Class I
1 (0.2%)
1 (0.4%)
2 (0.3%)
Class II
150 (28.0%)
63 (27.6%)
221 (27.9%)
Class III
357 (66.6%)
159 (69.7%)
534 (67.5%)
Class IV
16 (3.0%)
3 (1.3%)
19 (2.4%)
Non-HF Subject
3 (0.6%)
0 (0%)
3 (0.4%)
Not Available
9 (1.7%)
2 (0.9%)
12 (1.5%)
N
536
228
791
Mean ± SD
25.5 ± 6.3
24.6 ± 6.5
25.2 ± 6.5
Range
10.0 - 35.0
10.0 - 35.0
10.0 - 45.0
N
536
228
791
Mean ± SD
152 ± 22
151 ± 24
152 ± 23
Range
0 - 226
86 - 218
0 - 226
N
536
228
791
Mean ± SD
172 ± 10
172 ± 10
172 ± 10
Range
142 - 198
142 - 195
142 - 198
N
536
228
791
Mean ± SD
90 ± 23
90 ± 23
90 ± 23
Range
41 - 199
35 - 201
35 - 201
N
536
228
791
Mean ± SD
129 ± 20
127 ± 22
128 ± 21
Range
76 - 201
52 - 198
52 - 201
* Patients may contribute to more than one category
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Characteristic
Diastolic Blood Pressure
(mm Hg)
Heart Rate (bpm)
Medications* [N (%)]
Etiology [N (%)]
Conduction Disorder [N
(%)]
Ventricular Arrhythmia
History* [N (%)]
Atrial Arrhythmia History*
[N (%)]
Measurement
Cohort 1
Cohort 2
ACUITY X4
ACUITY X4
Spiral
Straight
(N=536)
(N=228)
All Patients
(N=791)
N
536
228
791
Mean ± SD
74 ± 12
73 ± 14
73 ± 13
Range
43 - 110
42 - 141
42 - 141
N
536
228
791
Mean ± SD
74 ± 15
73 ± 15
73 ± 15
Range
34 - 150
34 - 139
34 - 150
Potassium Channel Blockers
67 (12.5%)
30 (13.2%)
100 (12.6%)
Sodium Channel Blockers
3 (0.6%)
0 (0%)
3 (0.4%)
Congenital Heart Disease
0 (0%)
0 (0%)
1 (0.1%)
Hypertrophic Cardiomyopathy
12 (2.2%)
4 (1.8%)
17 (2.1%)
Idiopathic Cardiomyopathy
253 (47.2%)
102 (44.7%)
364 (46.0%)
Ischemic Cardiomyopathy
254 (47.4%)
103 (45.2%)
373 (47.2%)
No Disease
11 (2.1%)
13 (5.7%)
24 (3.0%)
Valvular Cardiomyopathy
6 (1.1%)
6 (2.6%)
12 (1.5%)
Left Bundle Branch Block
434 (81.0%)
182 (79.8%)
638 (80.7%)
None
41 (7.6%)
12 (5.3%)
53 (6.7%)
Other
23 (4.3%)
23 (10.1%)
47 (5.9%)
Right Bundle Branch Block
38 (7.1%)
11 (4.8%)
53 (6.7%)
Premature Ventricular
Contractions (PVC)
73 (13.6%)
30 (13.2%)
106 (13.4%)
Non-sustained VT (NSVT)
47 (8.8%)
29 (12.7%)
79 (10.0%)
Monomorphic VT (MVT)
11 (2.1%)
9 (3.9%)
21 (2.7%)
Ventricular Fibrillation (VF)
11 (2.1%)
3 (1.3%)
15 (1.9%)
Polymorphic VT (PVT)
7 (1.3%)
1 (0.4%)
8 (1.0%)
Torsades de Pointes (TdP)
1 (0.2%)
1 (0.4%)
2 (0.3%)
Other Ventricular Arrhythmia
24 (4.5%)
8 (3.5%)
32 (4.0%)
Paroxysmal Atrial Fibrillation
91 (17.0%)
40 (17.5%)
135 (17.1%)
Permanent Atrial Fibrillation
41 (7.6%)
20 (8.8%)
61 (7.7%)
Persistent Atrial Fibrillation
45 (8.4%)
15 (6.6%)
61 (7.7%)
Atrial Flutter
41 (7.6%)
11 (4.8%)
53 (6.7%)
Atrial Tachycardia
21 (3.9%)
6 (2.6%)
27 (3.4%)
Other Atrial Arrhythmia
18 (3.4%)
8 (3.5%)
26 (3.3%)
* Patients may contribute to more than one category
5
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CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Characteristic
Brady Arrhythmia History*
[N (%)]
Associated Diseases and
Risk Factors* [N (%)]
Measurement
Cohort 1
Cohort 2
All Patients
ACUITY X4
ACUITY X4
Spiral
Straight
(N=536)
(N=228)
Sinus Bradycardia
85 (50.0%)
29 (34.9%)
1st Degree AV Block
71 (41.8%)
34 (41.0%)
110 (42.3%)
Sinus Node Dysfunction
7 (4.1%)
8 (9.6%)
15 (5.8%)
3rd Degree AV Block - Permanent
6 (3.5%)
4 (4.8%)
10 (3.8%)
2nd Degree AV Block Intermittent
5 (2.9%)
3 (3.6%)
8 (3.1%)
2nd Degree AV Block - Permanent
3 (1.8%)
3 (3.6%)
6 (2.3%)
(N=791)
116 (44.6%)
3rd Degree AV Block - Intermittent
3 (1.8%)
3 (3.6%)
6 (2.3%)
Sinus Arrest
2 (1.2%)
3 (3.6%)
5 (1.9%)
Chronotropic Incompetence
1 (0.6%)
0 (0%)
1 (0.4%)
Other
39 (22.9%)
22 (26.5%)
62 (23.8%)
Hypertension
455 (84.9%)
176 (77.2%)
651 (82.3%)
Diabetes
212 (39.6%)
83 (36.4%)
303 (38.3%)
Chronic Pulmonary Disease
130 (24.3%)
58 (25.4%)
194 (24.5%)
Renal Disease
117 (21.8%)
58 (25.4%)
179 (22.6%)
Cerebrovascular Disease
69 (12.9%)
32 (14.0%)
104 (13.1%)
Peripheral Vascular Disease
65 (12.1%)
28 (12.3%)
98 (12.4%)
Other Disease
288 (53.7%)
142 (62.3%)
445 (56.3%)
* Patients may contribute to more than one category
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Study Endpoint Results
Safety and Effectiveness Endpoint results are summarized in Table 2 on page 7.
Table 2. Summary of Study Endpoints Results
Effectiveness
Safety
Endpoint
Statistic
Performance
Result
Result
(Confidence Limit)
Conclusion
Primary
LV Lead
Complication-Free
Rate (Implant-6
months)
Spiral: 98.5%
(97.0%)
Straight: 96.5%
(93.8%)
Spiral: >87%
Straight: >85%
Endpoint
met
Primary 1
(Cohorts 1 & 2
Combined)
LV Lead Pacing
Capture Threshold
in Programmed
Configuration
94.0% (92.0%)
Responder = subjects with
PCT ≤ 2.5V in programmed
configuration.
Responder rate in
programmed configuration
(3 months) >75%
Endpoint
met
Primary 2
Cohort 1
LV lead Pacing
Capture Threshold in
Configuration using
Best Electrode
91.1% (88.2%)
Responder = subjects
with PCT ≤ 2.5V in best
proximal.
Responder rate in
configuration using best
electrode (3 months) >75%
Endpoint
met
Secondary 1
(Cohorts 1 & 2
Separate)
Mean sensed
amplitude with 97.5%
lower one-side C.I.
Spiral: 17.4 mV
(16.7 mV)
Straight: 16.1 mV
(15.1 mV)
>3.0 mV (Separated by
Spiral and Straight)
Endpoint
met
Secondary 2
(Cohorts 1 & 2
Separate)
Mean pacing
impedance with
97.5% lower one-side
C.I.
Spiral: 776Ω
(753Ω)
Straight: 805Ω
(763Ω)
> 300Ω (Separated by
Spiral and Straight)
Endpoint
met
Safety Endpoint 1 Results – ACUITY X4 Cohort 1 Lead-Related Complication-Free Rate from 0 to 6
Months.
The complication-free rate from 0 to 6 months for ACUITY X4 Spiral leads (Cohort 1) was 98.5% with a onesided 97.5% lower confidence limit of 97.0%. The lower confidence limit is greater than the performance goal of
85.0%, resulting in a rejection of the null hypothesis. The results can be found in Figure 2 on page 8.
The complication-free rate from 0 to 6 months for ACUITY X4 Straight leads (Cohort 2) was 96.5% with a onesided 97.5% lower confidence limit of 93.8%. The lower confidence limit is greater than the performance goal of
85.0%, resulting in a rejection of the null hypothesis. The results can be found in Figure 3 on page 8.
7
8
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Figure 2. Safety Endpoint 1 Results – ACUITY X4 Cohort 1 Lead-Related Complication-Free Rate from 0
to 6 Months.
Safety Endpoint 1 Results – ACUITY X4 Cohort 2 Lead-Related Complication-Free Rate from 0 to 6
Months.
Figure 3. Safety Endpoint 2 Complication-free Rate from 3-12 months post-implant. Results for all leads.
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
9
Table 3 on page 9 presents a breakdown of the lead-related complications that contributed to the ACUITY X4
Primary Safety Endpoints
Table 3. Primary Safety Endpoint ACUITY X4 Lead-Related Complications
Cohort 1
ACUITY X4 Spiral Leads
(N = 536)
Classification
Cohort 2
ACUITY X4 Straight Leads
(N = 228)
Leads
with LRC
LRC-Free
Rate
97.5% Lower
One-Sided
LCL
Leads
with LRC
LRC-Free
Rate
95% Lower
One-Sided
LCL
Dislodgement - LV
5
99.1%
97.8%
3
98.7%
96.6%
Extracardiac stimulation - LV
2
99.6%
98.5%
1
99.6%
97.7%
Coronary venous perforation
with tamponade
1
99.8%
98.7%
1
99.6%
97.7%
LV - Incomplete connection
to header
0
100.0%
100.0%
1
99.6%
97.7%
RA,RV,LV - Myocardial
Perforation
0
100.0%
100.0%
1
99.6%
97.7%
Other - Lead procedure*
0
100.0%
100.0%
1
99.6%
97.7%
Total
8
98.5%
97.0%
8
96.5%
93.8%
* Other - Lead procedure: Incomplete lead insertion noted after pocket closure due to LV lead impedance out of range.
Pocket reopened and LV lead removed from device and re-inserted back into device. Impedances were then OK.
ACUITY X4 Primary Effectiveness Endpoint 1
The first Primary Effectiveness Endpoint for ACUITY X4 assessed pacing capture thresholds (PCT) in the
programmed configuration. This endpoint evaluated data collected at 3 month visit. ACUITY X4 Cohorts 1
and 2 were analyzed together. For this endpoint, responders were defined as subjects with PCT ≤ 2.5 V in the
programmed configuration.
Hypotheses
The following hypotheses will be used to evaluate Primary Effectiveness Endpoint 1 for ACUITY X4 Cohorts 1
and 2 combined:
• Ho: 3 month responder rate ≤ 75%
• Ha: 3 month responder rate > 75%​
Data Analysis
Subjects eligible for analysis of ACUITY X4 Primary Effectiveness Endpoint 1 included all Phase 1 subjects who
were successfully implanted with an ACUITY X4 lead. Subjects with LV pacing threshold data in the programmed
configuration collected at the 3-month follow-up visit contributed data to the endpoint analysis.
A one-sided 97.5% lower exact binomial (Clopper-Pearson) confidence limit for the responder rate was
computed and compared to the performance goal of 75%. If the lower confidence limit exceeded the
performance goal, then the null hypothesis will be rejected.
10 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Results
Panel B:
Straight Leads
Panel A:
Spiral Leads
See Figure 4 on page 10 for a histogram of the pacing threshold data from Cohorts 1 (Panel A) and 2 (Panel
B) in the programmed configuration at 3 months.
Figure 4. Primary Effectiveness Endpoint 1 Results – Histogram of Pacing Threshold in Programmed
Configuration (Panel A Spiral Leads; Panel B Straight Leads)
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
11
A total of 94.0% of subjects had pacing thresholds ≤ 2.5 V at 3 months, and were therefore defined as
responders. The lower confidence limit of the responder rate was 91.9%, significantly greater than the
performance goal of 75% (p < 0.001). Separately, the responder rates for ACUITY X4 Spiral Leads and Straight
Leads were 95.6% and 90.0%, respectively. Results of the endpoint analysis can be found in Figure 5 on
page 11.
Figure 5. Primary Effectiveness Endpoint 1 Results: Pacing Threshold in Programmed Configuration
Conclusion
The responder rate for the ACUITY X4 Lead, as defined by pacing thresholds at 3 months, significantly
exceeded the performance goal of 75%. The data support the effectiveness of the ACUITY X4 lead.
ACUITY X4 Primary Effectiveness Endpoint 2
The second Primary Effectiveness Endpoint for ACUITY X4 assessed pacing capture thresholds (PCT) in the
proximal zone (E2, E3, or E4) for ACUITY X4 Cohort 1. This endpoint evaluated data collected at 3 month visit.
Clustering electrodes on the spiral is expected to position at least one electrode adjacent to the myocardium.
Physician investigators were therefore instructed to use the “best” proximal electrode (E2, E3 or E4) as the
cathode and the RV lead coil as the anode. For this endpoint “best” was defined as the electrode with the lowest
PCT without PNS. The PG was allowed to used as an anode, depending on the clinical scenario or physician
12 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
preference. For this endpoint, responders were defined as patients with PCT ≤ 2.5 V in the best proximal zone at
3 months post-implant.
Hypotheses
The following hypotheses were used to evaluate Primary Effectiveness Endpoint 2 for X4 Cohort 1:
• Ho: 3 month responder rate ≤ 75%
• Ha: 3 month responder rate > 75%
Data Analysis
All subjects in the PMA Population who were successfully implanted with an ACUITY X4 spiral lead (Cohort 1)
were eligible for inclusion in this analysis. Subjects with a best proximal zone LV pacing threshold measurement
collected at the 3-month follow-up visit contributed data to the endpoint analysis.
A one-sided 97.5% lower exact binomial (Clopper-Pearson) confidence limit for the responder rate was
computed and compared to the performance goal of 75%. In order to reject the null hypothesis, the lower
confidence limit must the performance goal.
Results
See Figure 6 on page 12 for a histogram of the pacing threshold data from Cohort 1 in the best configuration
at 3 months.
Figure 6. Effectiveness Endpoint 2 Results – Histogram of Cohort 1 Pacing Thresholds with Best
Electrode
A total of 484 threshold measurements were taken with ACUITY X4 Spiral leads at the 3 month follow-up visit
and included in the endpoint analysis.
A total of 484 subjects in Cohort 1 had threshold measurements taken with ACUITY X4 Spiral leads at the 3
month follow-up visit and included in the endpoint analysis. Of these 484 subjects, 91.1% had pacing thresholds
≤ 2.5 V in the best configuration at 3 months, and were therefore defined as responders. The lower confidence
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
13
limit of the responder rate was 88.2%, significantly greater than the performance goal of 75% (p < 0.001).
Results of the endpoint analysis can be found in Figure 7 on page 13.
Figure 7. Primary Effectiveness Endpoint 2 Results – Cohort 1 Pacing Thresholds with Best Electrode
Conclusion
The responder rate for pacing threshold obtained at three months for the ACUITY X4 Spiral leads was
significantly higher than the performance goal of 75%. The data support the effectiveness of the ACUITY X4
Spiral lead.
ACUITY X4 Secondary Effectiveness Endpoint 1
The first Secondary Effectiveness Endpoint for ACUITY X4 assessed sensed amplitudes in the programmed
configuration. This endpoint was evaluated using data collected at the 3 month follow-up visit.
Hypotheses
The following hypotheses were used to evaluate the sensed amplitude Secondary Effectiveness Endpoint 1 for
X4 Cohorts 1 and 2 separately:
• Ho: The three-month mean R-wave amplitude ≤ 3.0 mV
• Ha: The three-month mean R-wave amplitude > 3.0 mV
14 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Data Analysis
Analysis of Secondary Effectiveness Endpoint 1 included all PMA Population subjects with an ACUITY X4 LV
sensed R-wave amplitude measurement at three months. The analysis was performed separately for ACUITY
X4 Cohorts 1 and 2. Sensed amplitude measurements in the programmed configuration from the three-month
follow-up visit were analyzed using a one-sided t-test with an alpha of 2.5%.
Results
A total of 646 sensed amplitude measurements (457 with ACUITY X4 Spiral Leads and 189 with ACUITY X4
Straight Leads) were taken at the 3 month follow-up visit and included in the endpoint analysis. A total of 99.1%
and 99.5% of subjects with ACUITY X4 Spiral Leads and ACUITY X4 Straight Leads, respectively, had R-wave
amplitudes greater than or equal to the performance goal value of 3.0 mV. Histograms of the R-wave amplitudes
are presented in Figure 8 on page 14 and Figure 9 on page 15.
Figure 8. Secondary Effectiveness Endpoint 1 Results – Histogram of Sensed Amplitudes for Cohort 1
ACUITY X4 Spiral Leads
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
15
Figure 9. Secondary Effectiveness Endpoint 1 Results – Histogram of Sensed Amplitudes for Cohort 2
ACUITY X4 Straight Leads
The mean R-wave amplitude for the ACUITY X4 Spiral Leads was 17.4 mV with a lower one-sided 97.5%
confidence limit of 16.7 mV, significantly greater than the performance goal of 3 mV (p-value < 0.001). The mean
R-wave amplitude for the ACUITY X4 Straight Leads was 16.1 mV with a lower one-sided 97.5% confidence limit
of 15.1 mV, significantly greater than the performance goal of 3 mV (p-value < 0.001). The null hypothesis was
rejected for both cohorts. Endpoint results are presented in Figure 10 on page 16.
16 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Figure 10. Secondary Effectiveness Endpoint 1 Results by Cohort
Conclusion
The mean R-wave amplitudes for the ACUITY X4 Spiral Leads and ACUITY X4 Straight Leads were significantly
greater than the performance goal of 3 mV. The data support the effectiveness of the ACUITY X4 lead.
ACUITY X4 Secondary Effectiveness Endpoint 2
The second Secondary Effectiveness Endpoint for ACUITY X4 assessed pacing impedances in the programmed
configuration. This endpoint evaluated data collected at the 3 month follow-up visit.
Hypotheses
The following hypotheses were used to evaluate the pacing impedance Secondary Effectiveness Endpoint for X4
Cohorts 1 and 2 separately:
• Ho: The three -month mean LV lead impedance ≤ 300 Ω
• Ha: The three -month mean LV lead impedance > 300 Ω
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
17
Data Analysis
Analysis of Secondary Effectiveness Endpoint 2 included all PMA Population subjects with an ACUITY X4
LV pacing impedance measurement at three months. The analysis was performed separately for ACUITY X4
Cohorts 1 and 2. Pacing impedance measurements in the programmed configuration from the three-month
follow-up visit were analyzed using a one-sided t-test with an alpha of 2.5%.
Results
A total of 684 pacing impedance measurements (482 with ACUITY X4 Spiral Leads and 202 with ACUITY X4
Straight Leads) were taken at the 3 month follow-up visit and included in the endpoint analysis. All subjects
(100%) with ACUITY X4 Spiral Leads and ACUITY X4 Straight Leads had pacing impedance measurements
greater than or equal to the performance goal value of 300 Ω. Histograms of the pacing impedances are
presented in Figure 11 on page 17 and Figure 12 on page 18.
Figure 11. Secondary Effectiveness Endpoint 2 Results – Histogram of Pacing Impedance for Cohort 1
Leads
18 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Figure 12. Secondary Effectiveness Endpoint 2 Results – Histogram of Pacing Impedance for Cohort 2
Leads
The mean pacing impedance for the ACUITY X4 Spiral Leads was 776 Ω with a lower one-sided 97.5%
confidence limit of 753 Ω, significantly greater than the performance goal of 300 Ω (p-value < 0.001). The mean
pacing impedance for the ACUITY X4 Straight Leads was 805 Ω with a lower one-sided 97.5% confidence limit
of 763 Ω, significantly greater than the performance goal of 300 Ω (p-value < 0.001). The null hypothesis was
rejected for both cohorts. Endpoint results are presented in Figure 13 on page 19.
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
19
Figure 13. Secondary Effectiveness Endpoint 2: Results by Cohort
Conclusion
The mean pacing impedances for the ACUITY X4 Spiral Leads and ACUITY X4 Straight Leads were significantly
greater than the performance goal of 300 Ω. The data support the effectiveness of the ACUITY X4 lead.
Utility of ACUITY X4 Leads
The utility of a quadripolar lead is to provide electrical pacing options away from the tip of the lead and eliminate
the need for reoperation. Desired pacing performance (PCT ≤ 2.5 V and PNS ≥ PCT + 3 V) was available on
the proximal electrodes in 89.0% of patients implanted with Spiral leads and 81.3% of patients implanted with
20 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Straight leads. Resultantly, the need for reoperation due to issues with left ventricular extracardiac stimulation or
pacing capture issues (elevated threshold, unable to capture) was virtually eliminated (0.4% of all patients).
Table 4. Utility of ACUITY X4’s Proximal Electrodes Compared to All Electrodes
Spiral
Criteria
All
Straight
E2-E3-E4
All
E2-E3-E4
PCT ≤ 2.5 V
473/485
(97.5%)
444/484
(91.7%)
192/204
(94.1%)
173/203
(85.2%)
PCT ≤ 2.5 V and PNS ≥ PCT + 3 V
467/485
(96.3%)
431/484
(89.0%)
187/204
(91.7%)
165/203
(81.3%)
Utility of ACUITY X4 in PCT management:
• Using the conventional configurations3 available on prior lead models, 8.2% of subjects (56/683 total subjects
with 3 month testing performed) had poor PCT4; using alternative electrode configurations available only on
this lead, 57.1% (32/56) of subjects with poor PCT had at least one option of programming to a configuration
with good PCT5. Zero patients required surgery to reposition the lead to address poor PCT.
Utility of ACUITY X4 in PNS management:
• Using the conventional configurations3 available on prior lead models, 6.9% of subjects (47/683 total subjects
with 3 month testing performed) had phrenic nerve stimulation6 during testing; using alternative electrode
configurations available only on this lead 76.6% (36/47) of subjects with phrenic nerve stimulation during
testing had at least one option of programming to a configuration without phrenic nerve stimulation. 0.4% of
patients required surgery to reposition the lead to address PNS.
Lead Measurements in Programmed Configurations throughout Follow-up
The following sections present pacing threshold, sensed amplitude and pacing impedance data for ACUITY X4
leads in the programmed configuration over the course of follow-up.
Pacing Capture Threshold Measurements in Programmed Configurations throughout
Follow-up
Figure 14 on page 21 presents the mean pacing capture thresholds (and standard deviations) for the
ACUITY X4 Straight and Spiral leads for all programmed configurations over time. All possible programmed
configurations for each lead type (Spiral or Straight) were grouped for the analysis. ACUITY X4 Straight leads
were observed to have slightly higher mean pacing capture thresholds than ACUITY X4 Spiral leads. However,
mean thresholds were acceptable for each lead type.
3
4
5
6
Conventional configurations: E1-RV Coil, E1-PG, E1-E2, E2-RV Coil, E2-PG
Poor PCT defined as PCT > 2.5 V
Good PCT defined as PCT ≤ 2.5 V
Phrenic nerve stimulation defined as phrenic nerve stimulation threshold minus pacing capture threshold < 3 V
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
21
Figure 14. ACUITY X4 Pacing Threshold Measurements throughout Follow-Up
(Eligible for Lead Measurements = 738 ACUITY X4 Leads Successfully Implanted During Initial Procedure)
The following tables (Table 4 for Spiral Leads and Table 5 for Straight Leads) present data separately for each
programmed pacing cathode. The percentage of leads that were programmed to a given cathode as well as the
corresponding pacing threshold summary statistics were calculated. For the Spiral lead, the E2 cathode was the
most commonly programmed. For the Straight lead, the E1 cathode was the most commonly programmed.
Table 5. ACUITY X4 Spiral Lead Programmed Cathode – Usage and Pacing Threshold Measurements
throughout Follow-Up
(Leads Eligible for Programming = 738 ACUITY X4 Leads Successfully Implanted During Initial Procedure)
ACUITY X4 Spiral Leads
Implant
Cathode
%
Patients
N
Mean
Pre-Discharge
SD
Med
%
Patients
N
Mean
3 Months
SD
Med
%
Patients
N
Mean
SD
Med
E1
cathode
22.0%
113
1.7
1.2
1.4
23.2%
118
1.8
1.4
1.3
22.7%
110
1.2
0.8
1.0
E2
cathode
45.9%
235
1.2
0.7
1.0
45.1%
232
1.3
0.8
1.0
44.5%
215
1.2
0.6
1.0
E3
cathode
18.0%
93
1.2
0.8
0.9
18.4%
95
1.2
0.9
0.9
18.1%
88
1.2
0.7
1.0
E4
cathode
14.1%
73
1.3
1.1
1.0
13.3%
68
1.1
0.7
0.9
14.6%
70
1.2
0.7
1.0
22 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Table 6. ACUITY X4 Straight Lead Programmed Cathode – Usage and Pacing Threshold Measurements
throughout Follow-Up
(Eligible for Lead Measurements = 218 ACUITY X4 Straight Leads Successfully Implanted During Initial Procedure)
ACUITY X4 Straight Leads
Implant
Cathode
%
Patients
N
Mean
Pre-Discharge
SD
Med
%
Patients
N
Mean
3 Months
SD
Med
%
Patients
N
Mean
SD
Med
E1
cathode
37.6%
82
1.6
1.3
1.1
35.8%
75
1.4
1.1
1.0
34.8%
71
1.1
0.7
1.0
E2
cathode
29.8%
65
1.6
1.0
1.4
33.5%
72
1.5
1.0
1.2
33.3%
68
1.5
0.9
1.3
E3
cathode
15.6%
34
1.7
1.2
1.4
14.0%
30
2.2
1.5
1.8
19.1%
39
1.9
1.2
1.6
E4
cathode
17.0%
37
1.8
1.2
1.5
16.7%
36
1.6
1.0
1.4
12.7%
24
1.7
0.9
1.6
Sensed Amplitude Measurements in Programmed Configurations throughout Follow-up
Figure 15 on page 23 presents the mean sensed amplitudes (and standard deviations) for the ACUITY X4
Straight and Spiral leads for all programmed sensing configurations over time. All possible programmed sensing
configurations for each lead type (Spiral or Straight) were grouped for the analysis. ACUITY X4 Straight leads
were observed to have slightly lower mean sensed amplitudes than ACUITY X4 Spiral leads. However, mean
amplitudes were acceptable for each lead type.
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
23
Figure 15. ACUITY X4 Sensed Amplitude Measurements throughout Follow-Up
(Eligible for Lead Measurements = 738 ACUITY X4 Leads Successfully Implanted During Initial Procedure)
The following tables (Table 6 on page 23 for Spiral Leads and Table 7 on page 24 for Straight Leads)
present data separately for each programmed sensing cathode. Consistent with ACUITY X4 labeling, E2-E4, as
well as E3 and E4 are not programmable sense vectors. The percentage of leads that were programmed to a
given configuration as well as the corresponding sensed amplitude summary statistics were calculated. For both
the Spiral and Straight leads, the E1 cathode was the most commonly programmed for sensing.
Table 7. ACUITY X4 Spiral Lead Programmed Configurations – Usage and Sensed Amplitude
Measurements throughout Follow-Up
(Eligible for Lead Measurements = 520 ACUITY X4 Spiral Leads Successfully Implanted During Initial Procedure)
ACUITY X4 Spiral Leads
Implant
Cathode
%
Patients
N
Mean
Pre-Discharge
SD
Med
%
Patients
N
Mean
3 Months
SD
Med
%
Patients
N
Mean
SD
Med
E1
cathode
80.5%
398
16.6
7.0
17.3
80.5%
392
16.0
6.9
16.0
82.1%
379
17.8
6.8
18.6
E2
cathode
19.5%
92
12.1
6.1
11.3
19.5%
92
11.5
5.6
10.8
17.9%
78
15.3
6.8
14.6
24 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Table 8. ACUITY X4 Spiral Lead Programmed Configurations – Usage and Sensed Amplitude
Measurements throughout Follow-Up
(Eligible for Lead Measurements = 218 ACUITY X4 Straight Leads Successfully Implanted During Initial Procedure)
ACUITY X4 Straight Leads
Implant
Cathode
%
Patients
N
Mean
Pre-Discharge
SD
Med
%
Patients
N
Mean
3 Months
SD
Med
%
Patients
N
Mean
SD
Med
E1
cathode
83.9%
171
14.2
7.1
13.2
84.7%
170
13.8
6.9
12.7
84.8%
161
16.3
7.0
16.8
E2
cathode
16.1%
33
11.3
5.9
9.0
15.3%
27
10.5
5.7
9.0
15.2%
28
15.0
6.1
14.8
Pacing Impedance Measurements in Programmed Configurations throughout Follow-up
Figure 16 on page 25 presents the mean pacing impedances (and standard deviations) for the ACUITY X4
Straight and Spiral leads for all programmed configurations over time. All possible programmed configurations
for each lead type (Spiral or Straight) were grouped for the analysis. ACUITY X4 Spiral and Straight leads were
observed to have acceptable and nearly identical mean pacing impedances.
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
25
Figure 16. ACUITY X4 Pacing Impedance Measurements throughout Follow-Up
(Eligible for Lead Measurements = 738 ACUITY X4 Leads Successfully Implanted During Initial Procedure)
The following tables (Table 8 on page 26 for Spiral Leads and Table 9 on page 26 for Straight Leads)
present data separately for each programmed pacing cathode. The percentage of leads that were programmed
to a given cathode as well as the corresponding pacing impedance summary statistics were calculated. For the
Spiral lead, the E2 cathode was the most commonly programmed. For the Straight lead, the E1 cathode was the
most commonly programmed.
26 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Table 9. ACUITY X4 Spiral Lead Programmed Configurations – Usage and Pacing Impedance
Measurements throughout Follow-Up
(Eligible for Lead Measurements = 520 ACUITY X4 Spiral Leads Successfully Implanted During Initial Procedure)
ACUITY X4 Spiral Leads
Implant
Cathode
%
Patients
N
Mean
Pre-Discharge
SD
Med
%
Patients
N
Mean
3 Months
SD
Med
%
Patients
N
Mean
SD
Med
E1
cathode
22.0%
113
991
291
925
23.2%
118
910
267
841
22.7%
110
875
253
817
E2
cathode
45.9%
235
775
238
729
45.1%
231
701
222
636
44.5%
214
780
275
686
E3
cathode
18.0%
93
806
273
742
18.4%
95
700
215
635
18.1%
88
720
245
643
E4
cathode
14.1%
73
759
244
691
13.3%
67
712
235
674
14.6%
70
681
233
618
Table 10. ACUITY X4 Straight Lead Programmed Configurations – Usage and Pacing Impedance
Measurements throughout Follow-Up
(Eligible for Lead Measurements = 218 ACUITY X4 Straight Leads Successfully Implanted During Initial Procedure)
ACUITY X4 Straight Leads
Implant
Cathode
%
Patients
N
Mean
Pre-Discharge
SD
Med
%
Patients
N
Mean
3 Months
SD
Med
%
Patients
N
Mean
SD
Med
E1
cathode
37.6%
82
997
312
927
35.8%
75
889
280
784
34.8%
71
863
288
763
E2
cathode
29.8%
64
811
332
732
33.5%
72
697
252
616
33.3%
68
818
323
729
E3
cathode
15.6%
34
768
295
643
14.0%
30
669
263
549
19.1%
39
760
295
678
E4
cathode
17.0%
37
754
306
604
16.7%
36
654
272
524
12.7%
24
671
273
606
Programmed Cathode at 3 Months
Table 10 on page 27 compares the ACUITY X4 programmed cathode at 3 months between patients with
Spiral leads and those with Straight leads. Two groupings of the cathodes were assessed, with the intent to
evaluate the following comparisons: (1) Spiral vs. Straight programming of E1, E2, E3, E4, and (2) Spiral vs.
Straight programming of E1 and grouped E2/E3/E4. The second grouping was performed in order to compare
the programming of the 3 electrodes (E2, E3, E4) that are placed on the 3D spiral of the ACUITY X4 Spiral leads
vs. the same electrode set for the Straight lead configuration. The ACUITY X4 lead family was designed to place
more electrodes in a mid or basal location (proximal zone) of the left ventricle.
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
27
Table 11. ACUITY X4 Lead Programmed Cathode
(Leads Eligible for Programming = 738 ACUITY X4 Leads Successfully Implanted During Initial Procedure)
Number (%) of Patients
Grouping
1
2
Spiral
Straight
P-value
E1
Cathode
110 (22.7%)
71 (34.8%)
0.005
E2
216 (44.5%)
68 (33.3%)
E3
88 (18.1%)
39 (19.1%)
E4
71 (14.6%)
26 (12.7%)
E1
110 (22.7%)
71 (34.8%)
E2/E3/E4
375 (77.3%)
133 (65.2%)
< 0.001
Two groupings of the cathodes were assessed to evaluate the following comparisons:
(1) Spiral vs. Straight programming of E1, E2, E3, E4, and
(2) Spiral vs. Straight programming of E1 and grouped E2/E3/E4.
In both cathode groupings, there were significant differences between the programming of the Spiral and
Straight leads. An additional logistic regression analysis showed that the odds of programming the E2, E3 or E4
as a cathode at 3 months are 82% greater for the ACUITY X4 Spiral lead vs the Straight lead (p = 0.001).
PCT for ACUITY X4 Spiral and Straight Leads in All Tested Configurations
Figure 17 on page 28 and Figure 18 on page 29 provide data on the pacing capture threshold (PCT) in
all tested pacing configurations at Implant, Pre-Discharge, and 3 Month follow ups for ACUITY X4 Spiral and
ACUITY X4 Straight leads, respectively. Median data is provided in each of the graphs, as the data is not
normally distributed. The mean and standard deviation, along with the median of PCT for each tested pacing
configuration is provided in a table along with each of the graphs.
28 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Figure 17. Median PCT for ACUITY X4 Spiral Leads in All Tested Configurations
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
29
Figure 18. Median PCT for ACUITY X4 Straight Leads in All Tested Configurations
Pacing Impedance for ACUITY X4 Leads in all Tested Configurations
Figure 19 on page 30 and Figure 20 on page 31 provide data on the pacing impedance in all tested pacing
configurations at Implant, Pre-Discharge, and 3 Month follow ups for ACUITY X4 Spiral and ACUITY X4 Straight
leads, respectively. Median data is provided in each of the graphs, as the data is not normally distributed. The
mean and standard deviation, along with the median of pacing impedance for each tested pacing configuration is
provided in a table along with each of the graphs.
30 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Figure 19. Median Pacing Impedance for ACUITY X4 Spiral Leads in all Tested Configurations
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
Figure 20. Median Pacing Impedance for ACUITY X4 Straight Leads in all Tested Configurations
31
32 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
ACUITY X4 Lead Placement Times
ACUITY X4 lead placement times, including implant procedures that resulted in a successful ACUITY X4 lead
implant are included in Table 11 on page 32.
Table 12. ACUITY X4 Lead Procedure and Placement Times
(N = 752 Procedures Resulting in Successful Implant of an ACUITY X4 Lead)
Statistic
(minutes)
ACUITY X4 Spiral
(N=526)
ACUITY X4 Straight
(N=226)
All ACUITY X4 Leads
(N=752)
Lead Placement Time
Median (IQR)
6 (3, 14)
10 (4, 19)
7 (3, 15)
Skin-to-Skin Time
Median (IQR)
82 (61, 115)
98 (67, 132)
86 (62, 120)
The LV lead placement time was defined as the time from the LV lead entering the catheter to the first PSA
measurement. The median LV lead placement time for all ACUITY X4 leads was 7 minutes with the 25th and
75th percentiles at 3 minutes and 15 minutes, respectively.
The overall median procedure time (skin-to-skin time) took 86 minutes with the 25th and 75th percentiles at 62
minutes and 120 minutes, respectively.
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
RESULTS
33
ACUITY X4 Lead Location
The placement locations of the ACUITY X4 Spiral and Straight leads, as reported by the sites, are displayed in
Figure 21 and Figure 22 on page 34. There are no significant differences in location for the ACUITY X4 Spiral
and Straight leads; suggesting consistent positive fixation for both lead types throughout the heart.
Figure 21. ACUITY X4 Spiral Lead Location
(N = 520 Successfully Implanted ACUITY X4 Spiral Leads during initial procedure)
34 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
Adverse Events Summary
Figure 22. ACUITY X4 Straight Lead Location
(N = 218 Successfully Implanted ACUITY X4 Straight Leads During Initial Procedure)
ADVERSE EVENTS SUMMARY
The data in the Adverse Events Summary table is complete as of July 17, 2015.
Table 13. Adverse Events Summary
Classification
Total
Complication
Observation
Events
Patients (%)
Events
Patients (%)
Events
Patients (%)
1417
485 (62.8%)
496
266 (34.5%)
921
402 (52.1%)
PG (N at risk = 772)
54
48 (6.2%)
9
9 (1.2%)
45
39 (5.1%)
Elevated DFT - Defibrillation
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Inappropriate tachy therapy - SVT
16
16 (2.1%)
2
2 (0.3%)
14
14 (1.8%)
Inappropriate tachy therapy - Other
2
2 (0.3%)
0
0 (0.0%)
2
2 (0.3%)
Pacemaker-mediated tachycardia
(PMT)
23
18 (2.3%)
0
0 (0.0%)
23
18 (2.3%)
Infection (> 30 days post-implant)
10
10 (1.3%)
6
6 (0.8%)
4
4 (0.5%)
Psychological effect due to device
therapy
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Migration
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
RA Lead (N at risk = 707)
18
18 (2.5%)
15
15 (2.1%)
3
3 (0.4%)
Total (N at risk = 772)
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
Adverse Events Summary
Classification
Total
Complication
Observation
Events
Patients (%)
Events
Patients (%)
Events
Patients (%)
Over sensing - RA
3
3 (0.4%)
0
0 (0.0%)
3
3 (0.4%)
Impedance > 2000 ohms - RA
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
Dislodgement - RA
14
14 (2.0%)
14
14 (2.0%)
0
0 (0.0%)
RV Lead - RELIANCE 4-FRONT (N
at risk = 664)
21
18 (2.7%)
15
13 (2.0%)
6
6 (0.9%)
Over sensing - RV
2
2 (0.3%)
0
0 (0.0%)
2
2 (0.3%)
Elevated threshold - RV
4
3 (0.5%)
3
3 (0.5%)
1
1 (0.2%)
Extracardiac stimulation - RV
3
3 (0.5%)
1
1 (0.2%)
2
2 (0.3%)
Myocardial perforation postimplant - RV
2
2 (0.3%)
2
2 (0.3%)
0
0 (0.0%)
Dislodgement - RV
8
6 (0.9%)
8
6 (0.9%)
0
0 (0.0%)
Other: RV Lead - Myopotential
1
1 (0.2%)
0
0 (0.0%)
1
1 (0.2%)
Other: low amplitude/R wave - RV
1
1 (0.2%)
1
1 (0.2%)
0
0 (0.0%)
RV Lead - Commercial (N at risk =
111)
4
4 (3.6%)
3
3 (2.7%)
1
1 (0.9%)
Extracardiac stimulation - RV
1
1 (0.9%)
0
0 (0.0%)
1
1 (0.9%)
Dislodgement - RV
3
3 (2.7%)
3
3 (2.7%)
0
0 (0.0%)
LV Lead - ACUITY X4 (N at risk =
765)
90
79 (10.3%)
13
13 (1.7%)
77
68 (8.9%)
Unable to capture - LV
4
4 (0.5%)
0
0 (0.0%)
4
4 (0.5%)
Elevated threshold - LV
8
8 (1.0%)
0
0 (0.0%)
8
8 (1.0%)
Extracardiac stimulation - LV
66
58 (7.6%)
3
3 (0.4%)
63
56 (7.3%)
Dislodgement - LV
10
10 (1.3%)
9
9 (1.2%)
1
1 (0.1%)
Other: LV - Incomplete connection
to header
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
Other: LV - Myocardial Perforation
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
LV Lead - Commercial (N at risk =
27)
3
3 (11.1%)
3
3 (11.1%)
0
0 (0.0%)
Extracardiac stimulation - LV
1
1 (3.7%)
1
1 (3.7%)
0
0 (0.0%)
Dislodgement - LV
2
2 (7.4%)
2
2 (7.4%)
0
0 (0.0%)
RV & LV Lead - ACUITY X4 &
RELIANCE 4-FRONT (N at risk =
685)
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
RA,RV,LV - Myocardial Perforation
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
35
36 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
Adverse Events Summary
Classification
Total
Complication
Observation
Events
Patients (%)
Events
Patients (%)
Events
Patients (%)
Lead - Commercial - Other (N at
risk = 715)
3
3 (0.4%)
0
0 (0.0%)
3
3 (0.4%)
Electrical Noise
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Electrical Noise - RV
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Spontaneous atrial flutter post RA
implant
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Procedure (N at risk = 772)
154
122 (15.8%)
46
42 (5.4%)
108
90 (11.7%)
Post-surgical wound discomfort
22
21 (2.7%)
5
5 (0.6%)
17
16 (2.1%)
Post-surgical pocket hemorrhage
7
7 (0.9%)
0
0 (0.0%)
7
7 (0.9%)
Post-surgical infection (<= 30 days
post-implant)
3
3 (0.4%)
2
2 (0.3%)
1
1 (0.1%)
Adverse reaction - General
24
23 (3.0%)
7
7 (0.9%)
17
16 (2.1%)
Adverse reaction - Respiratory
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
Adverse reaction - Hypotension
11
11 (1.4%)
8
8 (1.0%)
3
3 (0.4%)
Inadvertent VT/VF
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Inadvertent SVT
2
2 (0.3%)
1
1 (0.1%)
1
1 (0.1%)
Hematoma - Pocket (<=30 days
post-implant)
35
34 (4.4%)
3
3 (0.4%)
32
32 (4.1%)
Seroma - Pocket (<=30 days postimplant)
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Thromboembolic events
6
6 (0.8%)
2
2 (0.3%)
4
4 (0.5%)
Pneumothorax - Procedure
5
5 (0.6%)
4
4 (0.5%)
1
1 (0.1%)
Pleural effusion - Procedure
3
3 (0.4%)
0
0 (0.0%)
3
3 (0.4%)
Coronary venous dissection
10
10 (1.3%)
1
1 (0.1%)
9
9 (1.2%)
Coronary venous perforation
without tamponade
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
Coronary venous perforation with
tamponade
2
2 (0.3%)
2
2 (0.3%)
0
0 (0.0%)
Myocardial perforation without
tamponade
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
Myocardial perforation with
tamponade
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
AV block (transient) - Procedure
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Pericardial effusion
3
3 (0.4%)
0
0 (0.0%)
3
3 (0.4%)
Other - Lead procedure
2
2 (0.3%)
2
2 (0.3%)
0
0 (0.0%)
Other - PG system procedure
12
12 (1.6%)
5
5 (0.6%)
7
7 (0.9%)
CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
Adverse Events Summary
Classification
Total
Complication
Observation
Events
Patients (%)
Events
Patients (%)
Events
Patients (%)
213
133 (17.2%)
117
81 (10.5%)
96
82 (10.6%)
Syncope - Heart failure
2
2 (0.3%)
2
2 (0.3%)
0
0 (0.0%)
Dizziness - Heart failure
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Chest pain - Heart failure
7
7 (0.9%)
2
2 (0.3%)
5
5 (0.6%)
Dyspnea - Heart failure
62
51 (6.6%)
27
23 (3.0%)
35
32 (4.1%)
Peripheral edema - Heart failure
8
8 (1.0%)
2
2 (0.3%)
6
6 (0.8%)
Pulmonary edema - Heart failure
3
3 (0.4%)
3
3 (0.4%)
0
0 (0.0%)
Fatigue - Heart failure
5
5 (0.6%)
0
0 (0.0%)
5
5 (0.6%)
Renal insufficiency - Heart failure
10
9 (1.2%)
4
4 (0.5%)
6
5 (0.6%)
Hypotension - Heart failure
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
Weight gain - Heart failure
3
3 (0.4%)
1
1 (0.1%)
2
2 (0.3%)
Heart failure symptoms Unspecified
17
15 (1.9%)
14
13 (1.7%)
3
3 (0.4%)
Multiple heart failure symptoms
89
67 (8.7%)
56
45 (5.8%)
33
31 (4.0%)
Other - Heart failure patient
condition
2
2 (0.3%)
2
2 (0.3%)
0
0 (0.0%)
Multi-system failure - Heart failure
3
3 (0.4%)
3
3 (0.4%)
0
0 (0.0%)
Cardiovascular - Non-HF (N at risk
= 772)
366
244 (31.6%)
115
94 (12.2%)
251
193 (25.0%)
2nd degree AV block
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
3rd degree AV block
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Chronotropic incompetence
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Ventricular fibrillation (VF)
13
12 (1.6%)
4
4 (0.5%)
9
9 (1.2%)
Ventricular tachycardia (VT)
51
40 (5.2%)
22
18 (2.3%)
29
27 (3.5%)
Non-sustained ventricular
tachycardia (NSVT)
15
15 (1.9%)
1
1 (0.1%)
14
14 (1.8%)
Atrial fibrillation (AF)
58
52 (6.7%)
17
17 (2.2%)
41
37 (4.8%)
Atrial flutter
6
5 (0.6%)
2
2 (0.3%)
4
4 (0.5%)
Sinus tachycardia
4
3 (0.4%)
1
1 (0.1%)
3
2 (0.3%)
Other SVT (e.g. AVRT, AVNRT, EAT)
8
8 (1.0%)
3
3 (0.4%)
5
5 (0.6%)
Premature ventricular contractions
(PVC)
9
9 (1.2%)
1
1 (0.1%)
8
8 (1.0%)
Premature atrial contractions (PAC)
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Hypotension
37
36 (4.7%)
9
9 (1.2%)
28
28 (3.6%)
Hypertension
17
17 (2.2%)
3
3 (0.4%)
14
14 (1.8%)
Cardiovascular - HF (N at risk =
772)
37
38 CLINICAL STUDY - SUMMARY OF NAVIGATE X4 STUDY
Adverse Events Summary
Classification
Total
Complication
Observation
Events
Patients (%)
Events
Patients (%)
Events
Patients (%)
Cardiogenic shock
3
3 (0.4%)
3
3 (0.4%)
0
0 (0.0%)
Cardiac arrest
2
2 (0.3%)
2
2 (0.3%)
0
0 (0.0%)
Myocardial infarction
9
9 (1.2%)
7
7 (0.9%)
2
2 (0.3%)
Coronary Artery Disease
7
6 (0.8%)
5
5 (0.6%)
2
2 (0.3%)
Peripheral vascular disease
8
6 (0.8%)
3
3 (0.4%)
5
4 (0.5%)
Intermittent claudication
2
2 (0.3%)
0
0 (0.0%)
2
2 (0.3%)
Pseudoaneurysm with hematoma
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
Aortic regurgitation
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Syncope
18
17 (2.2%)
7
7 (0.9%)
11
10 (1.3%)
Dizziness
23
21 (2.7%)
2
2 (0.3%)
21
19 (2.5%)
Chest pain - Ischemic
7
7 (0.9%)
3
3 (0.4%)
4
4 (0.5%)
Chest pain - Other
19
19 (2.5%)
1
1 (0.1%)
18
18 (2.3%)
Dyspnea
2
2 (0.3%)
0
0 (0.0%)
2
2 (0.3%)
Palpitations
10
10 (1.3%)
0
0 (0.0%)
10
10 (1.3%)
Fatigue
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Transient ischemic attack (TIA)
3
3 (0.4%)
1
1 (0.1%)
2
2 (0.3%)
Cerebrovascular accident (CVA)
10
9 (1.2%)
4
4 (0.5%)
6
6 (0.8%)
Deep vein thrombosis (DVT)
2
2 (0.3%)
2
2 (0.3%)
0
0 (0.0%)
Pulmonary embolism (PE)
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
Distal thromboemboli
1
1 (0.1%)
0
0 (0.0%)
1
1 (0.1%)
Pericardial effusion - Unrelated to
procedure
6
6 (0.8%)
5
5 (0.6%)
1
1 (0.1%)
Hematoma - Unrelated to procedure
or device
2
2 (0.3%)
1
1 (0.1%)
1
1 (0.1%)
Hemorrhage
1
1 (0.1%)
1
1 (0.1%)
0
0 (0.0%)
Other - Patient condition
5
5 (0.6%)
3
3 (0.4%)
2
2 (0.3%)
490
241 (31.2%)
159
108 (14.0%)
331
184 (23.8%)
Non-cardiovascular (N at risk =
772)
There have been 58 PMA Population patients (7.6%) with reported cases of extracardiac stimulation related
to the ACUITY X4 lead. Of these 58 patients, 32 subsequently had modifications made to their programmed
pacing configuration (note that 2 patients had 2 cases each of extracardiac stimulation reported prior to
reprogramming). Following reprogramming, 1 of the 32 patients (3.1%) had a subsequent case of extracardiac
stimulation reported, approximately half of the originally reported rate of extracardiac stimulation. Of the
remaining 26 patients that did not have their device reprogrammed, 4 (15.4%) had a subsequent case of
extracardiac stimulation reported, approximately double the originally reported rate of extracardiac stimulation.
DEATH SUMMARY
Table 13 provides an overview of the subject deaths that have been reported in the ACUITY X4 PMA Population.
Classification of the deaths was provided by the independent Clinical Events Committee (CEC). There are 4
deaths “pending classification” at the time of data cutoff.
Table 14. Death Summmary
Number (%) of Patients
Primary
Organ Cause
Related to ACUITY X4 Lead
(CEC Classification)
Classification Source
Site
CEC
Yes
No
Not
Applicable
Pending
Classification
Cardiac: Arrhythmic
4 (0.5%)
2 (0.3%)
0 (0.0%)
2 (0.3%)
0 (0.0%)
0 (0.0%)
Cardiac: Ischemic
2 (0.3%)
2 (0.3%)
0 (0.0%)
1 (0.1%)
0 (0.0%)
0 (0.0%)
Cardiac: Other Cardiac
4 (0.5%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
Cardiac: Pump Failure
11 (1.4%)
11 (1.4%)
0 (0.0%)
11 (1.4%)
0 (0.0%)
0 (0.0%)
Cardiac: Unknown
4 (0.5%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
Non Cardiac
13 (1.6%)
12 (1.5%)
0 (0.0%)
9 (1.1%)
3 (0.4%)
0 (0.0%)
Unknown
8 (1.0%)
15 (1.9%)
0 (0.0%)
12 (1.5%)
0 (0.0%)
0 (0.0%)
Pending Classification
0 (0.0%)
4 (0.5%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
4 (0.5%)
Total
46 (5.8%)
46 (5.8%)
0 (0.0%)
35 (4.4%)
3 (0.4%)
4 (0.5%)
CONCLUSIONS
The results from this clinical study indicate that the ACUITY X4 Safety Endpoint and all Effectiveness Endpoints
were met. The Safety Endpoint analyzed the lead-related complication-free rate through 6 month post-implant
follow up period which demonstrated safety for the ACUITY X4 leads. Effective performance of the leads were
exhibited by evaluation of pacing thresholds, sensed amplitude, and pacing impedance through 3 months of
follow-up post-implant. The results indicate clinically acceptable values for all categories. In conclusion, this
clinical study provides reasonable assurance of safety and effectiveness of ACUITY X4 quadripolar coronary
venous leads when used in accordance with its labeling.
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358487-022 EN US 2016-01
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