SMART CRT: Strategic Management to Optimize Response To Cardiac Resynchronization Therapy

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03089281
• Collaborator: (none)
• Enrollment: 699
• Locations: 72
• Arms: 2
• Actual Duration (Months): 37.5
• Patients Per Site: 9.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective is to evaluate the benefit of the SmartDelay™ algorithm in patients with a prolonged RV-LV interval.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Device: CRT-D	N/A

Detailed Description

The primary hypothesis of SMART CRT is that among cardiac resynchronization therapy defibrillator (CRT-D) patients with prolonged inrerventricular delay between the RV and LV leads, CRT with atrioventricular optimization (AVO) will result in greater reverse LV remodeling compared with CRT programmed at nominal settings (120 ms).

Study Design

• Study Type: Interventional
• Actual Enrollment: 699 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Strategic Management to Optimize Response To Cardiac Resynchronization Therapy
• Actual Study Start Date: Aug 1, 2017
• Actual Primary Completion Date: Sep 15, 2020
• Actual Study Completion Date: Sep 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: SmartDelay™ algorithm Subjects programmed with AV Delay and pacing chamber determined by SmartDelay	Device: CRT-D; Commercially approved quadripolar Boston Scientific Cardiac Resynchronization Therapy Defibrillator (CRT-D) devices and future generations of BSC X4 CRT-D devices approved by the appropriate regulatory bodies will be included in the trial. All devices utilized in the study will include SmartDelay™ and must be capable of providing SmartDelay recommendations for both biventricular pacing (BiV) and Left Ventricular (LV) only pacing. All enrolled subjects with implanted BSC X4 CRT-D system and identified with an RV-LV delay of ≥70ms were 1:1 randomized. Randomization occurred in the electronic data capturing system.
Other: Fixed AV Delay with BiV pacing Subjects programmed with a Fixed AV Delay of 120ms with BiV pacing	Device: CRT-D; Commercially approved quadripolar Boston Scientific Cardiac Resynchronization Therapy Defibrillator (CRT-D) devices and future generations of BSC X4 CRT-D devices approved by the appropriate regulatory bodies will be included in the trial. All devices utilized in the study will include SmartDelay™ and must be capable of providing SmartDelay recommendations for both biventricular pacing (BiV) and Left Ventricular (LV) only pacing. All enrolled subjects with implanted BSC X4 CRT-D system and identified with an RV-LV delay of ≥70ms were 1:1 randomized. Randomization occurred in the electronic data capturing system.

Outcome Measures

Primary Outcome Measures

1. CRT Response [Pre-Implant baseline to 6 months]

   Comparing cardiac resynchronization therapy (CRT) response rates between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. A negative change in LVESV is considered an improvement; CRT response is defined by a change in Left Ventricular End Systolic Volume (LVESV) < -15% at 6 months compared to pre-implant baseline.

Secondary Outcome Measures

1. Change in Left Ventricular End Systolic Volume (Absolute Change) [Implant to 6 Months]

   Comparing absolute changes in Left Ventricular End Systolic Volume from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 6-Month measurement - Implant measurement, in milliliters. A negative change in LVESV is considered an improvement.

2. Change in Left Ventricular End Systolic Volume (Relative Change) [Implant to 6 Months]

   Comparing relative changes in Left Ventricular End Systolic Volume from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 100*(6-Month measurement - Implant measurement)/(Implant Measurement), in %. A negative change in LVESV is considered an improvement.

3. Change in Left Ventricular Ejection Fraction (Absolute Change) [Implant to 6 Months]

   Comparing absolute changes in Left Ventricular Ejection Fraction from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 6-Month measurement - Implant measurement, in % of blood ejected during LV contraction. A positive change in LVEF is considered an improvement.

4. Change in Left Ventricular Ejection Fraction (Relative Change) [Implant to 6 Months]

   Comparing relative changes in Left Ventricular Ejection Fraction from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 100*(6-Month measurement - Implant measurement)/(Implant Measurement), in %. A positive change in LVEF is considered an improvement.

5. Clinical Composite Score (CCS) [Implant to 6 Months]

   Th CCS combines four metrics: all-cause mortality, heart failure hospitalization (HFH), New York Heart Association (NYHA) Class, and quality of life as measured with the patient global assessment (GA) instrument. The CCS categorizes each subject into one of three groups: Improved, Unchanged or Worsened. Improved: Subjects that survived without a HFH through the 6-month visit window and had either an improvement in NYHA class or responded to GA with "much better" or "very much better". Unchanged: All patients that reached the end of 6-month visit window that were not categorized as either "Improved" or "Worsened". Worsened: Subjects that died or had HFH within 6-month visit window or had either a worsening in NYHA class or responded to GA with "much worse" or "very much worse".

6. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score [Implant to 6 Months]

   The KCCQ is a disease-specific instrument for monitoring the health status and quality of life of subjects with congestive heart failure. It includes a total of 23 items that assess quality of life in the following domains: physical function, symptom frequency and severity, symptom stability, self-efficacy and knowledge, social function, and overall quality of life. These domains can be combined into a functional status summary score (derived from the physical function and symptom scales) and an overall summary score which combines the physical function, symptom, social function and quality of life domains. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.

Other Outcome Measures

1. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Social Limitation Score [Implant to 6 Months]

   The KCCQ Social Limitation Domain quantifies the extent to which heart failure symptoms impair patients' ability to interact in a number of gender-neutral social activities. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.

2. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life Score [Implant to 6 Months]

   KCCQ Quality of Life Domain is designed to reflect patients' assessment of their quality of life, given the current status of their heart failure. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.

3. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Self-Efficacy Score [Implant to 6 Months]

   KCCQ Self-efficacy Domain quantifies patients' perceptions of how to prevent heart failure exacerbations and manage complications when they arise. This scale is not included in the summary scores. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.

4. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom Frequency Score [Implant to 6 Months]

   KCCQ Symptom Domain quantifies the frequency of clinical symptoms in heart failure, including fatigue, shortness of breath, paroxysmal nocturnal dyspnea and patients' edema/swelling. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.

5. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom Burden Score [Implant to 6 Months]

   KCCQ Symptom Domain quantifies the burden of clinical symptoms in heart failure, including fatigue, shortness of breath, paroxysmal nocturnal dyspnea and patients' edema/swelling. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.

6. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation Score [Implant to 6 Months]

   KCCQ Physical Function Domain measures the limitations patients experience, due to their heart failure symptoms, in performing routine activities. Activities are common, gender-neutral, and generalizable across cultures, while also capturing a range of exertional requirements. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subject must be indicated to receive a de novo quadripolar Boston Scientific Cardiac Resynchronization Therapy Defibrillator (CRT-D) in conjunction with an ACUITY X4 LV lead. This includes subjects who are indicated to receive an upgrade to a BSC X4 CRT-D from a previously implanted device.

• In order to achieve a homogenous population for the study, qualifying subjects are those with heart failure who meet BSC US indications for use defined as those subjects who receive stable optimal pharmacologic therapy (OPT) for heart failure and who meet any one of the following classifications:

• Moderate to severe heart failure (NYHA Class III-IV) with EF ≤ 35% and QRS duration ≥ 120 ms

• Left bundle branch block (LBBB) with QRS duration ≥ 130 ms, EF ≤ 30%, and mild (NYHA Class II) ischemic or nonischemic heart failure or asymptomatic (NYHA Class

1. ischemic heart failure

• Subject is age 18 or above, or of legal age to give informed consent specific to each country and national laws

• Subject is willing and capable of providing informed consent

• Subject is willing and capable of complying with visits and procedures as defined by this protocol

Exclusion Criteria:

• Subjects with documented permanent complete AV block

• Subjects with permanent or chronic atrial fibrillation (AF) or in AF at the time of enrollment

• Subjects who have previously received cardiac resynchronization therapy with pacing in the left ventricle

• Subjects on the active heart transplant list or who has or is to receive ventricular assist device (VAD)

• Life expectancy shorter than 12 months due to any medical condition (e.g., cancer, uremia, liver failure, etc…)

• Subject with a known or suspected sensitivity to dexamethasone acetate (DXA)

• Subject is enrolled in any other concurrent clinical study, with the exception of local mandatory governmental registries and observational studies/registries, without the written approval from Boston Scientific

• Women of childbearing potential who are or plan to become pregnant during the course of the trial

• Subjects currently requiring dialysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Affinity Hospital, LLC d/b/a Granview Medical Center	Birmingham	Alabama	United States	35243
2	Heart Center Research LLC	Huntsville	Alabama	United States	35801
3	University of Arizona Sarver Heart Center	Tucson	Arizona	United States	85724
4	Cardiology Associates of NE Arkansas	Jonesboro	Arkansas	United States	72401
5	Glendale Adventist Medical Center	Glendale	California	United States	91206
6	Salinas Valley Memorial Healthcare System	Salinas	California	United States	93901
7	Christiana Care Health Services	Newark	Delaware	United States	19718
8	Baptist Health Research Institute	Jacksonville	Florida	United States	32207
9	Watson Clinic Center for Research, Inc	Lakeland	Florida	United States	33805
10	Winter Haven Hospital	Winter Haven	Florida	United States	33881
11	Emory University Hospital	Atlanta	Georgia	United States	30322
12	Northside Hospital	Atlanta	Georgia	United States	30342
13	The University of Chicago	Chicago	Illinois	United States	60637
14	St. John's Hospital	Springfield	Illinois	United States	62701
15	Heart Group at Deaconness Hospital	Newburgh	Indiana	United States	47630
16	University of Iowa Hospitals	Iowa City	Iowa	United States	52242
17	St. Elizabeth Healthcare	Edgewood	Kentucky	United States	41017
18	Baptist Health Lexington	Lexington	Kentucky	United States	40503
19	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
20	Southcoast Health	Fall River	Massachusetts	United States	02720
21	Cardiovascular Institute of Michigan	Roseville	Michigan	United States	48066
22	Trinity Health Michigan d/b/a Michigan Heart	Ypsilanti	Michigan	United States	48197
23	HealthEast St. Joseph's Hospital	Saint Paul	Minnesota	United States	55102
24	The International Heart Institute on Montana Foundation	Missoula	Montana	United States	59802
25	Cardiovascular Associates of the Delaware Valley	Haddon Heights	New Jersey	United States	08035
26	The Valley Hospital	Paramus	New Jersey	United States	07652
27	New York Methodist Hospital	Brooklyn	New York	United States	11215
28	Novant Health Heart and Vascular Institute	Charlotte	North Carolina	United States	28204
29	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
30	The Ohio Health Research Institute- Grant Medical Center	Columbus	Ohio	United States	43215
31	Providence Heart Institute	Portland	Oregon	United States	97225
32	Geisinger Clinic	Danville	Pennsylvania	United States	17822
33	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
34	Pottstown Medical Specialist, Inc	Pottstown	Pennsylvania	United States	19464
35	Medical University of South Carolina	Charleston	South Carolina	United States	29425
36	North Central Heart	Sioux Falls	South Dakota	United States	57108
37	Dallas VA Research Corporation	Dallas	Texas	United States	75216
38	Michael E. DeBakey VA Medical Center	Houston	Texas	United States	77030
39	Foundation for Advancing Veterans' Health Research	San Antonio	Texas	United States	78229
40	Virginia Commonwealth University Medical Center	Richmond	Virginia	United States	23298
41	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
42	Institut universitaire de Cardiologie et de Pneumologie de Quebec	Québec		Canada
43	Centre hospitalier du pays d'Aix	Aix en Provence		France	13616
44	CHU Grenoble	Grenoble		France	38043
45	CHRU de Lille	Lille		France	59037
46	Hopital Saint Philibert	Lille		France	59160
47	CHRU Hopital Pontchaillou	Rennes		France	35000
48	Centre Hôpital Universitaire Rouen, Hôpital Charles Nicolle	Rouen		France	76031
49	Centre Hôpital Universitaire Rangueil	Toulouse		France	31059
50	Unfalkrankenhaus Marzahn	Berlin		Germany	12683
51	University of Berlin, Charite Virchow Standort	Berlin		Germany	13353
52	Uni Jena	Jena		Germany	07747
53	Krankenhaus Landshut-Achdorf	Landshut		Germany	84036
54	Otto-von-Guericke-Universitaet Magdeburg	Magdeburg		Germany	39120
55	Mater Misericordiae University Hospital	Dublin		Ireland	D07 R2WY
56	Ospedale S. Orsola - Malpighi	Bologna		Italy	40138
57	Azienda Sanitaria Universtitaria Integrata di Trieste	Trieste		Italy	34129
58	Hirosaki University Hospital	Hirosaki-shi	Aomori	Japan	036-8562
59	Hiroshima Prefectural Hospital	Hiroshima-shi	Hiroshima	Japan	734-8530
60	Tokyo Medical University Hospital	Shinjuku-Ku	Tokyo	Japan	162-8666
61	Shinshu University Hospital	Nagano		Japan
62	St. Antonius Ziekenhuis	Nieuwegein		Netherlands	3435 CM
63	Hospital Infanta Cristina	Badajoz	Extremadura	Spain	06080
64	Hospital 12 de Octubre Madrid	Madrid		Spain	28041
65	Hospital Universitario La Fe	Valencia		Spain	46026
66	Cardiocentro Ticino	Lugano		Switzerland	CH-6900
67	Royal Sussex County Hospital	Brighton		United Kingdom	BN2 5BE
68	University Hospital of Wales	Cardiff		United Kingdom	CF144XW
69	Hammersmith Hospital	London		United Kingdom	W12 0HS
70	Freeman Hospital	Newcastle Upon Tyne		United Kingdom	NE7 7DN
71	Nottingham University Hospital	Nottingham		United Kingdom	NG5 1PB
72	Southampton University Hospital	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

• Boston Scientific Corporation

Investigators

• Principal Investigator: Michael R. Gold, MD, Medical University of South Carolina

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 10, 2017

More Information

Publications

None provided.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT03089281
• Other Study ID Numbers: C2067
• First Posted: Mar 24, 2017
• Last Update Posted: Apr 5, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Recruitment Details

Commercially approved quadripolar Boston Scientific CRT-D devices and future generations of BSC X4 CRT-D devices approved by the appropriate regulatory bodies were included in the trial. All devices utilized in the study will include SmartDelay™ and must be capable of providing SmartDelay recommendations for both biventricular pacing (BiV) and Left Ventricular (LV) only pacing.

Pre-assignment Detail

699 subjects were enrolled. 259 were exited prior to randomization (88 not implanted, 7 no RV-LV measurement, 161 RV-LV < 70ms, 3 no viable pacing vector). Subjects with an RV-LV delay >= 70ms were randomized (n = 440). Randomized subjects received a Boston Scientific Cardiac Resynchronization Therapy Defibrillator (CRT-D) and were randomized 1:1 to have either an AV Delay and pacing chamber determined by SmartDelay or a Fixed AV Delay of 120ms with BiV pacing.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Period Title: Overall Study
STARTED	225	215
COMPLETED	197	198
NOT COMPLETED	28	17

Baseline Characteristics

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing	Total
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed	Total of all reporting groups
Overall Participants	225	215	440
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.0 (10.6)	67.6 (10.1)	66.8 (10.4)
Sex: Female, Male (Count of Participants)
Female	89 39.6%	72 33.5%	161 36.6%
Male	136 60.4%	143 66.5%	279 63.4%
Race/Ethnicity, Customized (Count of Participants)
Black or African Heritage	30 13.3%	22 10.2%	52 11.8%
Caucasian	160 71.1%	155 72.1%	315 71.6%
Hispanic or Latino	12 5.3%	9 4.2%	21 4.8%
Asian	3 1.3%	3 1.4%	6 1.4%
Other	1 0.4%	1 0.5%	2 0.5%
Region of Enrollment (participants) [Number]
United States	134 59.6%	123 57.2%	257 58.4%
France	18 8%	19 8.8%	37 8.4%
Canada	15 6.7%	16 7.4%	31 7%
Germany	14 6.2%	16 7.4%	30 6.8%
United Kingdom	14 6.2%	13 6%	27 6.1%
Spain	14 6.2%	12 5.6%	26 5.9%
Japan	5 2.2%	5 2.3%	10 2.3%
Netherlands	5 2.2%	4 1.9%	9 2%
Italy	4 1.8%	4 1.9%	8 1.8%
Switzerland	2 0.9%	2 0.9%	4 0.9%
Ireland	0 0%	1 0.5%	1 0.2%
New York Heart Association (NYHA) Classification (Count of Participants)
Class I	4 1.8%	5 2.3%	9 2%
Class II	97 43.1%	91 42.3%	188 42.7%
Class III	122 54.2%	115 53.5%	237 53.9%
Class IV	2 0.9%	4 1.9%	6 1.4%
Left Ventricular Ejection Fraction (LVEF) (% of blood ejected during LV contraction) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% of blood ejected during LV contraction]	27.4 (9.9)	28.0 (8.9)	27.7 (9.4)
Left Ventricular End Systolic Volume (LVESV) (milliliters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliters]	148 (64)	140 (60)	144 (62)
Conduction Disorder (Count of Participants)
Left Bundle Branch Block (LBBB)	204 90.7%	193 89.8%	397 90.2%
Right Bundle Branch Block (RBBB)	2 0.9%	4 1.9%	6 1.4%
Intraventricular Conduction Delay (IVCD)	19 8.4%	17 7.9%	36 8.2%
QRS width (ms) (milliseconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliseconds]	164 (20)	160 (16)	162 (18)

Outcome Measures

1. Primary Outcome

Title	CRT Response
Description	Comparing cardiac resynchronization therapy (CRT) response rates between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. A negative change in LVESV is considered an improvement; CRT response is defined by a change in Left Ventricular End Systolic Volume (LVESV) < -15% at 6 months compared to pre-implant baseline.
Time Frame	Pre-Implant baseline to 6 months

Outcome Measure Data

Analysis Population Description

A total of 130 randomized subjects did not contribute data to the primary endpoint analysis due to death or withdrawal prior to six months, missed six-month visit or incomplete/insufficient echocardiogram.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	155	155
Count of Participants [Participants]	116 51.6%	105 48.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Change in Left Ventricular End Systolic Volume (Absolute Change)
Description	Comparing absolute changes in Left Ventricular End Systolic Volume from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 6-Month measurement - Implant measurement, in milliliters. A negative change in LVESV is considered an improvement.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

A total of 130 randomized subjects did not contribute data to the secondary endpoint analysis due to death or withdrawal prior to six months, missed six-month visit or incomplete/insufficient echocardiogram.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	155	155
Mean (Standard Deviation) [milliliters]	-51.5 (51.1)	-37.8 (42.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Change in Left Ventricular End Systolic Volume (Relative Change)
Description	Comparing relative changes in Left Ventricular End Systolic Volume from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 100*(6-Month measurement - Implant measurement)/(Implant Measurement), in %. A negative change in LVESV is considered an improvement.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

A total of 130 randomized subjects did not contribute data to the secondary endpoint analysis due to death or withdrawal prior to six months, missed six-month visit or incomplete/insufficient echocardiogram.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	155	155
Mean (Standard Deviation) [% change]	-33.2 (25.2)	-26.7 (27.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Change in Left Ventricular Ejection Fraction (Absolute Change)
Description	Comparing absolute changes in Left Ventricular Ejection Fraction from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 6-Month measurement - Implant measurement, in % of blood ejected during LV contraction. A positive change in LVEF is considered an improvement.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

A total of 129 randomized subjects did not contribute data to the secondary endpoint analysis due to death or withdrawal prior to six months, missed six-month visit or incomplete/insufficient echocardiogram.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	155	156
Mean (Standard Deviation) [% of blood ejected during LV contraction]	12.6 (11.5)	10.2 (11.4)

5. Secondary Outcome

Title	Change in Left Ventricular Ejection Fraction (Relative Change)
Description	Comparing relative changes in Left Ventricular Ejection Fraction from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 100*(6-Month measurement - Implant measurement)/(Implant Measurement), in %. A positive change in LVEF is considered an improvement.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

A total of 129 randomized subjects did not contribute data to the secondary endpoint analysis due to death or withdrawal prior to six months, missed six-month visit or incomplete/insufficient echocardiogram.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	155	156
Mean (Standard Deviation) [% change]	57.5 (60)	44.8 (54.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.050
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Clinical Composite Score (CCS)
Description	Th CCS combines four metrics: all-cause mortality, heart failure hospitalization (HFH), New York Heart Association (NYHA) Class, and quality of life as measured with the patient global assessment (GA) instrument. The CCS categorizes each subject into one of three groups: Improved, Unchanged or Worsened. Improved: Subjects that survived without a HFH through the 6-month visit window and had either an improvement in NYHA class or responded to GA with "much better" or "very much better". Unchanged: All patients that reached the end of 6-month visit window that were not categorized as either "Improved" or "Worsened". Worsened: Subjects that died or had HFH within 6-month visit window or had either a worsening in NYHA class or responded to GA with "much worse" or "very much worse".
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

Subjects that were followed through the end of the 6-month visit window and those that died and/or or had a heart failure hospitalization within the 6-month visit window contributed to this endpoint. A total of 34 subjects did not meet these conditions are were therefore excluded from endpoint analysis.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	207	199
Improved	153 68%	154 71.6%
Unchanged	31 13.8%	25 11.6%
Worsened	23 10.2%	20 9.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Cochran-Armitage Trend Test
	Comments

7. Secondary Outcome

Title	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Description	The KCCQ is a disease-specific instrument for monitoring the health status and quality of life of subjects with congestive heart failure. It includes a total of 23 items that assess quality of life in the following domains: physical function, symptom frequency and severity, symptom stability, self-efficacy and knowledge, social function, and overall quality of life. These domains can be combined into a functional status summary score (derived from the physical function and symptom scales) and an overall summary score which combines the physical function, symptom, social function and quality of life domains. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

Subjects that completed the KCCQ at both the implant and 6 month visits contributed to this endpoint. A total of 51 subjects did not contribute data to the endpoint.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	194	195
Mean (Standard Deviation) [score on a scale]	18.3 (21.0)	20.2 (19.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	t-test, 2 sided
	Comments

8. Other Pre-specified Outcome

Title	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Social Limitation Score
Description	The KCCQ Social Limitation Domain quantifies the extent to which heart failure symptoms impair patients' ability to interact in a number of gender-neutral social activities. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

Subjects that completed the KCCQ at both the implant and 6 month visits contributed to this endpoint. A total of 51 subjects did not contribute data to the endpoint.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	194	195
Mean (Standard Deviation) [score on a scale]	17.1 (28.1)	20.6 (25.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	t-test, 2 sided
	Comments

9. Other Pre-specified Outcome

Title	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life Score
Description	KCCQ Quality of Life Domain is designed to reflect patients' assessment of their quality of life, given the current status of their heart failure. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

Subjects that completed the KCCQ at both the implant and 6 month visits contributed to this endpoint. A total of 51 subjects did not contribute data to the endpoint.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	194	195
Mean (Standard Deviation) [score on a scale]	25.0 (26.9)	27.6 (26.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	t-test, 2 sided
	Comments

10. Other Pre-specified Outcome

Title	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Self-Efficacy Score
Description	KCCQ Self-efficacy Domain quantifies patients' perceptions of how to prevent heart failure exacerbations and manage complications when they arise. This scale is not included in the summary scores. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

Subjects that completed the KCCQ at both the implant and 6 month visits contributed to this endpoint. A total of 51 subjects did not contribute data to the endpoint.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	194	195
Mean (Standard Deviation) [score on a scale]	6.5 (21.8)	4.9 (21.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.46
	Comments
	Method	t-test, 2 sided
	Comments

11. Other Pre-specified Outcome

Title	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom Frequency Score
Description	KCCQ Symptom Domain quantifies the frequency of clinical symptoms in heart failure, including fatigue, shortness of breath, paroxysmal nocturnal dyspnea and patients' edema/swelling. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

Subjects that completed the KCCQ at both the implant and 6 month visits contributed to this endpoint. A total of 51 subjects did not contribute data to the endpoint.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	194	195
Mean (Standard Deviation) [score on a scale]	15.6 (23.5)	17.4 (23.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	t-test, 2 sided
	Comments

12. Other Pre-specified Outcome

Title	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom Burden Score
Description	KCCQ Symptom Domain quantifies the burden of clinical symptoms in heart failure, including fatigue, shortness of breath, paroxysmal nocturnal dyspnea and patients' edema/swelling. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

Subjects that completed the KCCQ at both the implant and 6 month visits contributed to this endpoint. A total of 51 subjects did not contribute data to the endpoint.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	194	195
Mean (Standard Deviation) [score on a scale]	15.9 (23.5)	15.6 (23.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	t-test, 2 sided
	Comments

13. Other Pre-specified Outcome

Title	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation Score
Description	KCCQ Physical Function Domain measures the limitations patients experience, due to their heart failure symptoms, in performing routine activities. Activities are common, gender-neutral, and generalizable across cultures, while also capturing a range of exertional requirements. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life.
Time Frame	Implant to 6 Months

Outcome Measure Data

Analysis Population Description

Subjects that completed the KCCQ at both the implant and 6 month visits contributed to this endpoint. A total of 51 subjects did not contribute data to the endpoint.

Arm/Group Title	SmartDelay™ Algorithm	Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm	Fixed AV Delay of 120ms with BiV pacing was programmed
Measure Participants	194	195
Mean (Standard Deviation) [score on a scale]	14.6 (23.0)	15.9 (23.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SmartDelay™ Algorithm, Fixed AV Delay With BiV Pacing
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse events were collected for the entire duration of subject participation in the study. Subjects were followed for median of 6.5 months.
Arm/Group Title	SmartDelay™ Algorithm		Fixed AV Delay With BiV Pacing
Arm/Group Description	AV Delay and pacing chamber were determined by SmartDelay algorithm		Fixed AV Delay of 120ms with BiV pacing was programmed
All Cause Mortality
	SmartDelay™ Algorithm		Fixed AV Delay With BiV Pacing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/225 (3.1%)		0/215 (0%)
Serious Adverse Events
	SmartDelay™ Algorithm		Fixed AV Delay With BiV Pacing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/225 (21.8%)		46/215 (21.4%)
Cardiac disorders
Heart Failure	14/225 (6.2%)	17	16/215 (7.4%)	24
Ventricular Fibrillation	3/225 (1.3%)	3	2/215 (0.9%)	2
Ventricular Tachycardia/Monomorphic VT	1/225 (0.4%)	1	2/215 (0.9%)	2
Atrial Fibrillation	2/225 (0.9%)	3	1/215 (0.5%)	1
Premature Ventricular Contractions (PVC)	1/225 (0.4%)	1	0/215 (0%)	0
Hypotension/Orthostatic Hypotension	1/225 (0.4%)	1	0/215 (0%)	0
Cardiogenic Shock	2/225 (0.9%)	2	0/215 (0%)	0
Myocardial Infarction	1/225 (0.4%)	1	1/215 (0.5%)	1
Coronary Artery Disease	1/225 (0.4%)	1	0/215 (0%)	0
Peripheral Vascular Disease	0/225 (0%)	0	2/215 (0.9%)	2
Mitral Stenosis	0/225 (0%)	0	1/215 (0.5%)	1
Valvular Damage/Valvular Insufficiency	0/225 (0%)	0	1/215 (0.5%)	1
Syncope	0/225 (0%)	0	1/215 (0.5%)	1
Dizziness	0/225 (0%)	0	1/215 (0.5%)	1
Chest Pain - Ischemic	0/225 (0%)	0	1/215 (0.5%)	1
Dyspnea	1/225 (0.4%)	1	0/215 (0%)	0
Cerebrovascular Accident (CVA)	0/225 (0%)	0	1/215 (0.5%)	1
Pulmonary Embolism	1/225 (0.4%)	1	2/215 (0.9%)	2
Intracardiac Thrombus	1/225 (0.4%)	1	0/215 (0%)	0
Pericarditis	0/225 (0%)	0	1/215 (0.5%)	1
Atrial Septal Defect	0/225 (0%)	0	1/215 (0.5%)	1
Endocrine disorders
Endocrine	1/225 (0.4%)	1	0/215 (0%)	0
Gastrointestinal disorders
Gastrointestinal	6/225 (2.7%)	6	4/215 (1.9%)	4
General disorders
Adverse Reaction - General	1/225 (0.4%)	1	0/215 (0%)	0
Adverse reaction - Medication	0/225 (0%)	0	1/215 (0.5%)	1
Death	1/225 (0.4%)	1	0/215 (0%)	0
Fever/Virus	0/225 (0%)	0	1/215 (0.5%)	1
Physical Trauma	3/225 (1.3%)	3	3/215 (1.4%)	5
Abnormal Laboratory Values	1/225 (0.4%)	1	1/215 (0.5%)	2
Neurological	2/225 (0.9%)	2	2/215 (0.9%)	2
Cancer	3/225 (1.3%)	3	2/215 (0.9%)	2
Immune system disorders
Adverse reaction - Allergic Reaction	1/225 (0.4%)	1	0/215 (0%)	0
Immune	0/225 (0%)	0	1/215 (0.5%)	1
Infections and infestations
Systemic Infection	1/225 (0.4%)	1	3/215 (1.4%)	3
Injury, poisoning and procedural complications
Post-Surgical Wound Discomfort/Bruising/Swelling	0/225 (0%)	0	1/215 (0.5%)	1
Post-Surgical Infection (<=30 Days Post-Implant)	1/225 (0.4%)	1	2/215 (0.9%)	2
Adverse Reaction - General	0/225 (0%)	0	1/215 (0.5%)	1
Hematoma - Pocket (<=30 Days Post-Implant)	3/225 (1.3%)	3	0/215 (0%)	0
Thromboembolic Events	1/225 (0.4%)	1	0/215 (0%)	0
Pneumothorax	1/225 (0.4%)	1	1/215 (0.5%)	1
Venous Occlusion	1/225 (0.4%)	1	0/215 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal	1/225 (0.4%)	1	2/215 (0.9%)	3
Product Issues
Infection > 30 Days Post-Implant (Pulse Generator-related)	2/225 (0.9%)		0/215 (0%)
Unable to Capture (Right Atrial Lead-related)	0/225 (0%)	0	1/215 (0.5%)	1
Dislodgment (Right Atrial Lead-Related)	0/225 (0%)	0	1/215 (0.5%)	1
Dislodgment (Right Ventricular Lead-Related)	1/225 (0.4%)	1	0/215 (0%)	0
Dislodgment (Left Ventricular Lead-Related)	5/225 (2.2%)	5	4/215 (1.9%)	4
Psychiatric disorders
Psychological	0/225 (0%)	0	1/215 (0.5%)	0
Renal and urinary disorders
Genitourinary	1/225 (0.4%)	1	1/215 (0.5%)	1
Renal	4/225 (1.8%)	6	2/215 (0.9%)	3
Respiratory, thoracic and mediastinal disorders
Pulmonary	3/225 (1.3%)	3	2/215 (0.9%)	2
Skin and subcutaneous tissue disorders
Integumentary	1/225 (0.4%)	1	1/215 (0.5%)	1
Other (Not Including Serious) Adverse Events
	SmartDelay™ Algorithm		Fixed AV Delay With BiV Pacing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/225 (8.9%)		22/215 (10.2%)
Cardiac disorders
Heart Failure	3/225 (1.3%)	7	2/215 (0.9%)	2
Ventricular Tachycardia	1/225 (0.4%)	1	0/215 (0%)	0
Atrial Flutter	0/225 (0%)	0	1/215 (0.5%)	1
Atrial Tachycardia / Other Supraventricular Tachycardia (SVT)	1/225 (0.4%)	1	0/215 (0%)	0
Chest Pain	1/225 (0.4%)	1	0/215 (0%)	0
Fatigue / Weakness	0/225 (0%)	0	1/215 (0.5%)	1
Product Issues
Oversensing (Pulse Generator-related)	0/225 (0%)	0	1/215 (0.5%)	1
Inappropriate Tachy Therapy (Pulse Generator-Related)	2/225 (0.9%)	2	1/215 (0.5%)	1
Fatigue (Pulse Generator-Related)	1/225 (0.4%)	1	0/215 (0%)	0
Dislodgment (Right Atrial Lead-Related)	1/225 (0.4%)	1	1/215 (0.5%)	1
Dislodgment (Right Ventricular Lead-Related)	0/225 (0%)	0	1/215 (0.5%)	1
Extracardiac Stimulation (Right Ventricular Lead-Related)	1/225 (0.4%)	1	0/215 (0%)	0
Inappropriate Tachy Therapy (Right Ventricular Lead-Related)	0/225 (0%)	0	1/215 (0.5%)	1
Unable to Capture (Left Ventricular Lead-Related)	2/225 (0.9%)	2	2/215 (0.9%)	2
Extracardiac Stimulation (Left Ventricular Lead-Related)	4/225 (1.8%)	4	7/215 (3.3%)	7
Perforation at Implant (Left Ventricular Lead-Related)	1/225 (0.4%)	1	0/215 (0%)	0
Dislodgment (Left Ventricular Lead-Related)	2/225 (0.9%)	2	3/215 (1.4%)	3
Surgical and medical procedures
Hematoma - Pocket (<=30 days post-implant)	1/225 (0.4%)	1	1/215 (0.5%)	1
Pneumothorax	1/225 (0.4%)	1	0/215 (0%)	0
Lower Extremity Edema	0/225 (0%)	0	1/215 (0.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.