Trial Outcomes & Findings for Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure (NCT NCT00588692)

NCT ID: NCT00588692

Last Updated: 2014-05-06

Results Overview

Peak oxygen uptake (VO2) is the maximum rate of oxygen consumption as measured during incremental exercise, most typically on a motorized treadmill. Maximal oxygen consumption reflects the aerobic physical fitness of the individual. VO2 data was obtained via standard breath-by-breath expired gas analysis. Ejection Fraction Subgroups are based on participants reported at baseline.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 60 participants
• Primary outcome timeframe: baseline, 6 months
• Results posted on: 2014-05-06

Participant Flow

Participant milestones

Measure	SphygmoCor Unblinded The use of the sphygmocor values will determine medication adjustments to optimize heart failure (HF) treatment. SphygmoCor: The SphygmoCor, a hand-held tonometer will assess central blood pressure noninvasively. This pencil-lide device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure.	SphygmoCor Blinded Sphygmocor values will be blinded to the investigator. SphygmoCor: The SphygmoCor, a hand-held tonometer will assess central blood pressure noninvasively. This pencil-lide device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure.
Overall Study STARTED	30	30
Overall Study COMPLETED	23	27
Overall Study NOT COMPLETED	7	3

Reasons for withdrawal

Measure	SphygmoCor Unblinded The use of the sphygmocor values will determine medication adjustments to optimize heart failure (HF) treatment. SphygmoCor: The SphygmoCor, a hand-held tonometer will assess central blood pressure noninvasively. This pencil-lide device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure.	SphygmoCor Blinded Sphygmocor values will be blinded to the investigator. SphygmoCor: The SphygmoCor, a hand-held tonometer will assess central blood pressure noninvasively. This pencil-lide device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure.
Overall Study Withdrawal by Subject	4	2
Overall Study Hip Surgery	0	1
Overall Study Severe Peptic Ulcer Disease	1	0
Overall Study Cancer	1	0
Overall Study Death	1	0

Baseline Characteristics

Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure

Baseline characteristics by cohort

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.	Total n=50 Participants Total of all reporting groups
Age, Continuous	74 years STANDARD_DEVIATION 8 • n=5 Participants	72 years STANDARD_DEVIATION 8 • n=7 Participants	73 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	23 Participants n=7 Participants	39 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	27 participants n=7 Participants	50 participants n=5 Participants
Body Mass Index	29.2 kg/m^2 STANDARD_DEVIATION 4.5 • n=5 Participants	29.9 kg/m^2 STANDARD_DEVIATION 4.6 • n=7 Participants	29.6 kg/m^2 STANDARD_DEVIATION 4.6 • n=5 Participants
History of Hypertension Prior Hypertension	20 participants n=5 Participants	26 participants n=7 Participants	46 participants n=5 Participants
History of Hypertension No Prior Hypertension	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Diabetes Prior History of Diabetes	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants
Diabetes No History of Diabetes	11 participants n=5 Participants	15 participants n=7 Participants	26 participants n=5 Participants
Obesity Obese at Baseline	10 participants n=5 Participants	14 participants n=7 Participants	24 participants n=5 Participants
Obesity Not Obese at Baseline	13 participants n=5 Participants	13 participants n=7 Participants	26 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 6 months

Population: For the EF subgroup 25-49%, n=48, 24 SphygmoCor Unblinded, 24 SphygmoCor Blinded. For the EF subgroup 35-49%, n=33, 14 SphygmoCor Unblinded,. 19 SphygmoCor Blinded. 2 subjects had EF either \<25 or \>50, and they were not included in the analysis.

Peak oxygen uptake (VO2) is the maximum rate of oxygen consumption as measured during incremental exercise, most typically on a motorized treadmill. Maximal oxygen consumption reflects the aerobic physical fitness of the individual. VO2 data was obtained via standard breath-by-breath expired gas analysis. Ejection Fraction Subgroups are based on participants reported at baseline.

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Peak Oxygen Uptake (VO2) During Maximal Effort Exercise Stress Test According to Ejection Fraction Subgroups Ejection Fraction Subgroup 25-49%, n=48	1.5 percentage of change in Peak VO2 Standard Deviation 3.8	-0.5 percentage of change in Peak VO2 Standard Deviation 2.5
Change in Peak Oxygen Uptake (VO2) During Maximal Effort Exercise Stress Test According to Ejection Fraction Subgroups Ejection Fraction Subgroup 35-49%, n=33	2.0 percentage of change in Peak VO2 Standard Deviation 5.4	-1.0 percentage of change in Peak VO2 Standard Deviation 1.9

PRIMARY outcome

Timeframe: baseline, 6 months

Aortic stiffness increases with aging, further augmenting cardiac load. One important repercussion of aortic stiffening is an increase in pulse wave velocity. As the outgoing pressure wave caused by ventricular ejection encounters zones of impedance mismatch, it is partially reflected backward, summing with the incident wave, to increase central aortic blood pressure. The magnitude of this systolic pressure wave reflection can be quantified by AIx.

Aortic pressures were assessed in the seated position after 5 minutes rest. Aortic pulse waveform analysis was performed using a noninvasive, high-fidelity hand held tonometer placed over the radial artery. The built-in, custom software was then used to convert radial pressure waveforms to central aortic waveforms, which more accurately reflect LV afterload. The ratio of this augmented pressure to aortic pulse pressure is defined as the augmentation index (AIx).

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Aortic Augmentation Index (AIx) According to Ejection Fraction Subgroups Ejection Fraction Subgroup 25-49%	-6.9 percentage of change in AIx Standard Deviation 8.8	-4.9 percentage of change in AIx Standard Deviation 6.3
Change in Aortic Augmentation Index (AIx) According to Ejection Fraction Subgroups Ejection Fraction Subgroup 35-49%	-8.3 percentage of change in AIx Standard Deviation 8.7	-5.5 percentage of change in AIx Standard Deviation 6.0

SECONDARY outcome

Timeframe: baseline, six months

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Heart Rate	3 bpm Standard Deviation 7	-1 bpm Standard Deviation 10

SECONDARY outcome

Timeframe: baseline, 6 months

End-diastolic volume (EDV) is the volume of blood in the right and/or left ventricle at end load or filling in (diastole). An increase in EDV increases the preload on the heart and, through the Frank-Starling mechanism of the heart, increases the amount of blood ejected from the ventricle during systole (stroke volume).

Ventricular Data was derived from comprehensive echo-Doppler/Tissue Doppler Echo (TDE) study performed at rest, during and immediately after exercise, along with noninvasive blood pressure assessment (GE Vivid7). LV EDV was determined from the apical 4 and 2 chamber views using Simpson's method of discs, along with ejection fraction (EF).

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Left Ventricle (LV) End Diastolic Volume	-24 ml Standard Deviation 30	-17 ml Standard Deviation 32

SECONDARY outcome

Timeframe: baseline, 6 months

End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. ESV is the lowest volume of blood in the ventricle at any point in the cardiac cycle. End systolic volume can be used clinically as a measurement of the adequacy of cardiac emptying, related to systolic function.

Ventricular Data was derived from comprehensive echo-Doppler/Tissue Doppler Echo (TDE) study performed at rest, during and immediately after exercise, along with noninvasive blood pressure assessment (GE Vivid7). LV end systolic volumes was determined from the apical 4 and 2 chamber views using Simpson's method of discs, along with EF.

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in LV End Systolic Volume	-18 ml Standard Deviation 18	-11 ml Standard Deviation 20

SECONDARY outcome

Timeframe: baseline, 6 months

The ejection fraction is the percentage of the volume in the left ventricle ejected during a cardiac cycle. The normal ejection fraction is 55 to 75 percent. EF = (EDV - ESV) / EDV where EF = ejection fraction, EDV = volume of blood in the left ventricle at end-diastole, ESV = volume of blood in the left ventricle at end-systole.

Ventricular Data was derived from comprehensive echo-Doppler/Tissue Doppler Echo (TDE) study performed at rest, during and immediately after exercise, along with noninvasive blood pressure assessment (GE Vivid7).

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in LV Ejection Fraction	2 percentage of LV blood volume Standard Deviation 2	-0.0 percentage of LV blood volume Standard Deviation 2

SECONDARY outcome

Timeframe: baseline, 6 months

Stroke volume (SV) is the volume of blood pumped from one ventricle of the heart with each beat. SV was determined from pulse wave (PW) and continuous wave (CW) Doppler in the LV outflow tract.

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Stroke Volume	10 ml Standard Deviation 21	10 ml Standard Deviation 21

SECONDARY outcome

Timeframe: baseline, 6 months

The Mitral E velocity is the speed at which blood fills the ventricle. It is determined by echocardiography, an ultrasound-based cardiac imaging modality.

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Mitral E Velocity	5 cm/sec Standard Deviation 15	4 cm/sec Standard Deviation 12

SECONDARY outcome

Timeframe: baseline, 6 months

The E/A ratio is a marker of the function of the left ventricle of the heart; it is determined by echocardiography, an ultrasound-based cardiac imaging modality. Abnormalities in the E/A ratio on Doppler echocardiography suggest that the left ventricle, which pumps blood into the circulation, cannot fill with blood properly in the period between contractions. The E/A ratio is the ratio of peak early transmitral inflow velocity and peak late mitral inflow velocity.

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Mitral E/A Ratio	-0.1 ratio Standard Deviation 0.3	-0.1 ratio Standard Deviation 0.3

SECONDARY outcome

Timeframe: baseline, 6 months

The deceleration time (DT) is the time taken from the maximum E point to baseline. Normally in adults it is less than 220 milliseconds. The DT was measured by pulse wave doppler.

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Mitral E Wave Deceleration Time	-25 milliseconds (ms) Standard Deviation 58	-5 milliseconds (ms) Standard Deviation 43

SECONDARY outcome

Timeframe: baseline, 6 months

Blood pressure is a measure of the force of the blood flowing against the walls of your arteries as it moves through your body.

There are two numbers in a blood pressure reading. This tells how high in millimeters the pressure of your blood raises a column of mercury. The numbers usually are expressed in the form of a fraction; an example of a blood pressure reading is 120/80 mm Hg. The first, or top, number (120 in the example) is the systolic pressure. The systolic pressure is the measure of your blood pressure as the heart contracts and pumps blood. The second or lower number is the diastolic pressure and is the measure taken when your heart is at rest (80 in the example)

Brachial systolic BP was determined by a standard oscillometric device (Dinemap, Critikon).

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Brachial Systolic Blood Pressure (BP)	-9 mmHg Standard Deviation 17	-9 mmHg Standard Deviation 24

SECONDARY outcome

Timeframe: baseline, 6 months

Blood pressure is a measure of the force of the blood flowing against the walls of your arteries as it moves through your body.

There are two numbers in a blood pressure reading. This tells how high in millimeters the pressure of your blood raises a column of mercury. The numbers usually are expressed in the form of a fraction; an example of a blood pressure reading is 120/80 mm Hg. The first, or top, number (120 in the example) is the systolic pressure. The systolic pressure is the measure of your blood pressure as the heart contracts and pumps blood. The second or lower number is the diastolic pressure and is the measure taken when your heart is at rest (80 in the example)

Brachial diastolic BP was determined by a standard oscillometric device (Dinemap, Critikon).

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Brachial Diastolic BP	-2 mmHg Standard Deviation 8	-4 mmHg Standard Deviation 14

SECONDARY outcome

Timeframe: baseline, 6 months

Central blood pressure (CBP) is the pressure in the aorta, which is the large artery into which the heart pumps. This was determined by noninvasive radial tonometry, which undergoes transfer function using customized software to derive CBP tracings.

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Central Systolic BP	-8 mmHg Standard Deviation 19	-9 mmHg Standard Deviation 18

SECONDARY outcome

Timeframe: baseline, 6 months

Central blood pressure (CBP) is the pressure in the aorta, which is the large artery into which the heart pumps. This was determined by noninvasive radial tonometry, which undergoes transfer function using customized software to derive CBP tracings.

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Central Diastolic BP	-7 mmHg Standard Deviation 10	-3 mmHg Standard Deviation 9

SECONDARY outcome

Timeframe: baseline, 6 months

Aortic stiffness increases with aging, further augmenting cardiac load. One important repercussion of aortic stiffening is an increase in pulse wave velocity. As the outgoing pressure wave caused by ventricular ejection encounters zones of impedance mismatch, it is partially reflected backward, summing with the incident wave, to increase central aortic blood pressure. The magnitude of this systolic pressure wave reflection can be quantified by AIx.

Aortic pressures were assessed in the seated position after 5 minutes rest. Aortic pulse waveform analysis was performed using a noninvasive, high-fidelity hand held tonometer placed over the radial artery. The built-in, custom software was then used to convert radial pressure waveforms to central aortic waveforms, which more accurately reflect LV afterload. The ratio of this augmented pressure to aortic pulse pressure is defined as the augmentation index (AIx).

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Augmentation Index	-7 percentage of change in AIx Standard Deviation 9	-5 percentage of change in AIx Standard Deviation 6

SECONDARY outcome

Timeframe: baseline, 6 months

Elastance is a measure of the tendency of a hollow organ to recoil toward its original dimensions upon removal of a distending or compressing force. Effective arterial elastance was determined by the ratio of end systolic BP/stroke volume (SV).

Outcome measures

Measure	SphygmoCor Unblinded n=23 Participants The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.	SphygmoCor Blinded n=27 Participants Sphygmocor values will be blinded to the investigator.
Change in Arterial Elastance	-0.3 mmHg/ml Standard Deviation 0.4	-0.3 mmHg/ml Standard Deviation 0.4

Adverse Events

Treatment

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Control

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment n=24 participants at risk The use of the sphygmocor values will determine medication adjustments to optimize HF treatment. SphygmoCor: The SphygmoCor, a hand-held tonometer will assess central blood pressure noninvasively. This pencil-like device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure.	Control n=27 participants at risk Sphygmocor values will be blinded to the investigator. SphygmoCor: The SphygmoCor, a hand-held tonometer will assess central blood pressure noninvasively. This pencil-like device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure.
Cardiac disorders Death	4.2% 1/24 • Number of events 1 • Participants were followed for safety reporting at monthly visits over the 6-month study period. The adverse event subject population did not include the six subject who were loss to follow up, and the three subjects who withdrew because of noncardiac medical conditions that developed during the study period. Therefore adverse events are reported on 27 subjects in the control arm, and 24 subjects in the treatment arm.	0.00% 0/27 • Participants were followed for safety reporting at monthly visits over the 6-month study period. The adverse event subject population did not include the six subject who were loss to follow up, and the three subjects who withdrew because of noncardiac medical conditions that developed during the study period. Therefore adverse events are reported on 27 subjects in the control arm, and 24 subjects in the treatment arm.
Cardiac disorders Heart Failure Hospitalization	8.3% 2/24 • Number of events 2 • Participants were followed for safety reporting at monthly visits over the 6-month study period. The adverse event subject population did not include the six subject who were loss to follow up, and the three subjects who withdrew because of noncardiac medical conditions that developed during the study period. Therefore adverse events are reported on 27 subjects in the control arm, and 24 subjects in the treatment arm.	7.4% 2/27 • Number of events 2 • Participants were followed for safety reporting at monthly visits over the 6-month study period. The adverse event subject population did not include the six subject who were loss to follow up, and the three subjects who withdrew because of noncardiac medical conditions that developed during the study period. Therefore adverse events are reported on 27 subjects in the control arm, and 24 subjects in the treatment arm.

Other adverse events

Measure	Treatment n=24 participants at risk The use of the sphygmocor values will determine medication adjustments to optimize HF treatment. SphygmoCor: The SphygmoCor, a hand-held tonometer will assess central blood pressure noninvasively. This pencil-like device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure.	Control n=27 participants at risk Sphygmocor values will be blinded to the investigator. SphygmoCor: The SphygmoCor, a hand-held tonometer will assess central blood pressure noninvasively. This pencil-like device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure.
Nervous system disorders Dizziness	33.3% 8/24 • Number of events 8 • Participants were followed for safety reporting at monthly visits over the 6-month study period. The adverse event subject population did not include the six subject who were loss to follow up, and the three subjects who withdrew because of noncardiac medical conditions that developed during the study period. Therefore adverse events are reported on 27 subjects in the control arm, and 24 subjects in the treatment arm.	18.5% 5/27 • Number of events 5 • Participants were followed for safety reporting at monthly visits over the 6-month study period. The adverse event subject population did not include the six subject who were loss to follow up, and the three subjects who withdrew because of noncardiac medical conditions that developed during the study period. Therefore adverse events are reported on 27 subjects in the control arm, and 24 subjects in the treatment arm.
Renal and urinary disorders Worsening Renal Function	8.3% 2/24 • Number of events 2 • Participants were followed for safety reporting at monthly visits over the 6-month study period. The adverse event subject population did not include the six subject who were loss to follow up, and the three subjects who withdrew because of noncardiac medical conditions that developed during the study period. Therefore adverse events are reported on 27 subjects in the control arm, and 24 subjects in the treatment arm.	0.00% 0/27 • Participants were followed for safety reporting at monthly visits over the 6-month study period. The adverse event subject population did not include the six subject who were loss to follow up, and the three subjects who withdrew because of noncardiac medical conditions that developed during the study period. Therefore adverse events are reported on 27 subjects in the control arm, and 24 subjects in the treatment arm.

Additional Information

Dr. Barry A. Borlaug

Mayo Clinic

Phone: 507-284-4442

Email: borlaug.barry@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place