Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure (SACAR)

This study has been completed.
Sponsor:
Collaborator:
AtCor Medical, Inc.
Information provided by (Responsible Party):
Barry Borlaug, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00588692
First received: December 21, 2007
Last updated: April 23, 2013
Last verified: April 2013

December 21, 2007
April 23, 2013
July 2007
November 2012   (final data collection date for primary outcome measure)
Peak Oxygen consumption during maximal effort exercise stress test [ Time Frame: Full enrollment and completion of the study. ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00588692 on ClinicalTrials.gov Archive Site
Specific Aim 2: Determine whether CPT is associated with improvements in LV systolic and diastolic function at rest and with dynamic exercise, assessed noninvasively via comprehensive echo-Doppler examination. [ Time Frame: full enrollment and completion in the study. ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure
Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure

Heart failure (HF) is the leading cause of hospitalization among Americans over the age of 65 years, affecting greater than 5 million in the U.S. alone. Significant improvements in morbidity and mortality have been achieved through the use of medications that antagonize adverse neurohormonal signaling pathways, particularly therapies that reduce left ventricular (LV) afterload.

Vascular stiffness increases with aging, contributing to the increase in cardiac load. One important repercussion of such stiffening is an increase in pulse wave velocity. As the incident pressure wave generated by cardiac ejection encounters zones of impedance mismatch (such as arterial bifurcations), part of the wave is reflected backward, summing with the incident wave, increasing central blood pressure (CBP). With normal aging, hypertension, and heart failure, increased wave velocity causes the reflected wave to reach the heart earlier, in mid to late systole, considerably increasing late-systolic load, impairing cardiac ejection, and diastolic relaxation in the ensuing cardiac cycle.

The magnitude of this reflected pressure wave can be quantified by the augmentation index (AIx). The use of vasoactive agents which antagonize this increase in late systolic load (and AIx) may prove useful in the treatment of heart failure, by facilitating cardiac ejection during late systole when reflected pressure waves predominate. However, it has never been conclusively shown in humans that CBP-targeted therapy is useful in the management of HF.

LV afterload, measured centrally in the ascending aorta, may differ considerably from brachial cuff-measured pressure, and has traditionally required invasive hemodynamic assessment to determine, limiting the applicability of techniques targeting CBP and late-systolic load. Recently, a novel, hand-held tonometer (SphygmoCor, Atcor Medical) has been developed for the noninvasive assessment of CBP. This pencil-like device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure. This device has received FDA approval for clinical use in the assessment of central pressures. However, it remains unknown whether knowledge of CBP and late-systolic load (AIx) confers any clinically-significant incremental benefit in the management of patients with heart failure. The primary objective of the proposed investigation will be to determine if this assessment might have such a role.

Research Design and Methods

Hypotheses Knowledge of central aortic pressure waveforms (central pressure therapy, CPT) will affect the intensity of antihypertensive medication prescription, and treatment decisions based upon this knowledge in turn will lead to an enhanced reduction in CBP and AIx. Finally, it is hypothesized that this reduction in AIx/CBP will lead to improved exercise performance and LV systolic and diastolic reserve function.

Basic Study Plan This is a single-blind, randomized, controlled, parallel group intervention study examining the effects of a novel, noninvasive diagnostic test for determining AIx and CBP (SphygmoCor, Atcor Medical) on medical care, blood pressure control, exercise performance, and LV functional reserve in patients with chronic heart failure (HF) and systolic dysfunction (25%<EF<50%) and with preserved systolic function (EF>50%). Eligible subjects will undergo resting echocardiogram, noninvasive CBP assessment, and metabolic exercise stress testing on a recumbent cycle ergometer to quantify exercise performance. Echocardiography and CBP assessment will be performed at rest, during graded exercise, and immediately after peak exercise to determine indexes of LV systolic and diastolic performance and changes in CBP. Subjects will then be randomized (1:1) to subsequent determination of CBP at 1 month heart failure clinic visits versus sham (tonometry information acquired, but not shared with investigator). Investigators will then make adjustments to subject's medical therapy and antihypertensive regimen based upon the additional data procured via the Sphygmocor device. Subjects randomized to sham will have adjustments made as per standard clinical judgment based upon brachial blood pressure assessment and other clinical variables. In addition to standard clinical assessment, each subject will undergo 6 minute walk test at each visit, administered by the study coordinator.

At the 6 month follow up visit, subjects will undergo resting and exercise echo/CBP/metabolic stress testing exactly as performed at visit 1. The co-primary endpoints will be the change in central augmentation index (defined below) and change in peak oxygen uptake (VO2) from baseline. Secondary endpoints will include the changes in resting and exercise-induced CBP and brachial blood pressures, number of antihypertensive medications prescribed, resting and exercise change in LV systolic and diastolic function (see below), changes in: cardiac output, exercise time, anaerobic threshold, VE/VCO2 slope (ventilatory efficiency). There will be a total of 7 visits, the first and last for exercise testing; the intervening 5 visits will be routine heart failure clinic follow up appointments.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Heart Failure
  • Device: sphygmocor device
    central blood pressures will be obtained noninvasively to determine medication adjustment in optimizing treatment for heart failure.
  • Device: sphygmocor device
    data collection blinded to investigator for medication adjustment.
  • Active Comparator: Treatment
    The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.
    Intervention: Device: sphygmocor device
  • Placebo Comparator: Control
    Sphygmocor values will be blinded to the investigator.
    Intervention: Device: sphygmocor device
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
61
December 2012
November 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • >/= 18 years
  • EF >25% by echo within 12 months
  • Stable NYHA class IIor>
  • Stable ACE/ARB dosage for >3months
  • HF consultation within the last 12 months
  • Ability to exercise.

Exclusion Criteria:

  • Enrollment in a concurrent study
  • limiting medical conditions
  • Pregnancy
  • SBP<120mmHg
  • Baseline AIx<15%
  • Cardiac Surgery with 60 days of enrollment
  • >mild/stenotic valve disease
  • thyroid disease; active myocarditis
  • HgB<9.0
  • Creat >2.0
  • Significant pHTN
  • Cor pumonale
  • afib
  • Dyspnea due to pulmonary disease
  • Uninterpretable echo/radial tonometry data
  • Significant competing cause for exercise intolerance.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00588692
07-002008, SACAR
No
Barry Borlaug, Mayo Clinic
Mayo Clinic
AtCor Medical, Inc.
Principal Investigator: Barry A. Borlaug, MD Staff Physician, Mayo Clinic
Mayo Clinic
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP