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
  Purpose

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.


Condition Intervention
Heart Failure
Device: sphygmocor device

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Peak Oxygen consumption during maximal effort exercise stress test [ Time Frame: Full enrollment and completion of the study. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 61
Study Start Date: July 2007
Study Completion Date: December 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment
The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.
Device: sphygmocor device
central blood pressures will be obtained noninvasively to determine medication adjustment in optimizing treatment for heart failure.
Placebo Comparator: Control
Sphygmocor values will be blinded to the investigator.
Device: sphygmocor device
data collection blinded to investigator for medication adjustment.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00588692

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
AtCor Medical, Inc.
Investigators
Principal Investigator: Barry A. Borlaug, MD Staff Physician, Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Barry Borlaug, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00588692     History of Changes
Other Study ID Numbers: 07-002008, SACAR
Study First Received: December 21, 2007
Last Updated: April 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Heart Failure
Afterload Reduction
Sphygmocor

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 16, 2014