Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure

NCT00588692 | Completed Results

• 1 other identifier: 07-002008
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Heart Failure

Keywords

Heart Failure; Afterload Reduction; Sphygmocor

Outcome Measures

Primary Outcomes (2)

• Change in Peak Oxygen Uptake (VO2) During Maximal Effort Exercise Stress Test According to Ejection Fraction Subgroups

  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.

  baseline, 6 months

• Change in Aortic Augmentation Index (AIx) According to Ejection Fraction Subgroups

  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).

  baseline, 6 months

Secondary Outcomes (14)

• Change in Heart Rate

  baseline, six months

• Change in Left Ventricle (LV) End Diastolic Volume

  baseline, 6 months

• Change in LV End Systolic Volume

  baseline, 6 months

• Change in LV Ejection Fraction

  baseline, 6 months

• Change in Stroke Volume

  baseline, 6 months

Study Arms (2)

SphygmoCor Unblinded

ACTIVE COMPARATOR

The use of the sphygmocor values will determine medication adjustments to optimize HF treatment.

Device: SphygmoCor

SphygmoCor Blinded

PLACEBO COMPARATOR

Sphygmocor values will be blinded to the investigator.

Device: SphygmoCor

Interventions

SphygmoCor DEVICE

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.

SphygmoCor Blinded; SphygmoCor Unblinded

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or greater
• Cardiac Ejection Fraction (EF) greater than or equal to 25% by echocardiography within 12 months
• Stable New York Heart Association (NYHA) class II or greater
• Heart Failure consultation within the last 18 months
• Ability to exercise on a cycle ergometer
• Stable angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) dosage for greater than 3 months

You may not qualify if:

• Enrollment in a concurrent study that may confound the results of this study
• Subjects with medical conditions that would limit study participation
• Pregnancy
• Brachial Systolic Blood Pressure less than 110 mmHg
• Baseline AIx less than 15%
• Cardiac Surgery with 60 days of potential study enrollment
• Myocardial infarction within 30 days of potential study enrollment
• Hemodynamically significant valvular stenosis (greater than mild)
• Heart failure due to thyroid disease
• Active myocarditis or anemia defined as hemoglobin less than 9 mg/dl
• Presence of severe renal insufficiency with serum creatinine greater than 2.5 mg/dl
• Significant pulmonary hypertension or Cor pumonale
• Irregular heart rhythms
• Dyspnea due to pulmonary disease
• Uninterpretable echocardiographic images or radial tonometry data

Sponsors & Collaborators

• Mayo Clinic: lead
• AtCor Medical, Inc.: collaborator

Study Sites (2)

University of Arizona

Phoenix, Arizona, 85004, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• Wohlfahrt P, Melenovsky V, Redfield MM, Olson TP, Lin G, Abdelmoneim SS, Hametner B, Wassertheurer S, Borlaug BA. Aortic Waveform Analysis to Individualize Treatment in Heart Failure. Circ Heart Fail. 2017 Feb;10(2):e003516. doi: 10.1161/CIRCHEARTFAILURE.116.003516.

  PMID: 28159826 DERIVED

• Borlaug BA, Olson TP, Abdelmoneim SS, Melenovsky V, Sorrell VL, Noonan K, Lin G, Redfield MM. A randomized pilot study of aortic waveform guided therapy in chronic heart failure. J Am Heart Assoc. 2014 Mar 20;3(2):e000745. doi: 10.1161/JAHA.113.000745.

  PMID: 24650926 DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Dr. Barry A. Borlaug
• Organization: Mayo Clinic

borlaug.barry@mayo.edu

507-284-4442

Study Officials

• Barry A. Borlaug, MD

  Staff Physician, Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 8, 2008
• Study Start: July 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: December 1, 2012
• Last Updated: May 6, 2014
• Results First Posted: May 6, 2014

Record last verified: 2014-04

Locations

US (2)