Myocardial Lipid and Creatine of Heart Failure on MRS

Myocardial Lipid Clinical Trial

Official title:

Exploring Myocardial Lipid and Creatine as Imaging Biomarkers for Patients of Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02378402
• Other study ID #: 102-2772A3
• Status: Completed
• Start date: January 2014
• Est. completion date: December 2016

Study information

• Verified date: October 2019
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objective of this 3-year project is to develop myocardial MRS, in particular lipid (triglyceride) and creatine resonances, as imaging biomarkers for patients with heart failure (HF). Investigators will elucidate how and, to what extent, lipid and creatine levels of the heart contribute to heart failure. The first year is a cross-sectional study. Investigators aim to compare the MRS of normal subjects and that of stable HF patients in recovery with normal or impaired ejection fraction (EF). Total 60 subjects will be enrolled, with 20 subjects in each group. In the 2nd and 3rd years, investigators plan a prospective longitudinal study of 40 subjects. Enrolled patients will be evaluated with cardiac MRS at three time points, i.e., disease onset, 6 months and one year after treatment, and will be followed up until the end of this project (1.5~3-year follow up). In total 120 MR scans will be performed in the 2nd and 3rd years. The resonances from cardiac MRS, including creatine and lipids, will be correlated with the disease course, patient biochemistry data and clinical outcome. Investigators expect to make MRS to become an integral part of a clinical cardiac MR protocol.

Description:

Heart failure (HF) is a major societal burden due to its high prevalence, poor prognosis and high cost. A potential therapeutic target is to supply the energy-starved heart. Lipid content of the heart is highly dynamic and myocardial lipid overload has been implicated in the pathophysiology of cardiac disease. The measurement of total creatine, a crucial actor in the creatine kinase system, gives an insight into the energy storage and buffering capacity in the heart. Magnetic Resonance Spectroscopy (MRS) is an imaging technique that allows non-invasive biochemical analysis in the clinical setting using routine MR scanner. It has the combined advantages of inherently providing molecular information, being free of ionizing radiation, and not requiring administration of external tracers. The objective of this 3-year project is to develop myocardial MRS, in particular lipid (triglyceride) and creatine resonances, as imaging biomarkers for patients with heart failure (HF). Investigators will elucidate how and, to what extent, lipid and creatine levels of the heart contribute to heart failure. The first year is a cross-sectional study. Investigators aim to compare the MRS of normal subjects and that of stable HF patients in recovery with normal or impaired ejection fraction (EF). Total 60 subjects will be enrolled, with 20 subjects in each group. In the 2nd and 3rd years, investigators plan a prospective longitudinal study of 40 subjects. Enrolled patients will be evaluated with cardiac MRS at three time points, i.e., disease onset, 6 months and one year after treatment, and will be followed up until the end of this project (1.5~3-year follow up). In total 120 MR scans will be performed in the 2nd and 3rd years. The resonances from cardiac MRS, including creatine and lipids, will be correlated with the disease course, patient biochemistry data and clinical outcome. Investigators expect to make MRS to become an integral part of a clinical cardiac MR protocol. The advance in knowledge is to prove the association between heart failure and myocardial impairment in lipids and/or creatine. The knowledge gained from MRS could potentially translate as a non-invasive biomarker for heart failure patients. This biomarker can help to early detect treatable causes of HF, and to monitor and evaluate treatment response in a non-invasive fashion. The inherited non-invasiveness and non-radiation nature makes MR an ideal technique for clinical application and biotechnology development.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

1. heart failure patients diagnosed in the Keelung Chang Gung Memorial Hospital

2. without previous history of coronary artery disease

3. patients must be = 20 and = 80 years of age

4. patients must be willing to undergo standard treatment and follow up in the Heart Failure Center

5. patients must be able to give informed consent.

Exclusion Criteria:

1. patients who are judged to be noncompliant to treatment or not accessible for follow up

2. patients with contraindications to MR scanning, such as claustrophobia, cardiac pacemaker, metal implants, or unable to cooperate for MRI study due to mental status

3. Severe renal function impairment (glomerular filtration rate less than 30 mL/min/1.73m2)

4. pregnant or breast-feeding status

5. history of open-heart surgery.

Related Conditions & MeSH terms

• Heart Failure
• Myocardial Lipid

Intervention

Other:
• Proton (1H-) magnetic resonance (MR) spectroscopy
PRESS localized 1D MRS sequence was used on a 3-T MR system. The lipid resonances will be analyzed using the LC-Model algorithm, and a Cramer-Rao lower bound (CRLB) threshold of 50% was used as quality control. Resonances of fatty acid (FA, lipid resonances d 0.9, 1.3 and 1.6 ppm) and polyunsaturated fatty acid (PUFA, lipid resonance d 2.1 and 2.3, 2.8, 5.3 ppm) will be evaluated on MRS, with ratios normalized with total TG value.

Locations

Country	Name	City	State
Taiwan	Department of Radiology, Chang Gung Memorial Hospital	Guishan	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (1)

Liao PA, Lin G, Tsai SY, Wang CH, Juan YH, Lin YC, Wu MT, Yang LY, Liu MH, Chang TC, Lin YC, Huang YC, Huang PC, Wang JJ, Ng SH, Ng KK. Myocardial triglyceride content at 3 T cardiovascular magnetic resonance and left ventricular systolic function: a cross-sectional study in patients hospitalized with acute heart failure. J Cardiovasc Magn Reson. 2016 Feb 5;18:9. doi: 10.1186/s12968-016-0228-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocaridal Lipid on MRS	We quantified the total myocardial TG resonance as well as its components including FA (lipid resonances d 0.9, 1.3 and 1.6 ppm) and UFA (lipid resonance d 2.1 and 2.3, 2.8, 5.3 ppm) from water-suppressed spectra. We also determined the water resonance (~ d 4.7 ppm) from spectra without water suppression. Myocardial TG content relative to water as well as relative amounts of myocardial TG was calculated from the available data.	12 month

External Links

•   Myocardial triglyceride content at 3 T cardiovascular magnetic resonance and left ventricular systolic function: a cross-sectional study in patients hospitalized with acute heart failure.