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Myocardial Lipid and Creatine of Heart Failure on MRS

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

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT02378402
Enrollment
71
Registered
2015-03-04
Start date
2014-01-31
Completion date
2016-12-31
Last updated
2019-10-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Myocardial Lipid

Keywords

Creatine, heart failure, lipid, MRS, myocardium

Brief 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.

Detailed 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.

Interventions

OTHERProton (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 δ 0.9, 1.3 and 1.6 ppm) and polyunsaturated fatty acid (PUFA, lipid resonance δ 2.1 and 2.3, 2.8, 5.3 ppm) will be evaluated on MRS, with ratios normalized with total TG value.

Sponsors

Chang Gung Memorial Hospital
Lead SponsorOTHER

Study design

Observational model
CASE_ONLY
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
Yes

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.

Design outcomes

Primary

MeasureTime frameDescription
Myocaridal Lipid on MRS12 monthWe quantified the total myocardial TG resonance as well as its components including FA (lipid resonances δ 0.9, 1.3 and 1.6 ppm) and UFA (lipid resonance δ 2.1 and 2.3, 2.8, 5.3 ppm) from water-suppressed spectra. We also determined the water resonance (\ δ 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.

Countries

Taiwan

Participant flow

Participants by arm

ArmCount
Unstable HF Group
Patients with acute HF episode with hospitalization treatment within 12 months, currently LVEF\<50%. Proton (1H-) magnetic resonance (MR) spectroscopy. 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 δ 0.9, 1.3 and 1.6 ppm) and polyunsaturated fatty acid (PUFA, lipid resonance δ 2.1 and 2.3, 2.8, 5.3 ppm) will be evaluated on MRS, with ratios normalized with total TG value.
25
Stable HF Group
Patients with acute HF episode with hospitalization treatment within 12 months, LVEF\>=50%. Proton (1H-) magnetic resonance (MR) spectroscopy. 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 δ 0.9, 1.3 and 1.6 ppm) and polyunsaturated fatty acid (PUFA, lipid resonance δ 2.1 and 2.3, 2.8, 5.3 ppm) will be evaluated on MRS, with ratios normalized with total TG value.
23
Control Group
Age- and gender-matched healthy volunteers recruited as normal control group. Proton (1H-) magnetic resonance (MR) spectroscopy. 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 δ 0.9, 1.3 and 1.6 ppm) and polyunsaturated fatty acid (PUFA, lipid resonance δ 2.1 and 2.3, 2.8, 5.3 ppm) will be evaluated on MRS, with ratios normalized with total TG value.
21
Total69

Baseline characteristics

CharacteristicUnstable HF GroupStable HF GroupControl GroupTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
1 Participants3 Participants3 Participants7 Participants
Age, Categorical
Between 18 and 65 years
24 Participants20 Participants18 Participants62 Participants
Age, Continuous56.0 years
STANDARD_DEVIATION 7.7
56.1 years
STANDARD_DEVIATION 8.7
58.9 years
STANDARD_DEVIATION 7.2
56.9 years
STANDARD_DEVIATION 7.9
Sex: Female, Male
Female
4 Participants1 Participants4 Participants9 Participants
Sex: Female, Male
Male
21 Participants22 Participants17 Participants60 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
0 / 250 / 230 / 21
serious
Total, serious adverse events
0 / 250 / 230 / 21

Outcome results

Primary

Myocaridal Lipid on MRS

We quantified the total myocardial TG resonance as well as its components including FA (lipid resonances δ 0.9, 1.3 and 1.6 ppm) and UFA (lipid resonance δ 2.1 and 2.3, 2.8, 5.3 ppm) from water-suppressed spectra. We also determined the water resonance (\ δ 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.

Time frame: 12 month

ArmMeasureGroupValue (MEAN)Dispersion
Unstable HF GroupMyocaridal Lipid on MRSfatty acids/triglyceride0.53 ratiosStandard Deviation 0.41
Unstable HF GroupMyocaridal Lipid on MRSunsaturated fatty acids/water0.79 ratiosStandard Deviation 1.38
Unstable HF GroupMyocaridal Lipid on MRStriglyceride/water1.72 ratiosStandard Deviation 2.63
Unstable HF GroupMyocaridal Lipid on MRSfatty acids/water0.93 ratiosStandard Deviation 2.13
Unstable HF GroupMyocaridal Lipid on MRSunsaturated fatty acids/triglyceride0.47 ratiosStandard Deviation 0.41
Stable HF GroupMyocaridal Lipid on MRSunsaturated fatty acids/water0.21 ratiosStandard Deviation 0.28
Stable HF GroupMyocaridal Lipid on MRStriglyceride/water1.18 ratiosStandard Deviation 1.82
Stable HF GroupMyocaridal Lipid on MRSfatty acids/water0.97 ratiosStandard Deviation 1.64
Stable HF GroupMyocaridal Lipid on MRSfatty acids/triglyceride0.68 ratiosStandard Deviation 0.4
Stable HF GroupMyocaridal Lipid on MRSunsaturated fatty acids/triglyceride0.32 ratiosStandard Deviation 0.4
Control GroupMyocaridal Lipid on MRSunsaturated fatty acids/triglyceride0.29 ratiosStandard Deviation 0.32
Control GroupMyocaridal Lipid on MRSfatty acids/triglyceride0.71 ratiosStandard Deviation 0.32
Control GroupMyocaridal Lipid on MRStriglyceride/water1.53 ratiosStandard Deviation 1.78
Control GroupMyocaridal Lipid on MRSunsaturated fatty acids/water0.14 ratiosStandard Deviation 0.2
Control GroupMyocaridal Lipid on MRSfatty acids/water1.39 ratiosStandard Deviation 1.67

Source: ClinicalTrials.gov · Data processed: Mar 2, 2026