Myocardial Lipid
Conditions
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
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
Study design
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocaridal Lipid on MRS | 12 month | 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. |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 |
| Total | 69 |
Baseline characteristics
| Characteristic | Unstable HF Group | Stable HF Group | Control Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 20 Participants | 18 Participants | 62 Participants |
| Age, Continuous | 56.0 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 Participants | 1 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 21 Participants | 22 Participants | 17 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 23 | 0 / 21 |
| serious Total, serious adverse events | 0 / 25 | 0 / 23 | 0 / 21 |
Outcome results
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Unstable HF Group | Myocaridal Lipid on MRS | fatty acids/triglyceride | 0.53 ratios | Standard Deviation 0.41 |
| Unstable HF Group | Myocaridal Lipid on MRS | unsaturated fatty acids/water | 0.79 ratios | Standard Deviation 1.38 |
| Unstable HF Group | Myocaridal Lipid on MRS | triglyceride/water | 1.72 ratios | Standard Deviation 2.63 |
| Unstable HF Group | Myocaridal Lipid on MRS | fatty acids/water | 0.93 ratios | Standard Deviation 2.13 |
| Unstable HF Group | Myocaridal Lipid on MRS | unsaturated fatty acids/triglyceride | 0.47 ratios | Standard Deviation 0.41 |
| Stable HF Group | Myocaridal Lipid on MRS | unsaturated fatty acids/water | 0.21 ratios | Standard Deviation 0.28 |
| Stable HF Group | Myocaridal Lipid on MRS | triglyceride/water | 1.18 ratios | Standard Deviation 1.82 |
| Stable HF Group | Myocaridal Lipid on MRS | fatty acids/water | 0.97 ratios | Standard Deviation 1.64 |
| Stable HF Group | Myocaridal Lipid on MRS | fatty acids/triglyceride | 0.68 ratios | Standard Deviation 0.4 |
| Stable HF Group | Myocaridal Lipid on MRS | unsaturated fatty acids/triglyceride | 0.32 ratios | Standard Deviation 0.4 |
| Control Group | Myocaridal Lipid on MRS | unsaturated fatty acids/triglyceride | 0.29 ratios | Standard Deviation 0.32 |
| Control Group | Myocaridal Lipid on MRS | fatty acids/triglyceride | 0.71 ratios | Standard Deviation 0.32 |
| Control Group | Myocaridal Lipid on MRS | triglyceride/water | 1.53 ratios | Standard Deviation 1.78 |
| Control Group | Myocaridal Lipid on MRS | unsaturated fatty acids/water | 0.14 ratios | Standard Deviation 0.2 |
| Control Group | Myocaridal Lipid on MRS | fatty acids/water | 1.39 ratios | Standard Deviation 1.67 |