{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST000166","ANALYSIS_ID":"AN000259","VERSION":"1","CREATED_ON":"02-08-2024"},

"PROJECT":{"PROJECT_TITLE":"Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure","PROJECT_SUMMARY":"Background: Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value for the response to CRT. Methods: This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia but not CRT. Blood samples were collected before and 3 months after CRT. Metabolomic profiling of plasma samples was performed using gas chromatography–mass spectrometry and nuclear magnetic resonance. Results: The plasma metabolomic profile was altered in the HF patients, with a distinct panel of metabolites, including Krebs cycle and lipid, amino acid, and nucleotide metabolism. CRT improved the metabolic profile. The succinate/glutamate ratio, an index of Krebs cycle activity, improved from 0.58?0.13 to 2.84?0.60 (P<.05). The glucose/palmitate ratio, an indicator of the balance between glycolytic and fatty acid metabolism, increased from 0.96?0.05 to 1.54?0.09 (P<.01). Compared with the nonresponders to CRT, the responders had a distinct baseline plasma metabolomic profile, including higher isoleucine, phenylalanine, leucine, glucose, and valine levels and lower glutamate levels at baseline (P<.05). Conclusion: CRT improves plasma metabolomic profile of HF patients indicating harmonization of myocardial energy substrate metabolism. CRT responders may have a favorable metabolic profile as a potential biomarker for predicting CRT outcome.","INSTITUTE":"Mayo Clinic","DEPARTMENT":"Department of Medicine","LAST_NAME":"Cha","FIRST_NAME":"Yong-Mei","EMAIL":"ycha@mayo.edu","DOI":"http://dx.doi.org/10.21228/M8C01P"},

"STUDY":{"STUDY_TITLE":"Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure","STUDY_TYPE":"intervention","STUDY_SUMMARY":"This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia but not CRT. Blood samples were collected before and 3 months after CRT. Metabolomic profiling of plasma samples was performed using gas chromatography–mass spectrometry and nuclear magnetic resonance.","INSTITUTE":"Mayo Clinic","DEPARTMENT":"Department of Medicine","LAST_NAME":"Cha","FIRST_NAME":"Yong-Mei","EMAIL":"ycha@mayo.edu","SUBMIT_DATE":"2015-05-14"},

"SUBJECT":{"SUBJECT_TYPE":"Human","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606","SPECIES_GROUP":"Human"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"3M_2",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"71","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"1","Beta (1)":"0","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"0","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_20",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"76","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_23",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"44","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"0","Ace (1)":"1","Statin (1)":"0","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_26",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"43","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"0","Ace (1)":"0","Statin (1)":"0","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_28",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"69","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_30",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"1","Age":"74","Diabetes (1)":"1","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_34",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"76","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_6",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"1","Age":"80","Diabetes (1)":"1","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_7",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"52","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_9",
"Factors":{"Group":"3M","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"58","Diabetes (1)":"1","HTN (1)":"1","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_10",
"Factors":{"Group":"3M","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"47","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"1","Beta (1)":"0","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_14",
"Factors":{"Group":"3M","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"77","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_17",
"Factors":{"Group":"3M","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"87","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"0","Ace (1)":"1","Statin (1)":"0","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_24",
"Factors":{"Group":"3M","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"47","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"0","Ace (1)":"1","Statin (1)":"0","EF%":"NA","EF < 25":"1":"NA"}
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{
"Subject ID":"-",
"Sample ID":"3M_27",
"Factors":{"Group":"3M","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"61","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_33",
"Factors":{"Group":"3M","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"76","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"0","Ace (1)":"0","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
},
{
"Subject ID":"-",
"Sample ID":"3M_4",
"Factors":{"Group":"3M","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"82","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"0","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
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{
"Subject ID":"-",
"Sample ID":"3M_5",
"Factors":{"Group":"3M","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"42","Diabetes (1)":"1","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"0","Ace (1)":"0","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
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{
"Subject ID":"-",
"Sample ID":"3M_8",
"Factors":{"Group":"3M","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"63","Diabetes (1)":"1","HTN (1)":"0","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"NA","EF < 25":"1":"NA"}
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{
"Subject ID":"-",
"Sample ID":"11_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"66","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"65","EF < 25":"1":"0"}
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{
"Subject ID":"-",
"Sample ID":"12_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"-","Ischemia (1)":"0","Age":"62","Diabetes (1)":"0","HTN (1)":"-","CAD (1)":"-","Beta (1)":"-","Digoxin (1)":"-","warfarin (1)":"-","ASA (1)":"-","Ace (1)":"-","Statin (1)":"-","EF%":"-","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"13_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"65","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"0","Ace (1)":"0","Statin (1)":"0","EF%":"65","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"15_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"71","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"0","Ace (1)":"0","Statin (1)":"0","EF%":"64","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"16_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"37","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"0","Ace (1)":"0","Statin (1)":"0","EF%":"63","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"18_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"83","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"65","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"19_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"69","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"66","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"21_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"51","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"59","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"22_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"72","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"55","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"29_1",
"Factors":{"Group":"Control","State":"Control"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"72","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"63","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"2_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"71","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"1","Beta (1)":"0","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"0","EF%":"18","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"23_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"44","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"0","Ace (1)":"1","Statin (1)":"0","EF%":"12","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"25_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"1","Age":"67","Diabetes (1)":"1","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"20","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"26_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"43","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"0","Ace (1)":"0","Statin (1)":"0","EF%":"14","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"28_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"69","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"21","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"30_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"1","Age":"74","Diabetes (1)":"1","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"20","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"3_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"39","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"21","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"34_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"76","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"1","EF%":"18","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"6_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"1","Age":"80","Diabetes (1)":"1","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"1","EF%":"15","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"7_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"52","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"21","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"9_1",
"Factors":{"Group":"HF","State":"Res"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"58","Diabetes (1)":"1","HTN (1)":"1","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"33","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"20_1",
"Factors":{"Group":"HF","State":"uc"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"76","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"45","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"32_1",
"Factors":{"Group":"HF","State":"uc"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"1","Age":"56","Diabetes (1)":"1","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"25","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"10_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"47","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"1","Beta (1)":"0","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"1","EF%":"30","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"1_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"1","Age":"76","Diabetes (1)":"1","HTN (1)":"1","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"15","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"14_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"77","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"0","Statin (1)":"0","EF%":"23","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"17_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"1","Age":"87","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"0","Ace (1)":"1","Statin (1)":"0","EF%":"25","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"24_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"47","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"0","Ace (1)":"1","Statin (1)":"0","EF%":"43","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"27_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"0","Ischemia (1)":"0","Age":"61","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"0","Beta (1)":"0","Digoxin (1)":"0","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"21","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"33_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"76","Diabetes (1)":"0","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"0","Ace (1)":"0","Statin (1)":"1","EF%":"30","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"4_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"82","Diabetes (1)":"0","HTN (1)":"1","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"1","Ace (1)":"0","Statin (1)":"1","EF%":"20","EF < 25":"1":"1"}
},
{
"Subject ID":"-",
"Sample ID":"5_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"42","Diabetes (1)":"1","HTN (1)":"0","CAD (1)":"0","Beta (1)":"1","Digoxin (1)":"0","warfarin (1)":"1","ASA (1)":"0","Ace (1)":"0","Statin (1)":"1","EF%":"26","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"8_1",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"63","Diabetes (1)":"1","HTN (1)":"0","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"25","EF < 25":"1":"0"}
},
{
"Subject ID":"-",
"Sample ID":"8_1A",
"Factors":{"Group":"HF","State":"Unres"},
"Additional sample data":{"Obesity (BMI>30":"1)":"1","Ischemia (1)":"0","Age":"63","Diabetes (1)":"1","HTN (1)":"0","CAD (1)":"1","Beta (1)":"1","Digoxin (1)":"1","warfarin (1)":"0","ASA (1)":"1","Ace (1)":"1","Statin (1)":"1","EF%":"25","EF < 25":"1":"0"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Blood samples were taken from a peripheral vein. These blood samples (5 mL) were collected into EDTA tubes containing 100 ?L of injected stop solution (dipyrimidole,10 ?M; EHNA, 5 ?M; iodotubercidin, 2 ?M; AOPCP, 50 ?M, in 0.9% NaCl) to reduce blood nucleotide metabolism; stored on ice; and then centrifuged at 3,200 rpm for 10 minutes at 4°C. Plasma aliquots were stored at ?80°C until analyses.","SAMPLE_TYPE":"Blood"},

"TREATMENT":{"TREATMENT_SUMMARY":"Heart failure|3-month follow up after cardiac resynchronization therapy (CRT)|Controls","TREATMENT_PROTOCOL_COMMENTS":"All HF patients underwent a baseline evaluation before CRT, including assessment of New York Heart Association (NYHA) functional class, concomitant cardiovascular conditions (e.g., hypertension, coronary artery disease, and diabetes mellitus), electrocardiographic QRS duration and morphologic characteristics, and transthoracic echocardiography. Echocardiographic parameters included LV end-systolic and diastolic dimensions, LVEF, and pulmonary artery systolic pressure. Medication use was recorded and confirmed that patients were taking optimal medication dose for HF. Patients continued on stable medication dosage during the study.|The HF patients returned for a clinical follow-up 3 months after CRT. The NYHA functional class was reassessed, and echocardiography was repeated.|Ten age-matched control patients underwent catheter ablation for supraventricular arrhythmia with a normal left ventricular ejection fraction (LVEF) of greater than 55%."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"For gas chromatography–mass spectrometry (GC-MS), plasma (100 ?L) was extracted using a 900-?L methanol:water (8:1, v/v) mixture containing 5 ?g internal standard, myristic-d27 acid, at ambient temperature 33. Supernatant (900 ?L) was transferred and completely dried in a vacuum concentrator. Subsequently, the tubes were methoximated and derivatized and then analyzed using an Agilent 6890 GC oven with Agilent 5973 MS 34.
Sample Treatment and Instrumental Conditions for 1H NMR Metabolomic Analysis
 For nuclear magnetic resonance (NMR) imaging, plasma (60 ?L) was diluted 140 ?L with 0.2M phosphate buffer (pH 7.4):D2O containing a mixture of 16 mM formate and 4 mM TSP (1:1, v/v). After filtering (0.22 ?m), the samples were transferred into a 3-mm-diameter NMR tube. High-resolution 1H NMR spectra were acquired at 600 MHz on a Bruker Avance III 600 spectrometer. Spectra peaks were identified according to Chenomx NMR Suite 6.1 software and data in the literature 35, 36.
","SAMPLEPREP_PROTOCOL_FILENAME":"Methods-For-Upload.docx"},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_SUMMARY":"For gas chromatographymass spectrometry (GC-MS), plasma (100 ?L) was extracted using a 900-?L methanol:water (8:1, v/v) mixture containing 5 ?g internal standard, myristic-d27 acid, at ambient temperature 33. Supernatant (900 ?L) was transferred and completely dried in a vacuum concentrator. Subsequently, the tubes were methoximated and derivatized and then analyzed using an Agilent 6890 GC oven with Agilent 5973 MS 34.
Sample Treatment and Instrumental Conditions for 1H NMR Metabolomic Analysis
 For nuclear magnetic resonance (NMR) imaging, plasma (60 ?L) was diluted 140 ?L with 0.2M phosphate buffer (pH 7.4):D2O containing a mixture of 16 mM formate and 4 mM TSP (1:1, v/v). After filtering (0.22 ?m), the samples were transferred into a 3-mm-diameter NMR tube. High-resolution 1H NMR spectra were acquired at 600 MHz on a Bruker Avance III 600 spectrometer. Spectra peaks were identified according to Chenomx NMR Suite 6.1 software and data in the literature 35, 36.
","INSTRUMENT_NAME":"Agilent 6890 GC","CHROMATOGRAPHY_TYPE":"GC"},

"ANALYSIS":{"LABORATORY_NAME":"Mayo Clinic Metabolomics Core","ANALYSIS_TYPE":"MS","ANALYSIS_COMMENTS":"GC-MS"},

"MS":{"INSTRUMENT_NAME":"Agilent 5973","INSTRUMENT_TYPE":"Single quadrupole","MS_TYPE":"EI","ION_MODE":"POSITIVE"},

"MS_METABOLITE_DATA":{
"Units":"Peak area",

"Data":[{"Metabolite":"2-HB (2-hydroxybutyric acid)","3M_2":"0.3766","3M_20":"0.5248","3M_23":"0.4917","3M_26":"0.3380","3M_28":"0.5304","3M_30":"0.3847","3M_34":"0.2351","3M_6":"0.4828","3M_7":"1.9819","3M_9":"2.1263","3M_10":"0.6662","3M_14":"0.3271","3M_17":"0.2094","3M_24":"0.6143","3M_27":"0.2937","3M_33":"0.4733","3M_4":"0.3986","3M_5":"0.4174","3M_8":"0.4664","11_1":"1.3473","12_1":"4.3238","13_1":"1.0380","15_1":"2.1264","16_1":"0.3890","18_1":"0.6249","19_1":"1.3016","21_1":"0.8563","22_1":"1.0852","29_1":"1.2712","2_1":"0.9965","23_1":"0.6015","25_1":"1.2090","26_1":"0.8416","28_1":"2.9405","30_1":"1.1482","3_1":"1.2937","34_1":"1.5876","6_1":"1.1172","7_1":"1.0244","9_1":"1.2320","20_1":"0.9391","32_1":"0.2692","10_1":"0.7743","1_1":"0.9992","14_1":"0.8224","17_1":"1.1560","24_1":"1.1581","27_1":"0.8696","33_1":"0.8827","4_1":"1.0049","5_1":"0.7959","8_1":"1.7203","8_1A":"1.9136"},{"Metabolite":"2-hydroxypyridine","3M_2":"0.7190","3M_20":"1.1716","3M_23":"1.0718","3M_26":"1.2630","3M_28":"1.2288","3M_30":"2.4652","3M_34":"1.6602","3M_6":"1.0393","3M_7":"1.2006","3M_9":"0.9472","3M_10":"0.8550","3M_14":"1.0150","3M_17":"0.7939","3M_24":"1.5166","3M_27":"1.5677","3M_33":"2.1665","3M_4":"0.7777","3M_5":"0.9877","3M_8":"0.9884","11_1":"0.6046","12_1":"0.3361","13_1":"0.8921","15_1":"0.6067","16_1":"1.3441","18_1":"0.7394","19_1":"0.6493","21_1":"1.3447","22_1":"0.8134","29_1":"0.9194","2_1":"1.0016","23_1":"1.1908","25_1":"0.2197","26_1":"0.4290","28_1":"0.6425","30_1":"0.8507","3_1":"0.4554","34_1":"0.7021","6_1":"0.7554","7_1":"0.4965","9_1":"0.8166","20_1":"1.0392","32_1":"1.0686","10_1":"0.5121","1_1":"0.7768","14_1":"1.2072","17_1":"0.9558","24_1":"1.5494","27_1":"0.8529","33_1":"1.7241","4_1":"0.6194","5_1":"1.1924","8_1":"1.1817","8_1A":"1.0752"},{"Metabolite":"3-AIB (a-amino[1-(14)C]isobutyric acid)","3M_2":"1.4075","3M_20":"0.4856","3M_23":"0.6095","3M_26":"1.5564","3M_28":"1.2780","3M_30":"1.4054","3M_34":"0.4379","3M_6":"0.7342","3M_7":"1.7727","3M_9":"1.6023","3M_10":"2.5394","3M_14":"0.9647","3M_17":"0.7443","3M_24":"0.8738","3M_27":"1.3842","3M_33":"1.2538","3M_4":"1.3107","3M_5":"1.5651","3M_8":"1.9159","11_1":"0.3392","12_1":"1.5518","13_1":"0.9825","15_1":"1.1494","16_1":"0.8827","18_1":"0.6962","19_1":"1.1169","21_1":"0.3179","22_1":"0.4473","29_1":"0.3661","2_1":"0.4166","23_1":"0.3553","25_1":"0.5767","26_1":"0.4247","28_1":"1.0360","30_1":"0.9144","3_1":"1.1068","34_1":"1.1609","6_1":"0.5583","7_1":"0.6242","9_1":"1.3882","20_1":"0.4278","32_1":"0.6885","10_1":"1.7649","1_1":"0.6789","14_1":"0.8538","17_1":"1.3679","24_1":"1.1672","27_1":"1.1139","33_1":"1.1485","4_1":"1.5097","5_1":"1.1241","8_1":"0.4223","8_1A":"0.4790"},{"Metabolite":"3-HB (3-hydroxybutyric acid)","3M_2":"1.1499","3M_20":"0.5836","3M_23":"0.6087","3M_26":"1.4039","3M_28":"1.1441","3M_30":"1.2484","3M_34":"0.6594","3M_6":"0.9124","3M_7":"1.6621","3M_9":"1.4655","3M_10":"2.3938","3M_14":"0.8728","3M_17":"0.7198","3M_24":"0.8805","3M_27":"1.2656","3M_33":"1.0761","3M_4":"1.1477","3M_5":"1.3467","3M_8":"1.6905","11_1":"0.5479","12_1":"1.3454","13_1":"0.8977","15_1":"1.1421","16_1":"0.9093","18_1":"0.7306","19_1":"1.1372","21_1":"0.4517","22_1":"0.6879","29_1":"0.6738","2_1":"0.6675","23_1":"0.5492","25_1":"0.7331","26_1":"0.6643","28_1":"1.0847","30_1":"0.9610","3_1":"1.0051","34_1":"1.1681","6_1":"0.5915","7_1":"0.7876","9_1":"1.2749","20_1":"0.6313","32_1":"0.7178","10_1":"1.6998","1_1":"0.6343","14_1":"0.8291","17_1":"1.2935","24_1":"1.0230","27_1":"1.0511","33_1":"1.0541","4_1":"1.4056","5_1":"1.1647","8_1":"0.6659","8_1A":"0.5875"},{"Metabolite":"Acetate","3M_2":"1.9563","3M_20":"0.4411","3M_23":"0.2794","3M_26":"2.1482","3M_28":"1.6576","3M_30":"1.8673","3M_34":"0.2817","3M_6":"0.5428","3M_7":"1.9509","3M_9":"1.6945","3M_10":"2.9076","3M_14":"0.4451","3M_17":"0.6186","3M_24":"0.3900","3M_27":"1.7503","3M_33":"1.8677","3M_4":"1.6966","3M_5":"2.3235","3M_8":"2.2607","11_1":"0.1532","12_1":"1.4426","13_1":"1.3412","15_1":"1.5850","16_1":"0.3944","18_1":"0.3559","19_1":"0.4474","21_1":"0.1956","22_1":"0.9591","29_1":"0.2670","2_1":"0.4747","23_1":"0.2968","25_1":"0.5582","26_1":"0.3694","28_1":"0.5064","30_1":"1.4149","3_1":"0.4506","34_1":"1.5110","6_1":"0.5044","7_1":"0.5056","9_1":"0.4764","20_1":"1.3682","32_1":"0.1722","10_1":"2.3560","1_1":"0.2017","14_1":"0.3443","17_1":"0.7587","24_1":"1.3599","27_1":"1.5737","33_1":"0.4662","4_1":"1.9040","5_1":"0.4928","8_1":"0.3149","8_1A":"0.3978"},{"Metabolite":"Acetoacetate","3M_2":"1.6393","3M_20":"0.5711","3M_23":"0.3178","3M_26":"1.8255","3M_28":"1.3536","3M_30":"1.4262","3M_34":"0.5277","3M_6":"0.8010","3M_7":"1.6949","3M_9":"1.3185","3M_10":"2.2888","3M_14":"0.4472","3M_17":"0.5524","3M_24":"0.8587","3M_27":"1.3361","3M_33":"1.4649","3M_4":"1.3653","3M_5":"1.8124","3M_8":"1.8126","11_1":"0.2314","12_1":"1.3225","13_1":"1.0025","15_1":"1.3633","16_1":"0.9308","18_1":"0.5153","19_1":"0.4531","21_1":"0.5023","22_1":"1.0154","29_1":"0.6320","2_1":"1.0134","23_1":"0.6472","25_1":"0.8671","26_1":"0.6425","28_1":"1.0039","30_1":"1.5595","3_1":"0.7405","34_1":"1.3961","6_1":"0.8289","7_1":"0.9295","9_1":"0.4044","20_1":"1.4201","32_1":"0.2776","10_1":"2.1087","1_1":"0.3080","14_1":"0.3586","17_1":"0.7365","24_1":"1.2339","27_1":"1.3467","33_1":"0.4978","4_1":"1.6211","5_1":"0.5029","8_1":"0.5410","8_1A":"0.6318"},{"Metabolite":"Acetone","3M_2":"1.1866","3M_20":"0.5184","3M_23":"0.4538","3M_26":"1.6081","3M_28":"1.3804","3M_30":"1.2966","3M_34":"0.4348","3M_6":"0.8365","3M_7":"2.1310","3M_9":"1.2258","3M_10":"2.0608","3M_14":"0.7253","3M_17":"0.4383","3M_24":"1.3976","3M_27":"0.9638","3M_33":"1.1806","3M_4":"1.0930","3M_5":"1.0880","3M_8":"1.8374","11_1":"0.2387","12_1":"2.6841","13_1":"0.6085","15_1":"0.9903","16_1":"0.7704","18_1":"0.2886","19_1":"0.4913","21_1":"1.0043","22_1":"0.4862","29_1":"0.4282","2_1":"0.5578","23_1":"1.0630","25_1":"0.6078","26_1":"0.5948","28_1":"0.9519","30_1":"1.2850","3_1":"1.4116","34_1":"0.8647","6_1":"0.5548","7_1":"0.8521","9_1":"0.5949","20_1":"1.1152","32_1":"0.2480","10_1":"2.1724","1_1":"0.8976","14_1":"0.5288","17_1":"0.8919","24_1":"1.9185","27_1":"0.9613","33_1":"0.6424","4_1":"1.1468","5_1":"0.6442","8_1":"1.2042","8_1A":"1.4426"},{"Metabolite":"Acetylsalicylic 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