A Metabolomic Approach to Probing Myocardial Fuel Shifts in Human Heart Failure

Study Overview
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Brief Summary
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This proposal is designed to test the hypothesis that humans shift to reliance on ketone bodies as a cardiac fuel source during the development of HF. The investigator also propose that this shift to ketone utilization can be detected by metabolomic profiling of blood. Specific Aim 1: To determine if the failing human heart exhibits increased extraction of blood-borne ketone bodies. Ketone bodies will be measured in coronary sinus, arterial, and central venous blood samples to determine AV differences. The HF group will be comprised of patients undergoing cardiac resynchronization therapy with an implantable cardioverter-defibrillator. The Control group will be compromised of patients without evidence of structural heart disease who are undergoing catheter ablation for supraventricular tachycardia. Specific Aim 2: To determine whether blood samples from humans with HF display metabolomic signatures indicative of increased myocardial ketone body utilization. Quantitative targeted metabolomics will be performed on the samples described in Aim 1 to determine if metabolite markers (e.g. C4-OH acylcarnitine, acetylcarnitine, succinate) found to be associated with increased myocardial ketone body oxidation in animal models are increased in the human HF group compared to the controls.

Detailed Description
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After subjects agree to participate in this study and are scheduled to have cardiac resynchronization therapy, the research personnel will take 1 teaspoon of blood before and after the scheduled cardiac procedure for comparison. Once subjects agree to participate in this study and are scheduled to have a catheter ablation procedure, research personnel will take 1 teaspoon of blood during the scheduled cardiac procedure. These samples will be taken from catheters already placed during the scheduled cardiac procedure. Blood will be sent to a lab at the Sanford-Burnham Metabolomics Core Facility in Orlando, Florida for analysis.

Official Title
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A Metabolomic Approach to Probing Myocardial Fuel Shifts in Human Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Other: Blood Drawn


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing cardiac resynchronization therapy Undergoing sinus cannulation Exclusion Criteria: NYHA class II-IV heart failure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Heart failure subjects<br>Heart failure subjects undergoing cardiac resynchronization will have a blood drawn for this study. | Other: Blood Drawn<br>* Both groups will have 1 teaspoon of blood drawn for analysis.<br>|
| Heart arrhythmia patients<br>Heart arrhythmia patients undergoing ablation will have a blood drawn for this study. | Other: Blood Drawn<br>* Both groups will have 1 teaspoon of blood drawn for analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increased extraction of blood-borne ketone bodies | Ketone bodies will be measured in coronary sinus, arterial, and central venous blood samples to determine AV differences | 1 day | 
| Determine whether heart failure blood samples display metabolomic signatures | Quantitative targeted metabolomics will be performed on the samples described in Outcome 1 to determine if metabolite markers (e.g. C4-OH acylcarnitine, acetylcarnitine, succinate) found to be associated with increased myocardial ketone body oxidation in animal models are increased in the human HF group compared to the controls. | 1 day |