Improving Metabolic Health in Patients With Diastolic Dysfunction
Condition: Obesity; Heart Failure, Diastolic; Metabolic Syndrome
MeSH terms: Heart Failure, Diastolic; Metabolic Syndrome
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether 1 year of supervised exercise training in
      obese individuals at high risk for developing HF, incorporating high intensity interval
      training (HIIT) two to three times per week in conjunction with daily oral administration of
      omega-3 poly-unsaturated fatty acids will lead to reduction in visceral adiposity, regression
      of myocardial triglyceride levels and improvements in cardiac diastolic and vascular
      function.
    

Detailed description: 
      The global objective of this project is to test novel strategies to prevent obesity related
      abnormalities in diastolic function that may progress to heart failure with preserved
      ejection fraction (HFpEF). These include: a) identifying high risk individuals by using
      population derived imaging and blood biomarkers; and b) implementing novel exercise training
      and "nutri-ceutical" strategies in obese middle aged individuals with high amounts of
      visceral fat, an important risk factor in the development of heart failure and adverse
      cardiac remodeling.

      Prior work has demonstrated that: a) high levels of myocardial triglyceride content are
      associated with a smaller and less distensible left ventricle with reduced tissue relaxation
      rates compared to those with low levels and b) low fitness and high body mass index were the
      strongest predictors of elevated myocardial content. The consequences of excess visceral
      adiposity (intra- and retro-peritoneal adipose tissue) on cardiac remodeling suggest
      individuals with high visceral fat content and low fitness are at particularly high risk for
      heart failure.

      The primary objective of this project is therefore to identify high risk, sedentary, middle
      aged obese individuals with high visceral fat levels, and initiate an exercise program in
      conjunction with omega-3 fatty acid supplementation designed to reduce visceral adiposity and
      regress myocardial triglyceride accumulation. Findings from this aim would have enormous
      public health significance and establish a novel, practical exercise training program and
      "nutria-ceutical" strategy to reverse obesity related cardiovascular remodeling.

      Hypothesis:

      High aerobic exercise training in conjunction with daily omega-3 supplementation will reduce
      visceral myocardial triglyceride accumulation by reducing visceral adiposity. A reduction of
      myocardial fat will lead to improved LV structure and diastolic function by an approach that
      is not necessarily predicated on weight loss.

      Specific Aim:

      To test our hypothesis that reduction in myocardial triglyceride content will improve markers
      of diastolic function, we have designed a randomized, double blind, placebo controlled trial.
      We will study four groups of previously sedentary obese middle aged subjects at high risk for
      development of HF for one year with the following interventions: A) sedentary controls taking
      placebo; B) sedentary subjects taking omega-3 fatty acids; C) subjects undergoing high
      intensity aerobic exercise training while on placebo and D) subjects undergoing high
      intensity aerobic exercise training while taking omega-3 fatty acids. Subjects will be
      categorized as high risk and enrolled on the basis of elevated serum biomarkers (cTnT) and
      high visceral fat content (>2.5 kg). We will perform comprehensive non-invasive assessments
      of cardiovascular structure and systolic/diastolic function before and after 1 year of an
      exercise intervention involving high intensity intervals and omega-3 administration. We
      anticipate the combination of high intensity aerobic exercise in conjunction with high dose
      omega-3 supplementation will reduce visceral adiposity, decrease myocardial triglyceride
      content and improve markers of diastolic and vascular function.
    

Intervention name(s): High intensity exercise; Omega-3 fish oil; Yoga; olive oil capsules
Intervention type(s): Behavioral; Dietary Supplement; Behavioral; Dietary Supplement
Intervention description(s): Subjects will be randomized to the exercise groups will undergo 1 year aerobic exercise training comprised of high intensity exercise sessions 2-3 days per week. Sessions will be supervised remotely via heart rate monitors.; Subjects randomized to omega-3 fatty acids will take 2 grams total of omega-3 per day for 1 year.; Subjects randomized to yoga will undergo yoga training as a control to those randomized to high intensity aerobic exercise.; Subjects randomized to receive olive oil placebo will take 1 gram total of olive oil capsule per day.
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: 2x2 factorial design. Subjects are randomized to aerobic exercise or yoga as well as high dose omega-3 fatty acids or olive oil placebo.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment