Effect of mechanIcal circulatoRy Support ON Exercise Capacity aMong pAtieNts With Heart Failure

Study Overview
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Brief Summary
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This study will evaluate how the cardiovascular system interacts with mechanical hearts to provide blood flow to the body during exercise. Two aims are proposed: 1) to determine the impact of a mechanical heart on exercise pressor reflexes in heart failure patients; and 2) to define the primary determinant(s) of exercise capacity in heart failure patients before and after device implantation.

Official Title
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Effective Mechanical Circulatory Support on Exercise Capacity in Heart Failure

Conditions
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Heart Failure，Congestive

Participation Criteria
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Eligibility Criteria
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Advanced Heart Failure- Inclusion Criteria: Individuals with severely reduced left ventricular systolic function that are scheduled to undergo LVAD insertion Exclusion Criteria: uncontrolled diabetes with peripheral neuropathy (interferes with acquisition of MSNA signal) Individuals with clinical right ventricular failure, defined as moderate-severely reduced RV systolic function on echocardiography, or clinical evidence of RV failure (elevated jugular venous pressures, significant peripheral edema) Individuals with moderate-severe preexisting aortic insufficiency, as these patients will typically undergo a Park stitch at time of CF-LVAD insertion to permanently close the aortic valve and prevent worsening aortic insufficiency; and Disorders that adversely influence exercise ability (e.g. arthritis, peripheral vascular disease, pulmonary disease) Mild Heart Failure - Inclusion Criteria: Individuals with medically managed left ventricular systolic function that are NOT scheduled to undergo LVAD insertion HF patients with ejection fraction <35-40% Exclusion Criteria: Individuals requiring systemic anticoagulation with vitamin-K antagonists or new/direct oral anticoagulants (NOAC/DOAC) Disorders that adversely influence exercise ability (e.g. arthritis, peripheral vascular disease, pulmonary disease) History of uncontrolled arrhythmias (e.g. ventricular tachycardia or nonsustained ventricular tachycardia). Healthy Controls - Inclusion Criteria: - Persons without a past medical history of cardiovascular disease or related disease (e.g. hypertension, diabetes, peripheral vascular disease, arrhythmias, stroke/transient ischemic attack) and are not taking any cardiac-related medications (e.g. antihypertensive medications) Exclusion Criteria: Individuals requiring systemic anticoagulation with vitamin-K antagonists or new/direct oral anticoagulants (NOAC/DOAC) Disorders that adversely influence exercise ability (e.g. arthritis, peripheral ascular disease).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Advanced Heart Failure<br>40 patients with advanced heart failure scheduled to undergo Left Ventricular Assist Device (LVAD) insertion will be recruited for testing. Test subjects will complete testing prior to, and following LVAD implantation. | |
| Healthy controls<br>10 age-matched healthy individuals will be recruited to establish normal/reference values. | |
| Mild Heart Failure<br>A second control group comprised of 10 age-matched individuals will be recruited to establish normal/reference values for individuals with mild, medically managed heart failure. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the sympathetic neural response. | The primary outcome will be the difference in the muscle sympathetic neural response (MSNA) to handgrip and post-exercise circulatory arrest (PECA) before and after Continuous-flow left ventricular assist device (CF-LVAD) insertion | 4 weeks prior to implantation and 6 months post implantation. | 
| Change in VO2. | The primary outcome will be the change in the VO2 (maximum rate of oxygen consumption) before and after CF-LVAD insertion. | 4 weeks prior to implantation and 6 months post implantation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the hemodynamic response. | This outcome will evaluate any difference in the hemodynamic response (heart rate and blood pressure) to handgrip and PECA before and after CF-LVAD | 4 weeks prior to implantation and 6 months post implantation. | 
| VO2 relationship and ventilatory threshold (1) | Cardiac output (Qc): VO2 relationship and ventilatory threshold before and after CF-LVAD insertion. | 4 weeks prior to implantation and 6 months post implantation. | 
| VO2 relationship and ventilatory threshold (2). | Determinants of Qc after CF-LVAD insertion (ie, contribution from device v. contribution from left ventricle). | 4 weeks prior to implantation and 6 months post implantation. | 
| VO2 relationship and ventilatory threshold (3). | Qc, VO2, ventilatory threshold and exercise capacity at increased pump speed. | 4 weeks prior to implantation and 6 months post implantation. | 
| VO2 relationship and ventilatory threshold (4). | Bloodflow to the periphery, as measured by transcranial Doppler to assess brain bloodflow during exercise/activity. | 4 weeks prior to implantation and 6 months post implantation. | 
| Oxygen uptake and utilization | Cerebral and musculoskeletal oxygen uptake by near-infrared spectroscopy | 4 weeks prior to implantation and 6 months post implantation. |