Cardiopulmonary Stress Testing (CPET) AlloSure Study

Study Overview
=================
Brief Summary
-----------------
Cell-free DNA does not vary significantly as a function of the activity of immunologically quiescent cardiac transplant recipients, despite the metabolic demands of the transplanted organ. (The implication of the null result would be that no restrictions to patient activity, nor modification of cardiac rehabilitation prescription, would be necessary to maintain proper test characteristics of AlloSure testing). In immunologically active cardiac transplant allografts, exercise prior to assay of donor-derived cell-free DNA can be used to increase the sensitivity of the AlloSure test. (The implication of this would be that the optimal time-frame for drawing an Allosure may actually be post-exercise, and that window will be characterized).

Detailed Description
-----------------
The specific research questioned aimed to be addressed with this proposed study are: i. Are dd-cfDNA levels in heart transplant recipients independent of recent cardiopulmonary exercise? More specifically, does the metabolic demand of maximal cardiopulmonary exercise in recent heart transplant recipients trigger a release of dd-cfDNA (if so, then what is the time course for resolution back to baseline?) ii. If dd-cfDNA does not release to any significant degree with cardiac allografts with short donor-ischemic time, does this test characteristic continue to hold for cardiac allografts transplanted after longer donor ischemic times? iii. In cardiac transplant recipients with medically stabilized, treated antibody-mediated rejection (AMR) and persistent dd-cfDNA elevation, does a discrete episode of maximal cardiometabolic activity trigger any additional elevation of dd-cfDNA, and again, with what time course?

Official Title
-----------------
AlloSure Test Characteristics in Immunologically Quiescent and Immunologically Active Heart Transplant Recipients: Does Maximal Cardiopulmonary Stress Testing Prior to Assay Preserve Test Specificity While Enhancing Sensitivity?

Conditions
-----------------
Heart Failure, Transplant; Failure, Heart

Intervention / Treatment
-----------------
* Behavioral: CPET exercise testing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Post-orthotopic heart transplant patients Exclusion Criteria: orthopedic, neurologic and/or any other limitations that do not allow for exercise testing on a treadmill or cycle ergometer; individuals who require supplemental oxygen or have current permanent tracheostomies will be excluded from this study; individuals who are discharged to a long-term acute care facility; skilled nursing facility or with palliative care or hospice care will be excluded; (e) inmates and pregnant women; (f) patients with antibody-mediate rejection that are not felt to be safe for cardiopulmonary stress testing.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| transplant recipients <1year without AMR<br>20 recent transplant recipients (<1 year) without antibody-mediated rejection (AMR); | Behavioral: CPET exercise testing<br>* The cardiopulmonary exercise testing (CPET) is done. EKG testing will be done as part of the CPET test. Allosure testing will be done at baseline and then at 1 hr, 4 hrs, 1 day, 7 days after CPET.<br>|
| 3 months post-heart transplant with AMR<br>• 7 transplant recipients, at least 3 months post-transplant, with antibody-mediated rejection | Behavioral: CPET exercise testing<br>* The cardiopulmonary exercise testing (CPET) is done. EKG testing will be done as part of the CPET test. Allosure testing will be done at baseline and then at 1 hr, 4 hrs, 1 day, 7 days after CPET.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Cell-free DNA (AlloSure) levels after maximal cardiopulmonary exercise | • Cell-free DNA (AlloSure) levels after maximal cardiopulmonary exercise | 10 days | 
| • Comparison of maximal oxygen consumption (VO2) | • Comparison of maximal oxygen consumption (VO2) | 10 days | 
| • Comparison of level of cell-free DNA | Comparison of level of cell-free DNA | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Time-dependent changes in high-sensitivity troponin-levels | • Time-dependent changes in high-sensitivity troponin-levels | 10 days |