VALIDATION OF HEARTSBREATH TEST FOR HEART TRANSPLANT REJECTION

临床问题：全世界每年约有3,500人接受心脏移植。大多数心脏移植受者在手术后的前12个月内通过一系列肌内膜活检来监测器官排斥反应的发展。这个过程是侵入性的，痛苦的，并有潜在的危险。临床上需要一种能提供与肌内膜活检相同的关于心脏移植排斥反应的信息，但没有其侵入性、疼痛或危险的测试。临床问题的解决方案：Heartsbreath测试是一种本质安全，无痛，无创的呼吸测试，用于心脏移植排斥反应，采用氧化应激的挥发性生物标志物。在多中心临床研究中，Heartsbreath试验对3级心脏移植排斥反应（现在称为2 R级）具有敏感性和特异性。美国食品和药物管理局（FDA）批准心脏呼吸测试用于人道主义设备豁免（HDE）的临床使用。营销问题：尽管FDA已经批准该测试用于临床，但Heartsbreath测试尚未在临床实践中使用，因为保险公司尚未报销。由于其HDE状态，医疗保险尚未批准Heartsbreath测试的全国覆盖范围确定（NCD）。营销问题的解决方案：医疗保险现在通过其“以数据收集为覆盖条件的国家覆盖范围确定：以证据发展为覆盖范围”计划提供了一条心脏呼吸测试的保险报销途径。该程序通过开发和捕获额外的患者数据，为Heartsbreath测试提供了NCD的途径。实验计划：我们将验证Heartsbreath测试作为2 R级（以前称为3级）心脏移植排斥反应预测指标的准确性，以满足Medicare NCD要求。我们将对1,000名在过去12个月内接受过心脏移植的匿名患者进行一项横断面多中心研究。我们将对这些患者进行Heartsbreath测试，然后进行肌内膜活检，作为其常规临床护理的一部分，并比较两种测试的结果。本研究的长期目标是a。科学性：验证Heartsbreath试验作为心脏移植排斥反应呼吸试验B的准确性。商业：获得Medicare NCD以报销心脏呼吸测试，并在国内和国际上销售该测试。该研究的重要性：在临床实践中，Heartsbreath测试可以为心脏移植排斥反应提供完全安全和非侵入性的辅助测试，这将减少与肌内膜活检相关的疼痛和发病率，同时也降低了临床护理费用。 公共卫生相关性：心脏呼吸测试是FDA批准的心脏移植排斥反应呼吸测试，采用氧化应激的呼吸生物标志物。它可以为心脏移植排斥反应提供一种安全和非侵入性的辅助测试，这将减少与肌内膜活检相关的疼痛和发病率，并降低临床护理成本。我们将验证Heartsbreath测试作为2 R级心脏移植排斥反应的预测因子，以满足医疗保险的报销要求。

DESCRIPTION (provided by applicant): The clinical problem: Approximately 3,500 people worldwide now undergo heart transplantation every year. Most heart transplant recipients are monitored for the development of organ rejection with a series of endomyocardial biopsies during the first twelve months after operation. This procedure is invasive, painful, and potentially hazardous. There is a clinical need for a test to provide the same information about heart transplant rejection as an endomyocardial biopsy, but without its invasiveness, pain, or hazards. A solution to the clinical problem: The Heartsbreath test is an intrinsically safe, painless, and non-invasive breath test for heart transplant rejection that employs volatile biomarkers of oxidative stress. In multicenter clinical studies, the Heartsbreath test was sensitive and specific for Grade 3 heart transplant rejection (now known as Grade 2R). The Food & Drug Administration (FDA) approved the Heartsbreath test for clinical use with a Humanitarian Device Exemption (HDE). The marketing problem: Even though FDA has approved the test for clinical use, the Heartsbreath test is not yet employed in clinical practice because it is not yet reimbursed by insurers. Medicare has not approved a National Coverage Determination (NCD) of the Heartsbreath test because of its HDE status. A solution to the marketing problem: Medicare now offers a pathway to insurance reimbursement of the Heartsbreath test through its program "National Coverage Determinations with Data Collection as a Condition of Coverage: Coverage with Evidence Development". This program offers a pathway to an NCD for the Heartsbreath test by developing and capturing additional patient data. Experimental plans: We will validate the accuracy of the Heartsbreath test as a predictor of Grade 2R (formerly known as Grade 3) heart transplant rejection, in order to fulfill Medicare NCD requirements. We will perform a cross-sectional multicenter study of 1,000 anonymized patients who have received a heart transplant during the preceding 12 months. We will perform a Heartsbreath test on these patients prior to an endomyocardial biopsy performed as part of their regular clinical care, and compare the results of the two tests. The long-term aims of the research are a. Scientific: To validate the accuracy of the Heartsbreath test as a breath test for heart transplant rejection b. Commercial: To obtain Medicare NCD for reimbursement of the Heartsbreath test, and market the test nationally and internationally. The importance of the research: In clinical practice, the Heartsbreath test could provide a completely safe and non-invasive ancillary test for heart transplant rejection that would reduce the pain and morbidity associated with endomyocardial biopsy, while also reducing the costs of clinical care PUBLIC HEALTH RELEVANCE: The Heartsbreath test is an FDA-approved breath test for heart transplant rejection that employs breath biomarkers of oxidative stress. It could provide a safe and non-invasive ancillary test for heart transplant rejection that would reduce the pain and morbidity associated with endomyocardial biopsy, and also reduce the costs of clinical care. We will validate the Heartsbreath test as a predictor of Grade 2R heart transplant rejection in order to fulfill Medicare requirements for reimbursement.