IMR-Heart Trasplant Study

University Hospital Miguel Servet

Status

Enrolling

Conditions

Heart Transplant Rejection

Microvascular Resistance

Study type

Observational

Funder types

Other

Identifiers

NCT06656065

C.I. PI23/242

Details and patient eligibility

About

Endomyocardial biopsy (EMB) is the gold standard method to guide post-heart trasplant (HT) patients, as it represents the best tool to identify rejection in orthotopic HT. However, it is frequently repeated during the first year, with some variations depending on each center protocol and it is potentially associated with serious complications.Several studies have presented the association between acute allograft rejection, micro-vasculopathy and cardiac allograft epicardial vasculopathy (CAV). Index of microvascular resistance (IMR) measured early after HT has been significantly associated with the risk of acute cellular rejection (ACR). The aim of this study will be to evaluate if the use of IMR early after HT may improve the patients care after HT, by reducing the number of EMB.

Full description

Acute allograft rejection (ACR) is an important cause of mortality and re-transplantation in heart transplant (HT) patients, particularly during the first year. Endomyocardial biopsy (EMB) is the "gold standard" to guide post- HT treatment. EMB is repeatedly performed during the first year and is associated with complications that, despite infrequent, can be potentially serious. In order to avoid the inconveniences of EMB, non-invasive techniques have been studied to detect rejection. However, none of these techniques has been able to replace EMB. Index of microvascular resistance (IMR) is a specific physiological parameter to measure microvascular function. An increased index of microvascular resistance (IMR) measured early after HT has been associated with ACR, a higher all-cause mortality and adverse cardiac events regardless of epicardial vasculopathy. According to available data, no study has evaluated IMR impact on post-HT management (number of EMBs performed). The aim of this study will be to evaluate if the use of IMR early after HT may improve the patients care after HT, by reducing the number of EMB.

The IMR-HT study is a multicenter, prospective observational study that will include post-HT stable patients undergoing coronary physiological assessment in the first two months and one year. Assessment of IMR, coronary flow reserve (CFR) and fractional flow reserve (FFR) will be performed using the standard thermodilution technique. The left anterior descending coronary artery will be evaluated in all patients. Circumflex or right coronary artery could be additionally evaluated at operator's discretion. An intracoronary pressure and temperature sensor-tipped guidewire (Pressure Wire TM X guide- wire 0.014', Abbott, IL, USA) will be used to perform the measurements. The tip pressure sensor will be advanced into the mid-to-distal portion of the evaluated vessel. Baseline aortic pressure (Pa) and distal intracoronary pressure (Pd) will be obtained to calculate the resting index Pd/Pa. To measure the mean transit time (Tmn) under basal conditions, intracoronary administration of 3 mL of room-temperature saline will be manually injected three times in succession (3 mL/s). Then maximal hyperemia will be induced using adenosine iv (140 to 180 mg/kg/min) and three additional intracoronary room temperature saline boluses of 3 ml will be administered to determine the mean transit time at hyperemia (Tmnh). Finally, fractional flow reserve (FFR), coronary flow reserve (CFR) and IMR will be calculated using the software Coroventis Coroflow (Coroventis Abbott, Uppsala, Sweden).

Depending on IMR values obtained in the first two months, clinical status and the other complementary tests the physician could be able to modify the number of biopsies established in each center protocol. If the IMR is less than 15: the number of biopsies could be reduced or kept the same. No immunosuppressive therapy changes would be made. If the IMR is 15 or greater: the number of biopsies would be performed as usual per protocol, immunosuppressive therapy could be intensified or maintained the same.

Clinical conditions, laboratory findings and clinical events will be assessed at one month and one year. Data will be included in an online database specifically designed for the study on platform REDCap (Research Electronic Data Capture).Each center will specify the number of annual biopsies performed based on IMR values obtained between the first two months after HT.

A number will be assigned to each patient; their identity will not be disclosed in any case. All shared information will be anonymized. The principal investigator at each center will be responsible for keeping the data anonymized.Data will be processed in accordance with the protection legislation in force (Spanish Personal Data Protection and Guarantee of Digital Rights Act 3/2018, and Regulation (EU) 2016/679).

The study primary end point will be the number of EMB performed at one year. Other secondary endpoints include the association between IMR and mortality, ACR, cardiac failure, re-trasplantation and cardiac allograft vasculopathy. Patients will be followed for up to 5 years.

Enrollment

48 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Heart transplant patients >18 years.
Patients who have received and signed informed consent.

Exclusion criteria

Patients with hemodynamic instability after HT, including cardiogenic shock or severe coagulopathy.
Patients with acute cellular rejection before intracoronary physiological assessment.
Patients with bronchial asthma or bronchopathy with a positive bronchodilation test, which contraindicates the use of adenosine.
Patients with epicardial coronary lesions with a resting physiological index ≤0.89 or ≤0.80 at hyperemia.
Patients unlikely to cooperate or with inability or unwillingness to give informed consent.