Ross for Valve Replacement in AduLts Trial

The primary outcome is the rate of survival free of life-threatening valve-related complications (major bleeding, stroke or systemic thromboembolism, valve thrombosis, and operated-on valve reintervention) over duration of follow-up. Assessment of this composite over time is particularly important, as the Ross procedure may show initial benefit secondary to thromboembolic and bleeding reduction, however should the technique show high late rates of reoperation as suggested in some observational literature, the effect magnitude may change significantly over time.

The outcome measures of the pilot trial, in order of importance, are:

To evaluate the capacity to enroll a mean of 6 patients per centre per year.

To determine the rate of compliance with randomization allocation.

To validate the proportion of mechanical (at least 65%) versus biological (at most 35%) valves in the conventional arm.

Perioperative (index surgery only) Intraoperative: After administration of protamine, delay of chest closure for bleeding > 500 mL/hr requiring packing and transfusion of more than 3 units red blood cells /whole blood.

Upon leaving OR to 48hrs postop (modified BARC type 4)

• Intracranial bleeding within 48hrs
• Reoperation after sternum closure for purpose of controlling bleeding or relief of tamponade
• Transfusion of ≥ 5 units packed red blood cells /whole blood in the 48hr period
• Chest tube output ≥ 2L in the first 24hr

Non-perioperative Per the International Society of Thrombosis and Hemostasis (ISTH) major bleeding definition.

Stroke is acute focal brain dysfunction due to a vascular cause lasting ≥ 24 hrs in the absence of brain imaging or requires evidence of acute stroke on brain imaging (if there is a stroke documented by CT or MRI or at autopsy, the duration of symptoms/signs may be < 24 hours). Stroke is divided into 3 types: ischemic stroke, hemorrhagic stroke, and undetermined stroke. If death occurs within 24 hours, the neurological deficit must persist up to the time of death.

Systemic arterial embolism is an abrupt vascular insufficiency associated with evidence of arterial occlusion in the absence of other likely mechanisms. Clinical signs/symptoms must be consistent with embolic arterial occlusion, there must be clear evidence of abrupt occlusion of a systemic artery, with at least one type of supporting evidence (surgical report indicating evidence of arterial embolism, pathological specimens related to embolism removal, imaging evidence consistent with arterial embolism, or autopsy report).

Valve thrombosis is defined as any thrombus not caused by infection attached to or near an operated valve that occludes part of the blood flow path, interferes with valve function, or is large enough to warrant treatment. Valve thrombus found at autopsy in a patient whose cause of death was not valve related or found at operation for and unrelated indication is to be counted as valve thrombosis.

Rate of valve reintervention Any surgical or percutaneous procedure that repairs, or otherwise alters or adjusts, or replaces a previously implanted prosthesis or valve.

Rate of mortality within 30 days post-operatively

The SF-36 is a health related quality of life questionnaire that measure eight health domains and each survey provides psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores. The domains are physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. The questionnaire is calibrated such that scored values of 50 represent the norm and higher scored values according to the scoring key represent a more favourable health state. A baseline score will be obtained prior to the patient's surgery and the SF-36 will be administered annually thereafter over the duration of patient follow-up.

Defined as any infection involving a valve on which an operation has been performed. The diagnosis is based on one or more of the following: 1) reoperation with evidence of abscess, paravalvular leak, pus, or vegetation confirmed as secondary to infection by histologic or bacteriologic studies; 2) autopsy findings of abscess, pus, or vegetation involving an operated-on valve; or 3) the meeting of Duke criteria for endocarditis.

Any surgical or percutaneous procedure that repairs, or otherwise alters or adjusts, or replaces a previously implanted prosthesis or valve in the aortic position.

Any surgical or percutaneous procedure that repairs, or otherwise alters or adjusts, or replaces a previously implanted prosthesis or valve in the pulmonary position.

Measured through echocardiography

Measured through echocardiography

Measured through echocardiography, categorized as mild, moderate, or severe

Measured through echocardiography, categorized as mild, moderate, or severe

Myocardial infarction (Fourth universal definition)

Occurring after 48 hrs post-operative, clinical evidence of acute myocardial injury with detection of a rise and/or fall of cTn values with at least one value above the 99th percentile URL and at least one of:

• Symptoms of myocardial ischemia
• New ischemic ECG changes
• Development of pathological Q waves
• Imaging evidence of new loss of viable myocardium or a new regional wall motion abnormality in a pattern consistent with an ischemic etiology; indication of a coronary thrombus by angiography or autopsy.

Acute renal failure By AKIN classification - An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of more than or equal to 0.3 mg/dl (≥ 26.4 μmol/l), a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for more than six hours).

The rate of patients requiring new renal replacement therapy within 30 days of surgery.

Surgical re-exploration of the mediastinum for bleeding

Deep mediastinal wound infection