The acute effects of glyceryl trinitrate (GTN) on exercise capacity in patients who have an implantable cardiac pump (LVAD)

Cardiopulmonary Test: • Cardiopulmonary exercise testing (CPET) will be performed on an upright bicycle ergometer using a ramp protocol, limited by fatigue. Resistance will be increased every 3 minutes. • Breath-by-breath expired gas analysis will be measured by indirect calorimetry using a calibrated metabolic analysis system • Ventilatory anaerobic threshold (VAT) will be determined as the breakpoint between the increase in the carbon dioxide output and VO2 (V-slope) or the point at which the ventilator equivalent for oxygen and end-tidal oxygen partial pressure curves reach their respective minimum values and began to rise. • The test will be interrupted when the participant can no longer maintain the exercise intensity, ideally after maximal respiratory exchange ratio is greater than or equal to 1.1. • VO2 peak will be calculated as the highest 30 second average VO2 recorded during the exercise test. • Test duration will be 10-15 minutes • Subjects will undergo 2 CPETs in in total, 7-70 days apart o First CPET with GTN (Group A) or placebo (Group B) o Second CPET with GTN (Group B) or placebo (GroupA) Echocardiogram: • All patients will undergo a transthoracic echocardiogram prior to the CPET to ensure their pump speed is optimised. The goals are to achieve a midline interventricular septum position, reduction in mitral regurgitation and intermittent aortic valve opening. Blinded 6MWT: It should be noted that the randomisation for this part of the study is independent from the CPET randomisation. Tests will be conducted according to the 2002 American Thoracic Society guidelines, performed on two separate days (7-28 days apart). The test should take approximately 15 minutes. Patients will perform a test with placebo and a test with GTN, in a randomised order. The test should take approximately 15 minutes. Patients will be consented for both the CPET tests and the 6MWTs. Patients will undergo all tests(CPETs and 6MWTs) or one of them, depending on their availability. 6MWTs with placebo: • Randomisation will take place prior to test start. • Subject and nurse responsible for supervising 6MWT will record BP, oxygen saturation. They should remain blinded to pump speed setting. • Responsible physician is to remain available for duration of 6MWT but must not be involved in the conduct of the test. • Subjects will receive a translingual placebo dose 5 minutes prior to test initiation • At the end of the 6 minutes, record the distance covered, heart rate, oxygen saturation and Borg Fatigue score. 6MWTs with GTN (performed on a different day): • Randomisation will take place prior to test start. • Data collected will be same as described above. • Subjects will receive 400mcg of translingual GTN 5 minutes prior to test initiation • This step of the study will only take place if the mean arterial pressure of the subject is less than 70mmHg. • Both 6MWTs will be separated by at least 48 hours from the CPETs Dispensing of study drug: • Participants will be randomized to study drug vs placebo after enrolment. The study drug (active and placebo) will be obtained from St Vincent’s Hospital as discussed with the Clinical Trials Unit. • A health care worker not directly involved with the study will be responsible for administering the drug/placebo. Patients and supervising physicians will be blind to the administered drug. • Subjects will receive either 400mcg of translingual GTN 5 minutes prior to test initiation or placebo, in a randomised order. The study drug (active and placebo) will be obtained from St Vincent’s Hospital pharmacy. The placebo component will be made from peppermint water, which has a similar taste to translingual GTN. The spray containers will not be identical. To account for this and maintain blinding, patients will be blindfolded prior to drug administration. The drug will be administered by a healthcare professional that is not directly involved with the study.