1-037 Therapeutic potential of the mitochondrial antioxidant mitoquinone (MitoQ) in the treatment of diabetic cardiomyopathy

Introduction Type 2 diabetes (T2D) is an independent risk factor for heart failure. T2D causes a cardiac energy deficient state with subclinical contractile dysfunction even with a normal left ventricular ejection fraction (LVEF). Impaired cardiac energetics contributes to cardiac dysfunction in T2D. Novel treatments targeting mitochondrial dysfunction may improve cardiac energetics and function in T2D. Impaired mitochondrial function is driven by oxidative stress, with increased levels of reactive oxygen species (ROS). Antioxidant depletion leads to increased ROS generation and impaired energy production. Mitoquinone is a mitochondrial-targeted antioxidant, scavenging ROS to reduce oxidative stress. Methods In this parallel arm, prospective randomized (1:1) open blinded end-point standard care controlled trial of 70 patients with T2D we examined if mitoquinone can improve energy status. To monitor treatment response we used phosphorus-magnetic resonance spectroscopy scans (31P-MRS) to measure cardiac phosphocreatine to ATP ratio (PCr/ATP) as an indicator of myocardial energetic status and cardiovascular magnetic resonance (CMR) to measure cardiac rest and dobutamine-stress systolic and diastolic function. The study consisted of 2 research visits over a 16-week period. Participants were randomised to either receive a 16-week course of MitoQ (mitoquinone mesylate 40 mg/day MitoQ Limited,Auckland,NZ) or receive no additional supplementation. Results 70 patients were recruited and 57 patients completed the study (3 patients due to claustrophobia, 3 patients had evidence of myocardial infarction on CMR, 2 patients did not tolerate dobutamine, 5 patients did not return for visit 2). The groups were matched for baseline demographics. Baseline 31P-MRS and CMR characteristics were also balanced (table 1). Average baseline LVEF was 6261,63%. Four months mitoquinone administration led to a significant improvement in rest PCr/ATP (1.581.41,1.74 to 1.781.65,1.91;P=0.028), and stress PCr/ATP (1.251.13,1.36 to 1.461.34,1.59;P=0.0099) with no significant difference seen in the standard care group (table 2, figure 1). Improvements in energetics were accompanied by significant increases in peak early diastolic strain rate (PEDSR) as a measure of diastolic function (0.840.75,0.93 to 0.990.85,1.14s-1;P=0.0084) in the MitoQ arm with no significant change in the control group (table 2). There were no significant changes in any of the other CMR parameters measured including perfusion or LVEF (figure 2). Conclusions Four-month mitoquinone supplementation increased rest and haemodynamic stress myocardial energetics index and diastolic function in patients with T2D patients. This was independent of any significant changes in glycaemic control. In this patient focused study our findings highlight the potential therapeutic benefit of the antioxidant mitoquinone for prevention of heart failure development in patients with T2D with subclinical disease.