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Background Novel techniques to enhance cardiac function beyond pharmacological treatments are limited and even drug-based improvements in diastolic function, in clinical trials so far, have been minimal.Aim Our aim was to test the physiological and potential therapeutic effects of Photobiomodulation (PBM) on cardiac diastolic function. Utilising a PBM laser device guided by cardiac ultrasound to target and measure changes in E/A ratio. PBM has the theoretical capability to excite cardiac mitochondrial electron transport chain complexes and improve ATP generation. Therefore, providing increased energy production for the active myocardial process of diastolic relaxation.Methods The PBM laser device used was the THOR Giant Laser Cluster (THOR Photomedicine LTD, UK), A hand-held unit comprising 80 × 810 nm, 200 mWatt laser diodes (total output: 16 Watts) arranged in a 100 cm 2 active area (14.6 × 6.9 cm). Each laser diode produced a peak irradiance of 2 Watts/cm2 when applied in contact with the skin over the cardiac apex, located in the 5th intercostal space at the mid-axillary line and the left parasternal line. Treatment duration was 2 x 30 seconds. The energy delivered per laser diode was 6 Joules, with a fluence of 60 Joules/cm2 per diode. The total energy delivered (across all diodes) was 480 Joules. The average surface irradiance (total power divided by active area) was 160 mWatts/cm2, yielding an average surface fluence of 4.8 Joules/cm2. The E/A ratio was measured using echocardiographic ultrasound doppler at baseline and after treatment in cm/sec in 5 healthy volunteers and 1 patient with known prior diastolic dysfunction.Results Only one healthy volunteer, who partakes in daily PBM (and had already that day) had a high normal E Velocity and E/A ratio, that did not improve significantly post treatment (subject 3). One healthy volunteer had unknown existing diastolic dysfunction but this improved, as did the known diastolic dysfunction subject (Subjects 5 and 6). The other three normal volunteers also experienced gains in measured E velocity, which tended to exceed that seen in A velocity. Overall, the mean increase in E velocity was 18cm/s with the average pre-treatment E velocity being 57cm/s, increasing to a mean post treatment velocity of 75cm/s. This suggests an impressive mean 32% increase in early passive diastolic filling. For reference, the improvements seen in drug trials so far (SGLT2i and MRA) are in the order of 5-10%.Conclusion We have performed the first in man, pilot study, of echocardiography targeted, high quality, PBM of the heart muscle. This has confirmed a significant >30% mean increase in E velocity values and improvements in E/A ratios. Subjects with existing diastolic dysfunction were improved to a point of no longer meeting the criteria for this pathophysiology. The enhanced early ventricular filling, increasing end-diastolic volume (EDV) and stroke volume (SV), via the Frank-Starling mechanism, could lead to a potential greater cardiac output (CO) - without additional heart rate increases. Further larger and more robust studies are required in this exciting new field of Cardiovascular Phototherapeutics. Significant physiological gains appear possible both for those with existing cardiac pathology and the healthy athlete too.Abstract 139 Figure 1