Exploring diastolic pressure ratio to fractional flow reserve discordance and a hypothesis on tailoring diastolic pressure ratio cut-off values to improve diagnostic accuracy in the mid- and distal-LAD.

Previous studies have identified a higher rate of discordance between non-hyperaemic pressure ratios and FFR in the LAD when compared to the other two coronary arteries. We hypothesised that in keeping with recently published data, we would identify a higher discordance rate between diastolic pressure ratio (DPR) and FFR in the LAD compared to the RCA or LCx. In our study, 12.7% of LAD lesions had discordant results compared with 2.4% of non-LAD lesions. This represents a statistically significant increased rate of discordance in LAD lesions compared to non-LAD lesions (p = 0.04986). Note was made of a tendency for non-proximal LAD lesions to be associated with false-positive DPR results in the borderline range (0.88 and 0.89). In a speculative, hypothesis generating post-hoc analysis, we found an improved diagnostic accuracy of DPR when the cut-off value for a positive DPR in the non-proximal LAD was changed to ≤0.87. It is fathomable that improvements in the diagnostic accuracy of DPR for FFR may be improved by tailoring DPR cut-offs to the location of the lesion assessed.

Carbamyl phosphate-dependent ATP synthesis catalyzed by formyltetrahydrofolate synthetase.

Formyltetrahydrofolate synthetase (formate:tetrahydrofolate ligase (ADP-forming), EC 6.3.4.3) from Clostridium cylindrosporum catalyzes phosphate transfer from carbamyl phosphate to ADP. This activity is lost when monovalent cations are removed and is recovered when K+ is added back. Carbamyl phosphate is an inhibitor of the formyltetrahydrolfolate synthetase forward reaction, and formate as well as phosphate inhibit the ATP synthesis reaction. Acetyl phosphate and phosphonoacetate are inhibitors of both reactions. The results of kinetic studies support the concept that carbamyl phosphate is an analog of the putative intermediate of the formyltetrahydrofolate synthetase reaction, formyl phosphate.