Automatic assessment of collaterals physiology in chronic total occlusions by means of artificial intelligence.

BACKGROUND: Assessment of collaterals physiology in chronic total occlusions (CTO) currently requires dedicated devices, adds complexity, and increases the cost of the intervention. This study sought to derive collaterals physiology from flow velocity changes (ΔV) in donor arteries, calculated with artificial intelligence- aided angiography. METHODS: Angiographies with successful percutaneous coronary intervention (PCI) in 2 centers were retro- spectively analyzed. CTO collaterals were angiographically evaluated according to Rentrop and collateral connections (CC) classifications. Flow velocities in the primary and secondary collateral donor arteries (PCDA, SCDA) were automatically computed pre and post PCI, based on a novel deep-learning model to extract the length/time curve of the coronary filling in angiography. Parameters of collaterals physiology, Δcollateral-flow (Δfcoll) and Δcollateral-flow-index (ΔCFI), were derived from the ΔV pre-post. RESULTS: The analysis was feasible in 105 out of 130 patients. Flow velocity in the PCDA significantly decreased after CTO-PCI, proportionally to the angiographic collateral grading (Rentrop 1: 0.02 ± 0.01 m/s; Rentrop 2: 0.04 ± 0.01 m/s; Rentrop 3: 0.07 ± 0.02 m/s; p < 0.001; CC0: 0.01 ± 0.01 m/s; CC1: 0.04 ± ± 0.02 m/s; CC2: 0.06 ± 0.02 m/s; p < 0.001). Δfcoll and ΔCFI paralleled ΔV. SCDA also showed a greater reduction in flow velocity if its collateral channels were CC1 vs. CC0 (0.03 ± 0.01 vs. 0.01 ± 0.01 m/s; p < 0.001). For each individual patient, ΔV was more pronounced in the PCDA than in the SCDA. CONCLUSIONS: Automatic assessment of collaterals physiology in CTO is feasible, based on a deeplearning model analyzing the filling of the donor vessels in angiography. The changes in collateral flow with this novel method are quantitatively proportional to the angiographic grading of the collaterals.

Impact of dosing strategies on plasma concentrations of tenofovir: Implications in HIV pre-exposure prophylaxis in China.

BACKGROUND: Tenofovir disoproxil fumarate has been recommended for pre-exposure prophylaxis (PrEP) to prevent HIV infection. Several studies have shown short but potent intermittent PrEP could provide comparable protection to daily PrEP in men, suggesting such dosing strategy might be useful in Chinese as well. The objective of this study was to evaluate the impact of different dosing strategies on plasma concentrations of tenofovir. METHODS: An open label study in 40 Chinese healthy volunteers, randomized to receive the WHO-recommended dose of tenofovir (300mg) at four different dosing intervals: twice weekly for 4 weeks; once daily for 4 weeks with one missing dose in weeks 2-4; once daily for 4 weeks with two missing doses in weeks 2-4; and once every other day for 12 days. Plasma samples were collected at pre-dose, weekly trough and 24h post last dose and assayed using HPLC-UV. RESULTS: The tenofovir trough concentrations were below the lower limit of quantification with the twice weekly regimen. The trough concentrations (24h dosing interval) at the steady state were 51.7±12.1ng/ml and 53.5±13.8ng/ml (mean±SD) in the once daily groups. Missing doses, once or twice weekly, had no significant impact on trough concentrations. Prolongation of dosing interval to 48h resulted with concentrations at 24h and 48h (trough) of ∼40 and 20ng/ml, respectively. CONCLUSIONS: Intermittent tenofovir regimens resulted with remarkably low plasma concentrations in Chinese participants. Missing doses did not affect trough concentrations significantly.

Prognostic impact of diabetes mellitus and index of microcirculatory resistance in patients undergoing fractional flow reserve-guided revascularization.

BACKGROUND: The prognostic impact of diabetes mellitus (DM) with or without coronary microvascular dysfunction (CMD) in patients undergoing fractional flow reserve (FFR)-guided revascularization has not been clarified. We sought to investigate the clinical outcomes of patients undergoing FFR-guided revascularization according to the existence of DM and CMD. METHODS: A total of 283 patients with available FFR data as well as index of microcirculatory resistance (IMR) were selected from the 3 V FFR-FRIENDS study. CMD was defined as an IMR ≥25U. Patients were grouped according to the presence of DM and CMD into group A (DM-, CMD-), group B (DM-, CMD+), group C (DM+, CMD-), and group D (DM+, CMD+). The primary outcome was a major adverse cardiac event (MACE, a composite of myocardial infarction, ischemia-driven revascularization, and cardiac death) at 2 years. RESULTS: DM patients displayed a notably higher risk of MACEs in comparison with non-DM patients (HR 4.88, 95% CI 1.54-15.48, p = 0.003). MACEs at 2 years among the four groups were 2.2%, 2.0%, 7.0%, and 18.5%, respectively. Group D exhibited a significantly higher risk of MACEs as compared to group A (HR 8.98, 95% CI 2.15-37.41, p = 0.003). Multivariable regression analysis showed that the presence of DM and CMD was an independent predictor of a 2-year MACE (HR 11.24, 95% CI 2.53-49.88, p = 0.002), and integrating CMD into a model with DM increased discriminant ability (C-index 0.683 vs. 0.710, p = 0.010, integrated discrimination improvement 0.015, p = 0.040). CONCLUSION: Among the patients undergoing FFR-guided revascularization, those with DM and CMD were correlated with an augmented risk of MACEs. Integration of CMD improved risk stratification in predicting the occurrence of a MACE.