A stepwise strategy integrating dynamic stress CT myocardial perfusion and deep learning-based FFRCT in the work-up of stable coronary artery disease.

OBJECTIVES: To validate a novel stepwise strategy in which computed tomography-derived fractional flow reserve (FFRCT) is restricted to intermediate stenosis on coronary computed tomography angiography (CCTA) and computed tomography myocardial perfusion imaging (CT-MPI) was reserved for vessels with gray zone FFRCT values. MATERIALS AND METHODS: This retrospective study included 87 consecutive patients (age, 58 ± 10 years; 70% male) who underwent CCTA, dynamic CT-MPI, interventional coronary angiography (ICA), and fractional flow reserve (FFR) for suspected or known coronary artery disease. FFRCT was computed using a deep learning-based platform. Three stepwise strategies (CCTA + FFRCT + CT-MPI, CCTA + FFRCT, CCTA + CT-MPI) were constructed and their diagnostic performance was evaluated using ICA/FFR as the reference standard. The proportions of vessels requiring further ICA/FFR measurement based on different strategies were noted. Furthermore, the net reclassification index (NRI) was calculated to ascertain the superior model. RESULTS: The CCTA + FFRCT + CT-MPI strategy yielded the lowest proportion of vessels requiring additional ICA/FFR measurement when compared to the CCTA + FFRCT and CCTA + CT-MPI strategies (12%, 22%, and 24%). The CCTA + FFRCT + CT-MPI strategy exhibited the highest accuracy for ruling-out (91%, 84%, and 85%) and ruling-in (90%, 85%, and 85%) functionally significant lesions. All strategies exhibited comparable sensitivity for ruling-out functionally significant lesions and specificity for ruling-in functionally significant lesions (p > 0.05). The NRI indicated that the CCTA + FFRCT + CT-MPI strategy outperformed the CCTA + FFRCT strategy (NRI = 0.238, p < 0.001) and the CCTA + CT-MPI strategy (NRI = 0.233%, p < 0.001). CONCLUSIONS: The CCTA + FFRCT + CT-MPI stepwise strategy was superior to the CCTA + FFRCT strategy and CCTA+ CT-MPI strategy by minimizing unnecessary invasive diagnostic catheterization without compromising the agreement rate with ICA/FFR. CLINICAL RELEVANCE STATEMENT: Our novel stepwise strategy facilitates greater confidence and accuracy when clinicians need to decide on interventional coronary angiography referral or deferral, reducing the burden of invasive investigations on patients. KEY POINTS: • A stepwise CCTA + FFRCT + CT-MPI strategy holds promise as a viable method to reduce the need for invasive diagnostic catheterization, while maintaining a high level of agreement with ICA/FFR. • The CCTA + FFRCT + CT-MPI strategy performed better than the CCTA + FFRCT and CCTA + CT-MPI strategies. • A stepwise CCTA + FFRCT + CT-MPI strategy allows to minimize unnecessary invasive diagnostic catheterization and helps clinicians to referral or deferral for ICA/FFR with more confidence.

Dapagliflozin alleviates right heart failure by promoting collagen degradation by reducing ROS levels.

BACKGROUND: Right ventricular (RV) fibrosis is an important pathological change that occurs during the development of right heart failure (RHF) induced by pulmonary hypertension (PH). Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been shown to play a major role in left heart failure, but it is unclear whether it has a positive effect on RHF. This study aimed to clarify the effect of DAPA on PH-induced RHF and investigate the underlying mechanisms. METHODS: We conducted experiments on two rat models with PH-induced RHF and cardiac fibroblasts (CFs) exposed to pathological mechanical stretch or transforming growth factor-beta (TGF-ß) to investigate the effect of DAPA. RESULTS: In vivo, DAPA could improve pulmonary hemodynamics and RV function. It also attenuated right heart hypertrophy and RV fibrosis. In vitro, DAPA reduced collagen expression by increasing the production of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). Additionally, DAPA was found to reduce reactive oxygen species (ROS) levels in CFs and the right heart in rats. Similar to DAPA, the ROS scavenger N-acetylcysteine (NAC) exerted antifibrotic effects on CFs. Therefore, we further investigated the mechanism by which DAPA promoted collagen degradation by reducing ROS levels. CONCLUSIONS: In summary, we concluded that DAPA ameliorated PH-induced structural and functional changes in the right heart by increasing collagen degradation. Our study provides new ideas for the possibility of using DAPA to treat RHF.