The TFPI2-PPARγ axis induces M2 polarization and inhibits fibroblast activation to promote recovery from post-myocardial infarction in diabetic mice.

BACKGROUND: Diabetes mellitus is one of the causes of poor ventricular remodelling and poor cardiac recovery after myocardial infarction (MI). We previously reported that tissue factor pathway inhibitor-2 (TFPI2) was downregulated in response to hyperglycaemia and that it played a pivotal role in extracellular matrix (ECM) degradation and cell migration. Nonetheless, the function and mechanism of TFPI2 in post-MI remodelling under diabetic conditions remain unclear. Therefore, in the present study, we investigated the role of TFPI2 in post-MI effects in a diabetic mouse model. RESULTS: TFPI2 expression was markedly decreased in the infarcted myocardium of diabetic MI mice compared with that in non-diabetic mice. TFPI2 knockdown in the MI mouse model promoted fibroblast activation and migration as well as matrix metalloproteinase (MMP) expression, leading to disproportionate fibrosis remodelling and poor cardiac recovery. TFPI2 silencing promoted pro-inflammatory M1 macrophage polarization, which is consistent with the results of TFPI2 downregulation and M1 polarization under diabetic conditions. In contrast, TFPI2 overexpression in diabetic MI mice protected against adverse cardiac remodelling and functional deterioration. TFPI2 overexpression also inhibited MMP2 and MMP9 expression and attenuated fibroblast activation and migration, as well as excessive collagen production, in the infarcted myocardium of diabetic mice. TFPI2 promoted an earlier phenotype transition of pro-inflammatory M1 macrophages to reparative M2 macrophages via activation of peroxisome proliferator-activated receptor gamma. CONCLUSIONS: This study highlights TFPI2 as a promising therapeutic target for early resolution of post-MI inflammation and disproportionate ECM remodelling under diabetic conditions.

Temporal Trends and Early Outcomes of Transcatheter versus Surgical Mitral Valve Repair in Atrial Fibrillation Patients.

Objectives: To study trends of utilization, in-hospital outcomes, and short outcomes in patients undergoing transcatheter mitral valve repair (TMVR) vs. surgical mitral valve repair (SMVR) in atrial fibrillation (AF). Background: TMVR is a treatment option in inoperable or high-risk patients with mitral regurgitation (MR). AF is a common comorbidity of MR. Data comparing between TMVR and SMVR in MR patients with AF is lacking. Methods: The National Readmission Database from 2016 to 2019 was utilized to identify hospitalizations undergoing TMVR or SMVR with AF. Outcomes of interest included mortality, postoperative complications, length of stay, and 30-day readmission rate. Results: A total of 9,195 patients underwent TMVR and 16,972 patients underwent SMVR with AF; the number of AF undergoing TMVR was increasing from 1,342 in 2016 to 4,215 in 2019 and SMVR. The incidence of in-hospital mortality decreased from 2.6% in 2016 to 1.8% in 2019. We identified length of stay>5 days, dyslipidemia, cerebrovascular disease, heart failure with reduced ejection fraction, and urgent/emergent admissions as independent risk factors for in-hospital mortality. After matching, we included 4,680 patients in each group; the in-hospital death, transfusion, acute kidney injury, sepsis, stroke, and mechanical ventilation were lower in TMVR compared with SMVR. TMVR was associated with a similar rate of all-cause readmission at 30 days compared with SMVR. Conclusion: Patients with AF receiving TMVR have been increasing along with progressive improvement in in-hospital death and length of stay. Compared to SMVR, AF patients receiving TMVR had a lower rate of in-hospital death and postoperative complications.

Transcatheter versus surgical aortic valve replacement in patients with aortic regurgitation: A propensity-matched analysis.

This study aimed to analyze in-hospital and early-to-interim outcomes of pure aortic regurgitation (AR) using transcatheter aortic valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR). Background: Few studies have discussed and compared the safety and short-term prognosis of TAVR and SAVR in pure AR patients. As such, we looked to the National Readmissions Database (NRD) for records between 2016 and 2019 in order to identify patients diagnosed with pure AR who underwent SAVR or TAVR. We used the propensity score matching to minimize disparities between two groups. We included 23,276 pure AR patients: 1983 (8.5%) who underwent TAVR and 21,293 (91.5%) who underwent SAVR. We found 1820 matched pairs using propensity score matching. In the matching cohort, TAVR was associated with a low risk of in-hospital mortality. Although TAVR had lower incidences of 30-day all-cause readmission (hazard ratio (HR):0.73, 95% confidence interval (CI): 0.61-0.87; P < 0.01) and 6-month all-cause readmission (HR: 0.81, 95% CI: 0.67-0.97; P = 0.03), while TAVR had high incidences of 30-day permanent pacemaker implantation incidence (HR: 3.54, 95% CI: 1.62-7.74; P < 0.01) and 6-month permanent pacemaker implantation incidence (HR: 4.12, 95% CI: 1.17-14.4; P = 0.03).In conclusion, TAVR and SAVR had similar risks of hospital death and lower rates of 30-day and 6-month all-cause and cardiovascular readmission. But TAVR had a higher risk of permanent pacemaker implantation than SAVR in AR patients, suggesting that TAVR can be performed safely in pure AR patients.

Gender Differences in Age-Stratified Early Outcomes in Patients With Transcatheter Aortic Valve Implantation.

Few researchers have discussed the differences in gender between the age groups of patients who underwent transcatheter aortic valve implantation (TAVI). We searched the National Readmissions Database from 2012 to 2019 to identify adults who underwent TAVI. We studied hospital outcomes and short- to medium-term outcomes by age stratification (18 to 59, 60 to 69, 70 to 79, and 80 to 90 years) after TAVI and categorized by gender. We included 147,481 patients who underwent TAVI, and 54,802 pairs were matched using propensity score matching separately for each age group. Compared with men, women in all age groups had a similar rate of hospital death. Except the 18- to 59-year-old groups, female patients were less likely to undergo permanent pacemaker implantation and transfusion. Records of readmission at 30 days and 6 months were used as the follow-up outcome according to the presence or absence of readmission. Major adverse cardiovascular events (MACEs) were a composite of cardiovascular readmission, all-cause mortality during readmission, and stroke readmission. At the 30-day follow-up visit, there was no difference in the all-cause readmission and MACE between women and men in any group. At the 6-month follow-up visit, women in the 70- to 79-year-old and 80- to 90-year-old groups had a high risk of all-cause readmission. In conclusion, we reported that female patients have similar in-hospital death rates to male patients who underwent TAVI. During the 30-day follow-up visit, the all-cause readmission and MACE were not different in all age groups between men and women. At 6 months, women in the 70- to 79-year-old and 80- to 90-year-old groups had a higher risk of all-cause readmission.

Protective effect of ischaemic postconditioning combined with nicorandil on myocardial ischaemia‒reperfusion injury in diabetic rats.

BACKGROUND: The diabetic heart exhibits a high sensitivity to ischaemia/reperfusion (I/R) injury. Diabetes mellitus (DM) can affect the efficacy of cardioprotective interventions and reduce the therapeutic potential of existing treatment options. This study aimed to investigate the feasibility of shifting from monotherapy to combination therapy in diabetic myocardial I/R injury. METHODS: 6-8 week rats were randomized into 10 groups: sham, I/R, ischaemia postconditioning (I-Post), nicorandil (Nic), combination therapy (I-Post + Nic), DM sham, DM I/R, DM I-Post, DM Nic and DM I-Post + Nic. The extent of myocardial injury was clarified by measuring CK-MB and NO levels in plasma, ROS content in myocardial tissues, and TTC/Evans Blue staining to assess the area of myocardial infarction. Pathological staining of cardiac tissue sections were performed to clarify the structural changes in myocardial histopathology. Finally, Western blotting was performed to detect the phosphorylation levels of some key proteins in the PI3K/Akt signalling pathway in myocardial tissues. RESULTS: We confirms that myocardial injury in diabetic I/R rats remained at a high level after treatment with I-Post or nicorandil alone. I-Post combined with nicorandil showed better therapeutic effects in diabetic I/R rats, and the combined treatment further reduced the area of myocardial injury in diabetic I/R rats compared with I-Post or nicorandil treatment alone (P < 0.001), as well as the levels of the myocardial injury markers CK-MB and ROS (P < 0.001); it also significantly increased plasma NO levels. Pathological staining also showed that diabetic rats benefited significantly from the combination therapy. Further mechanistic studies confirmed this finding. The protein phosphorylation levels of PI3K/Akt signalling pathway in the heart tissue of diabetic I/R rats were significantly higher after the combination treatment than after one treatment alone (all P < 0.05). CONCLUSION: I-Post combined with nicorandil treatment maintains effective cardioprotection against diabetic myocardial I/R injury by activating the PI3K/Akt signalling pathway.