SGLT2-inhibitors effects on the coronary fibrous cap thickness and MACEs in diabetic patients with inducible myocardial ischemia and multi vessels non-obstructive coronary artery stenosis

Background: Sodium-glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids' plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up. Methods: In a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis. Results: At 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p < 0.05). SGLT2-I users vs. Non-SGLT2-I users, as evaluated by OCT, evidenced the highest values of minimum FCT, and lowest values of lipid arc degree and macrophage grade (p < 0.05). At the follow-up end, SGLT2-I users vs. Non-SGLT2-I users had a lower rate of MACEs [n 12 (10.8%) vs. n 57 (22.1%); p < 0.05]. Finally, Hb1Ac values (1.930, [CI 95%: 1.149-2.176]), macrophage grade (1.188, [CI 95%: 1.073-1.315]), and SGLT2-I therapy (0.342, [CI 95%: 0.180-0.651]) were independent predictors of MACEs at 1 year of follow-up. Conclusions: SGLT2-I therapy may reduce about 65% the risk to have MACEs at 1 year of follow-up, via ameliorative effects on glucose homeostasis, and by the reduction of systemic inflammatory burden, and local effects on the atherosclerotic plaque inflammation, lipids' deposit, and FCT in Mv-NOCS patients with T2DM

ECG-gated CT angiography of the thoracic aorta: the importance of evaluating the coronary arteries

Aim: To evaluate the feasibility of coronary artery disease (CAD) evaluation using electrocardiogram-gated computed tomography CT of the thoracic aorta. Materials and methods: A total of 477 patients, who underwent CT angiography of the thoracic aorta, were included retrospectively. Dose\u2013length products (DLP) were recorded. Two blinded readers graded image quality of the coronary arteries on a three-point scale. Coronary artery stenosis has only been reported if considered significant, i.e., 6550%. The type of plaque responsible for the stenosis was considered. The normal distribution of the data was assessed using Shapiro\u2013Wilk and Anderson\u2013Darling tests. Results were expressed as means and standard deviations and percentages. Inter-reader agreements were analysed by calculating the intraclass correlation coefficient, and by using Cohen kappa statistics. Results: The mean DLP was 566\ub190.4 mGy 19cm, corresponding to an effective dose of 9.6\ub11.5 mSv. Five point three percent of asymptomatic patients were positive for CAD with stenosis 6550%. All patients with coronary stenosis presented with a soft plaque. Two anomalous coronary origins were found. The inter-reader agreement was excellent in defining both the quality of the examination and the degree of coronary stenosis (k=0.85). Conclusion: The opportunity to prove the presence of CAD in asymptomatic patients during a ECG-gated CT of the thoracic aorta can have an extremely important clinical impact, promoting the best therapeutic pathway for the patient. Therefore, coronary arteries should always be analysed carefully and reported in ECG-gated CT angiography of the thoracic aorta

Cardiac resynchronization therapy and its effects in patients with type 2 DIAbetes mellitus OPTimized in automatic vs. echo guided approach. Data from the DIA-OPTA investigators

Objectives: To evaluate the effects of cardiac resynchronization therapy (CRTd) in patients with type 2 diabetes mellitus (T2DM) optimized via automatic vs. echocardiography-guided approach. Background: The suboptimal atrio-ventricular (AV) and inter-ventricular (VV) delays optimization reduces CRTd response. Therefore, we hypothesized that automatic CRTd optimization might improve clinical outcomes in T2DM patients. Methods: We designed a prospective, multicenter study to recruit, from October 2016 to June 2019, 191 consecutive failing heart patients with T2DM, and candidate to receive a CRTd. Study outcomes were CRTd responders rate, hospitalizations for heart failure (HF) worsening, cardiac deaths and all cause of deaths in T2DM patients treated with CRTd and randomly optimized via automatic (n 93) vs. echocardiography-guided (n 98) approach at 12 months of follow-up. Results: We had a significant difference in the rate of CRTd responders (68 (73.1%) vs. 58 (59.2%), p 0.038), and hospitalizations for HF worsening (12 (16.1%) vs. 22 (22.4%), p 0.030) in automatic vs. echocardiography-guided group of patients. At multivariate Cox regression analysis, the automatic guided approach (3.636 [1.271\u201310.399], CI 95%, p 0.016) and baseline highest values of atrium pressure (automatic SonR values, 2.863 [1.537\u20136.231], CI 95%, p 0.006) predicted rate of CRTd responders. In automatic group, we had significant difference in SonR values comparing the rate of CRTd responders vs. non responders (1.24 \ub1 0.72 g vs. 0.58 \ub1 0.46 g (follow-up), p 0.001), the rate of hospitalizations for HF worsening events (0.48 \ub1 0.29 g vs. 1.18 \ub1 0.43 g, p 0.001), and the rate of cardiac deaths (1.13 \ub1 0.72 g vs. 0.65 \ub1 0.69 g, p 0.047). Conclusions: Automatic optimization increased CRTd responders rate, and reduced hospitalizations for HF worsening. Intriguingly, automatic CRTd and highest baseline values of SonR could be predictive of CRTd responders. Notably, there was a significant difference in SonR values for CRTd responders vs. non responders, and about hospitalizations for HF worsening and cardiac deaths. Clinical trial ClinicalTrials.gov Identifier NCT04547244