Background: Insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM) represents a predictor of coronary artery disease (CAD). However, how IR is able to impact the severity of coronary atherosclerosis in non-diabetic patients is unknown. Objectives. We investigated the relation between the IR and the extent and severity of coronary atherosclerosis in non-diabetic patients referred to coronary angiography (CA) Methods: Consecutive patients undergoing to CA for acute coronary syndromes or stable angina were analyzed. The IR was assessed by mean of the homeostasis model assessment of insulin resistance (HOMA-IR) whereas the SYNTAX score (SS) was used as index of the severity of coronary atherosclerosis Results: Overall, 126 patients were included, with a median SS of 12 (IQR 5.25–20.5). Patients were divided in four groups according to the distribution in quartiles of SS (SS1-2-3-4). A significant correlation between HOMA-IR and SS was observed, especially in women. A progressive increase of HOMA-IR was observed in parallel with the increasing severity (from SS1 to SS4) and extension (1-2-3-vessel disease) of coronary atherosclerosis. Multivariable analysis showed that the HOMA-IR was the strongest independent predictor of severe (SS4) and extensive (three-vessel disease) coronary atherosclerosis. Conclusion: Insulin resistance goes hand in hand with the extension and severity of coronary atherosclerosis in non-diabetic patients. The HOMA index is an independent predictor of three-vessel disease at CA. The HOMA index could be useful for risk stratification of CAD even in absence of T2DM.

Background: More and more heart failure (HF) patients aged ≥ 75 years undergo cardiac resynchronization therapy (CRT) device implantation, however the data regarding the outcomes and their predictors are scant. We investigated the mid- to long-term outcomes and their predictors in CRT patients aged ≥ 75 years. Methods: Patients in the Cardiac Resynchronization Therapy Modular (CRT MORE) Registry were divided into three age-groups: 80 years, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). Over long-term follow-up (1020 days (IQR 680-1362)) mortality was higher in patients ≥ 75 years than in the other two groups. Hospitalization and composite event rates were similar in patients ≥ 75 years and those aged 65–74 (9 vs. 11.8%; p = 0.26, and 26.7 vs. 20.5%; p = 0.06). Conclusion: Positive clinical response and hospitalization rates do not differ between CRT recipients ≥ 75 years and those aged 65–74. However, age > 80 years, COPD and CKD are predictors of worse outcomes.

Aims. The occurrence of ventricular arrhythmias (VAs) in ischemic heart disease (IHD) patients is related to the presence and extent of fibrotic/scar tissue. As coronary atherosclerosis is the underlying cause of myocardial ischemia and fibrosis, in IHD patients implanted with an implantable cardioverter defibrillator (ICD) we investigated the relation between the VA burden and the complexity of coronary atherosclerotic lesions. Methods and results. In IHD patients who underwent coronary angiography and ICD implant, the Syntax scores I and II (SSI-II), as index of the severity of the coronary atherosclerotic disease, and the occurrence of VA were assessed. Overall 144 patients were included (123 males). Of these 22 patients (15%) experienced at least one episode of VA (cycle length 298 ± 19 msec) that required ICD intervention. The number of episodes per patient and per year was 4 ± 6 and 2.8 ± 4, respectively. Patients that experienced a VA compared to those free from arrhythmic events did not have distinct baseline clinical characteristics except for a higher SS I and SS II (21 (IQR 13–38) vs. 16 (IQR 10–23); p = 0.037; and 50 (IQR 39–62) vs. 42 (IQR 34–50); p = 0.012). In the binary logistic regression analyses the SS I and II were the only independent predictors of VA occurrence. A higher SS II was also associated with an earlier time to first event (p = 0.005). Conclusion. Higher SS I-II scores reflect a more severe coronary atherosclerosis and are associated with a greater VA burden. Further studies are needed to better clarify the ability of SSI-II to stratify the risk of IHD patients to develop life-threatening VA.

Background: Cardiac Implantable Electronic Device (CIED) infections represent a critical health threat with potentially fatal consequences. The TauroPace™ is an innovative solution that contains taurolidine specifically formulated to eradicate environmental microbial contamination on the surface of CIEDs. To date, scarce data are available in literature about Taurolidine’s effect on preventing CIED infections. Aims: To investigate the ability of the TauroPace™ to reduce major CIED infections through 12 months follow-up in fragile patients such as heart failure (HF) patients. Methods: This prospective cohort study included patients with HF and an ejection fraction ≤ 35%, who were referred for de novo implantation, upgrading or battery replacement of Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy with defibrillator (CRT-D), to the EP labs of two tertiary care hospitals. Patients with previous CIED infections were excluded. During the procedures, the catheters were submerged in the TauroPace™ solution and the pocket was irrigated with taurolidine. Starting from the main risk factors for the development of CIED-related infections as identified in the literature (including individuals with heart failure, diabetes, chronic kidney disease, and those undergoing defibrillators implantation, especially upgrades or revisions procedure), we conducted a meta-analysis and meta-regression to evaluate the relationship between the treatment effect's magnitude and various predictors. To estimate the incidence of CIED infections in high-risk subgroups, we utilized the percentage of patients with diabetes, chronic renal failure, or those undergoing replacement, upgrade, or revision procedures, along with other risk factors for CIED infections, as continuous variables and we were able to modify our comparison parameters based on the real percentage of risk factors that we obtained. Results: The study included 69 consecutive patients (53 male [76.8 %], 34 ischemic [49,3 %], median [IQR] age 68 [59-73] years, 19 diabetic [27.5 %] and 34 [49.2 %] with chronic renal failure), of whom 39 (56.5 %) received ICD and 30 (43.5 %) CRT-D, with 28 (40.6 %) replacement procedures, 2 (2.9 %) upgrades, and 39 (57%) de novo implantations. During the one-year follow-up period, 1 [1.45 (Standard Error, SE 0.014) %] patient undergoing a CRT replacement developed an infection. The available data from the literature estimate an incidence rate of 6% (SE 0.0106) when considering a selected patient population with a very high risk of infection similar to our population. This is significantly higher than our cohort (z-score -2.5447, p value = 0.011). Conclusions: Taurolidine has yielded promising results, demonstrating a low incidence rate of infections within our cohort of high-risk patients, which is below that reported in the literature. Further data will be necessary to validate and confirm these initial findings.

Background: While sacubitril/valsartan (ARNi), gliflozins (or SGLT2i) and cardiac resynchronization therapy (CRT) are firmly recognized as cornerstones of therapy for heart failure with reduced ejection fraction (HFrEF), robust evidence validating the long-term efficacy of their combination remains elusive. The few data suggesting a synergistic advantage of these drugs alongside CRT have not rigorously considered their time-varying administration, leading to potential selection bias, since only patients with longer initial survival could commence these treatments. As a result, the literature to date lacks a comprehensive and persuasive demonstration of the additional survival benefits conferred by ARNi and gliflozins over CRT alone in HFrEF. Purpose: To evaluate the impact of ARNi and gliflozins on reducing cardiovascular and overall mortality among HFrEF patients undergoing CRT. Methods: Patients with heart failure and an ejection fraction ≤ 35%, who were referred for CRT-D implantation from 2015 to 2023, were retrospectively recruited for the study. These patients were grouped into two cohorts: those not receiving drugs (no drugs group) and those treated with ARNi and/or SGLT2i (ARNi/SGLT2i group). Importantly, ARNi and SGLT2i treatments were considered as time-dependent covariates in order to account for patients who initiated or discontinued therapy during follow-up. Results: The cohort included 183 ischemic and non-ischemic HFrEF patients (148 male [80.9 %], 113 ischemic [61.7 %], median [IQR] age 73 [65-80] years). 117 (74 %) patients started ARNi (61, 52.1 %), gliflozins (7, 6 %) or both drugs (49, 41.9 %) and were assigned to ARNi/SGLT2i group. During a median follow-up of 5.67 (CI 95 %, 5 – 6.5) years, 63 (34.4 %) patients died, of whom 47 (74.6 %) died of cardiovascular HF-related death. Specifically, 44 (of whom 35 (79 %) due to HF-related death) died in the no drugs group vs 19 (12 (63 %) due to HF-related death) in ARNi/SGLT2i patients. At univariable analysis (Panel A in the Figure), ARNi and/or SGLT2i treatments reduced all-cause (HR 0.59 [0.34-1.02], p = 0.056) and cardiovascular (HR 0.47 [0.24-0.92], p = 0.029) mortality. However, after multivariable adjustment for key covariates (1-year CRT response, age, atrial fibrillation, baseline LVEF, chronic obstructive pulmonary disease, glomerular filtration rate), the survival benefits of ARNi and SGLT2i use diminished, and the only factor strongly associated with reduced mortality risk remained 1-year positive response to CRT (Panel B). Conclusions: Despite their recognized therapeutic benefits, ARNi and SGLT2i have not demonstrated additional survival benefit compared to CRT alone in patients with HFrEF. A 1-year positive response to CRT remains the most significant prognostic factor. Further studies with larger sample sizes and extended follow-up periods are needed to confirm this hypothesis, also evaluating whether the timing of introduction of these medications may impact survival.