Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial.

BACKGROUND: Both transcatheter edge-to-edge repair (TEER) of mitral regurgitation or left atrial appendage closure (LAAC) require periprocedural anticoagulation with unfractionated heparin (UFH) that is administered either before or immediately after transseptal puncture (TSP). The optimal timing of UFH administration (before or after TSP) is unknown. The Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions trial (STOP CLOT Trial) was designed to determine if early anticoagulation is effective in reducing ischemic complications without increasing the risk of periprocedural bleeding. METHODS: The STOP CLOT trial is a multicenter, prospective, double-blind, placebo-controlled, randomized trial. A total of 410 patients scheduled for TEER or LAAC will be randomized 1:1 either early UFH administration (iv. bolus of 100 units/kg UFH or placebo, given after obtaining femoral vein access and at least 5 minutes prior to the start of the TSP) or late UFH administration (iv. bolus of 100 units/kg UFH or placebo given immediately after TSP). Prespecified preliminary statistical analysis will be performed after complete follow-up of the first 196 randomized subjects. To ensure blinding, a study nurse responsible for randomization and UFH/placebo preparation is not involved in the care of the patients enrolled into the study. The primary study endpoint is a composite of (1) major adverse cardiac and cerebrovascular events (death, stroke, TIA, myocardial infarction, or peripheral embolization) within 30 days post-procedure, (2) intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transesophageal echocardiography, or (3) occurrence of new ischemic lesions (diameter ≥4 mm) on brain magnetic resonance imaging performed 2 to 5 days after the procedure. The safety endpoint is the occurrence of moderate or severe bleeding complications during the index hospitalization. CONCLUSIONS: Protocols of periprocedural anticoagulation administration during structural interventions have never been tested in a randomized clinical trial. The Stop Clot trial may help reach consensus on the optimal timing of initiation of periprocedural anticoagulation. CLINICAL TRIALS REGISTRATION NUMBER: The study protocol is registered at ClinicalTrials.gov, identifier NCT05305612.

MicroRNA Expression in Patients with Coronary Artery Disease and Hypertension-A Systematic Review.

Coronary artery disease (CAD) and hypertension significantly contribute to cardiovascular morbidity and mortality. MicroRNAs (miRNAs) have recently emerged as promising biomarkers and therapeutic targets for these conditions. This systematic review conducts a thorough analysis of the literature, with a specific focus on investigating miRNA expression patterns in patients with CAD and hypertension. This review encompasses an unspecified number of eligible studies that employed a variety of patient demographics and research methodologies, resulting in diverse miRNA expression profiles. This review highlights the complex involvement of miRNAs in CAD and hypertension and the potential for advances in diagnostic and therapeutic strategies. Future research endeavors are imperative to validate these findings and elucidate the precise roles of miRNAs in disease progression, offering promising avenues for innovative diagnostic tools and targeted interventions.

Anti-Inflammatory Effect of Very High Dose Local Vessel Wall Statin Administration: Poly(L,L-Lactide) Biodegradable Microspheres with Simvastatin for Drug Delivery System (DDS).

Atherosclerosis involves an ongoing inflammatory response of the vascular endothelium and vessel wall of the aorta and vein. The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver. The aim of this study was to test a vessel wall local drug delivery system (DDS) using PLA microstructures loaded with simvastatin. Wistar rats were fed high cholesterol chow as a model. The rat vessels were chemically injured by repeated injections of perivascular paclitaxel and 5-fluorouracil. The vessels were then cultured and treated by the injection of several concentrations of poly(L,L-lactide) microparticles loaded with the high local HMG-CoA inhibitor simvastatin (0.58 mg/kg) concentration (SVPLA). Histopathological examinations of the harvested vessels and vital organs after 24 h, 7 days and 4 weeks were performed. Microcirculation in mice as an additional test was performed to demonstrate the safety of this approach. A single dose of SVPLA microspheres with an average diameter of 6.4 µm and a drug concentration equal to 8.1% of particles limited the inflammatory reaction of the endothelium and vessel wall and had no influence on microcirculation in vivo or in vitro. A potent pleiotropic (anti-inflammatory) effect of simvastatin after local SVPLA administration was observed. Moreover, significant concentrations of free simvastatin were observed in the vessel wall (compared to the maximum serum level). In addition, it appeared that simvastatin, once locally administered as SVPLA particles, exerted potent pleiotropic effects on chemically injured vessels and presented anti-inflammatory action. Presumably, this effect was due to the high local concentrations of simvastatin. No local or systemic side effects were observed. This approach could be useful for local simvastatin DDSs when high, local drug concentrations are difficult to obtain, or systemic side effects are present.

Interleukin-1ß Gene (IL1B) Polymorphism and Risk of Developing Diabetic Nephropathy.

Objective: Cytokines play an important role in the pathogenesis of type 2 diabetes (T2DM) and its complications. The aim of the study was to evaluate an association of the -511 (C/T) polymorphism in the IL1B gene with diabetic nephropathy (DN). Methods: The study population included 860 patients with T2DM (506 with diabetic nephropathy and 354 without nephropathy) as well as 505 healthy individuals. Genomic DNA was genotyped for the IL1B -511 (C/T) polymorphism using PCR-RFLP technique. Results: The IL1B -511 C/T polymorphism was genotyped in 860 T2DM patients with or without DN and 505 healthy individuals. The average age of patients was 65.3 years in DN+ and 62.2 years in DN- subgroups. The genotype distribution did not differ significantly between patients and controls. Only a tendency to a slight increase of T allele frequency was observed in patient group. Genotype and allele frequencies of -511 C/T polymorphism were compared in patients with DN and those without it. The minor allele (T) and homozygote TT frequencies were significantly different between subgroups. The T allele was more frequent in DN+ patients, with odds ratio 1.45 (95% CI 1.2-1.8), p = 0.0003. The TT genotype frequency was also higher in DN+, with OR 1.76 (96% CI 1.1-2.7), p = 0.01. Conclusion: In a studied population the -511 C/T polymorphism in the IL1B gene is associated with diabetic nephropathy in dialyzed T2DM patients. Further studies are required to confirm the clinical significance of this finding.

Does gender influence the outcome of ischemic heart disease?

Diseases of the cardiovascular system (myocardial infarction, stroke, heart failure, hypertensive heart disease, cardiomyopathy) account for 40% of all deaths in men and up to 49% of all deaths in women. For a long time it was thought that the clinical picture of ischemic heart disease in men and women was similar. Now, however, there are more reports suggesting that diverse manifestations of the symptoms of ischemic disease may be related to differences between sexes. The disparity between women and men is also evident in the diagnostic process, and various pathological mechanisms of cardiovascular diseases, in particular myocardial ischemia in men and women, affect the differences in the results of diagnostic tests. Vasomotor dysfunction is particularly frequent in women, as their coronary vessels are more sensitive to the catecholamines released during mental stress, resulting in spasm and ischemic myocardium. Moreover, a much lower dose of acetylcholine induced vasoconstriction, which indicates that women are more sensitive to this neurotransmitter. Therefore, coronary vasomotor disorders in the form of epicardial and microvascular dysfunction are more often seen in women. All these mentioned factors resulted in higher mortality and poorer quality of life of women suffering from ischemic heart disease.

The Usefulness of Intravascular Ultrasound and Optical Coherence Tomography in Patients Treated with Rotational Atherectomy: An Analysis Based on a Large National Registry.

BACKGROUND: Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been shown to improve the clinical outcomes of percutaneous coronary interventions (PCIs) in selected subsets of patients. AIM: The aim was to investigate whether the use of OCT or IVUS during a PCI with rotational atherectomy (RA-PCI) will increase the odds for successful revascularization, defined as thrombolysis in myocardial infarction (TIMI) 3 flow. METHODS: Data were obtained from the national registry of PCIs (ORPKI) maintained by the Association of Cardiovascular Interventions (AISN) of the Polish Cardiac Society. The dataset includes PCIs spanning from January 2014 to December 2021. RESULTS: A total of 6522 RA-PCIs were analyzed, out of which 708 (10.9%) were guided by IVUS and 86 (1.3%) by OCT. The postprocedural TIMI 3 flow was achieved significantly more often in RA-PCIs guided by intravascular imaging (98.7% vs. 96.6%, p < 0.0001). Multivariable analysis revealed that using IVUS and OCT was independently associated with an increased chance of achieving postprocedural TIMI 3 flow by 67% (odds ratio (OR), 1.67; 95% confidence interval (CI): 1.40-1.99; p < 0.0001) and 66% (OR, 1.66; 95% CI: 1.09-2.54; p = 0.02), respectively. Other factors associated with successful revascularization were as follows: previous PCI (OR, 1.72; p < 0.0001) and coronary artery bypass grafting (OR, 1.09; p = 0.002), hypertension (OR, 1.14; p < 0.0001), fractional flow reserve assessment during angiogram (OR, 1.47; p < 0.0001), bifurcation PCI (OR, 3.06; p < 0.0001), and stent implantation (OR, 19.6, p < 0.0001). CONCLUSIONS: PCIs with rotational atherectomy guided by intravascular imaging modalities (IVUS or OCT) are associated with a higher procedural success rate compared to angio-guided procedures.

Complex, high-risk, and indicated percutaneous coronary angioplasty in essentially calcified stented coronary lesions using excimer laser coronary atherectomy with contrast mix injection.

Introduction: Complex, coronary stenosis remains a technical challenge that may be responsible for in-stent restenosis and vessel thrombosis. Here we investigated the efficacy and safety of excimer laser coronary atherectomy (ELCA) with contrast mix injection for improving vessel wall stent apposition in undilatable, mostly calcified lesions. Aim: To assess ELCA with contrast mix injection in complex, stented, calcified coronary lesions. Material and methods: This prospective single-center observational study enrolled 52 consecutive patients (73 lesions), with suboptimal stents implanted in de novo lesions and lesions requiring in-stent restenosis (ISR) due to stent underexpansion using all available means to achieve an optimal result. Patients presenting with ST-segment elevation myocardial infarction were excluded. All patients underwent coronary angiography 6 months after ELCA with intravascular ultrasound or optical coherence tomography study. We used contrast media mixed with saline (25-75%) to supply maximum laser energy output when a standard approach was unsuccessful. Procedural success was defined as relative stent expansion of > 80% minimal stent area (MSA) divided by average reference lumen area. Results: Procedural success was achieved in all cases. The cross-sectional area measured in treated segment improved significantly from 2.9 (0.72) mm2 to 7.3 (0.79) mm2 after ELCA. The in-hospital device-oriented major adverse cardiac event (DOCE) rate was 9.6%. No vessel perforation occurred during ELCA. After 6 months, the DOCE rate was 13.4%, while the rate of target lesion revascularization (TLR) was 8.2%. Conclusions: This registry confirms the efficacy and safety of ELCA with contrast mix injection as a possible approach for stent expansion/ISR in failed PCI.

Chemotactic cytokine receptor 5 gene polymorphism: relevance to microvascular complications in type 2 diabetes.

We investigated the involvement of chemotactic cytokine receptor 5 (CCR5) gene polymorphism in microvascular complications of T2DM. All subjects were genotyped with the 59029 SNP in the CCR5 gene. The genotype/allele frequencies did not differ between T2DM patients and controls. Genotype distribution was compared in patients with and without complications (nephropathy, retinopathy and neuropathy). The frequency of A allele was significantly higher in patients with complications (OR for A allele 3.07, 95% CI 2.49-3.77). The A allele carriage was associated with diabetic nephropathy (OR 6.17, 95% CI 3.28-11.6). An association was observed between 59029 polymorphism and age at T2DM onset. The A allele was more frequent in early onset than in late onset patients. For AA homozygotes OR was 2.38 (1.19-4.76) and 2.26 (1.12-4.58) in complicated and uncomplicated subgroups, respectively. These results suggest that CCR5 gene polymorphism is associated with diabetic nephropathy in T2DM.

Volatile anesthetics reduce biochemical markers of brain injury and brain magnesium disorders in patients undergoing coronary artery bypass graft surgery.

OBJECTIVES: Neuropsychological disorders are some of the most common complications of coronary artery bypass graft (CABG) surgery. The early diagnosis of postoperative brain damage is difficult and mainly based on the observation of specific brain injury markers. The aim of this study was to analyze the effects of volatile anesthesia (VA) on plasma total and ionized arteriovenous magnesium concentrations in the brain circulation (a-vtMg and a-viMg), plasma matrix metalloproteinase-9 (MMP-9), and glial fibrillary acidic protein (GFAP) in adult patients undergoing CABG surgery. DESIGN: An observational study. SETTING: The Department of Cardiac Surgery in a Medical University Hospital. PATIENTS AND METHODS: Studied parameters were measured during surgery and in the early postoperative period. Patients were assigned to 3 groups: group O, patients who did not receive VA; group ISO, patients who received isoflurane; and group SEV, patients who received sevoflurane. RESULTS: Ninety-two patients were examined. CABG surgery increased MMP-9 and GFAP. The highest MMP-9, GFAP, and the most dramatic disorders in a-vtMg and a-viMg were noted in group O. CONCLUSIONS: Cardiac surgery increased plasma MMP-9 and GFAP concentrations. Changes in MMP-9, GFAP, and arteriovenous tMg and iMg were significantly higher in group O. Volatile anesthetics, such as ISO or SEV, reduced plasma MMP-9, GFAP concentrations, and disturbances in a-vtMg and a-viMg.

[Myocardial infarction in the course of ethylene glycol poisoning--a case report]. / Zawal serca w przebiegu zatrucia glikolem etylenowym--opis przypadku.

The following paper describes the case of the 59-year-old patient moved from Clinical Cardiology to the Centre of Clinical Toxicology because of severe ethylene glycol poisoning, which occurred in the course of myocardial infarction of inferior wall. Ethylene glycol concentration was 85 mg/dl, the blood pH - 6.9, troponin >50 ng/ml, CK-MB 297.1 U/L. ECG current of injury was found at the bottom of the wall cuts reflective reductions in section ST in leads I, aVL and the precordial leads. In the coronarography was RCA occlusion, OM critical stenosis and suspected mouth of LAD stenosis. RCA urgent angioplasty was performed with implantation of bare metal stents 5. In addition, toxicological treatment consisted of mechanical ventilation, hemodialysis, ethanol, and intensive medical care. On 19 day of hospitalization the patient in good general condition was discharged home.

Thalidomide, dexamethasone and lovastatin with autologous stem cell transplantation as a salvage immunomodulatory therapy in patients with relapsed and refractory multiple myeloma.

The treatment of patients with multiple myeloma usually includes many drugs including thalidomide, lenalidomide and bortezomib. Lovastatin and other inhibitors of HMG-CoA reductase demonstrated to exhibit antineoplasmatic and proapoptotic properties in numerous in vitro studies involving myeloma cell lines. We treated 91 patients with relapsed or refractory multiple myeloma with thalidomide, dexamethasone and lovastatin (TDL group, 49 patients) or thalidomide and dexamethasone (TD group, 42 patients). A clinical response defined of at least 50% reduction of monoclonal band has been observed in 32% of TD patients and 44% of TDL patients. Prolongation of overall survival and progression-free survival in the TDL group as compared with the TD group has been documented. The TDL regimen was safe and well tolerated. The incidence of side effects was comparable in both groups. Plasma cells have been cultured in vitro with thalidomide and lovastatin to assess the impact of both drugs on the apoptosis rate of plasma cells. In vitro experiments revealed that the combination of thalidomide and lovastatin induced higher apoptosis rate than apoptosis induced by each drug alone. Our results suggest that the addition of lovastatin to the TD regimen may improve the response rate in patients with relapsed or refractory myeloma.

Incidence, clinical correlates, timing, and consequences of acute thrombus formation in patients undergoing the MitraClip procedure.

BACKGROUND: Despite adequate heparinization, formation of fresh intracardiac thrombi during the MitraClip procedure was reported. AIMS: We aimed to evaluate the incidence and clinical consequences of intracardiac thrombus formation during the MitraClip device implantation. METHODS: Clinical data and transesophageal echocardiography findings obtained during MitraClip procedures in 100 consecutive patients (81 men; mean [SD] age, 67.8 [8.3] years) were reviewed. In all patients, a heparin bolus was given immediately after a successful transseptal puncture, and the activated clotting time above 250 seconds was maintained throughout the procedure. RESULTS: Thrombus formation was documented in 9 patients (9%). In 6 patients, thrombi formed on a transseptal needle/sheath (2 attached to the sheath in the right atrium and 4 on the sheath immediately after the puncture in the left atrium), and in 3 patients, on the MitraClip device in the left atrium (2 on a steerable guiding catheter and 1 on the clip delivery system). Overall, 6 thrombi (67%) formed prior to and 3 (33%) after heparin administration. All thrombi were transient and disappeared within minutes. No periprocedural ischemic stroke, transient ischemic attack, or other embolic complications were reported. Clinical characteristics were similar in patients with and without thrombi, except for lower left ventricular ejection fraction (LVEF; mean [SD], 23% [10%] and 30% [10%], respectively; P = 0.03). In-hospital death was reported in 6 patients: 2 with a visible thrombus and 4 without (P = 0.09). CONCLUSIONS: Transient thrombus formation is relatively common during the MitraClip procedure, especially in patients with low LVEF; however, acute clinical consequences are benign.

Atrial Fibrillation Ablation with Multipolar Phased-Radiofrequency Catheter: The Learning Curve Effect for Procedural Parameters, but not for the Long-Term Outcome.

BACKGROUND: Pulmonary vein isolation (PVI) is a routine treatment in atrial fibrillation (AF). Single-shot techniques were introduced to simplify the procedure. We analyzed time-dependent changes in procedural parameters, acute success, complication rates, and long-term outcomes during our initial experience with multipolar phased-radiofrequency (RF) ablation. Methods and Results: The first 126 consecutive patients (98 male; age: 58.8 ± 8.7 years) who underwent PVI with phased-RF ablation at our center were included in the study. Procedural parameters, complication rate, acute success and 12-month efficacy were compared in the first, second and third group of 42 consecutive patients. In all patients, 516/526 PVs were effectively isolated (98.1%), with no differences between the tierces (p = 0.67). Procedure (169.8 vs. 132.9 vs. 105.8 min, p < 0.0001), fluoroscopy (32.9 vs. 24.3 vs. 14.1 min, p < 0.0001) and left atrial dwell (83.0 vs. 61.9 vs. 51.4 min, p < 0.0001) times were significantly reduced with experience in tierces 1-3, respectively. In the 12-month follow-up, 60.3% of patients were arrhythmia-free with no differences between the tierces (p = 0.88). In multivariate analysis, the relapse in the blanking period (p < 0.0001), time from AF diagnosis (p = 0.004) and left atrial diameter (p = 0.012) were the only independent predictors of AF recurrence. CONCLUSIONS: The learning curve effect was demonstrated in procedural parameters, but not in the complication rate nor the long-term success of PVI with phased-RF technique. The relapse in the blanking period was the strongest predictor of treatment failure in long-time observation.

The efficiency of magnesium supplementation in patients undergoing cardiopulmonary bypass: changes in serum magnesium concentrations and atrial fibrillation episodes.

UNLABELLED: The purpose of the study was to analyse the effects of different forms of magnesium supplementation on its serum concentrations and the frequency of atrial fibrillation in patients undergoing coronary artery bypass graft surgery with extracorporeal circulation (ECC). One hundred and twenty adult patients were examined. All of them received intravenous infusions of MgSO4 during surgery and the early postoperative period (18 hours). Moreover, some of them received preoperative Mg supplementation. Therefore, patients were divided into six groups: A) patients, receiving an intravenous infusion 3.33 mg of MgSO4 per min; B) those receiving preoperative, oral Mg supplementation (OPS-Mg) and intravenous 3.33 mg of MgSO4 per min; C) patients receiving intravenous 6.66 mg of MgSO4 per min; D) patients receiving OPS-Mg and 6.66 mg of MgSO4 per min; E) patients receiving intravenous 10 mg of MgSO4 per min; F) those receiving OPS-Mg and 10 mg of MgSO4 per min. Additionally, all patients were divided into three groups: O (patients, who did not receive dopamine or dobutamine infusions), DOP (those receiving dopamine infusions in doses dependent on their clinical state) and DOB (those receiving dobutamine infusions in doses dependent on their clinical state). Total serum Mg concentrations (Mg(t)) were measured at five points: 1) 10 min before anaesthesia; 2) 10 min after ECC; 3) 10 min after surgery, 4) in the morning of postoperative day 1, 5) in the morning of postoperative day 2. The data were analyzed statistically; values at the first measurement points were considered as baseline. In group A, Mg(t) decreased at time points 2, 3, 4. Similar changes were observed in group B, however, in both groups Mg(t) returned to the baseline value at time point 5. In groups C and D, Mg(t) decreased at point 2 and 3, whereas in groups E and F it was increased during all the study period. The changes in Mg(t) were slightly less in patients receiving OPS-Mg, these patients had a significantly higher Mg(t) at time point 1. Mg(t) decreased in the O, DOP and DOB groups at measurement points 2 and 3. Moreover, the lowest Mg(t) was observed in the DOP group. Atrial fibrillation (AF) was noted in 33 patients (27.5%). The highest percentage of patients with AF during the early postoperative days was observed in groups A and B (45%). In groups C, D, E and F, AF was detected in 25%, 20%, 20% and 10% of patients, respectively. The incidence of AF was significantly higher in groups A and B compared to the other groups. Moreover, episodes of AF were rarer in patients receiving preoperative, oral Mg supplementation. CONCLUSIONS: 1) ECC resulted in a decrease in Mg(t); 2) Mg infusion at the dose of 3.33 mg/min had little effect for the prevention of postoperative AF; 3) the infusion of 10 mg/min of MgSO4 maintained the level of Mg(t) during CABG and most effectively reduced AF; 4) OPS-Mg played a beneficial role in Mg(t) disturbances during CABG; 5) dopamine caused the most severe disturbances in serum Mg(t) concentration.

The effect of Toll-like receptor 4 gene polymorphism on vascular complications in type 2 diabetes patients.

OBJECTIVE: The aim of our study was to assess the association between the TLR4 Asp299Gly polymorphism and vascular complications in patients with type 2 diabetes. METHODS: We examined 1090 patients with T2DM and 716 healthy controls. All subjects were genotyped for the Asp299Gly polymorphism by polymerase chain reaction (PCR) and restriction analysis. RESULTS: The genotype frequencies of the Asp299Gly polymorphism were similar in T2DM patients and controls (p=0.512 and 0.311, respectively). The polymorphism was analyzed in subgroups of patients with macro- and microvascular complications. The distribution of genotypes was significantly different between patients with CVD and those without CVD. A significant increase of G allele frequency was observed in CVD+ patients, with odds ratio 2.06 (1.27-3.34), p=0.0035. The same effect was found when patients with diabetic retinopathy were compared with those without it (OR for G allele 2.12, 95% CI 1.43-3.12, p=0.0002). There were no statistically significant differences in genotype distribution between patients with diabetic nephropathy or neuropathy and those without these complications. CONCLUSIONS: The results of our study demonstrated that the G allele of the Asp299Gly polymorphism of the TLR4 gene is associated with increased risk of cardiovascular disease and diabetic retinopathy in type 2 diabetes patients.

Economic impact of contrast-induced acute kidney injury associated with invasive cardiology: role of iso-osmolar contrast media in Germany, Italy, Poland, and Spain.

OBJECTIVE: Iso-osmolar Iodixanol is associated with a lower rate of contrast-induced acute kidney injury (CI-AKI) in patients at increased risk compared to low-osmolar contrast media (LOCM). The aim of this study was to assess the financial consequences of CI-AKI risk reduction in patients undergoing coronary angiography (CA) with or without percutaneous coronary intervention (PCI) in German, Italian, Polish and Spanish hospitals. METHODS: This budget impact analysis (BIA) compared a scenario with iodixanol to a scenario without, where only LOCM were used, in patients at increased risk of CI-AKI over a 3-year horizon. A meta-analysis based on a systematic review observed a lower rate of CI-AKI with iodixanol compared to LOCM (Risk Reduction = 0.46) in patients with underlying impaired renal function (serum creatinine ≥1.6 mg/dl and estimated glomerular filtration rate ≤50 ml/min/1.73 m(2)). Contrast media and CI-AKI hospitalization costs were included in the analysis and unit costs were obtained from published literature, official sources or, when available, from hospital data. In the absence of country-specific data, resource utilization for a CI-AKI hospitalization was obtained by interviews with local clinicians in each country. The percentage of patients who received iodixanol was assumed to increase over time. RESULTS: Based on a percentage of patients at increased risk of CI-AKI equal to 20% in Germany, 24% in Italy, 23% in Poland and 10% in Spain, results showed that the introduction of iodixanol would bring a 3-years cumulative net percentage saving on the total hospital budget of 29%, 34%, 25%, and 33% in the four countries respectively. CONCLUSION: The results of the analysis for the four countries showed that iodixanol use in patients at increased risk of CI-AKI undergoing CA with or without PCI may bring considerable savings on the hospital's budget, due to the associated reduction in CI-AKI incidence.