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.

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.

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.

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.

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.

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.

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.

Polymorphism in microRNA-196a2 contributes to the risk of cardiovascular disease in type 2 diabetes patients.

AIMS: To investigate the effect of the microRNA-196a2 gene polymorphism (rs11614913) on risk of cardiovascular disease in type 2 diabetes patients. METHODS: We examined 920 patients with diabetes and 834 healthy controls. All subjects were genotyped for the miRNA-196a2 SNP by polymerase chain reaction (PCR) and restriction analysis. RESULTS: The genotype distribution among controls and patients was in Hardy-Weinberg equilibrium (p=0.227 and 0.308, respectively). The frequency of the T allele was lower in patients than in controls (p=0.044). The odds ratio 0.66 (95% CI 0.54-0.79) suggests an association of the T allele with decreased risk of T2DM. For the main purpose of the study, T2DM patients were stratified into patients with CVD and those without it. The T allele and TT genotype were significantly more frequent in patients with CVD compared to those without CVD (p=0.013, p<0.001, respectively). The odds ratio for the T allele in the CVD+subgroup vs. CVD- was 1.76 (1.35-2.30), p<0.0001, mostly due to the overrepresentation of TT homozygotes. The highest risk of development of CVD was observed in the additive model for TT homozygotes (OR 3.33, 95% CI 2.05-5.42, p<0.0001). CONCLUSION: Our findings suggest that miRNA-196a2 T/C polymorphism (rs11614913) is associated with an increased risk of CVD in type 2 diabetes patients. This provides further insights on pathogenesis of cardiovascular disease in type 2 diabetes patients.

Common polymorphism in the cannabinoid type 1 receptor gene (CNR1) is associated with microvascular complications in type 2 diabetes.

Endocannabinoids exert their biological effects via interaction with G-protein coupled cannabinoid receptors CB1 and CB2. Polymorphisms in the CNR1 gene (encoding CB1 receptor) were previously found to be associated with dyslipidemia and cardiovascular diseases. We investigated a role of the polymorphism in CNR1 gene in type 2 diabetes and its complications. The study involved 667 T2DM patients and 450 healthy individuals. All subjects were genotyped for G1359A polymorphism by PCR-RFLP procedure. Genotype frequencies did not differ significantly between patients and controls. The statistically significant differences were seen between T2DM patients with diabetic nephropathy (DN) and those without it (OR for risk allele 2.84, 95% CI 2.04-3.94, p<0.0001). There were also differences between patients with diabetic retinopathy (DR) and those without DR (OR for risk allele 1.81, 95% CI 1.30-2.53, p=0.0005). No differences were observed in diabetic neuropathy. The A allele was more frequent in patients with coexisting cardiovascular disease (CVD) compared to patients without CVD (p=0.0044). The novel finding of our study is the association of the G1359A polymorphism with diabetic nephropathy and diabetic retinopathy in patients with T2DM. This polymorphism was also associated with cardiovascular disease in the patient group.

Acute left main coronary artery occlusion following inadvertent delivery of radiofrequency energy during ventricular tachycardia ablation successfully treated by rescue angioplasty with stenting: a two-year follow-up.

Radiofrequency catheter ablation (RFCA) is a treatment mode in patients with recurrent, symptomatic, ventricular arrhythmias. A rare but potentially life-threatening complication of RFCA includes injury to the coronary arteries, which leads to acute occlusion and myocardial infarction. In the few reported cases, the most frequently affected vessel has been the left main coronary artery. We present the case of a 28 year-old female. During the RFCA procedure, an acute occlusion of the left main coronary artery occurred, which was treated successfully with emergency angioplasty.

Calpain-10 gene polymorphisms in type 2 diabetes and its micro- and macrovascular complications.

Genetic variations in the calpain 10 gene (CAPN10) were previously implicated with increased risk of type 2 diabetes (T2DM). We studied the association of single nucleotide polymorphisms in the CAPN10 gene, SNP -43, SNP -19 and SNP -63, with T2DM and its complications. Overall, we examined 1440 individuals: 880 patients with diabetes and 560 healthy subjects, all Caucasians of Polish origin. All subjects were genotyped for the CAPN10 SNPs by polymerase chain reaction (PCR). The frequencies of alleles, genotypes and haplotypes at three studied loci were similar between the groups. However, the -43 SNP was significantly more frequent in T2DM patients with coexisting cardiovascular disease (CVD) than in patients without CVD (p=0.001). The -43 SNP was still significantly associated with the risk of CVD after adjusting for potential risk factors including male gender, age, BMI, dyslipidemia and hypertension. The odds ratio for G allele for CVD+ versus CVD- patients was 1.89, 95% CI 1.52-2.35. None of the studied SNPs was significantly associated with microvascular diabetic complications. There was a tendency to increased frequency of SNP -43 1/1 homozygotes in patients with diabetic retinopathy (p=0.057). The homozygous haplotype combination 121/121 was more frequent in T2DM patients than in non-diabetic controls (18.4% vs 10.5%, p=0.019). In conclusion, the results of our study suggest the significant association of SNP -43 with the risk of CVD coexisting with T2DM. We also observed that 121/121 haplotype was associated with T2DM in the studied population.

[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.

Increase in intra-abdominal pressure raises brain venous pressure, leads to brain ischaemia and decreases brain magnesium content.

BACKGROUND: Intra-abdominal hypertension (IAH) may increase brain venous pressure, which may lead to brain injury. The aim of the present study was to analyse the effect of IAH on brain venous pressure and brain total and ionised magnesium (tMg and iMg), calcium (Ca) and zinc (Zn) contents in rats. MATERIAL AND METHODS: Forty four adult Wistar rats were examined. Animals were divided into two groups: control, and IAH: rats with intra-abdominal pressure (IAP) elevated to 25 mmHg. IAP was measured directly in the abdominal cavity. After retrograde cannulation of the jugular vein, the jugular venous pressure (JVP) was measured as the brain venous pressure. JVP and IAP were noted after induction of anaesthesia, immediately following induction of IAH and 90 min after induction of IAH. In all rats, brains were removed for biochemical and histological analysis. RESULTS: Biochemical analysis was performed in 30 rats, histological visualisation in 14. IAP elevated to 25 mmHg increased JVP in the IAH group. After 90 min, JVP decreased; however, its value was still higher compared with pre-IAH. In the IAH group, tMg and iMg were significantly lower than in the control group. Moreover, Ca and Zn levels were higher in the IAH group compared with the control group. The histological examination showed changes indicative of ischaemic neuronal cell stress. CONCLUSIONS: Firstly, increase in IAP elevates JVP. Secondly, raised JVP decreases tMg and iMg. Thirdly, raised JVP increases the Ca and Zn content in the rat brain. Fourthly, IAH leads to changed characteristics of brain ischaemia.

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.