Morphometrical features of left atrial appendage in the atrial fibrillation patients subjected to left atrial appendage closure.

BACKGROUND: This study aimed to evaluate the morphometrical features of left atrial appendage (LAA) in patients with atrial fibrillation, subjected to LAA percutaneous closure (LARIAT) for stroke prevention. MATERIALS AND METHODS: Computed tomography (CT) scans of 51 patients with atrial fibrillation subjected to LARIAT procedure were comparatively evaluated with 50 patients with sinus rhythm (control group). Three-dimensional reconstructions were created using volume-rendering for evaluation. RESULTS: No differences were found in LAA types of distribution (cauliflower: 25.5 vs. 34.0%, chicken wing: 45.1 vs. 46.0%, arrowhead: 29.4 vs. 20.0%, all p > 0.05) between groups. However, the study group was characterized by LAAs with a lower number of lobes. The LAA orifice anteroposterior and transverse diameters (19.3 ± 4.12 vs. 17.2 ± 4.0 mm, p = 0.01 and 25.1 ± 5.1 vs. 20.5 ± ± 4.4 mm, p = 0.001), orifice area (387.2 ± 133.9 vs. 327.1 ± 128.3 mm2, p = 0.02) and orifice perimeter (70.2 ± 12.5 vs. 61.2 ± 11.6 mm, p = 0.04) was significantly larger in atrial fibrillation patients. More oval LAA orifices was found in atrial fibrillation group (94.0 vs. 70.4%, p = 0.001). No statistically significant differences were found in LAA body length (47.4 ± 15.4 vs. 43.7 ± 10.9 mm, p = 0.17), body width (24.7 ± 5.6 vs. 24.4 ± 5.8 mm, p = 0.81), and chamber depth (17.7 ± 3.5 vs. 16.5 ± 3.8 mm, p = 0.11). Calculated LAA ejection fraction was significantly lower in study group compared to healthy patients (16.4 ± 14.9 vs. 48.2 ± 12.9%, p = 0.001). CONCLUSIONS: Important morphometrical differences in LAA orifice have been found, which was significantly larger and more oval in patients with atrial fibrillation compared to healthy controls. Although no difference in LAA body type and size was observed; the LAA ejection fraction was significantly lower in atrial fibrillation rhythm patients.

Serum rantes, transforming growth factor-ß1 and interleukin-6 levels correlate with cardiac muscle fibrosis in patients with aortic valve stenosis.

Regulated on Activation Normal T Expressed and Secreted (RANTES) chemokine is involved in the initiation of inflammation and immune-cell recruitment. Interleukin -6 (IL-6) is used as a general index of severity of the chronic inflammatory process. Finally, transforming growth factor-ß (TGF-ß) is an immune biomarker potentially involved in the regulation of valve fibrosis and calcification. The aim of this study was to analyze selected biomarkers associated with the different stages of immune-pathogenesis in aortic stenosis. Forty consecutive patients with moderate to severe aortic stenosis (AS) and without previous myocardial infarction history were included in the study and divided into two groups. Two imaging techniques, echocardiography and magnetic resonance, were used to estimate the degree of AS and left ventricular muscle function. Inflammatory biomarker serum levels including CCL5/RANTES, IL-6, and TGF-ß1 were determined based on ELISA measurements. Mean levels of RANTES, IL-6, and TGF-ß1 did not significantly differ between both groups. A negative correlation was found between RANTES serum level and left ventricle (LV) mass as assessed by MRI (r = -0.3358, P = 0.0341). A positive correlation (r = 0.3283, P = 0.0387) was found between IL-6 serum levels and LV mass as measured by MRI. In addition, a positive correlation (r = 0.6803, P = 0.01) was seen between IL-6 serum levels and LV muscle mass with positive late gadolinium enhancement (LGE). There was a positive correlation between TGF-ß1 serum level and ejection fraction as measured by echocardiography (r = 0.3217, P = 0.043). The relationship between selected inflammatory biomarkers, LV ejection fraction, LV mass, and LV muscle mass with LGE appeared to be independent of valvular pathobiologic process severity, as we did not observe differences in IL-6, RANTES, or TGF-ß1 between groups differing in severity. On the contrary, these markers appear to be linked to myocardial function and remodeling, which may provide valuable insights into the pathobiology of AS and provide a basis for future detection strategies of AS.

Lactate in cardiogenic shock - current understanding and clinical implications.

Adenosine triphosphate (ATP) is an essential substrate metabolite in human beings. Mitochondrial oxidative phosphorylation provides > 95% of ATP with the remainder derived from glycolysis or tricarboxylic acid cycle (TCA). In normal hearts, acetyl-CoA is synthesized from the ß-oxidation of free fatty acids (FFA) and the oxidation of pyruvate. Pyruvate is synthesized from glycolysis and can be submitted either for decarboxylation to acetyl-CoA or for dehydrogenation to lactate. Moreover, pyruvate, as well as lactate, plays a key role in aerobic glucose metabolism which is highly dependent on ubiquitous regulatory mechanisms. Many recent advances in molecular biology, genetics, and physiology have revealed new insights into the metabolic flux of lactate. The initial perception characterized by increased lactate production and accumulation in peripheral tissues in anaerobic conditions has been recently contested. The paradigm of increased lactate concentration in the anaerobic setting is discussed according to contemporary reports. Nevertheless, the clinical role of lactate as a prognostic factor in cardiovascular diseases is undisturbed, especially in the field of innovative technology of left/bi ventricular-assist devices and biochips where it reassured its diagnostic and prognostic impact on the cardiovascular system.

Atrial natriuretic peptide and brain natriuretic peptide changes after epicardial percutaneous left atrial appendage suture ligation using LARIAT device.

Percutaneous left atrial appendage closure is an alternative treatment for stroke and systemic thromboembolism risk reduction in non-valvular atrial fibrillation (AF). However, the neurohormonal impact of epicardial exclusion of the left atrial appendage (LAA) with the LARIAT procedure is unknown. Evaluation of changes in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in AF patients underwent percutaneous LAA suture ligation. Sixty six patients underwent successfully percutaneous LAA suture ligation using LARIAT device. The level of ANP and BNP was measured before and 3 months after procedure. Mean ANP level before procedure was 249 ± 77 pg/mL (range from 95 pg/mL to 503 pg/mL) and mean BNP level was 481 ± 517 pg/mL (range from 34 pg/mL to 2508 pg/mL). Three months after procedure mean ANP level was 249 ± 79 pg/mL (range from 98 pg/mL to 492 pg/mL) and mean BNP level was 495 ± 526 pg/mL (range from 52 pg/mL to 2420 pg/mL). At 3 months follow up after percutaneous LAA suture ligation there were no significant differences in ANP and BNP levels.

Chemokine RANTES is increased at early stages of coronary artery disease.

Cardiovascular diseases, and in particular coronary artery disease (CAD), are the leading causes of death in Europe and represent around 50% of overall mortality. Numerous cardiovascular markers have been proposed in relation to cardiovascular risk prediction, in relation to cardiac and vascular and cerebral events. Chemokines which regulate immune cell vascular chemotaxis, including CCL5/RANTES are points of great interest. We hypothesized that chemokine RANTES level measured in peripheral blood may be associated with severity of atherosclerosis in patients with stable angina undergoing coronary angiography. RANTES and interleukin 18 (IL-18) levels were measured by ELISA. Classical and novel cardiovascular risk factors like brachial flow mediated dilation and intima-media thickness were analyzed in the context of chemokine levels and severity of atherosclerosis. Study included 62 consecutive patients with coronary atherosclerosis demonstrated by coronary angiography, (mean age 59.3 years (S.D. = 7.4)), divided into two groups: group I with lower severity of atherosclerosis, (n = 45) and group 2 with severe CAD (n = 17) based on coronary angiography. Groups were well balanced for classic risk factors for atherosclerosis. Mean RANTES level were significantly higher in patients in group I (67.9 ng/ml, S.E.M. = 3.97) than in group II (50.5 ng/ml, S.E.M. = 7.49; P = 0.03). In contrast, IL-18 levels were similar in both groups (255 pg/ml in group I and 315 pg/ml, S.E.M. = 40.91 in group I, P = 0.12), as well as hsCRP concentration (3.45 S.E.M. = 2.66 ng/ml and 4.69 ng/ml S.E.M.= 1.64 ng/ml respectively; P = 0.47). Flow-mediated dilatation (FMD) values have been significantly lower in group II than in group I (6.31; S.E.M. = 0.61; vs 4.41; S.E.M. = 0,56, respectively, P = 0.026), while nitroglycerine-mediated dilatation (NMD) did not differ, indicating more pronounced endothelial dysfunction. No significant correlations between chemokine RANTES levels and intima-media thickness (IMT), FMD measurements have been found in the total population studied. Chemokine RANTES level could become a useful marker of severity of coronary artery disease. Its lower levels were observed in patients with more diffuse disease. Elevated level of chemokine RANTES in patients with stable angina pectoris may evaluate patients to high risk group in plaque formation at early stages of atherosclerosis.

Long-term mortality and follow-up after carotid artery stenting.

BACKGROUND: Carotid artery stenting (CAS) is an alternative to carotid endarterectomy for the prevention of stroke and transient ischemic attack (TIA). The high long-term mortality among patients who underwent CAS seems to be related to the high comorbidity burden, including coronary and peripheral artery disease. However, limited data on very long-term mortality (over four years) and predictors of death are available. AIM: We sought to investigate the very long-term survival after CAS and the impact of comorbidities on mortality at follow-up. METHODS: Data of 194 symptomatic and asymptomatic patients who underwent CAS with cerebral protection systems from December 2002 to March 2014 were analyzed. All cause mortality during long-term follow-up was assessed. Univariate and multivariate Cox regression analysis was used to find independent predictors of death. RESULTS: The median age of patients was 66 [interquartile range (IQR): 60-73] years and 78.9 % of patients were male. The median follow-up was 7.6 (IQR: 4.4-10.2) years. The all-cause mortality rate after 30 days, one year, four years, and at maximum follow-up was 0 %, 5.1 %, 17.5 % and 31.4 %, respectively. Out of 61 deaths, 37 (60 %) were cardio-cerebral vascular related deaths, 15 (25 %) non-cardiovascular deaths, and 9 (15 %) due to unknown reasons. Among cardio-cerebral vascular deaths, there were 12 fatal strokes, 18 fatal myocardial infarctions and seven other cardiac related deaths. Non-cardiac deaths were due mainly to cancer (9/15). Age and diabetes mellitus were independent predictors of all-cause death during long-term follow-up. CONCLUSIONS: The mortality rate during short and long-term follow-up after CAS was lower than reported in the literature. Age and diabetes mellitus were independent predictors of all-cause death. Further research is needed to confirm the potential association between those risk factors and decreased survival. Hippokratia 2016, 20(3): 204-208.

On the selectivity of neuronal NOS inhibitors.

BACKGROUND AND PURPOSE: Isoform-selective inhibitors of NOS enzymes are desirable as research tools and for potential therapeutic purposes. Vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine (l-VNIO) and N(ω) -propyl-l-arginine (NPA) purportedly have good selectivity for neuronal over endothelial NOS under cell-free conditions, as does N-[(3-aminomethyl)benzyl]acetamidine (1400W), which is primarily an inducible NOS inhibitor. Although used in numerous investigations in vitro and in vivo, there have been surprisingly few tests of the potency and selectivity of these compounds in cells. This study addresses this deficiency and evaluates the activity of new and potentially better pyrrolidine-based compounds. EXPERIMENTAL APPROACH: The inhibitors were evaluated by measuring their effect on NMDA-evoked cGMP accumulation in rodent hippocampal slices, a response dependent on neuronal NOS, and ACh-evoked cGMP synthesis in aortic rings of the same animals, an endothelial NOS-dependent phenomenon. KEY RESULTS: l-VNIO, NPA and 1400W inhibited responses in both tissues but all showed less than fivefold higher potency in the hippocampus than in the aorta, implying useless selectivity for neuronal over endothelial NOS at the tissue level. In addition, the inhibitors had a 25-fold lower potency in the hippocampus than reported previously, the IC(50) values being approximately 1 µM for l-VNIO and NPA, and 150 µM for 1400W. Pyrrolidine-based inhibitors were similarly weak and nonselective. CONCLUSION AND IMPLICATIONS: The results suggest that l-VNIO, NPA and 1400W, as well as the newer pyrrolidine-type inhibitors, cannot be used as neuronal NOS inhibitors in cells without stringent verification. The identification of inhibitors with useable selectivity in cells and tissues remains an important goal.

Chondroitin sulphate proteoglycans: key modulators of spinal cord and brain plasticity.

Chondroitin sulphate proteoglycans (CSPGs) are a family of inhibitory extracellular matrix molecules that are highly expressed during development, where they are involved in processes of pathfinding and guidance. CSPGs are present at lower levels in the mature CNS, but are highly concentrated in perineuronal nets where they play an important role in maintaining stability and restricting plasticity. Whilst important for maintaining stable connections, this can have an adverse effect following insult to the CNS, restricting the capacity for repair, where enhanced synapse formation leading to new connections could be functionally beneficial. CSPGs are also highly expressed at CNS injury sites, where they can restrict anatomical plasticity by inhibiting sprouting and reorganisation, curbing the extent to which spared systems may compensate for the loss function of injured pathways. Modification of CSPGs, usually involving enzymatic degradation of glycosaminoglycan chains from the CSPG molecule, has received much attention as a potential strategy for promoting repair following spinal cord and brain injury. Pre-clinical studies in animal models have demonstrated a number of reparative effects of CSPG modification, which are often associated with functional recovery. Here we discuss the potential of CSPG modification to stimulate restorative plasticity after injury, reviewing evidence from studies in the brain, the spinal cord and the periphery.

Allogenic heart valve bank in the Department of Cardiovascular Surgery and Transplantology of Jagiellonian University in Cracow - 23 years experience in the treatment of aortic valve or aortic root diseases.

Allogenic aortic valves are widely used in case of native aortic valve or root disease as well as failed prosthetic valves with great success. At the Department of Cardiovascular Surgery and Transplantology of the Jagiellonian University in Cracow, aortic valve or aortic root replacement with allogenic aortic valve has been performed for 23 years. Allogenic heart valve bank was founded in 1980. In the bank we prepare both aortic allografts for adult cardiac surgical procedures and pulmonary allografts that are mostly used for repair of congenital heart disease.Allogenic aortic valves implantation was usually considered in our clinic for older patients, patients with infective endocarditis of the native or prosthetic valve, young women in reproductive age and patients with Marfan syndrome. Allografts exhibit excellent clinical performance and acceptable durability with no early failure if properly inserted. Between 1980 and 1992, allografts were obtained only from cadavers during routine autopsies. More than 10% of prepared allografts were exported to other cardiac surgery centres in Poland and foreign countries. Aortic valve replacement using allogenic aortic valves can be performed with acceptable mortality and good long-term results. The procedure although surgically more challenging has the advantage of not requiring anticoagulation therapy, hemodynamic performance of the allogenic valve is excellent, it demonstrates freedom from thromboembolism and infective endocarditis. We would like to emphasize the importance and advantages of the fact that allogenic heart valve bank is placed in the department of cardiovascular surgery and it is able to supply the department in heart valve allografts 24 h a day.