Developing a novel positronium biomarker for cardiac myxoma imaging.

PURPOSE: Cardiac myxoma (CM), the most common cardiac tumor in adults, accounts for 50-75% of benign cardiac tumors. The diagnosis of CM is often elusive, especially in young stroke survivors and transthoracic echocardiography (TTE) is the initial technique for the differential diagnostics of CM. Less invasive cardiac computed tomography (CT) and magnetic resonance imaging (MRI) are not available for the majority of cardiac patients. Here, a robust imaging approach, ortho-Positronium (o-Ps) imaging, is presented to determine cardiac myxoma extracted from patients undergoing urgent cardiac surgery due to unexpected atrial masses. We aimed to assess if the o-Ps atom, produced copiously in intramolecular voids during the PET imaging, serves as a biomarker for CM diagnosing. METHODS: Six perioperative CM and normal (adipose) tissue samples from patients, with primary diagnosis confirmed by the histopathology examination, were examined using positron annihilation lifetime spectroscopy (PALS) and micro-CT. Additionally, cell cultures and confocal microscopy techniques were used to picture cell morphology and origin. RESULTS: We observed significant shortening in the mean o-Ps lifetime in tumor with compare to normal tissues: an average value of 1.92(02) ns and 2.72(05) ns for CM and the adipose tissue, respectively. Microscopic differences between tumor samples, confirmed in histopathology examination and micro-CT, did not influenced the major positronium imaging results. CONCLUSIONS: Our findings, combined with o-Ps lifetime analysis, revealed the novel emerging positronium imaging marker (o-PS) for cardiovascular imaging. This method opens the new perspective to facilitate the quantitative in vivo assessment of intracardiac masses on a molecular (nanoscale) level.

Positronium imaging with the novel multiphoton PET scanner.

In vivo assessment of cancer and precise location of altered tissues at initial stages of molecular disorders are important diagnostic challenges. Positronium is copiously formed in the free molecular spaces in the patient's body during positron emission tomography (PET). The positronium properties vary according to the size of inter- and intramolecular voids and the concentration of molecules in them such as, e.g., molecular oxygen, O2; therefore, positronium imaging may provide information about disease progression during the initial stages of molecular alterations. Current PET systems do not allow acquisition of positronium images. This study presents a new method that enables positronium imaging by simultaneous registration of annihilation photons and deexcitation photons from pharmaceuticals labeled with radionuclides. The first positronium imaging of a phantom built from cardiac myxoma and adipose tissue is demonstrated. It is anticipated that positronium imaging will substantially enhance the specificity of PET diagnostics.

Early experience with the Thopaz+ chest drainage system - is this a new era in the management of post-cardiotomy bleeding?

INTRODUCTION: Monitoring postoperative drainage is a key aspect of patient assessment in the early postoperative period. Accurate assessment of drainage allows rapid diagnosis of postoperative bleeding, preventing excessive hemoglobin drop and cardiac tamponade. However, traditional methods of mediastinal drainage appear to be inaccurate and measurement can often be subjective, delaying the procedure. AIM: To demonstrate our initial experience with a digital chest drainage system that can be used to closely monitor postoperative drainage. MATERIAL AND METHODS: The Thopaz+ system allows manual regulation of negative pressure in the chest. The digital system analyzes the current and long-term values of the drainage, which facilitates therapeutic decisions. The advantage of the system is its mobility, without the need for built-in vacuums in the hospital wall. This allows early rehabilitation of the patient, which is crucial in the perioperative period. The Thopaz system has been used in 42 consecutive patients in all types of cardiac surgery procedures with good key results. RESULTS: We did not observe any complications with the system and the learning curve of the staff was very fast, both for the physicians and the operating room nurses, intensive care nurses and postoperative nurses. CONCLUSIONS: The first experiences with the Topaz+ system were very positive. The system brings a lot of safety and comfort to the cardiac surgical care we provide. These conclusions are consistent with data published in randomized trials.

Impaired fibrinolysis in degenerative mitral and aortic valve stenosis.

Valvular heart disease is associated with an increased thromboembolic risk. Impaired fibrinolysis was reported in severe aortic stenosis (AS). Little is known about fibrinolysis in mitral stenosis (MS). We sought to compare fibrinolysis impairment in AS and MS. We studied 121 individuals scheduled for elective aortic valve (AV) or mitral valve (MV) surgery for AS (n = 76) or MS (n = 45), in order to compare fibrinolysis impairment. Fibrinolytic capacity was assessed by determination of clot lysis time (t50%) and fibrinolysis inhibitors, including plasma plasminogen activator inhibitor-1 (PAI-1) antigen (PAI-1:Ag) and activity, thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and activity. Prolonged t50% (+ 29%), elevated TAFI activity (+ 12%), TAFI:Ag (+ 21%), and PAI-1:Ag (+ 84%) were observed in patients with MS, compared with those with AS. t50% Correlated with mean and maximal MV gradients (r = 0.43, p < 0.0001 and r = 0.39, p < 0.0001, respectively), but not with AV gradients. Mean and maximal MV gradients correlated with TAFI activity and PAI:Ag. Patients with permanent atrial fibrillation (AF; 35 with MS and 5 with AS) had longer t50% (by 22%, p = 0.0002) and higher PAI-1:Ag (by 74%, p < 0.0001) than the remainder. In the whole group, postoperative drainage volumes correlated inversely with PAI-1:Ag (r = - 0.22, p = 0.02). MS is associated with more pronounced impairment of global fibrinolytic capacity than AS at the stage of surgical intervention, which is in part driven by AF. Our findings suggest that hypofibrinolysis might be implicated in the progression of MS and its thromboembolic complications.

CD14+CD16++ "nonclassical" monocytes are associated with endothelial dysfunction in patients with coronary artery disease.

Endothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14++CD16- "classical - Mon1", CD14++CD16+ "intermediate - Mon2" and CD14+CD16++ "nonclassical - Mon3"), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting. This allowed for direct nitric oxide (NO) bioavailability assessment using isometric tension studies ex vivo (acetylcholine; ACh- and sodium-nitropruside; SNP-dependent) in segments of internal mammary arteries. The expression of CD14 and CD16 antigens and activation markers were determined in peripheral blood mononuclear cells using flow cytometry. Patients with high CD14+CD16++ "nonclassical" and low CD14++CD16- "classical" monocytes presented impaired endothelial function. High frequency of CD14+CD16++ "nonclassical" monocytes was associated with increased vascular superoxide production. Furthermore, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14+CD16++ monocytes. Nonclassical and classical monocyte frequencies remained independent predictors of endothelial dysfunction when major risk factors for atherosclerosis were taken into account (ß=0.18 p=0.04 and ß=-0.19 p=0.03, respectively). In summary, our data indicate that CD14+CD16++ "nonclassical" monocytes are associated with more advanced vascular dysfunction measured as NO- bioavailability and vascular reactive oxygen species production.

Respiratory System Function in Patients after Aortic Valve Replacement through Right Anterior Minithoracotomy.

Background The aim of the study was to analyze respiratory system function after minimally invasive aortic valve replacement through right anterior minithoracotomy (RAT-AVR). Methods An observational study of 187 patients electively scheduled for RAT-AVR between January 2010 and December 2013. Pulmonary complications were analyzed and spirometry examinations were performed preoperatively, 1 week, 1 month, and 3 months after surgery. Results Hospital mortality was 1.1%. A double-lumen intratracheal tube was used in 88.2% and single-lumen intratracheal tube was used in 11.8% of patients. Pulmonary complications occurred in 10.8% of the patients. Prolonged (>24 hours) mechanical ventilation time was present in five patients (2.7%). The reasons were stroke (n = 1), perioperative myocardial infarction (n = 2), and pneumothorax (n = 2). Right pleural effusion, which occurred in 7.7% (n = 14) of patients, was the most frequent respiratory system complication. One week after surgery, the spirometry parameters decreased in comparison to the preoperative period, then after 3 months statistically significant improvement occurred; however, the spirometry parameters still had not returned to preoperative values. Multivariable median regression analysis shows that the presence of chronic obstructive pulmonary disease and pulmonary complications were associated with lower values of forced expiratory volume in 1 second after surgery. There was no statistically significant difference regarding spirometry values or incidence of pulmonary complications after surgery between patients in whom single-lung or double-lung ventilation was applied. Conclusion Pulmonary functional status measured with spirometry parameters was diminished after RAT-AVR surgery. Single-lung ventilation did not result in a higher rate of respiratory complications after RAT-AVR surgery.

Hyperbaric oxygen therapy as additional treatment in deep sternal wound infections - a single center's experience.

INTRODUCTION: Deep sternal wound infection (DSWI) is one of the most serious complications after cardiac surgery procedures, observed in 5% of patients. Current standard medical therapy for DSWI includes antibiotics, surgical debridement, resuturing or negative pressure wound therapy (NPWT). Unfortunately, in some cases these methods are insufficient, and additional therapeutic options are needed. AIM: To assess the effects and usefulness of additional hyperbaric oxygen therapy (HBO2) in patients with DSWI after cardiac surgery procedures. MATERIAL AND METHODS: A retrospective analysis of 10 patients after cardiac surgery who developed DSWI in the period 2010-2012 was performed. After 3 months of ineffective conventional therapy including targeted antibiotic, surgical sternal debridement and NPWT, patients were qualified for additional HBO2 therapy. A total of 20 sessions of HBO2 therapy were performed, each 92 minutes long. RESULTS: After 4 weeks of HBO2 treatment, 7 patients presented complete wound healing with fibrous scar formation. One patient was qualified for the another cycle of HBO2 therapy with 20 additional sessions, and complete wound healing was observed. In 2 cases, after 5 and 19 sessions, HBO2 was interrupted because of improper qualifications. CONCLUSIONS: The HBO2 as an additional therapy in DSWI was successful in 80% of cases, and no complications were observed. However, due to the small number of published studies with a small number of patients, randomized, clinical trials are needed to assess the clinical results of HBO2 in DSWI after cardiac surgery procedures.

A comparison of minimally invasive and standard aortic valve replacement.

OBJECTIVE: The study objective was to compare aortic valve replacement through a right anterior minithoracotomy with aortic valve replacement through a median sternotomy. METHODS: With propensity score matching, we selected 211 patients after aortic valve replacement through a right anterior minithoracotomy and 211 patients after aortic valve replacement who underwent operation between January 2010 and December 2013. Perioperative outcomes were analyzed, and multivariable logistic regression analysis of risk factors of postoperative morbidity was performed. RESULTS: For propensity score-matched patients, hospital mortality was 1.0% in the aortic valve replacement through a right anterior minithoracotomy group and 1.4% in the aortic valve replacement group (P = 1.000). Stroke occurred in 0.5% versus 1.4% (P = .615), myocardial infarction occurred in 1.4% versus 1.9% (P = 1.000), and new onset of atrial fibrillation occurred in 12.8% versus 24.2% (P = .003) of patients in the aortic valve replacement through a right anterior minithoracotomy and aortic valve replacement groups, respectively. Postoperative drainage was 353.5 ± 248.6 mL versus 544.3 ± 324.5 mL (P < .001) and blood transfusion was required for 48.8% versus 67.3% (P < .001) of patients in the aortic valve replacement through a right anterior minithoracotomy and aortic valve replacement groups, respectively. Mediastinitis occurred in 2.8% of patients after aortic valve replacement and in 0.0% of patients after aortic valve replacement through a right anterior minithoracotomy surgery (P = .040). Intensive care unit stay (1.3 ± 1.2 days vs 2.6 ± 2.6 days) and hospital stay (5.7 ± 1.6 days vs 8.7 ± 4.4 days) were statistically significantly shorter in the aortic valve replacement through a right anterior minithoracotomy group. Aortic valve replacement through a right anterior minithoracotomy surgery resulted in reduced postoperative morbidity (odds ratio, 0.4; P < .001) and postoperative bleeding and blood transfusion requirements (odds ratio, 0.4; P < .001). CONCLUSIONS: Aortic valve replacement through a right anterior minithoracotomy surgery resulted in a reduced infection rate, diminished postoperative bleeding and blood transfusion requirements, reduced occurrence of new onset of atrial fibrillation, and shorter intensive care unit and hospital stays.

Computed Tomography Helps to Plan Minimally Invasive Aortic Valve Replacement Operations.

BACKGROUND: This study evaluated the role of multidetector computed tomography (MDCT) in preparation for minimally invasive aortic valve replacement (MIAVR). METHODS: An analysis of 187 patients scheduled for MIAVR between June 2009 and December 2014 was conducted. In the study group (n = 86), MDCT of the thorax, aorta, and femoral arteries was performed before the operation. In the control group (n = 101), patients qualified for MIAVR without receiving preoperative MDCT. RESULTS: The surgical strategy was changed preoperatively in 12.8% of patients from the study group and in 2.0% of patients from the control group (p = 0.010) and intraoperatively in 9.9% of patients from the control group and in none from the study group (p = 0.002). No conversion to median sternotomy was necessary in the study group; among the controls, there were 4.0% conversions. On the basis of the MDCT measurements, optimal access to the aortic valve was achieved when the angle between the aortic valve plane and the line to the second intercostal space was 91.9 ± 10.0 degrees and to the third intercostal space was 94.0 ± 1.4 degrees, with the distance to the valve being 94.8 ± 13.8 mm and 84.5 ± 9.9 mm for the second and third intercostal spaces, respectively. The right atrium covering the site of the aortotomy was present in 42.9% of cases when MIAVR had been performed through the third intercostal space and in 1.3% when through the second intercostal space (p = 0.001). CONCLUSIONS: Preoperative MDCT of the thorax, aorta, and femoral arteries makes it possible to plan MIAVR operations.

Perioperative Outcomes of Minimally Invasive Aortic Valve Replacement through Right Anterior Minithoracotomy.

Background The aim of the study was to analyze perioperative outcomes after minimally invasive aortic valve replacement through right anterior minithoracotomy (RAT-AVR). Patient selection criteria, anesthesia protocol, and surgical technique are presented. Methods A retrospective analysis of 194 patients electively scheduled for RAT-AVR was performed between January 2009 and June 2013. For preoperative planning, computed tomography was performed. Results Among studied patients, there were 48.5% females and 51.5% males with a mean age of 69.9 ± 9.2 years. The predicted mortality calculated with EuroSCORE II was 3.2 ± 0.9%, and observed mortality of RAT-AVR patients was 1.5%. Finally, RAT-AVR surgery was performed on 97.9% of patients (n = 190). Reasons for conversions to median sternotomy were bleeding from aortotomy site (n = 4) and from the right ventricle after epicardial pacing wire placement (n = 1), pleural adhesions (n = 2), and ascending aorta hidden under the sternum (n = 2). The second intercostal space was chosen for surgical access in 97.9% of patients.There were 3.6% reoperations for bleeding: aortotomy place (n = 1), epicardial pacing wire placement (n = 3), right lung tear (n = 2), and intercostal vessels (n = 1). The intensive care unit and hospital length of stays were 1.3 ± 1.2 and 5.7 ± 1.4 days, respectively. Strokes were present in 1.5% of patients. The perioperative complications rate diminished with time, occurring in 44.9% of the patients between 2009 and 2010 and in 15.6% of patients in 2013. Conclusions RAT-AVR can be safely performed without increased morbidity and mortality. Reduced complication rates over time reflect a learning curve.

Mechanisms of oxidative stress in human aortic aneurysms--association with clinical risk factors for atherosclerosis and disease severity.

UNLABELLED: Aortic abdominal aneurysms (AAA) are important causes of cardiovascular morbidity and mortality. Oxidative stress may link multiple mechanisms of AAA including vascular inflammation and increased metalloproteinase activity. However, the mechanisms of vascular free radical production remain unknown. Accordingly, we aimed to determine sources and molecular regulation of vascular superoxide (O2(-)) production in human AAA. METHODS AND RESULTS: AAA segments and matched non-dilated aortic samples were obtained from 40 subjects undergoing AAA repair. MDA levels (determined by HPLC/MS) were greater in plasma of AAA subjects (n=16) than in risk factor matched controls (n=16). Similarly, superoxide production, measured by lucigenin chemiluminescence and dihydroethidium fluorescence, was increased in aneurysmatic segments compared to non-dilated aortic specimens. NADPH oxidases and iNOS are the primary sources of O2(-) in AAA. Xanthine oxidase, mitochondrial oxidases and cyclooxygenase inhibition had minor or no effect. Protein kinase C inhibition had no effect on superoxide production in AAA. NADPH oxidase subunit mRNA levels for p22phox, nox2 and nox5 were significantly increased in AAAs while nox4 mRNA expression was lower. Superoxide production was higher in subjects with increased AAA repair risk Vanzetto score and was significantly associated with smoking, hypercholesterolemia and presence of CAD in AAA cohort. Basal superoxide production and NADPH oxidase activity were correlated to aneurysm size. CONCLUSIONS: Increased expression and activity of NADPH oxidases are important mechanisms underlying oxidative stress in human aortic abdominal aneurysm. Uncoupled iNOS may link oxidative stress to inflammation in AAA. Oxidative stress is related to aneurysm size and major clinical risk factors in AAA patients.

Lipoprotein-associated phospholipase A2 is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory mediator involved in atherosclerosis. Since aortic valve stenosis (AVS) is regarded as an atherosclerosis-like inflammatory disease, we sought to investigate whether AVS is associated with elevated Lp-PLA2. METHODS: Plasma Lp-PLA2 levels were determined in 48 consecutive patients with severe AVS without atherosclerotic vascular disease and compared with the values obtained in 48 controls matched for age, sex and cardiovascular risk factors. RESULTS: Lp-PLA2 was higher in AVS than in controls (242.3±50.4 vs. 151.9±28.1 ng/mL, p<0.0001). Lp-PLA2 correlated inversely with aortic valve area (AVA) (r=-0.53; p=0.0001) and positively with mean pressure gradient (PG) (r=0.32; p=0.029). In multivariable analysis C-reactive protein (CRP) (OR=1.42; 95% CI 0.95-2.1; p=0.09) and AVA (OR=0.003; 95% CI 0.00004-0.23; p<0.01) were independently associated with Lp-PLA2 above a mean of 242 ng/mL. After adjustment for CRP, AVA was the only independent predictor of Lp-PLA2 in AVS patients (p<0.001). CONCLUSIONS: This study is the first to show that AVS is characterized by increased plasma Lp-PLA2 levels associated with the severity of AVS, which suggests active involvement of Lp-PLA2 in the pathogenesis of AVS.

Factor XIII expression within aortic valves and its plasma activity in patients with aortic stenosis: association with severity of disease.

Aortic valve stenosis (AS) shares several similarities with atherosclerosis. Factor XIII (FXIII) has been detected within atherosclerotic plaques and may contribute to the development of atherosclerosis via multiple mechanisms. In the current study, we sought to investigate FXIII expression within human stenotic aortic valves and its association with severity of the disease. We prospectively enrolled 91 consecutive patients with AS scheduled for isolated valve replacement. Valvular FXIII subunit A (FXIII-A), fibrin and macrophages expression was evaluated by immunostaining. FXIII-A subunit transcripts and FXIII-A Val34Leu polymorphism was determined by real-time PCR. Plasma FXIII (pFXIII) activity was measured. We demonstrated that the valvular FXIII-A was predominantly expressed on the aortic side of leaflets, colocalized with alternatively activated macrophages (AAM). Areas stained for FXIII-A showed positive correlations with valvular fibrin presence, degree of calcification, pFXIII activity and the severity of AS, reflected by mean and maximum transvalvular gradients (all, p<0.001). The FXIII-A mRNA in the stenotic leaflets was significantly elevated compared to control leaflets. Interestingly, pFXIII activity was also positively correlated with mean (p<0.001) and maximum (p=0.001) transvalvular gradient. The FXIII-A Val34Leu polymorphism did not affect FXIII-A and fibrin expression in AS valves. In conclusion, the study is the first to show abundant expression of FXIII-A at the mRNA and protein levels within human stenotic aortic valves, which is associated with the severity of AS. Our findings might suggest that FXIII in the stenotic valves is presented in AAM and may be involved in the AS progression.

Does diabetes accelerate the progression of aortic stenosis through enhanced inflammatory response within aortic valves?

Diabetes predisposes to aortic stenosis (AS). We aimed to investigate if diabetes affects the expression of selected coagulation proteins and inflammatory markers in AS valves. Twenty patients with severe AS and concomitant type 2 diabetes mellitus (DM) and 40 well-matched patients without DM scheduled for valve replacement were recruited. Valvular tissue factor (TF), TF pathway inhibitor (TFPI), prothrombin, C-reactive protein (CRP) expression were evaluated by immunostaining and TF, prothrombin, and CRP transcripts were analyzed by real-time PCR. DM patients had elevated plasma CRP (9.2 [0.74-51.9] mg/l vs. 4.7 [0.59-23.14] mg/l, p = 0.009) and TF (293.06 [192.32-386.12] pg/ml vs. 140 [104.17-177.76] pg/ml, p = 0.003) compared to non-DM patients. In DM group, TF-, TFPI-, and prothrombin expression within valves was not related to demographics, body mass index, and concomitant diseases, whereas increased expression related to DM was found for CRP on both protein (2.87 [0.5-9]% vs. 0.94 [0-4]%, p = 0.01) and transcript levels (1.3 ± 0.61 vs. 0.22 ± 0.43, p = 0.009). CRP-positive areas were positively correlated with mRNA TF (r = 0.84, p = 0.036). Diabetes mellitus is associated with enhanced inflammation within AS valves, measured by CRP expression, which may contribute to faster AS progression.

Adiponectin, leptin, and resistin in patients with aortic stenosis without concomitant atherosclerotic vascular disease.

INTRODUCTION: Early stages of atherosclerosis and aortic stenosis (AS) are similar. Advanced coronary artery disease is characterized by altered profile of circulating adipocytokines. We hypothesized that plasma profile of adipocytokines is associated with the severity of AS. OBJECTIVES: The aim of the study was to evaluate the relationship between AS and adipocytokines. PATIENTS AND METHODS: In 74 patients with AS without atherosclerosis and left ventricular ejection fraction above 50% (57 men, 17 women, aged 58 ±9.1 years) and 74 controls, resistin, leptin, and adiponectin levels were determined by the Bio-Rad Luminex system. Aortic valve area indexed to body surface area (AVAI) as well as the mean and peak transvalvular pressure gradients (PG) were assessed by echocardiography. RESULTS: We observed similar adiponectin and leptin levels in patients with AS and controls (20.8 ±7.9 vs. 20.4 ±3.9 µg/ml, P = 0.67 and 17.0 ±6.4 vs. 16.4 ±5.9 ng/ml, P = 0.52, respectively). Twenty-one patients had mild, 21 moderate, and 32 severe AS. After adjusting for age and the body mass index, adiponectin levels were 20.3 ±0.5 µg/ml in controls, 26.7 ±0.9 µg/ml in mild, 20.2 ±0.9 µg/ml in moderate, and 17.5 ±0.7 µg/ml in severe AS (P <0.001). Leptin levels were 16.4 ±0.7 ng/ml in controls, 21.1 ±1.3 ng/ml in mild, 16.9 ±1.3 ng/ml in moderate, and 14.4 ±1.1 ng/ml in severe AS (P = 0.003). Adiponectin and leptin correlated with the AVAI (r = 0.70, P <0.001; r = 0.37, P = 0.001; respectively), mean PG (r = -0.72, P <0.001; r = -0.27, P = 0.009; respectively), and peak PG (r = -0.67, P <0.001; r = -0.23, P = 0.03; respectively). In a multivariable analysis, the mean PG was the only independent echocardiographic predictor of adiponectin levels (P <0.001), while the AVAI was the only independent echocardiographic predictor of leptin levels in AS patients (P = 0.049). CONCLUSIONS: Lower levels of adiponectin and leptin, but not resistin, are associated with severe AS, suggesting that adipocytokines may be involved in the progression of AS, and especially adiponectin, which plays a protective role in this process.

[The predicting role of high sensitive troponin testing after coronary artery bypass graft surgery]. / Znaczenie prognostyczne wysokoczulych oznaczen troponin sercowych po operacjach pomostowania tetnic wiencowych.

An article is a short review which summarize the utility of high sensitive cardiac troponins measurements after coronary artery bypass grafting surgery and their prognostic value in the short- and the long-term survival.