Differential gene expression of leaflet tissue in chronic ovine functional tricuspid regurgitation.

OBJECTIVES: Severe functional tricuspid regurgitation (FTR) is associated with subvalvular remodelling, but leaflet tissue alterations may also contribute. We set out to investigate molecular mechanisms driving leaflet remodelling in chronic ovine FTR. METHODS: Thirteen adult sheep (55 ± 4kg) underwent left thoracotomy, epicardial echocardiography, and pulmonary artery banding (PAB) to induce right heart failure and FTR. After 16 weeks, 13 banded (FTR) and 12 control (CTL) animals underwent median sternotomy for epicardial echocardiography and were subsequently sacrificed with each tricuspid leaflet tissue harvested for RNA-seq and histology. RESULTS: After 16 weeks, 7 animals developed severe, 2 moderate, and 4 mild tricuspid regurgitation (TR). Relative to CTL, FTR animals had increased PAP, TR, tricuspid annular diameter, and right atrial volume, while tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change decreased. FTR leaflets exhibited altered constituents and an increase in cellularity. RNA-seq identified 85 significantly differentially expressed genes (DEG) with 17, 53, and 127 within the anterior, posterior, and septal leaflets respectively. RRM2, PRG4, and CXCL8 (IL-8) were identified as DEGs across all leaflets and CXCL8 was differentially expressed between FTR severity grades. RRM2, PRG4, and CXCL8 significantly correlated with TAPSE, and this correlation was consistent regardless of the anatomical location of the leaflet. CONCLUSIONS: PAB in our ovine model resulted in RV failure and FTR. Leaflet RNA-seq identified several DEGs, specifically RRM2, PRG4, and CXCL8, with known roles in tissue remodelling. These data along with an overall increase in leaflet cellularity suggest tricuspid leaflets actively remodel in FTR.

Papillary muscle approximation in chronic ovine functional tricuspid regurgitation.

OBJECTIVE: Isolated tricuspid ring annuloplasty remains the surgical standard for functional tricuspid regurgitation repair but offers suboptimal results when right ventricular dilation and remodeling along with papillary muscle displacement is present. Addressing subvalvular remodeling with papillary muscle approximation may improve clinical outcomes. METHODS: Functional tricuspid regurgitation and biventricular dysfunction were induced in 8 healthy sheep by rapid ventricular pacing (200-240 bpm) for 27 ± 6 days. Subsequently, animals underwent cardiopulmonary bypass for implantation of sonomicrometry crystals on the tricuspid annulus, right ventricle, and papillary muscle tips. Papillary approximation sutures were anchored between anterior-posterior and anterior-septal papillary muscles and externalized through right ventricular free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, sequential papillary muscle approximations were performed. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were collected at baseline and after each papillary muscle approximation. RESULTS: With rapid pacing, right ventricular fractional area change decreased from 59 ± 6% to 38 ± 8% (P < .001), whereas tricuspid annulus diameter increased from 2.4 ± 0.3 cm to 3.3 ± 0.6 cm (P = .003). Tricuspid regurgitation (0-4+) increased from +0 ± 0 to +3.3 ± 0.7 (P < .001). Both anterior-posterior and anterior-septal papillary muscle approximation significantly reduced functional tricuspid regurgitation from +3.3 ± 0.7 to +2 ± 0.5 and +1.9 ± 0.6, respectively (P < .001). Reduction of tricuspid insufficiency with both subvalvular interventions was associated with decreased distance of the anterior papillary muscle to the annular centroid. CONCLUSIONS: Papillary muscle approximations were effective in reducing severe ovine functional tricuspid regurgitation associated with right ventricular dilation and papillary muscle displacement. Further studies are needed to evaluate efficacy of this adjunct to ring annuloplasty in repair of severe functional tricuspid regurgitation.

Effect of papillary muscle approximation on acute ovine functional tricuspid regurgitation.

OBJECTIVES: Ring annuloplasty represents the standard surgical treatment, but offers suboptimal results in patients with severe functional tricuspid regurgitation. Addition of papillary muscles (PMs) approximation may improve clinical outcomes. METHODS: Eight healthy adult male sheep (56 ± 4 kg) underwent cardiopulmonary bypass and implantation of sonomicrometry crystals on the tricuspid annulus, PM tips and right ventricular (RV) free wall. Papillary muscles approximation sutures were anchored between anterior-posterior and anterior-septal PMs and their loose ends externalized through RV free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, acute right heart failure and tricuspid regurgitation were induced, and subsequent sequential anterior-posterior and anterior-septal PM approximations were performed. Echocardiographic, haemodynamic and sonomicrometry data were collected. RESULTS: Tricuspid regurgitation at baseline in eight sheep was none or trace in 3 and mild in 5, and after induction of acute right heart failure increased significantly to moderate in 5, moderately severe in 1 and severe in 2 (P = 0.011). RV pressure increased from 31 [28; 43] to 51 [47; 55] mmHg (P = 0.012). Anterior-posterior PM approximation decreased regurgitation grade to none or trace in 1, mild in 4 and moderate in 3 (P = 0.016) and reduced PM area from 208 [160; 241] to 108 [48; 181] mm2 (P = 0.008), and anterior-posterior PM distance from 18 [16; 20] to 10 [7; 13] mm (P = 0.037). Anterior-septal approximation also significantly reduced PM area but had no effect on regurgitation grade. CONCLUSIONS: Anterior-posterior but not anterior-septal PM approximation alleviated acute ovine tricuspid regurgitation. Selective PM approximation may offer better control of tricuspid regurgitation.

Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation.

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to suboptimal clinical results. We set out to establish a chronic ovine model of FTR and right heart failure to investigate the mechanisms of FTR. Twenty adult male sheep (6-12 months old, 62 ± 7 kg) underwent a left thoracotomy and baseline echocardiography. A pulmonary artery band (PAB) was placed and cinched around the main pulmonary artery (PA) to at least double the systolic pulmonary artery pressure (SPAP), inducing right ventricular (RV) pressure overload and signs of RV dilatation. PAB acutely increased the SPAP from 21 ± 2 mmHg to 62 ± 2 mmHg. The animals were followed for 8 weeks, symptoms of heart failure were treated with diuretics, and surveillance echocardiography was used to assess for pleural and abdominal fluid collection. Three animals died during the follow-up period due to stroke, hemorrhage, and acute heart failure. After 2 months, a median sternotomy and epicardial echocardiography were performed. Of the surviving 17 animals, 3 developed mild tricuspid regurgitation, 3 developed moderate tricuspid regurgitation, and 11 developed severe tricuspid regurgitation. Eight weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and significant FTR. This large animal platform can be used to further investigate the structural and molecular basis of RV failure and functional tricuspid regurgitation.

Septal annular dilation in chronic ovine functional tricuspid regurgitation.

INTRODUCTION: Annular reduction with prosthetic rings represents the current surgical treatment of functional tricuspid regurgitation (FTR). However, alterations of annular geometry and dynamics associated with FTR are not well characterized. METHODS: FTR was induced in 29 adult sheep with either 8 weeks of pulmonary artery banding (PAB, n = 15) or 3 weeks of tachycardia-induced cardiomyopathy (TIC, n = 14). Eight healthy sheep served as controls (CTL). At the terminal procedure, all animals underwent sternotomy, epicardial echocardiography, and implantation of sonomicrometry crystals on the tricuspid annulus (TA) and right ventricular free wall while on cardiopulmonary bypass. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were acquired after weaning from cardiopulmonary bypass and stabilization. Annular geometry and dynamics were calculated from 3-dimensional crystal coordinates. RESULTS: Mean FTR grade (0-4) was 3.2 ± 1.2 and 3.2 ± 0.5 for PAB and TIC, respectively, with both models of FTR associated with similar degree of right ventricular dysfunction (right ventricular fractional area contraction 38 ± 7% and 37 ± 9% for PAB and TIC, respectively). Left ventricular ejection fraction was significantly reduced in TIC versus baseline (33 ± 9%, vs 58 ± 4%, P = .0001). TA area was 651 ± 109 mm2, 881 ± 242 mm2, and 995 ± 232 mm2 for CTL, FTR, and TIC, respectively (P = .006) with TA area contraction of 16.6 ± 4.2%, 11.5 ± 8.0%, and 6.0 ± 4.0%, respectively (P = .003). Septal annulus increased from 33.8 ± 3.1 mm to 39.7 ± 6.4 mm and 43.1 ± 3.2 mm for CTL, PAB, and TIC, respectively (P < .0001). CONCLUSIONS: Ovine FTR was associated with annular dilation and reduced annular area contraction. Significant dilation of septal annulus was observed in both models of FTR. As tricuspid rings do not completely stabilize the septal annulus, continued remodeling may contribute to recurrent FTR after repair.

Valvular complex and tissue remodelling in ovine functional tricuspid regurgitation.

OBJECTIVES: Pathophysiology of function tricuspid regurgitation (FTR) is incompletely understood. We set out to comprehensively evaluate geometric and tissue remodelling of the tricuspid valve complex in ovine FTR. METHODS: Twenty adult sheep underwent left thoracotomy and pulmonary artery banding (PAB) to induce right heart pressure overload and FTR. After 8 weeks, 17 surviving animals and 10 healthy controls (CTL) underwent sternotomy, echocardiography and implantation of sonomicrometry crystals on right ventricle and tricuspid valvular apparatus. Haemodynamic and sonomicrometry data were acquired in all animals after weaning from cardiopulmonary bypass. Leaflet tissue was harvested for pentachrome histologic analysis and biomechanical testing. RESULTS: Animal weight was 62 ± 5 and 63 ± 3 kg for CTL and PAB, respectively (P = 0.6). At terminal procedure, systolic pulmonary artery pressure was 22 ± 3 and 40 ± 7 mmHg for CTL and PAB, respectively (P = 0.0001). The mean TR grade (+0-4) was 0.8 ± 0.4 and 3.2 ± 1.2 (P = 0.0001) for control and banded animals, respectively. Right ventricle volume (126 ± 13 vs 172 ± 34 ml, P = 0.0019), tricuspid annular area (651 ± 109 vs 865 ± 247 mm2, P = 0.037) and area between papillary muscle tips (162 ± 51 vs 302 ± 75 mm2, P = 0.001) increased substantially while systolic excursion of anterior leaflet decreased significantly (23.8 ± 6.1° vs 7.4 ± 4.5°, P = 0.001) with banding. Total leaflet surface area increased from 806 ± 94 to 953 ± 148 mm2 (P = 0.009), and leaflets became thicker and stiffer. CONCLUSIONS: Detailed analysis of the tricuspid valve complex revealed significant ventricular, annular, subvalvular and leaflet remodelling to be associated with ovine functional tricuspid regurgitation. Durable surgical repair of severe FTR may require a multi-level approach to the valvular apparatus.

8-Isoprostanes and Asymmetric Dimethylarginine as Predictors of Mortality in Patients Following Coronary Bypass Surgery: A Long-Term Follow-Up Study.

BACKGROUND: We previously demonstrated that enhanced oxidative stress and reduced nitric oxide bioavailability are associated with unfavorable outcomes early after coronary artery bypass grafting. It is not known whether these processes may impact long-term results. We sought to assess whether during long-term follow-up, markers of oxidative stress and nitric oxide bioavailability may predict cardiovascular mortality following bypass surgery. METHODS: We studied 152 consecutive patients (118 men, age 65.2 ± 8.3 years) who underwent elective, primary, isolated on-pump bypass surgery. We measured plasma 8-iso-prostaglandin F2α and asymmetric dimethylarginine before surgery and twice after surgery (18-36 h and 5-7 days). We assessed all-cause and cardiovascular death in relation to these two biomarkers during a mean follow-up time of 11.7 years. RESULTS: The overall mortality was 44.7% (4.7 per 100 patient-years) and cardiovascular mortality was 21.0% (2.2 per 100 patient-years). Baseline 8-iso-prostaglandin F2α was associated with cardiovascular mortality (HR 1 pg/mL 1.010, 95% CI 1.001-1.021, p = 0.036) with the optimal cut-off ≤ 364 pg/mL for higher survival rate (HR 0.460, 95% CI 0.224-0.942, p = 0.030). Asymmetric dimethylarginine > 1.01 µmol/L measured 18-36 h after surgery also predicted cardiovascular death (HR 2.467, 95% CI 1.140-5.340, p = 0.020). Additionally, elevated 8-iso-prostaglandin F2α measured at the same time point associated with all-cause mortality (HR 1 pg/mL 1.007, 95% CI 1.000-1.014, p = 0.048). CONCLUSIONS: Our findings indicate that in advanced coronary disease, increased oxidative stress, reflected by 8-iso-prostaglandin F2α before bypass surgery and enhanced asymmetric dimethylarginine accumulation just after the surgery are associated with cardiovascular death during long-term follow-up.

Remifentanil and sevoflurane based anesthesia combined with bilateral erector spinae plane block in patients undergoing off-pump coronary artery bypass graft surgery.

INTRODUCTION: Working on the institutional Enhanced Recovery After Surgery (ERAS Cardio) protocol for off-pump coronary artery bypass graft surgery (OP-CABG) we have noticed that patients treated according to the modified anesthesia protocol had not only significantly shorter time of respiratory support and intensive care unit stay but also lower postoperative troponin T concentration than patients who had standard fentanyl/sevoflurane-based anesthesia. AIM: To compare the perioperative course of patients undergoing OP-CABG surgery and receiving standard fentanyl/sevoflurane anesthesia and those anesthetized according to the institutional ERAS Cardio protocol with remifentanil, sevoflurane, and bilateral extensor spinae plane (ESP) block. MATERIAL AND METHODS: Design: a prospective, open-label, observational study performed in a tertiary health center. Participants: 30 consecutive patients undergoing off-pump coronary bypass graft surgery. Interventions: 15 patients had standard anesthesia with etomidate, fentanyl, and rocuronium for induction and fentanyl/sevoflurane for maintenance (standard group); 15 others had bilateral single shot ESP block, then etomidate, remifentanil and rocuronium for induction, and remifentanil/sevoflurane for maintenance of anesthesia. RESULTS: Median time to extubation was 7.6 (5.5-12.5) h and 1.7 (1-3.25) h in "standard care" and ERAS groups, respectively (p = 0.00002). Length of stay in the intensive care unit was also shorter for patients in the ERAS group 20.5 (18-24) vs. 48 (42-48) h (p = 0.00001). Troponin concentration increased to a lesser extent in patients from the ERAS group: an increase of 151.8 (71.9-174.3) ng/ml vs. 253.8 (126.6-373.1) ng/ml, p = 0.008. CONCLUSIONS: Remifentanil/sevoflurane anesthesia combined with bilateral ESP block shortens mechanical ventilation time and ICU stay, and decreases postoperative troponin-T concentration in patients undergoing off-pump coronary bypass graft surgery.

Effects of rivaroxaban and dabigatran on local expression of coagulation and inflammatory factors within human aortic stenotic valves.

BACKGROUND: Treatment with non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran (a direct thrombin inhibitor) or rivaroxaban (a direct inhibitor of factor [F] Xa) attenuates atherosclerotic plaque progression in hypercholesterolemic mice. PURPOSE: To evaluate the effect of NOACs application on the expression of coagulation proteins in loco within stenotic aortic valves and in valve interstitial cells (VICs) from patients with severe aortic stenosis (AS). METHODS: Primary cultures of VICs obtained from 90 patients undergoing aortic valve replacement were stimulated with TNF-α (50 ng/mL) and pre-treated with rivaroxaban (1 and 10 ng/mL) or dabigatran (25 and 250 ng/mL). The expression of coagulation proteins was analyzed by immunofluorescence. Cytokine levels were measured by ELISA. RESULTS: FX, FXa, FVII, thrombin and PAR1/2 were present in loco within human aortic stenotic valves. Cultured VICs exhibited constant expression of FX, TF, PAR1/2. Exposure of VICs to TNF-α caused the upregulated expression of TF, PAR1/2 and induced expression of thrombin, FVII and FXa. FX was expressed by 80% of VICs, regardless of stimulation. Cultured VICs were able to synthesize metalloproteinases 1-3, IL-6, IL-32, IL-34, osteopontin and osteocalcin, the levels of which increased under TNF-α stimulation. NOACs added to culture inhibited coagulation factor and PAR1/2 expression. Moreover, NOACs down-regulated VIC-derived proteins responsible for valve calcification and extracellular matrix remodeling. CONCLUSIONS: NOACs at therapeutic concentrations may inhibit the effects of FXa and thrombin at in vitro level. It might be speculated that long-term treatment with rivaroxaban or dabigatran could attenuate the progression of AS in humans.

Erector spinae-plane block as an analgesic alternative in patients undergoing mitral and/or tricuspid valve repair through a right mini-thoracotomy - an observational cohort study.

INTRODUCTION: One of the main challenges in cardiac surgery is effective postoperative analgesia. Erector spinae-plane block (ESP block) is a novel regional technique, introduced by Forero in 2016 for neuropathic chest pain, then used successfully for mastectomy. AIM: To establish the efficacy of the ESP block in patients undergoing mitral and/or tricuspid valve repair through a right mini-thoracotomy. MATERIAL AND METHODS: It is a prospective observational cohort study performed in a tertiary health center. In the treatment group, a single-shot ESP block was performed before anesthetic induction. General anesthesia was induced with etomidate, remifentanil, and rocuronium, and continued with sevoflurane and remifentanil. Remifentanil infusion was continued for 2 h post-operatively, then stopped, and the patient's trachea was extubated. Patient-controlled analgesia was started with oxycodone immediately. Total oxycodone consumption and pain severity on the visual analog scale during the first 24 h were analyzed. In the control group, no regional block was performed. Instead of remifentanil, fentanyl was used. Patients were extubated on the second day. Pain was treated with morphine, administered according to nurses' discretion. Pain intensity was evaluated on the numerical rating scale. RESULTS: Nineteen patients were evaluated in the ESP and 25 in the control group. Mechanical ventilation time was shorter in the ESP group (0.6 (0.4-1.1) h) than in the control one (10 (8-17) h, p = 0.00001). Moreover, patients in the ESP group spent fewer days in the intensive care unit (1 (1-1) vs. (2 (2-2), p = 0.0001). CONCLUSIONS: The ESP block seems to be safe and efficient for pain control in patients undergoing right mini-thoracotomy for mitral and/or tricuspid valve repair.

Postoperative pain treatment with erector spinae plane block and pectoralis nerve blocks in patients undergoing mitral/tricuspid valve repair - a randomized controlled trial.

BACKGROUND: Effective postoperative pain control remains a challenge for patients undergoing cardiac surgery. Novel regional blocks may improve pain management for such patients and can shorten their length of stay in the hospital. To compare postoperative pain intensity in patients undergoing cardiac surgery with either erector spinae plane (ESP) block or combined ESP and pectoralis nerve (PECS) blocks. METHODS: This was a prospective, randomized, controlled, double-blinded study done in a tertiary hospital. Thirty patients undergoing mitral/tricuspid valve repair via mini-thoracotomy were included. Patients were randomly allocated to one of two groups: ESP or PECS + ESP group (1:1 randomization). Patients in both groups received a single-shot, ultrasound-guided ESP block. Participants in PECS + ESP group received additional PECS blocks. Each patient had to be extubated within 2 h from the end of the surgery. Pain was treated via a patient-controlled analgesia (PCA) pump. The primary outcome was the total oxycodone consumption via PCA during the first postoperative day. The secondary outcomes included pain intensity measured on the visual analog scale (VAS), patient satisfaction, Prince Henry Hospital Pain Score (PHHPS), and spirometry. RESULTS: Patients in the PECS + ESP group used significantly less oxycodone than those in the ESP group: median 12 [interquartile range (IQR): 6-16] mg vs. 20 [IQR: 18-29] mg (p = 0.0004). Moreover, pain intensity was significantly lower in the PECS + ESP group at each of the five measurements during the first postoperative day. Patients in the PECS + ESP group were more satisfied with pain management. No difference was noticed between both groups in PHHPS and spirometry. CONCLUSIONS: The addition of PECS blocks to ESP reduced consumption of oxycodone via PCA, reduced pain intensity on the VAS, and increased patient satisfaction with pain management in patients undergoing mitral/tricuspid valve repair via mini-thoracotomy. TRIAL REGISTRATION: The study was registered on the 19th July 2018 (first posted) on the ClinicalTrials.gov identifier: NCT03592485.

Plasma fibrin clot properties affect blood loss after surgical aortic valve replacement for aortic stenosis.

OBJECTIVES: Cardiac surgery is associated with elevated bleeding risk. We sought to study whether fibrin clot phenotype influences postoperative blood loss after surgery for aortic stenosis (AS). METHODS: We studied 77 isolated AS patients, including 62 who underwent aortic valve replacement and 15 who underwent the Bentall procedure due to post-stenotic aortic dilation. Plasma clot properties, including the tPA-induced clot lysis time (CLT) and clot permeability (Ks), along with fibrinolysis inhibitors, a calibrated automated thrombogram and platelet activation markers, were assessed preoperatively. RESULTS: In the whole AS group, the median chest tube output after 12 h was 360 ml (range of 110-2290 ml). Patients with drainage in the top quartile after 12 h (≥600 ml) had lower fibrinogen, shorter CLT, higher Ks, lower plasma plasminogen activator inhibitor-1 antigen, peak thrombin generation and ß-thromboglobulin levels than those in the lowest drainage quartile (≤260 ml) with no difference in platelets or von Willebrand factor. A multivariable model that was built after the exclusion of Bentall patients, adjusted for age, sex, body mass index and fibrinogen, showed that high drainage, which was defined as the top quartile after 12 h postaortic valve replacement (≥460 ml), was predicted by ß-thromboglobulin [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.90-0.99, P = 0.03], fibrinogen (OR 0.13, 95% CI 0.00-0.47, P = 0.02) and the CLT (OR 0.95, 95% CI 0.91-0.99, P = 0.02). The CLT was inversely related to the number of transfused platelet units (r = -0.27, P = 0.04). CONCLUSIONS: Fibrin clot susceptibility to lysis is a modulator of postoperative blood loss after cardiac surgery for AS, which may have practical implications.

Lymphocyte and monocyte subpopulations in severe aortic stenosis at the time of surgical intervention.

INTRODUCTION: Aortic stenosis (AS) is the most common acquired valvular heart disease in adults. Immune system involvement becomes evident during AS development. We sought to investigate the role of different circulating lymphocyte and monocyte subpopulations, with focus on CD4+CD8+ and natural killer T (NKT) cells, in AS. MATERIAL AND METHODS: Blood samples and aortic valves were obtained from patients undergoing elective aortic valve surgery. Valves were dissected and underwent genetic analyses and calcium content assessment. Lymphocytes and monocytes subsets were assessed by flow cytometry. RESULTS: Thirty-eight AS patients were studied. Maximal transvalvular pressure gradient (PGmax) as well as mean transvalvular pressure gradient (PGmean) correlated with the CD4+CD8+ lymphocyte count (r=0.35, P=.03 and r=0.43, P=.006, respectively) and fraction (r=0.43, P=.007 and r=0.48, P=.002, respectively). PGmax and PGmean correlated with CD16+CD56+CD3+ NKT cell count (r=0.39, P=.01 and r=0.43, P=.007, respectively) and fraction (r=0.49, P=.002 and r=0.47, P=.003, respectively). The classical monocyte subpopulation increased after the surgery by 68% (P<.0001). Patients after mini-sternotomy surgery had 47% lower nonclassical monocyte counts than those with full-sternotomy (P=.03). Patients treated with statins had significantly lower postoperative levels of both classical (-25%, P=.04) and nonclassical monocytes (-37%, P=.004) than nontreated individuals. CONCLUSIONS: In patients with severe isolated AS, CD4+CD8+ T cells and CD16+CD56+CD3+ NKT cells are associated with AV pressure gradients. Postoperative monocyte levels are affected by procedure invasiveness and use of statins.

Stenotic Bicuspid and Tricuspid Aortic Valves　- Micro-Computed Tomography and Biological Indices of Calcification.

BACKGROUND: Valve calcification is well estimated by ex-vivo micro-computed tomography (micro-CT). The objective of this study was to investigate the associations between micro-CT findings and biological indices of calcification in aortic stenosis (AS), as well as differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).Methods and Results:Aortic valves and plasma were obtained from patients undergoing valve surgery. Valves were dissected and underwent micro-CT, genetic analyses, and calcium content assessment. Plasma levels of calcification markers were measured. Forty-two patients with isolated severe AS, including 22 with BAV, were studied. BAV patients had a lower median CT value (140.0 [130.0-152.0] vs. 157.0 [147.0-176.0], P=0.002) and high-density calcification (HDC) fraction (9.3 [5.7-23.3] % vs. 21.3 [14.3-31.2] %, P=0.01), as compared with TAV. Calcification fraction (CF) correlated with AS severity (measured as maximal transvalvular pressure gradient [r=0.34, P=0.03], maximal flow velocity [r=0.38, P=0.02], and indexed aortic valve area [r=-0.37, P=0.02]). For TAV patients only, mRNA expression of integrin-binding sialoprotein correlated with CF (r=0.45, P=0.048), and the receptor activator of the nuclear factor κ-B ligand transcript correlated with HDC corrugation (r=0.54, P=0.01). CONCLUSIONS: TAV patients with AS present more mineralized calcifications in micro-CT than BAV subjects. The relative volume of calcifications increases with the AS severity. In TAV patients, upregulated expression of genes involved in osteoblastogenesis in AS correlates with leaflet mineralization in micro-CT.

Fibrin structure in organized thrombotic material removed during pulmonary artery endarterectormy: the effect of vessel calibre.

Pulmonary endarterectomy (PEA) is a curative therapeutic approach in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The location-dependent structural differences of thrombotic material found in pulmonary arteries in CTEPH are poorly investigated. We present the case of a 47-year-old woman with antiphospholipid syndrome, diabetes mellitus and abnormal fibrin phenotype, who underwent PEA for CTEPH. Intravascular material removed bilaterally during PEA (from lobar, segmental and sub-segmental arteries) has been studied using light and scanning electron microscopy (SEM). Light microscopy showed tighter fibrous network in the portions of intraluminal thrombotic material facing the vessel wall, which contained collagen and fibrin fibers, and abundant cells. Cells, evaluated by immunostaining, were present in the whole removed material. Tissue factor expression was also observed with the highest values in the portions of intravascular material facing the vessel wall. In the main pulmonary arteries, SEM images revealed thick fibers of fibrous proteins loosly meshed and few erythrocytes and platelets between them (both dysmorphic "wedged" and fresh cells were present). In the fibrotic layers, containing mainly collagen and fibrin, removed from the lobar/segmental pulmonary arteries we found a stepwise increase in fiber density with decreasing vessel calibre, followed by denser fibrous networks composed of thinner fibers. Elastic fibers in the lobar and segmental arteries were aligned along the blood flow vector. These findings demonstrate differences in the structure of endarterectomized PEA material dependent on the vessel calibre and might contribute to understanding of CTEPH pathophysiology.

Function of the Respiratory System in Elderly Patients After Aortic Valve Replacement.

OBJECTIVE: To compare the function of the respiratory system after aortic valve replacement through median sternotomy (AVR) or the minimally invasive right anterior minithoracotomy (RAT-AVR) approach among elderly (aged≥75 years) patients. DESIGN: Observational cohort study. SETTINGS: University hospital. PARTICIPANTS: The study included 65 elderly patients scheduled for RAT-AVR and 82 for standard AVR. INTERVENTIONS: Pulmonary function tests (PFT) were performed preoperatively, 1 week, 1 month, and 3 months after surgery. In addition, respiratory complications were analyzed. MEASUREMENTS AND MAIN RESULTS: Respiratory complications occurred in 12.3% of patients in the RAT-AVR group and 18.3% of patients in the AVR group (p = 0.445). Mechanical ventilation time in the intensive care unit was 7.7±3.6 hours for RAT-AVR patients and 9.7±5.4 hours for AVR patients (p = 0.003). Most PFT were worse in the AVR group than in the RAT-AVR group when performed 1 week after surgery. After 1 month, forced expiratory volume in the first second, vital capacity, and total lung capacity differed significantly in favor of the RAT-AVR group (p = 0.002, p<0.001, and p = 0.001, respectively). After 3 months, the PFT parameters still had not returned to preoperative values, but the differences were no longer significant between the RAT-AVR and AVR groups. The multivariable median regression analysis demonstrated that RAT-AVR surgery was a key factor in a patient's higher postoperative PFT parameter values. CONCLUSIONS: RAT-AVR surgery resulted in shorter postoperative mechanical ventilation time and improved the recovery of pulmonary function in elderly patients, but it did not reduce the incidence of pulmonary complications when compared with surgery performed through a median sternotomy.

Residual iliofemoral thrombosis in a 31-year-old woman on oral contraceptives possessing heterozygous factor V Leiden, factor XIII Val34Leu allele and alpha-fibrinogen Thr312Ala allele: case report.

We present the case of a 31-year-old woman on oral contraceptives with a 3-year history of iliofemoral thrombosis resistant to recanalization despite satisfactory anticoagulation therapy and absence of concomitant diseases. Thrombophilia screening revealed heterozygous factor V Leiden mutation. We also detected the presence of factor XIII (FXIII) Leu34 allele and alpha-chain fibrinogen 312Ala allele, which are known to adversely affect fibrin clot structure and lysis. It might be speculated that the presence of 3 polymorphisms in this patient could contribute to proximal thrombosis resistant to treatment. We postulate that determination of FXIII and alpha-fibrinogen polymorphisms can be useful in the evaluation of some young patients with deep vein thrombosis.

[Use of the harmonic scalpel for harvesting radial artery as a conduit for myocardial revascularization]. / Zastosowanie noza harmonicznego do pobierania tetnicy promieniowej w chirurgicznej tetniczej rewaskularyzacji serca.

Radial artery (RA) as a conduit for coronary artery bypass grafting (CABG) was introduced in 1973 by Carpantier and within two years its use was abondoned because of high incidence of narrowing and occlusion. The reason for early RA's graft failure became clear in the late 1980s and it was its propensity for vasospasm. In recent years in conjuction with availability of antispasm agents and less invasive harvesting techniques, the RA is increasingly used for CABG. The RA has become the second arterial graft of choice after the internal thoracic artery, mainly because of its promising patency rates. In order to avoid graft traumatization less invasive techniques have been introduced lately. The purpose of this paper was to asses the clinical effect of harvesting RA with the use of the Harmonic Scalpel. We examined the results of this technique among 140 patients operated in our Department in years 2005 and 2006.