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Objectives: Transcriptomics of atrial fibrillation (AFib) in the setting of chronic primary mitral regurgitation (MR) remains to be characterized. We aimed to compare the gene expression profiles of patients with degenerative MR in AFib and sinus rhythm (SR) for a clearer picture of AFib pathophysiology., Methods: After transcriptomic analysis and bioinformatics ( n = 59), differentially expressed genes were defined using 1.5-fold change as the threshold. Additionally, independent datasets from GEO were included as meta-analyses., Results: QRT-PCR analysis confirmed that AFib persistence was associated with increased expression molecular changes underlying a transition to heart failure ( NPPB , P = 0.002; ANGPTL2 , P = 0.002; IGFBP2 , P = 0.010), structural remodeling including changes in the extracellular matrix and cellular stress response ( COLQ , P = 0.003; COMP , P = 0.028; DHRS9 , P = 0.038; CHGB , P = 0.038), and cellular stress response ( DNAJA4 , P = 0.038). Furthermore, AFib persistence was associated with decreased expression of the targets of structural remodeling ( BMP7 , P = 0.021) and electrical remodeling ( CACNB2 , P = 0.035; MCOLN3 , P = 0.035) in both left and right atrial samples. The transmission electron microscopic analysis confirmed ultrastructural atrial remodeling and autophagy in human AFib atrial samples., Conclusions: Atrial cardiomyocyte remodeling in persistent AFib is closely linked to alterations in gene expression profiles compared to SR in patients with primary MR. Study findings may lead to novel therapeutic targets. This trial is registered with ClinicalTrials.gov identifier: NCT00970034., Competing Interests: The authors declare no competing interests., (Copyright © 2021 Günseli Çubukçuoğlu Deniz et al.)

Objective: We investigated the long-term results of autologous bone marrow mononuclear cells (ABMMNCs) implantation in patients with Buerger's disease (BD)., Methods: Twenty-eight patients (25 males and 3 females) who had BD and critical unilateral limb ischemia were investigated between April 2003 and August 2005. The patients were administered multiple injections of CD34+ and CD45+ positive ABMMNCs into the gastrocnemius muscle, the intermetatarsal region, and the dorsum of the foot (n=26) or forearm (n=2) and saline injection into the contralateral limb., Results: The mean follow-up time was 139.6±10.5 months. No complication related to stem cell therapy was observed during the follow-up. The ankle-brachial pressure index evaluated at 6 months and 120 months was compared to the baseline scores (p<0.001 and p=0.021, respectively). Digital subtraction angiography (DSA) was performed for all patients at baseline, 6 months, and 120 months. The angiographic improvement was 78.5% and 57.1% at 6 and 120 months, respectively. Patients demonstrated a significant improvement in the quality of life parameters at 6 months compared to baseline (p=0.008) and 120 months compared to the baseline (p=0.009). The 10-year amputation-free rate was 96% (95% CI=0.71-1) in ABMMNC-implanted limbs and 93% (95% CI=0.33-0.94) in saline-injected limbs (p=1)., Conclusion: Autologous stem cell therapy could be an alternative therapeutic method for BD at long-term follow-up.

Background: To evaluate the results of patients with chronic hepatitis C virus (HCV) following cardiac surgery in the TurcoSCORE (TrS) database., Methods: Sixty patients with HCV who underwent cardiac surgery between 2005 and 2016 in our clinic out of a total 8,018 patients from the TrS database were included in the study. The perioperative morbidity and mortality rates in these patients were compared with a matched cohort., Results: The mean follow-up time was 96.6 ± 12.3 months. Hospital mortality rates (HCV group 5% vs. control group 1.7%, p  = 0.61) were similar between the groups. No significant difference was found in the duration of cardiopulmonary bypass (HCV 79.1 ± 12.3 vs. control 82.6 ± 11.8, p  = 0.88) and cross clamps (HCV 33.4 ± 6.9 vs control 33.8 ± 7.2 p  = 0.76) between the two groups. The rate of patients who were revised due to postoperative hemorrhage was significantly higher in the HCV arm compared with the matched cohort (HCV 13.3% vs. control 1.7%, p  < 0.05). Although the measured prothrombin time (PT) and international normalized ratio (INR) in the postoperative 24th hour were in normal ranges in both arms, they were significantly higher in the HCV arm (HCV 11.2 ± 1.2 vs. control 10.5 ± 0.8, p  < 0.05; HCV 0.99 ± 0.06, vs. control 0.92 ± 0.03, p  < 0.0001)., Conclusion: The presence of HCV can be an important prognostic factor for morbidity in patients undergoing cardiac surgery. It can also play an important role in the risk models generated for cardiac surgery., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: This study aims to evaluate the efficacy and safety of ultrasound-accelerated catheter-directed thrombolysis (UACDT) in the treatment of massive and submassive pulmonary embolism (PE)., Methods: We conducted a prospective, observational cohort study of consequtive patients with massive or submassive PE treated with low-dose UACDT using EKOS EkoSonic® system at single center from May 2014 until April 2015. Overall, thirty-eight patients (median age, 64.5 years) were included. The primary safety outcomes were change in right ventricular (RV) to left ventricular (LV) diameter ratio within 24 hours of procedure initiation, at 1- and 6-month follow-up and major bleeding within 96 hours of the procedure initiation. BNP, troponin and D-dimer levels were also measured., Results: The ultrasound-accelerated thrombolytic catheters were bilaterally placed in 25 (65.8%) patients. The median tissue plasminogen activator (tPA) dose for all patients in our study was 21.0 mg and the median infusion time was 15 hours. Measurements before and after treatment showed a decrease in pulmonary artery pressure. The median value of RV/LV diameter ratio decreased from 0.9 (0.7-1.1) at baseline to 0.7 (0-0.97) at 6-month follow-up (P=0.001) and pulmonary artery pressure from 61.4 ±16.7 to 37.2±9.1 mmHg (P=0.001). The median BNP level at baseline was 169 (29-721) pg/mL and 45.5 (0-328) pg/mL at 6 month follow-up (P=0.001). Of 38 patients with PE, one had intracranial hemorrage, one gastrointestinal bleeding and two developed puncture site bleeding., Conclusions: This prospective study provides alternative treatment option and an addition to the treatment algorithm for the management of pulmonary embolism.

Background: Many of the previous studies on tricuspid valve surgery were on the materials that were used and the advantages and disadvantages of them. In this study, effects of preoperative tricuspid valve diameter on early postoperative outcomes were investigated. Methods: A total of 43 patients who underwent tricuspid valve repair surgery with the ring between the years 2012-2014 were included in this study. Tricuspid valve diameters and other cardiac functions of patients undergoing tricuspid intervention were evaluated with transthoracic echocardiography.Patients included in this study were divided into 2 groups: those with minimal, minimal-to-1st degree and 1st-degree tricuspid valve regurgitation found on thoracic echocardiography in the early postoperative period were considered as having a successful tricuspid repair (Group 1). Those with 1st-2nd degree and higher degrees of tricuspid regurgitation were considered as having an unsuccessful tricuspid repair (Group 2).The relationship between tricuspid valve dimensions and early tricuspid valve regurgitation was assessed with the help of preoperative, intraoperative, and postoperative data., Results: Thirty patients (Group 1) were found to have a successful tricuspid valve repair in the postoperative period. The mean annulus diameter of the tricuspid valve at end-diastole in patients from Group 1 was similar to Group 2 (4.24 ± 0.44 cm versus 3.99 ± 0.40; P = .080). Also, tricuspid valve end-systolic diameter in Group 1 was similar to patients in Group 2 (3.59 ± 0.38 cm versus 3.42 ± 0.33 cm; P = .151). Conclusion: A direct relationship was not found between tricuspid valve diameter and post-operative development of moderate to severe regurgitation in tricuspid valve surgery in this study.

Background: This study aims to evaluate the efficacy and safety of ultrasound-accelerated catheter-directed thrombolysis (UACDT) in the treatment of upper extremity deep vein thrombosis (UEDVT)., Methods: We conducted a prospective, observational cohort study of consecutive patients with acute UEDVT with low-dose UACDT using the Ekosonic® Endovascular System (EKOS Corporation, Bothell, WA, USA) at a single center from September 2012 until October 2014. Overall, sixteen patients (11 males and 6 females, age range 18 to 70 years, mean age, 45.6 years) were included in the study protocol. The primary efficacy outcome was complete thrombus clearance. The primary safety outcomes were recurrence of thrombosis within the follow-up visit and major bleeding within 96 hours of the procedure initiation., Results: The median tissue plasminogen activator (tPA) dose for all patients in our study was 16.81±2.51 mg (range 15 to 28 mg) and the median infusion time was 15 hours. Complete thrombus clearance was achieved in 11 (68.8%) patients, and partial clearance was detected in 3 (18.8%) patients. Of 16 patients with UEDVT, two had gastrointestinal bleeding, and two had puncture site bleeding., Conclusions: This prospective study demonstrates effectiveness and safety of ultrasound accelerated thrombolysis in patients with UEDVT.

We report here on a 43-year-old female patient presenting with non-ST elevation myocardial infarction, severe mitral regurgitation, and mild mitral stenosis secondary to encroachment of the related structures by a primary cardiac angiosarcoma. A coronary angiography revealed significant stenosis in the left main and left circumflex arteries and at exploration, the tumour was arising from posterior left atrial free wall, invading the posterior mitral leaflet, and extending into all of the pulmonary veins and pericardium. Therefore, no further intervention was performed, except for left internal mammarian artery to left anterior descending artery anastomosis and biopsy. As far as we know, this case is unique with respect to its presentation.

Background: Atrial fibrillation (AF) is characterized by structural remodeling, contractile dysfunction, and AF progression. Histone deacetylases (HDACs) influence acetylation of both histones and cytosolic proteins, thereby mediating epigenetic regulation and influencing cell proteostasis. Because the exact function of HDACs in AF is unknown, we investigated their role in experimental and clinical AF models., Methods and Results: Tachypacing of HL-1 atrial cardiomyocytes and Drosophila pupae hearts significantly impaired contractile function (amplitude of Ca(2+) transients and heart wall contractions). This dysfunction was prevented by inhibition of HDAC6 (tubacin) and sirtuins (nicotinamide). Tachypacing induced specific activation of HDAC6, resulting in α-tubulin deacetylation, depolymerization, and degradation by calpain. Tachypacing-induced contractile dysfunction was completely rescued by dominant-negative HDAC6 mutants with loss of deacetylase activity in the second catalytic domain, which bears α-tubulin deacetylase activity. Furthermore, in vivo treatment with the HDAC6 inhibitor tubastatin A protected atrial tachypaced dogs from electric remodeling (action potential duration shortening, L-type Ca(2+) current reduction, AF promotion) and cellular Ca(2+)-handling/contractile dysfunction (loss of Ca(2+) transient amplitude, sarcomere contractility). Finally, atrial tissue from patients with AF also showed a significant increase in HDAC6 activity and reduction in the expression of both acetylated and total α-tubulin., Conclusions: AF induces remodeling and loss of contractile function, at least in part through HDAC6 activation and subsequent derailment of α-tubulin proteostasis and disruption of the cardiomyocyte microtubule structure. In vivo inhibition of HDAC6 protects against AF-related atrial remodeling, disclosing the potential of HDAC6 as a therapeutic target in clinical AF.

Introduction: Seventy-five percent of primary cardiac tumors are benign, and most are myxomas. Seventy-five percent of myxomas originate from the left atrium, and 2.5% arise from the left ventricle. Heart failure is a rare complication of myxoma., Case: A 54-year-old male patient with chronic obstructive pulmonary disease was admitted to the pulmonology department with a diagnosis of pneumonia and congestive heart failure during hospitalization. An echocardiography evaluation revealed a mobile mass (3.3 cm X 1.2 cm) in the left ventricle. The measured ejection fraction was 22%. Transthoracic and transesophageal echocardiography and magnetic resonance imaging examinations confirmed the presence of a myxoma in the left ventricle. The myxoma was a hanging mass with a stalk on the interventricular septum near the anterior mitral valve annulus. We visualized the gelatinous fragile mass on the septum; we then extracted the myxoma via a transaortic approach with the patient on cardiopulmonary bypass. The patient was discharged 10 days after surgery., Discussion: Myxoma is treated by early surgical resection because of the potential for serious complications. Left ventricular myxomas have been reported to lead to a silent heart failure. This case is important because of its location and the patient's resultant heart failure.

Aims: This study investigates the expression patterns of BCL2 (B-cell CLL/lymphoma2) family of proteins and the extent of vascular smooth muscle cell (VSMC) apoptosis in thoracic aortic aneurysms (TAA), type-A aortic dissections (TAD), and nondilated ascending aortic samples., Methods: Aortic wall specimens were obtained from patients undergoing surgical repair for TAA (n = 24), TAD (n = 20), and normal aortic tissues from organ donors (n = 6). The expression pattern of BCL2, BCL2L1 (BCL2-like1), BAK1 (BCL2-antagonist/killer1), and BAX (BCL2-associated X protein) proteins was investigated by immunohistochemistry. Furthermore, colocalization of alpha smooth muscle actin (ACTA2) and caspase3 (CASP3) in aortic VSMCs was analyzed by double-immunofluorescence staining. Onset of DNA fragmentation was measured by TUNEL assay., Results: Apoptotic index was significantly increased in both TAD group (31.3 ± 17.2, P < 0.001) and TAA group (21.1 ± 12.7, P = 0.001) relative to control aortas (2.0 ± 1.2). Anti-CASP3 and ACTA2 double-immunostaining confirmed apoptosis in VSMCs in TAA and TAD groups but not in controls. Proapoptotic BAX expression was significantly elevated in VSMCs of TAA patients, compared with that of controls (OR = 20; P = 0.02; 95% CI, 16-250). In contrast, antiapoptotic BCL2L1 expression was higher in controls compared with that of TAA group (OR = 11.2; P = 0.049; 95% CI, 1.0-123.9). Furthermore, BAX/BCL2 ratio was significantly increased in both TAA (1.2 ± 0.7, P < 0.001) and TAD (0.6 ± 0.4, P = 0.05) groups relative to controls (0.2 ± 0.1, P < 0.001)., Conclusions: Apoptotic VSMC depletion in human TAA/TAD is associated with disturbance of the balance between proapoptotic and antiapoptotic members of the BCL2 family proteins, which may have a role in the pathogenesis of vascular remodelling in aortic disease. In light of the future studies, targeting apoptotic pathways in TAA and TAD pathogenesis may provide therapeutic benefits to patients by slowing down the progression and even possibly preventing the TAD., (© 2012 Blackwell Publishing Ltd.)

Objectives: We investigated the effects of short-term use of atorvastatin on CD34+/VEGF-R2+/CD133+/CD45- endothelial progenitor cell (EPC) count after on-pump coronary artery bypass surgery (CABG)., Methods: Between Feb-2010 and May-2010, we randomly assigned, in a placebo-controlled, double-blind study, 60 consecutive patients who underwent isolated, first-time CABG to receive either 14-day atorvastatin (40 mg/day) or placebo preoperatively. Urgent CABG and recent myocardial infarction were excluded. EPCs were quantified (cells/μl) by flow cytometric phenotyping obtained from venous blood samples collected preoperatively (T(1)), 6-hours (T(2)), and on the 5th day postoperatively (T(3)). Levels of markers of inflammation and serum cardiac troponin I were also measured preoperatively and daily until day-5 after surgery., Results: There were no differences in baseline risk factors including cholesterol profiles, and EuroSCORES between the groups. The composite primary end-point, favored statin group with higher amount of circulating, early EPC count (cells/μl) at all time points compared with placebo (T(1), 2.30±0.02 versus 1.58±0.03, p<0.001; T(2), 5.00±0.06 versus 2.19±0.06, p<0.001; T(3), 3.03±0.08 versus 1.78±0.02, p<0.001). Postoperative hsCRP rise were inversely correlated with EPC count, and were significantly lower in the statin group (T(1), 0.8 ± 0.1 versus 2.2±1.5, p<0.001; T(2), 72.9±3.2 versus 96.0±3.6, p<0.001; T(3), 4.3±1.2 versus 11.4±4.1, p<0.001). Furthermore, the incidence of postoperative atrial fibrillation was significantly lower in the statin group compared to placebo (3.3% versus 23%, p=0.02)., Conclusions: Short-term atorvastatin use increases circulating early EPCs both pre- and post-operatively and is associated with better preservation of sinus rhythm and reduced hsCRP levels. (ClinicalTrials.gov number, NCT01096875).

Background: Coronary artery bypass grafting (CABG) with cardioplegic cardiac arrest and cardiopulmonary bypass (CPB) is associated with myocardial injury. The aim of this study was to investigate whether a modified mechanical post-conditioning (MMPOC) technique has a myocardial protective effect by enhancing early metabolic recovery of the heart following revascularization., Methods: A prospective, randomized trial was conducted at a single-center university hospital performing adult cardiac surgery. Seventy-nine adult patients undergoing first-time elective isolated multivessel coronary artery bypass grafting were prospectively randomized to MMPOC or control group. Anesthetic, cardiopulmonary bypass, myocardial protection, and surgical techniques were standardized. The post reperfusion cardiac indices, inotrope use and biochemical-electrocardiographic evidence of myocardial injury were recorded. The incidence of postoperative complications was recorded prospectively., Results: Operative characteristics, including CPB and aortic cross-clamp time, were similar between the two groups (p>0.05). The MMPOC group had lower troponin I and other cardiac biomarkers level post CPB and postoperatively, with greater improvement in cardiac indices (p<0.001). MMPOC shortened post surgery hospitalization from 9.1 ± 2.1 to 7.5 ± 1.6 days (p<0.001)., Conclusions: MMPOC technique promotes early metabolic recovery of the heart during elective CABG, leading to better myocardial protection and functional recovery.

Background: Bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with coronary heart disease are impaired with respect to number and functional activity. However, the relation between the functional activity of BM-CPCs and the number of diseased coronary arteries is yet not known. We analyzed the influence of the number of diseased coronary arteries on the functional activity of BM-CPCs in peripheral blood (PB) in patients with ischemic heart disease (IHD)., Methods: The functional activity of BM-CPCs was measured by migration assay and colony forming unit in 120 patients with coronary 1 vessel (IHD1, n = 40), coronary 2 vessel (IHD2, n = 40), coronary 3 vessel disease (IHD3, n = 40) and in a control group of healthy subjects (n = 40). There was no significant difference of the total number of cardiovascular risk factors between IHD groups, beside diabetes mellitus (DM), which was significantly higher in IHD3 group compared to IHD2 and IHD1., Results: The colony-forming capacity (CFU-E: p < 0.001, CFU-GM: p < 0.001) and migratory response to stromal cell-derived factor 1 (SDF-1: p < 0.001) as well as vascular endothelial growth factor (VEGF: p < 0001) of BM-CPCs were reduced in the group of patients with IHD compared to control group. The functional activity of BM-CPCs was significantly impaired in patients with IHD3 as compared to IHD1 (VEGF: p < 0.01, SDF-1: p < 0.001; CFU-E: p < 0.001, CFU-GM: p < 0.001) and to IHD2 (VEGF: p = 0.003, SDF-1: p = 0.003; CFU-E: p = 0.001, CFU-GM: p = 0.001). No significant differences were observed in functional activity of BM-CPCs between patients with IHD2 and IHD1 (VEGF: p = 0.8, SDF-1: p = 0.9; CFU-E: p = 0.1, CFU-GM: p = 0.1). Interestingly, the levels of haemoglobin AIc (HbAIc) correlated inversely with the functional activity of BM-CPCs (VEGF: p < 0.001, r = -0.8 SDF-1: p < 0.001, r = -0.8; CFU-E: p = 0.001, r = -0.7, CFU-GM: p = 0.001, r = -0.6) in IHD patients with DM., Conclusions: The functional activity of BM-CPCs in PB is impaired in patients with IHD. This impairment increases with the number of diseased coronary arteries. Moreover, the regenerative capacity of BM-CPCs in ischemic tissue further declines in IHD patients with DM. Furthermore, monitoring the level of BM-CPCs in PB may provide new insights in patients with IHD.

Recent increase in the interest in stem and progenitor cells may be attributed to their behavioural characteristics. A consensus has been reached that embryonic or adult stem cells have therapeutic potential. As cardiovascular health issues are still the major culprits in many developed countries, stem and progenitor cell driven approaches may give the clinicians a new arsenal to tackle many significant health issues. However, stem and progenitor cell mediated cardiovascular regeneration can be achieved via complex and dynamic molecular mechanisms involving a variety of cells, growth factors, cytokines, and genes. Functional contributions of transplanted cells on target organs and their survival are still critical problems waiting to be resolved. Moreover, the regeneration of contracting myocardial tissue has controversial results in human trials. Thus, moderately favourable clinical results should be interpreted carefully. Determining the behavioural programs, genetic and transcriptional control of stem cells, mechanisms that determine cell fate, and functional characteristics are the primary targets. In addition, ensuring the long-term follow-up of cells with efficient imaging techniques in human clinical studies may provide a resurgence of the initial enthusiasm, which has faded over time. Here, we provide a brief historical perspective on stem cell driven cardiac regeneration and discuss cardiac and vascular repair in the context of translational science.

Background: Emerging perioperative genomics may influence the direction of risk assessment and surgical strategies in cardiac surgery. The aim of this study was to investigate whether single nucleotide polymorphisms (SNP) affect the clinical presentation and predispose to increased risk for postoperative adverse events in patients undergoing coronary artery bypass grafting surgery (CABG)., Methods: A total of 220 patients undergoing first-time CABG between January 2005 and May 2008 were screened for factor V gene G1691A (FVL), prothrombin/factor II G20210A (PT G20210A), angiotensin I-converting enzyme insertion/deletion (ACE-ins/del) polymorphisms by PCR and Real Time PCR. End points were defined as death, myocardial infarction, stroke, postoperative bleeding, respiratory and renal insufficiency and event-free survival. Patients were compared to assess for any independent association between genotypes for thrombosis and postoperative phenotypes., Results: Among 220 patients, the prevalence of the heterozygous FVL mutation was 10.9% (n = 24), and 3.6% (n = 8) were heterozygous carriers of the PT G20210A mutation. Genotype distribution of ACE-ins/del was 16.6%, 51.9%, and 31.5% in genotypes I/I, I/D, and D/D, respectively. FVL and PT G20210A mutations were associated with higher prevalence of totally occluded coronary arteries (p < 0.001). Furthermore the risk of left ventricular aneurysm formation was significantly higher in FVL heterozygote group compared to FVL G1691G (p = 0.002). ACE D/D genotype was associated with hypertension (p = 0.004), peripheral vascular disease (p = 0.006), and previous myocardial infarction (p = 0.007)., Conclusions: FVL and PT G20210A genotypes had a higher prevalence of totally occluded vessels potentially as a result of atherothrombotic events. However, none of the genotypes investigated were independently associated with mortality.

Objective: The aim of this study was to validate additive and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) models on Turkish adult cardiac surgical population., Methods: TurkoSCORE project involves a reliable web-based database to build up Turkish risk stratification models. Current patient population consisted of 9443 adult patients who underwent cardiac surgery between 2005 and 2010. However, the additive and logistic EuroSCORE models were applied to only 8018 patients whose EuroSCORE determinants were complete. Observed and predicted mortalities were compared for low-, medium-, and high-risk groups., Results: The mean patient age was 59.5 years (± 12.1 years) at the time of surgery, and 28.6% were female. There were significant differences (all p<0.001) in the prevalence of recent myocardial infarction (23.5% vs 9.7%), moderate left ventricular function (29.9% vs 25.6%), unstable angina (9.8% vs 8.0%), chronic pulmonary disease (13.4% vs 3.9%), active endocarditis (3.2% vs 1.1%), critical preoperative state (9.0% vs 4.1%), surgery on thoracic aorta (3.7% vs 2.4%), extracardiac arteriopathy (8.6% vs 11.3%), previous cardiac surgery (4.1% vs 7.3%), and other than isolated coronary artery bypass graft (CABG; 23.0% vs 36.4%) between Turkish and European cardiac surgical populations, respectively. For the entire cohort, actual hospital mortality was 1.96% (n=157; 95% confidence interval (CI), 1.70-2.32). However, additive predicted mortality was 2.98% (p<0.001 vs observed; 95%CI, 2.90-3.00), and logistic predicted mortality was 3.17% (p<0.001 vs observed; 95%CI, 3.03-3.21). The predictive performance of EuroSCORE models for the entire cohort was fair with 0.757 (95%CI, 0.717-0.797) AUC value (area under the receiver operating characteristic, AUC) for additive EuroSCORE, and 0.760 (95%CI, 0.721-0.800) AUC value for logistic EuroSCORE. Observed hospital mortality for isolated CABG was 1.23% (n=75; 95%CI, 0.95-1.51) while additive and logistic predicted mortalities were 2.87% (95%CI, 2.82-2.93) and 2.89% (95%CI, 2.80-2.98), respectively. AUC values for the isolated CABG subset were 0.768 (95%CI, 0.707-0.830) and 0.766 (95%CI, 0.705-0.828) for additive and logistic EuroSCORE models., Conclusion: The original EuroSCORE risk models overestimated mortality at all risk subgroups in Turkish population. Remodeling strategies for EuroSCORE or creation of a new model is warranted for future studies in Turkey., (Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: We aimed to identify characteristics differentiating patients undergoing mitral valve replacement versus valve repair for mitral regurgitation (MR) and to investigate retrospectively mid-term clinical and functional outcomes., Methods: From January, 2004 to January, 2009 146 patients underwent mitral valve surgery (62 male / 84 female; age: 55.9+/-13.6 [18-80] years) by one surgical team. Mitral valve replacement was performed in 101 patients (69.2 %) and valve repair was performed in 45 patients (30.8%). Mean follow-up time was 586+/-413 days. Life tables were constructed for the analysis of 5-year complication free survival and comparisons were performed between the groups using Log-rank test within 95%CI., Results: The choice of surgical technique depended on the etiology of MR. Degenerative (p=0.001) and ischemic (p=0.014) MR were more common in patients undergoing repair whereas patients with complex rheumatic mitral valve disease (p=0.001) with subvalvular involvement commonly underwent replacement. Overall 30-day mortality was 3.2% (replacement, 3.96%vs repair, 2.22%, p=0.59). Although there was no significant difference between the groups regarding baseline left ventricular ejection fraction (EF) (ischemic p=0.61; non-ischemic p=0.34), improvement was more pronounced in the repair group for both etiologies (ischemic MR, p=0.001; non- ischemic MR p=0.002). Survival at 5-years was 91.7+/-4.7% after repair and 83.5+/-9.2% after replacement, respectively (p=0.83). Freedom from grade 2 or more mitral regurgitation, reoperation, endocarditis, and thromboembolism were 95+/-5% vs 97+/-3% (p=0.71); 95+/-4% vs 98+/-2% (p=0.98); 94+/-4% vs 100% (p=0.16); and 85+/-8% vs 100% (p=0.095) in replacement and repair groups, respectively., Conclusion: This study demonstrates that mitral valve repair is associated with an acceptable operative mortality, satisfactory mid-term survival and better preservation of left ventricular function. Significant differences in favor of repair are expected in long-term follow-up particularly regarding freedom from thromboembolism and endocarditis.

Objective: Cell therapy for patients with ischaemic cardiomyopathy (IC) is still an open issue. We aimed to assess the long-term safety and therapeutic potency of autologous bone marrow mononuclear cell (ABMMNC) implantation into ungraftable coronary artery (UCA) territories in patients with IC., Methods: Bone marrow was aspirated from the iliac crest, and transepicardial ABMMNC implantation (n=25, 24 men, aged 57+/-7 years) as an adjunct to coronary artery bypass grafting (CABG) was performed into an area of reversible ischaemia within the territory of UCA (1.29+/-0.09 x 10(9) ABMMNCs). Control group (n=25, 23 men, aged 59+/-7 years) underwent incomplete CABG due to poor target vessel graftability. The study protocol consisted of coronary angiography, stress echocardiography, nuclear imaging and Holter monitoring at baseline and follow-up. The mean follow-up time was 988+/-423 days., Results: There was no difference between the groups regarding postoperative complications and outcome. Overall 5-year survival for the ABMMNC group was 79+/-10%, and 71+/-12% for the controls (p=0.48). Left ventricular ejection fraction (LVEF) at baseline was 24.8+/-3.7 versus 25.9+/-3.1 in the ABMMNC group and the controls, respectively. After 6 months, mean global LVEF increased to 36.3+/-7.4 (p<0.001) versus 31.4+/-4.1 (p=0.001), respectively. A significant difference was noted in delta LVEF between the groups (p<0.001, 95% confidence interval (CI): 3.4-8.9) at 6 months, and (p=0.001, 95% CI: 2.0-7.4) at 1 year. Accordingly, perfusion scores in UCA segments detected by single-photon emission computed tomography (SPECT) improved with ABMMNC therapy to 18.0+/-24.4 from 7.1+/-25.7 (p=0.001 vs control UCA segments)., Conclusion: Cellular therapy for IC within UCA could augment myocardial perfusion and contractility but does not improve overall survival. No adverse events were detected after cell therapy at mid-term follow-up.

Mesenchymal stem cells (MSCs) have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, and cardiomyocytes. Several established methods are presently available for in vitro isolation of MSCs from bone marrow. However, the duration necessary to culture them can be a major handicap to cell-based therapies needed for such urgent cardiovascular conditions as acute myocardial infarction and acute hindlimb ischemia. The best timing of cardiomyocyte differentiation induction after MCS isolation and expansion is still an unresolved issue. Our goal was to investigate the possibility of obtaining functional cardiomyocytes from rat MSC within a shorter time period. We examined MSCs' colony-forming capacity, CD90 and CD34 immunoreactivity during the 14 days of culturing. Cardiomyocyte differentiation was induced by 5-azacytidine. Immunohistochemic staining, together with intracellular Ca2+ measurement experiments, revealed that MSCs do not differentiate into any specific cell lineage but show the characteristics of MSCs on both the 9th and 14th days of the culture. To check the potential for differentiation into cardiomyocytes, experiments with caffeine application and depolarization with KCl were performed. The cells possessed some of the specific biochemical features of contracting cells, with slightly higher capacities on the 14th day. Cells from 9th and 14th days of the culture that were treated with 5-azacytidine had a higher expression of cardiac-specific markers such as troponin I, alpha-sarcomeric actin, and MEF2D compared with the control groups. This study illustrates that it is possible to get functional cardiomyocytes from in vitro MSC culture in a shorter time period than previously achieved. This reduction in time may provide emergency cases with access to cell-based therapies that may have previously been unavailable.

Purpose: To assess the results of bilateral pectoralis major muscle flaps (BPMMF) and vacuum-assisted closure (VAC) at different stages of postcardiac surgery mediastinitis., Methods: Of 65 patients with a deep sternal wound infection (DSWI) after cardiac surgery, 33 with a stable sternum were treated with VAC (59.3 +/- 11.7 years of age) and 32 with an unstable sternum or osteomyelitis (63.3 +/- 9.8 years of age) were treated with early BPMMF and continuous irrigation. Delayed BPMMF reconstruction was necessary in six VAC patients., Results: The overall incidence of DSWI was 1.04% within the study period. Deep sternal wound infection was diagnosed 15.9 +/- 10.8 days (range 5-62 days) after surgery. Diabetes was more common in the BPMMF group than in the VAC group (P = 0.046). Hospital mortality after treatment was 4.6% (n = 3) overall. Causes of death were septic multiorgan failure and respiratory failure. The infective pathogens were methicillin-resistant Staphylococcus aureus (MRSA; n = 2) and Acinetobacter species (n = 1). The median hospital stay was 29 days (range 15-110 days). After 6 months, only one recurrent sternal infection had occurred in the VAC group., Conclusions: Early BPMMF is an effective surgical treatment for DSWI in patients with an unstable sternum and osteomyelitis. VAC may be considered for patients without osteomyelitis but a stable sternum, or as adjuvant therapy in patients with comorbidity.

In the era of proton-antiproton collisions, stem cell field has emerged as the newly recognized protons of regenerative medicine. Great interest and enthusiasm were depending on their behavioral difference such as self-renewal, clonogenicity and differentiation into functional progeny that may become vehicles for regenerative medicine. Although progress has evolved dramatically strategies using stem-cell-driven cardiac regeneration involve extremely complex and dynamic molecular mechanisms. Cell death in transplanted heart continues to be a significant issue. Every step from stem cell homing, and migration to retention, engraftment, survival and differentiation in cardiac cytotherapy deserves intense research for optimum results. Furthermore, regeneration of contractile tissue remains controversial for human studies and careful interpretation is warranted for modest benefit in clinical trials. Currently, the only realistic approach to replace the damaged cardiomyocytes is cardiac transplantation for patients with end-stage heart failure. Ultimately, the giant footsteps in cell-based cardiac repair can only be achieved by an enthusiastic but also skeptical teams adhering to good manufacturing practices. Better understanding of cell-fate decisions and functional properties in cardiac cytotherapy may change the erosion of initial enthusiasm and may open new prospects for cardiovascular medicine.

The present review addresses the issues related to innovative contributions in biotechnology and their potential role in stem cell research at present and in the future. We can expect that future developments and applications in biotechnological sciences and industry will effect the direction of emerging cellular therapies. The use of these advances may offer a unique opportunity to investigate the mechanisms related to the journey from embryonic cells or bone-marrow derived stem/progenitor cells to cardiomyocytes or endothelial cells and the molecular regulators of cell differentiation.

Objective: Acute renal failure remains a common and serious complication of cardiac surgery. In this randomized trial, we aimed to assess whether sodium nitroprusside (SNP) infusion during cardiopulmonary bypass (CPB) could prevent renal dysfunction after coronary artery bypass grafting (CABG) surgery., Methods: Between October 2004 and May 2006, 240 consecutive patients with stable angina undergoing elective CABG for multi-vessel coronary artery disease were prospectively randomized into control (n=116, 72 men, mean age 61.3+/-9.7 years) or SNP groups (n=124, 81 men, 60.8+/-10.8 years). SNP group received SNP after initiation of rewarming period during CPB at a dose of 0.1mg/kg/h and the infusion was concluded by weaning from CPB. The anesthetic and CPB regimes were standardized. Blood urea nitrogen (BUN), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), creatinine clearance (C(Cr)), urine output, serum cardiac specific troponin I (cTnI), creatine kinase cardiac isoenzyme (CKMB), and CPK were measured preoperatively and daily until day 5 after surgery., Results: There were no differences in baseline levels of BUN, SCr, eGFR, C(Cr), cTnI, CKMB, CPK levels and EuroSCORES between the groups. Although the durations of cross clamp, CPB times, and postoperative cardiac enzymes were similar in both groups; in the control group, there was a significantly lower urine excretion during CPB (p=0.002) and the operation (p=0.041). Peak postoperative SCr levels were significantly (p=0.001) lower in the SNP group than in the control group (1.29+/-0.28 vs 1.42+/-0.34mg/dl). The incidence of >or=50%DeltaSCr was significantly higher in the control group when compared with the SNP group (35.3 vs 13.7%, p<0.001). Development of new C(Cr) less than 50ml/min postoperatively was significantly higher in the control group compared with the SNP group (14 vs 38%, p<0.001)., Conclusion: SNP administration during rewarming period of non-pulsatile CPB in patients undergoing CABG surgery is associated with improved renal function compared with conventional medical treatment providing adequate preload and mean arterial pressures.

Background: This study investigated the efficacy and safety of autologous bone marrow-mononuclear cells (ABMMNC) implantation in patients with critical limb ischemia (CLI) due to thromboangiitis obliterans (Buerger's disease)., Methods: The study comprised 28 patients (25 men and 3 women) with a median age of 44 years (range, 25-54 years) who had thromboangiitis obliterans and unilateral critical limb ischemia, defined as ischemic rest pain in a limb with or without nonhealing ulcers. The patients received multiple injections of erythrocyte-depleted and volume-reduced ABMMNC into the gastrocnemius muscle, the intermetatarsal region, and the feet dorsum (n = 26) or forearm (n = 2) vs saline injections into the less ischemic contralateral limbs. The patients were nonresponders to previous Iloprost infusion and smoking cessation >or=6 months and were not candidates for nonsurgical or surgical revascularization. Primary end points were the total healing of the most important lesion while avoiding major or minor amputation, the relief of rest pain without the need for analgesics from baseline to 6 months' follow-up, and the safety and feasibility of the treatment. Secondary end points were the changes in ankle-brachial pressure index and peak walking time, the angiographic evidence of collateral vessel formation or remodeling, and the quality-of-life assessment. Two investigators blinded for treatment assignment performed image analyses., Results: Unilateral intramuscular administration of ABMMNC was not associated with any complications. The mean follow-up time was 16.6 +/- 7.8 months (range, 7.6 to 33.8 months). Only one patient required toe amputation during follow-up. A change in the ankle-brachial pressure index >0.15 was achieved in 8 patients at 3 months and in 14 patients at 6 months compared with baseline values. At 6 months, patients demonstrated a significant improvement in rest pain scores (P < .0001), peak walking time (P < .0001), and quality of life (P < .0083). Total healing of the most important lesion was achieved in 15 patients (83%) with ischemic ulcers, and relief of rest pain without the need of narcotic analgesics improved in all patients. Digital subtraction angiography studies before and 6 months after the ABMMNC implantation showed vascular collateral networks had formed across the affected arteries in 22 patients (78.5%)., Conclusions: ABMMNC implantation could be a safe alternative to achieve therapeutic angiogenesis in patients with thromboangiitis obliterans and critical limb ischemia refractory to other treatment modalities.

Cardiovascular disorders are the leading causes of mortality and morbidity in the developed world. Cell-based modalities have received considerable scientific attention over the last decade for their potential use in this clinical arena. This review was intended as a brief overview on the subject of therapeutic potential of adult stem cells in cardiovascular medicine with basic science findings and the current status of clinical applications. The historical perspective and basic concepts are reviewed and a description of current applications and potential adverse effects in cardiovascular medicine is given. Future improvements on cell-based therapies will likely provide remarkable improvement in survival and quality of life for millions of patients with cardiovascular disorders.

Bone marrow implantation into ischaemic limbs could enhance angiogenesis by supplying endothelialprogeniter cells and angiogenic cytokinesot factors. We investigated efficacy and safety of autologousimplantation of bonemarrow-mononuclearcells (BMMC)in patients with ischaemic limbs due to Buerger's disease. We commence daciinical study to test cell therapy with autologous BMMC in patients with ischaemic limbs at the University of Ankara School of Medicine. In order for the patients to qualify for BMMC implantation, they should have critical limb ischaemia define das ischaemic rest painin a limb with or without non healing ulcers, should not respond to previous iloprost infusions and smoking cessation six months prior to evaluation and should not be candidates for nonsurgicalor surgical revascularisation. Primaryend points were safety andfeasibility of the treatmentand total healing of the most importantlesion. Secondary endpoints were total relief of rest pain without the need for analgesies,change in peak walkingtime (PWT)at 12 weeks, improvements in ankle-brachial pressure index(ABI), transcutaneous oxygen saturation using pulse oximetry(SaO2),angiographic evidence of newcollatera lvesselformation, tissue perfusion in the affected extremity using Thallium perfusions cintigraphyW. hilepatients(meanage46.7: !: 10.3years)were undergeneraal naesthesiaw, eharvested bonemarrow(519: t 45.5mUfromtheposteridilriacspineA. fterredbloodcell(RBCd) epletiaannd volumereduction using a continuous flow cell separator,we achieved 91% RBC depletian and concentrated /~MMC to a final volume and concentration of 51.5: t io.1 mLand7.04: t 1.9 x ioe7/mL total nucleated cells, respectively W.eimplantedBMMC (mean12.16: t 4.3 x ioe8) within three hours after marrow aspiration by intramuscular injection into the gastrocnemiusmuscle of ischaemic legs. Isotonic saline were injected into the other extremityin as similar fashion as control. 13 Unilateral intramuscular administration of BMMC was not associated with any complications. The primary efficacy end point, total healing of the most importantlesion, was achieved in three patients. All patients were followed up for at least four weeks. The secondary measures; change in PWT(LlPWT)at 12 weeks, total relief of rest pain without the need of analgesics improved in three patjents. These improvements were sustained for 24 weeks in the first two patients. Digital subtraction angiographic studies before and 3 months after the BMMC implantation showed the presence of a new vascular collateral network across the affected arteries in three patients. Preliminary results of the presentedstudy are promising. Thus, bone marrow maybe a potential source of cells for Buerger'spatients with end-stage Iimbischaemia refractory to other medical treatment modalities.

Objective: The purpose of this study was to describe the clinical/pathological features and the outcome of the surgical treatment of cardiac hydatid disease in our unit and other hospitals of Anatolia over a fifteen-years period., Methods: Between 1984 and 2001, fifty cases of surgically treated cardiac hydatid disease were identified by systematic literature search from Anatolia. Twelve patients were operated at the Department of Cardiovascular Surgery, Ankara University within the same period. Overall thirty-nine patients were female (mean age 29.8+/-14 years). Sixty-three percent of patients were complaining of dyspnea at the time of referral to the hospital and 22% presented with signs of acute coronary syndrome., Results: The most common cardiac location was the left ventricle (46.7%) followed by the interventricular septum, the right ventricle and atria. The most common procedure was controlled puncture and aspiration of the cyst content, its excision and closure of the resulting cavity, which were performed under cardiopulmonary bypass. Overall Anatolian operative mortality was 4.8% (3 patients). No late deaths but recurrence in one patient have occurred., Conclusion: In view of the lack of efficient alternative treatment options, we recommend surgical intervention even in asymptomatic patients in order to prevent the occurrence of lethal complications.

Cardiac transplantation has emerged as the therapeutic procedure of choice for patients with end-stage heart disease but the availability of donor organs remains major limiting factor allowing only 1% of the candidates actually become transplant recipients. New therapeutic strategies are under intensive research for patients who do not meet patient selection criteria for transplantation or who suffer from donor organ shortage. Even though there are significant developments in the medical treatment of cardiac failure, the prognosis of this condition continues to be poor. The 20-40% of the candidates for cardiac transplantation die while they are included in the waiting list. Twenty percent mortality has been reported within the first year of transplantation with additional yearly mortality of 5% following the first year. Financial constraints, complications of immunosuppression and functional failure of the transplanted hearts are other limiting factors. This has brought up the necessity to search for alternative surgical treatment methods besides increasing the waiting periods of transplant candidates. The aim of this report is to summarize other currently available therapeutic alternatives for patients with end-stage cardiac disease.