Serkan Durdu

Five-year follow-up after transepicardial implantation of autologous bone marrow mononuclear cells to ungraftable coronary territories for patients with ischaemic cardiomyopathy

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.

Vacuum-assisted closure and bilateral pectoralis muscle flaps for different stages of mediastinitis after cardiac surgery

PurposeTo assess the results of bilateral pectoralis major muscle flaps (BPMMF) and vacuum-assisted closure (VAC) at different stages of postcardiac surgery mediastinitis.MethodsOf 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.ResultsThe 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.ConclusionsEarly 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.

Apoptotic Vascular Smooth Muscle Cell Depletion via BCL2 Family of Proteins in Human Ascending Aortic Aneurysm and Dissection

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.

Validation of the EuroSCORE risk models in Turkish adult cardiac surgical population

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.

The efficacies of modified mechanical post conditioning on myocardial protection for patients undergoing coronary artery bypass grafting

BackgroundCoronary 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.MethodsA 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.ResultsOperative 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).ConclusionsMMPOC technique promotes early metabolic recovery of the heart during elective CABG, leading to better myocardial protection and functional recovery.

Correlation between the functional impairment of bone marrow-derived circulating progenitor cells and the extend of coronary artery disease

BackgroundBone 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).MethodsThe 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.ResultsThe 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.ConclusionsThe 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.

Thrombotic gene polymorphisms and postoperative outcome after coronary artery bypass graft surgery

BackgroundEmerging 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).MethodsA 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.ResultsAmong 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).ConclusionsFVL 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.

Clinical outcome and factors affecting surgical decision for repair versus replacement in patients with mitral regurgitation

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.

Stem cell mediated cardiovascular repair

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.

Coronary rupture and pseudoaneurysm formation after extravascular migration of a paclitaxel eluting stent implanted in the left circumflex coronary artery

As the implantation of drug eluting stents (DES) has become one of the most common clinical practices in interventional cardiology, the complications secondary to this procedure appear to have emerged increasingly over the past decade, with many cases of development of new coronary artery true aneurysms after DES implantation being reported. Here we present a case of coil embolization of a coronary pseudoaneurysm which presumably formed after extravascular migration of a DES.ZusammenfassungDie Implantation medikamentenfreisetzender Stens (“drug eluting stents”, DES) ist eines der am häufigsten angewendeten Verfahren in der interventionellen Kardiologie, und Komplikationen infolge dieses Verfahrens scheinen in den letzten 10 Jahren zunehmend aufzutreten. Dabei gibt es viele Berichte von Fällen, in denen sich ein wahres Aneurysma in den Koronararterien nach DES-Implantation neu gebildet hat. Hier wird ein Fall vorgestellt, bei dem ein koronares Pseudoaneurysma, das sich vermutlich nach extravaskulärer Migration eines DES gebildet hatte, mit einer Mikrospirale („coil“) embolisiert wurde.