Turkish Society of Cardiovascular Surgery (TSCVS) Proposal for use of ECMO in respiratory and circulatory failure in COVID-19 pandemic era.

The document is prepared to guide the members of the The Turkish Society of Cardiovascular Surgery (TSCVS) and other extracorporeal membrane oxygenation (ECMO) centers worldwide to share experiences in using ECMO in COVID-19 pandemic.

Primary Left Cardiac Angiosarcoma with Mitral Valve Involvement Accompanying Coronary Artery Disease.

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.

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

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.

Rationale and design of the coronary artery bypass grafting surgery off or on pump revascularization study: a large international randomized trial in cardiac surgery.

BACKGROUND: Uncertainty remains regarding the benefits and risks of the technique of operating on a beating heart (off pump) for coronary artery bypass grafting (CABG) surgery versus on-pump CABG. Prior trials had few events and relatively short follow-up. There is a need for a large randomized, controlled trial with long-term follow-up to inform both the short- and long-term impact of the 2 approaches to CABG. METHODS: We plan to randomize 4,700 patients in whom CABG is planned to undergo the procedure on pump or off pump. The coprimary outcomes are a composite of total mortality, myocardial infarction (MI), stroke, and renal failure at 30 days and a composite of total mortality, MI, stroke, renal failure, and repeat revascularization at 5 years. We will also undertake a cost-effectiveness analysis at 30 days and 5 years after CABG surgery. Other outcomes include neurocognitive dysfunction, recurrence of angina, cardiovascular mortality, blood transfusions, and quality of life. RESULTS: As of May 3, 2011, CORONARY has recruited >3,884 patients from 79 centers in 19 countries. Currently, patient's mean age is 67.6 years, 80.7% are men, 47.0% have a history of diabetes, 51.4% have a history of smoking, and 34.4% had a previous MI. In addition, 20.9% of patients have a left main disease, and 96.6% have double or triple vessel disease. CONCLUSIONS: CORONARY is the largest trial yet conducted comparing off-pump CABG to on-pump CABG. Its results will lead to a better understanding of the safety and efficacy of off-pump CABG.

Rationale and design of the coronary artery bypass grafting surgery off or on pump revascularization study: a large international randomized trial in cardiac surgery

Background Uncertainty remains regarding the benefits and risks of the technique of operating on a beating heart(off pump) for coronary artery bypass grafting (CABG) surgery versus on-pump CABG. Prior trials had few events and relativelyshort follow-up. There is a need for a large randomized, controlled trial with long-term follow-up to inform both the short- andlong-term impact of the 2 approaches to CABG.Methods We plan to randomize 4,700 patients in whom CABG is planned to undergo the procedure on pump or offpump. The coprimary outcomes are a composite of total mortality, myocardial infarction (MI), stroke, and renal failure at30 days and a composite of total mortality, MI, stroke, renal failure, and repeat revascularization at 5 years. We will alsoundertake a cost-effectiveness analysis at 30 days and 5 years after CABG surgery. Other outcomes include neurocognitivedysfunction, recurrence of angina, cardiovascular mortality, blood transfusions, and quality of life.Results As of May 3, 2011, CORONARY has recruited N3,884 patients from 79 centers in 19 countries. Currently,patient's mean age is 67.6 years, 80.7% are men, 47.0% have a history of diabetes, 51.4% have a history of smoking, and34.4% had a previous MI. In addition, 20.9% of patients have a left main disease, and 96.6% have double or triplevessel disease.Conclusions CORONARY is the largest trial yet conducted comparing off-pump CABG to on-pump CABG. Its resultswill lead to a better understanding of the safety and efficacy of off-pump CABG. (Am Heart J 2012;163:1-6.)

Micronized purified flavonoid fraction in pretreating CABG patients.

The aim of the present study was to determine whether oral pretreatment with micronized purified flavonoid fraction (Daflon) has beneficial effects on cardiac function and outcome after cardiac operations. This prospective, randomized trial enrolled 43 patients who had an impaired preoperative left ventricular ejection fraction of less than 0.50 (mean, 0.45 +/- 0.04) and a mean New York Heart Association functional class status of 2.30 +/- 0.74; all were scheduled for elective coronary artery bypass grafting. Patients who were randomized to the Daflon group (n=21) received oral Daflon 500 mg (6 tablets daily for 4 days, followed by 2 tablets for 3 days) preoperatively. Outcome variables included perioperative hemodynamic data, inotropic requirements, morbidity, and death, as well as cardiac ischemia and various outcome markers. Hemodynamic and biochemical data were collected before induction of anesthesia, perioperatively before starting cardiopulmonary bypass, immediately after bypass, and at the 24th postoperative hour. There was only 1 death (in the Daflon group). During the post-cardiopulmonary bypass period, troponin I and lactate dehydrogenase levels were significantly lower in the Daflon group. Also, the New York Heart Association status of the patients in the Daflon group was significantly lower postoperatively. Differences between the 2 groups in lengths of stay in the intensive care unit and hospital, inotropic requirements, and left ventricular ejection fraction levels did not reach statistical significance. Orally administered Daflon might provide better outcomes for patients who have impaired cardiac function before undergoing cardiac operations that require cardiopulmonary bypass.

Timing of induction of cardiomyocyte differentiation for in vitro cultured mesenchymal stem cells: a perspective for emergencies.

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.

Off-pump coronary artery bypass graft surgery after stent implantation in a patient with combined thrombophilic risk factors.

The case of coronary artery bypass graft surgery in a 51-year-old woman with a heterozygous form of factor V Leiden, prothrombin mutation G20210A and tumour necrosis factor-alpha -308 G-A associated with high lipoprotein(a) and homocysteinemia levels, as well as elevated factors VIIIc and IX, is presented. She suffered from recurrent episodes of venous thromboembolism and left anterior descending artery subtotal occlusion eight months after percutaneous transluminal coronary angioplasty and stent implantation.

Coronary artery bypass grafting ameliorates the decreased plasma adiponectin level in atherosclerotic patients.

Adiponectin functions as an anti-inflammatory and anti-atherogenic factor, and the decreased plasma adiponectin is a risk factor for coronary disease. The aim of this study was to determine the changes in plasma levels of adiponectin, a potential parameter for atherosclerosis, in patients underwent surgical revascularization. We included forty patients with atherosclerosis (age, 58 +/- 9 years; body mass index [BMI] 26.93 +/- 2.3 kg/m(2)) undergoing coronary artery bypass grafting (CABG). Control group consisted of 40 healthy volunteers, matched for age, gender and BMI (age, 56 +/- 6 years; BMI, 26.78 +/- 2.3 kg/m(2)). We measured various parameters, including high sensitive C-reactive protein (hsCRP), homeostasis model assessment-insulin resistance (HOMA-IR) indexes, and adiponectin. The baseline profile of the patients before CABG showed higher levels of serum hsCRP (13.15 +/- 2.40 mg/l vs 3.97 +/- 1.07 mg/l) and HOMA-IR (1.86 +/- 0.30 vs 1.26 +/- 0.33) and lower plasma adiponectin levels (7.02 +/- 2.01 microg/ml vs 25.46 +/- 3.9 microg/ml), compared to controls (p < 0.001 for each parameter). Plasma adiponectin level was increased one month after CABG from the baseline level to 8.67 +/- 2.05 microg/ml(p < 0.001), although the level was still lower than the control value. Thus, postoperative adiponectin level might be helpful for evaluating the progression of atherosclerosis. Moreover, CABG significantly decreased hsCRP to 7.25 +/- 1.89 mg/l and HOMA-IR to 1.59 +/- 0.33, although these levels were higher than the controls. These results suggest that CABG decreases the cardiac risk factors in atherosclerotic patients.

Regenerative medicine for cardiovascular disorders-new milestones: adult stem cells.

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.

Early clinical experience with the On-X prosthetic heart valve.

The study aimed to assess the performance of the On-X valve (Medical Carbon Research Institute, Austin, TX). Between December 2000 and January 2003 On-X valves were implanted in 400 patients aged 19-85 years (mean: 55.6+/-16), 290 males and 210 females. There were 120 cases of aortic valve replacement (AVR), 258 mitral valve replacement (MVR) and 22 combined aortic and mitral valve replacement (DVR). Additional procedures were performed in 144 patients. Patients were followed up prospectively at 3- to 6-month intervals. Mean follow-up was 38.4+/-11.8 months (maximum 55.6 months). Overall hospital mortality was 3.5%. Freedom from adverse events at 4 years in the study were as follows: thromboembolism, 99.1% for AVR, 98.3% for MVR and 94.7% for DVR patients; thrombosis, 100% for AVR, 99.2% for MVR and 94.7% for DVR; bleeding events, 99.1% for AVR, 99.2% for MVR and 88.8% for DVR; prosthetic endocarditis, 98.2% for AVR, 99.2% for MVR and 94.7% for DVR. Overall survival at 4 years was 92+/-1%. At echocardiographical examination within 1 year of the AVR, the mean aortic valve gradient was 12.8+/-6, 10.3+/-3, 9.0+/-4, 8.3+/-3, and 6.2+/-3 mmHg for 19, 21, 23, 25, 27/29 mm valve sizes, respectively. MVR mean gradient was 4.9+/-2, 4.5+/-1.2 and 4.0+/-0.8 mmHg for 25, 27/29, 31/33 mm valve sizes, respectively. On-X valve is a highly effective mechanical valve substitute with low morbidity and mortality and good functional results.

Mitral valve relpair and revascularization for ischemic mitral regurgitation: predictors of operative mortality and survival.

BACKGROUND AND AIMS OF THE STUDY: Surgery for ischemic mitral regurgitation (IMR) is required in 4-5% of patients subjected to coronary artery surgery, and may be challenging. The study aim was to determine outcome following mitral valve repair and myocardial revascularization for moderate-to-severe IMR. METHODS: A total of 102 patients (mean age 68+/-7 years) underwent mitral valve repair for IMR between 1998 and 2001 at the authors' unit. Among patients, 28 had acute and 74 chronic mitral regurgitation (MR). Valve repair was achieved with an annuloplasty ring in all 102 patients, while 99 underwent concomitant myocardial revascularization. Preoperatively, 69 patients had MR grade III-IV, 62 had CCS angina class III-IV, 59 were in NYHA class II-IV, 81 had impaired left ventricular function, and 10 were in cardiogenic shock. Follow up was 100% complete (mean 14+/-7 months; range: 0-38 months). RESULTS: Overall operative mortality was 8.8% (n = 9) (17.8% for acute IMR, 5.4% for chronic, p = 0.048). On multiple logistic regression analysis, cardiogenic shock (p = 0.028) was the only significant risk factor for operative death. There were 11 late deaths. Kaplan-Meier survival at one and three years was 82+/-4% and 79+/-4%, respectively. On Cox proportional hazards regression model, preoperative left ventricular end-systolic diameter (LVESD) >4.5 cm (p = 0.01) and NYHA class III-IV (p = 0.02) were independent adverse predictors of survival. Three patients required reoperation. Kaplan-Meier three-year freedom from reoperation was 97+/-2%. CONCLUSION: Surgery for IMR carries a considerable, but acceptable, operative risk and provides satisfactory freedom from reoperation and mid-term survival. Cardiogenic shock before surgery is the major determinant of an unfavorable in-hospital outcome. LVESD >4.5 cm and poor preoperative NYHA status limit the probability of late survival. The study results support early surgical intervention for IMR, before ventricular dilatation occurs.

Use of stentless xenografts in the aortic position: determinants of early and late outcome.

BACKGROUND: Whether to perform a stentless aortic valve replacement (AVR) is not well established. Our aim was to determine the outcome after AVR with stentless xenograft valves. METHODS: Between 1996 and 2001, a total of 404 patients (mean age 70.4 years) underwent a stentless AVR by one surgeon in our unit. Concomitant procedures were performed in 132 patients (33%). Twenty patients (6.4%) had undergone previous AVR. Eleven types of stentless xenograft valves were implanted: Medtronic Freestyle in 221 patients (55%), Shelhigh in 55 (14%), Shelhigh composite conduit in 33 (8%), Sorin in 26 (6%), Cryolife O'Brien in 25 (6%), Aortech-Elan in 17 (4%), Edwards Prima in 14 (4%), Toronto SPV in 7 (2%), and other valves in 6 (1%). A subcoronary implantation technique was used in 302 cases (76%), complete root replacement in 62 (15%), and a modified Bentall-De Bono procedure in 33 (8%). Mean follow-up was 19.4 months (range, 1.2 to 60.6 months). RESULTS: Overall hospital mortality was 4.2%. This was 2.4% for isolated AVR, 3.6% for AVR and coronary artery bypass grafting, 5.5% for replacement of two or more valves, and 12% for the modified Bentall procedure. On multiple logistic regression redo cardiac operation (p = 0.0006), cardiogenic shock (p = 0.001), left ventricular ejection fraction less than 0.30 (p = 0.01), modified Bentall procedure (p = 0.03), and endocarditis (p = 0.04) were predictors of in-hospital death. Five-year freedom from thromboembolism, hemorrhage, prosthetic endocarditis, structural valve deterioration, and reoperation was 97%, 99%, 99%, 98%, and 96%, respectively. Kaplan-Meier survival at 5 years was 88%. On Cox regression, cardiogenic shock (p = 0.001) and older age (p = 0.03) were adverse predictors of survival. At echocardiographic examination within 6 months from the operation, mean aortic valve gradients were 15 +/- 6 mm Hg, 12.8 +/- 3 mm Hg, 10.8 +/- 4 mm Hg, 9.3 +/- 3 mm Hg, 9.1 +/- 4 mm Hg, and 8.2 +/- 3 mm Hg for valve sizes of 19, 21, 23, 25, 27, and 29 mm, respectively. CONCLUSIONS: The availability of several stentless valve designs facilitates the surgical treatment of diverse aortic valve or root diseases with encouraging early and mid-term results. Patients requiring concomitant procedures may also benefit from the excellent hemodynamic characteristics of a stentless valve. We consider stentless AVR the treatment of choice for patients older than 60 years and those having small aortic roots.

Primary pericardial mesothelioma.

Pericardial mesothelioma is a rare cancer for which treatment options are limited. Operative intervention in pericardial mesothelioma is primarily for effusion control, for cytoreduction before multimodal therapy, or to deliver and monitor innovative intrapericardial therapies. Misdiagnosis is common. Early detection of the disease is the only hope for survival. Echocardiography, pathologic examination of pericardial fluid and pericardial biopsy, Gallium-67 scintigraph, Ber-EP4 antibody, and immunohistochemical procedures can be used. Magnetic resonance imaging is emerging as the best modality for demonstrating the nature and extent of the constrictive process, and the infiltration to the cardiac wall and great vessels. Failure of surgical techniques is usually associated with mesothelioma with entrapped heart, a large solid tumor mass, and a long history of pericardial effusion. If the tumor is localized, resection is the only hope for this rare, but lethal, entity. No single treatment modality is efficient by itself. The exact role of intracavitary chemotherapy or irradiation remains to be defined. Preliminary clinical application of photodynamic therapy and attempts at inhibiting the effects of growth factors, such as vascular endothelial growth factor and platelet-derived growth factor, and vaccine treatments are being explored. Adenoviral molecular chemotherapy recently completed phase I testing. Clinical trials for pleural mesothelioma remain important as clinicians seek to improve the outcome for patients with pericardial mesothelioma. Early diagnosis and multidisciplinary patient care is essential for improved surgical outcome. In the future, combined therapeutic strategies involving radical surgery, radiotherapy, adjuvant chemotherapy, and immunomodulation may have a role in the treatment of pericardial mesotheliomas.