Issam Ismail

Higher frequencies of BCRP+ cardiac resident cells in ischaemic human myocardium

AIMS Several cardiac resident progenitor cell types have been reported for the adult mammalian heart. Here we characterize their frequencies and distribution pattern in non-ischaemic human myocardial tissue and after ischaemic events. METHODS AND RESULTS We obtained 55 biopsy samples from human atria and ventricles and used immunohistological analysis to investigate two cardiac cell types, characterized by the expression of breast cancer resistance protein (BCRP)/ABCG2 [for side population (SP) cells] or c-kit. Highest frequencies of BCRP+ cells were detected in the ischaemic right atria with a median of 5.40% (range: 2.48-11.1%) vs. 4.40% (1.79-7.75%) in the non-ischaemic right atria (P = 0.47). Significantly higher amounts were identified in ischaemic compared with non-ischaemic ventricles, viz. 5.44% (3.24-9.30%) vs. 0.74% (0-5.23%) (P = 0.016). Few numbers of BCRP+ cells co-expressed the cardiac markers titin, sarcomeric α-actinin, or Nkx2.5; no co-expression of BCRP and progenitor cell marker Sca-1 or pluripotency markers Oct-3/4, SSEA-3, and SSEA-4 was detected. C-kit+ cells displayed higher frequencies in ischaemic (ratio: 1:25 000 ± 2500 of cell counts) vs. non-ischaemic myocardium (1:105 000 ± 43 000). Breast cancer resistance protein+/c-kit+ cells were not identified. Following in vitro differentiation, BCRP+ cells isolated from human heart biopsy samples (n = 6) showed expression of cardiac troponin T and α-myosin heavy-chain, but no full differentiation into functional beating cardiomyocytes was observed. CONCLUSION We were able to demonstrate that BCRP+/CD31- cells are more abundant in the heart than their c-kit+ counterparts. In the non-ischaemic hearts, they are preferentially located in the atria. Following ischaemia, their numbers are elevated significantly. Our data might provide a valuable snapshot at potential progenitor cells after acute ischaemia in vivo, and mapping of these easily accessible cells may influence future cell therapeutic strategies.

Angiopoietin-2 is a potential mediator of endothelial barrier dysfunction following cardiopulmonary bypass

INTRODUCTION Endothelial activation leading to vascular barrier dysfunction and organ failure is a well-recognized complication of cardiovascular surgery with cardiopulmonary bypass (CPB). The endothelial-specific angiopoietin-Tie2 ligand-receptor system has been identified as a non-redundant regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to the Tie2 receptor antagonizes Tie2 signaling and renders the endothelial barrier responsive to pro-inflammatory cytokines. We aimed to study the time course and potential triggering factors of Ang-2 release after CPB, as well as the association of Ang-2 changes with surrogates of increased vascular permeability, organ dysfunction, and outcome. METHODS Serum levels of Ang-2 from 25 adult patients (140 screened) were measured before and at 0, 12, and 24h following CPB procedure by in-house immuno-luminometric assay (ILMA), and compared with indices of organ dysfunction, duration of mechanical ventilation (MV), length of stay (LOS) in the intensive care unit (ICU), and hospital mortality. The effect of Ang-2 was studied in vitro by incubating high Ang-2 patient serum with endothelial cells (EC). RESULTS Ang-2 levels steadily increased from 2.6 ± 2.4 ng/mL at 0 h up to 7.3 ± 4.6 ng/mL at 24h following CPB (P<0.001). The release of Ang-2 correlated with the duration of CPB, aortic cross-clamp time, and post-CPB lactate levels. Changes in Ang-2 during follow-up correlated with partial pressure of oxygen in arterial blood (PaO(2))/fraction of inspired oxygen (FiO(2)) ratio, alveolar-arterial oxygen tension difference (AaDO(2)), hemodynamics, fluid balance, and disease severity measures. Ang-2 levels at 12h predicted the duration of MV, ICU-LOS, and hospital mortality. High Ang-2 patient sera disrupted EC architecture in vitro, an effect reversed by treatment with the competitive Tie2 ligand angiopoietin-1 (Ang-1). CONCLUSIONS Collectively, our results suggest that Ang-2 is a putative mediator of endothelial barrier dysfunction after CPB. These findings suggest that targeting the Ang/Tie2 pathway may mitigate organ dysfunction and improve outcome in patients undergoing CPB.

Comparison between biological and mechanical aortic valve prostheses in middle-aged patients matched through propensity score analysis: long-term results

OBJECTIVES Choice of prosthesis type in middle-aged patients undergoing aortic valve replacement (AVR) is still debated. The aim of this study is to compare long-term follow-up results in middle-aged patients who underwent isolated AVR with a biological or mechanical prosthesis. METHODS A retrospective analysis of a single-centre database was performed to identify patients aged between 55 and 65 years old who underwent isolated AVR with a biological or mechanical prosthesis from January 1996 to January 2008. Sixty patients with a biological aortic valve prosthesis (Group A) were identified and matched through propensity score analysis to other 60 patients with a mechanical aortic valve prosthesis (Group B). RESULTS There was no difference among groups regarding postoperative complications. Follow-up amounted to 117 ± 51 months. In Group A and B patients, 10- and 15-year survival was 77 ± 6 vs 75 ± 6 and 54 ± 13 vs 53 ± 8%, respectively (P = 0.95); 10- and 15-year freedom from structural valve deterioration, 81 ± 7 vs 100 and 64 ± 12 vs 93 ± 5%, respectively (P = 0.003); 10- and 15-year freedom from redo AVR, 87 ± 6 vs 91 ± 5 and 73 ± 11 vs 91 ± 5%, respectively (P = 0.04); 10- and 15-year freedom from endocarditis, 94 ± 3 vs 98 ± 2 and 83 ± 8 vs 98 ± 2%, respectively (P = 0.05); 10- and 15-year freedom from bleeding events, 98 ± 2 vs 96 ± 5 and 88 ± 6 vs 77 ± 10%, respectively (P = 0.98); and 10- and 15-year freedom from cerebrovascular events, 94 ± 3 vs 97 ± 3 and 83 ± 8 vs 97 ± 3%, respectively (P = 0.03). CONCLUSIONS While survival was not different among groups, patients with a biological prosthesis showed a higher valve-related morbidity at follow-up. Therefore, middle-aged patients should preferably receive a mechanical prosthesis.

Surgical treatment of coronary artery aneurysms

Coronary artery aneurysms (CAA) are rare. We present our experience with the surgical treatment of patients with CAAs.

Right-Sided Heart Failure and Extracorporeal Life Support in Patients Undergoing Pericardiectomy for Constrictive Pericarditis: A Risk Factor Analysis for Adverse Outcome

Background Right ventricular failure is a life‐threatening postoperative complication after pericardiectomy. We conducted a retrospective study with a special emphasis on right ventricular failure. Methods Between June 1997 and September 2011, 69 patients underwent surgical pericardiectomy at our center. Mean age was 59 (± 15.5) years, and 49 (71%) patients were male. Causes of constrictive pericarditis included idiopathic (52%, n = 36), tuberculosis (9%, n = 6), postcardiotomy (12%, n = 8), radiation (4%, n = 3), renal insufficiency (12%, n = 8), and autoimmune disease (12%, n = 8). Concomitant cardiac surgery was performed in 33 (48%) patients. Results In‐hospital mortality rate was 14% (10/69 patients). Extracorporeal membrane oxygenation (ECMO) was necessary in 8 (12%) cases because of right (n = 7) or biventricular (n = 1) failure. Statistical analysis showed a significant correlation between early mortality and the following preoperative variables: postcardiotomy (p = 0.049), radiation (p = 0.009), pleural effusion (p = 0.012), ascites (p = 0.039), hepatic congestion (p = 0.023), absence of calcification on X‐ray (p = 0.041), tricuspid valve insufficiency (TI, p < 0.001), and low cardiac index (p = 0.003). Diuretic usage (p = 0.044), peripheral edema (p = 0.050), low voltage (p = 0.027), dip‐plateau sign (p = 0.027), elevated GGT (p < 0.001), and decreased serum protein (p < 0.001) correlated with ECMO implantation. Binary logistic regression identified pleural effusion (OR = 16.2, 95% CI = 1.4‐191.5), moderate/severe TI (OR = 28.8, 95% CI = 2.7‐306.8) and low cardiac index (OR = 25.3, 95% CI = 2.0‐315.6) as preoperative independent risk factors for early mortality, whereas elevated GGT (OR = 28.3, 95% CI = 2.4‐329.2) and decreased protein (OR = 24.7, 95% CI = 1.8‐343.7) could predict right ventricular failure with the need for ECMO. Conclusion We recommend nondelayed ECMO support in case of significant postoperative right‐sided heart failure. High‐risk patients might benefit from elective pre‐ or intraoperative ECMO implantation.

Long-term results of the Mitroflow aortic pericardial bioprosthesis in over 800 patients: limited durability and mechanisms of dysfunction†

OBJECTIVES The Mitroflow aortic pericardial bioprosthesis was widely employed in the past. However, some authors have recently reported early structural valve deterioration (SVD) of the Mitroflow LA/LXA model. Thus, we reviewed our experience with the Mitroflow bioprosthesis and studied the risk factors for SVD and mortality. METHODS Records of patients who underwent aortic valve replacement with a Mitroflow bioprosthesis between November 2005 and January 2015 were retrospectively evaluated with Kaplan-Meier, Cox-regression and multistate analysis. Only patients with a complete clinical follow-up were included in the study. Average follow-up was 45 months and ended on 1 April 2016. RESULTS Between November 2005 and January 2015, among the 916 patients undergoing aortic valve replacement with the Mitroflow prosthesis at our Institution, the 832 (90.8%) patients with follow-up information were included into the study. Fifty-two (6.2%) patients developed SVD (stenosis, n  = 38; regurgitation, n  = 7; mixed, n  = 7). Freedom from SVD was 95.4% and 67.9%, at 5 and 9 years, respectively, without differences after stratification according to the prosthesis model ( P  = 0.87) and prosthesis size ( P  = 0.70). At the multivariable analysis, increasing age was identified as a protective factor against SVD (hazard ratio = 0.94, P  < 0.001). Twenty (38.4%) patients with SVD underwent redo aortic valve replacement. At 5 and 9 years, survival was 64.5% and 43.1%, repectively. According to the multistate analysis, the fraction of patients living with degenerated valves at 9 years was 10.0%; 7.1% died following degeneration. CONCLUSIONS The LA/LXA Mitroflow model showed limited long-term durability. Degenerated prostheses showed more stenosis than regurgitation. Patient age played an important role in the development of SVD.

Long-term follow-up of total arterial revascularization with left internal thoracic artery and radial artery T-grafts: survival, cardiac morbidity and quality of life

OBJECTIVES Coronary artery bypass grafting is the gold standard for the treatment of patients with multiple-vessel coronary artery disease. The long-term outcome can be improved using arterial grafts. We analysed the initial series of patients who underwent total arterial revascularization at our institute using left internal thoracic artery (LITA) and radial artery (RA) composite T-grafts and had a follow-up of >10 years. METHODS We included all patients who received an isolated, non-emergent total arterial revascularization using LITA-RA T-grafts between September 1996 and August 2001 in our institution. We performed a follow-up of 138 patients (104 male, 60 ± 9 years old). RESULTS Early outcome was excellent. The 30-day mortality, reoperation, neurological complication and myocardial ischaemia rate was 1% (n = 2), 5% (n = 7), 2% (n = 3) and 2% (n = 3), respectively. Mean follow-up was 11 ± 3 years. Long-term survival was 79% (n = 86). There were seven cardiac deaths during follow-up. Freedom from major cardiovascular events for 1, 5 and 10 years was 97, 91 and 84%, respectively. A total of 95 coronary angiographies were performed 4.6 ± 4.1 years postoperatively. In total, 453 anastomoses using the composite graft (LITA-RA as T-graft) were performed. During follow-up, 35 anastomoses were occluded (30 RA anastomoses and 5 LITA anastomoses), leading to an occlusion rate of 7.7% during follow-up. Percutaneous coronary intervention was performed in 18 cases and coronary reoperation in two cases during follow-up. Quality-of-life assessment by Minnesota Living with Heart Failure Questionnaire revealed excellent results. CONCLUSIONS Total arterial revascularization using composite LITA-RA T-grafts leads to excellent long-term results after >10 years.

Retrosternal adhesiolysis through an anterior minithoracotomy: A novel approach facilitating complete median redo sternotomy with a patent internal thoracic artery graft

CONCLUSIONS Resection and reconstruction of the roof of the CS can be efficiently accomplished to ensure complete resection of the myxoma. References 1. Symbas PN, Hatcher Jr CR, Gravanis M. Myxoma of the heart: clinical and experimental observations. Ann Surg. 1976;183:470. 2. Nkere UU, Pugsley WB. Time relationships in the diagnosis and treatment of left-atrial myxoma. Thorac Cardiovasc Surg. 1993;41:301-3. 3. McCarthy PM, Piehler JM, Schaff HV, et al. The significance of multiple, recurrent, and ‘‘complex’’ cardiac myxomas. J Thorac Cardiovasc Surg. 1986;91:389-96. 4. Waller DA, Ettles DF, Saunders NR, Williams G. Recurrent cardiac myxoma: the surgical implications of two distinct group of patients. Thorac Cardiovasc Surg. 1989;37:226-30. 5. Morishita K, Fukada J, Abe T. Inverted T-shaped biatrial incision for large left atrial myxoma. J Card Surg. 1997;12:112-5. Brief Communications

HeartWare left ventricular assist device for the treatment of advanced heart failure

The importance of mechanical circulatory support in the therapy of advanced heart failure is steadily growing. The rapid developments in the field of mechanical support are characterized by continuous miniaturization and enhanced performance of the assist devices, providing increased pump durability and prolonged patient survival. The HeartWare left ventricular assist device system (HeartWare Inc., Framingham, MA, USA) is a mechanical ventricular assist device with over 8000 implantations worldwide. Compared with other available assist devices it is smaller in size and used in a broad range of patients. The possibility of minimally invasive procedures is one of the major benefits of the device - allowing implants and explants, as well as exchanges of the device with reduced surgical impact. We present here a review of the existing literature on the treatment of advanced heart failure using the HeartWare left ventricular assist device system.

Aortic root surgery in combination with hypothermic circulatory arrest: preserve or replace the aortic valve in the context of postoperative neurological outcome? A case match comparison.

The objective of this study was to compare the results of elective composite (C) vs. David (D) operations in patients requiring additional aortic arch surgery using hypothermic circulatory arrest (HCA) and selective antegrade cerebral perfusion (SACP), with the focus on postoperative neurological outcome and quality of life (SF-36). Between November 1999 and March 2006, 333 patients underwent aortic root surgery and ascending aortic replacement with HCA and SACP at our institution. Out of these patients, 46 were matched with respect to age, gender, HCA-time and year of surgery. Two patients, one in each group, died during hospital stay (4%), with no late deaths. Follow-up was completed in 95% [64 (6-90) months]. Cardiopulmonary bypass (CPB) time (141 min vs. 168 min, P=0.007) and aortic cross-clamp time (99 min vs. 123 min, P=0.004) were significantly longer in the David-group. The incidence of temporary neurological dysfunction (TND 7%: D n=1, C n=2) was not different between groups, no permanent dysfunction could be detected. Follow-up SF-36 scores were comparable. The combination of aortic arch surgery with more time consuming valve sparing aortic root surgery does not increase the risk for adverse outcome applying comparable periods of HCA and SACP.