Nadejda Monsefi

Comparison between homografts and Freestyle® bioprosthesis for right ventricular outflow tract replacement in Ross procedures

OBJECTIVES Although data from large series indicate the satisfactory performance of bioprosthetic valves in the right ventricular outflow tract (RVOT), replacement of the pulmonary valve in adult patients undergoing the Ross procedure is usually performed with pulmonary allografts. We evaluated the outcomes of homografts vs. bioprosthetic RVOT replacement after the Ross procedure in adults. METHODS Between 1996 and 2011, a total of 186 adult patients (141 male; mean age 44 ± 10 years) underwent aortic root replacement with a pulmonary autograft. The RVOT was replaced with a homograft in 113 patients and with stentless bioprostheses (Medtronic Freestyle(®)) in 73. Patients were followed for a mean of 6 years (range 1-15 years; 1106 patient years). RESULTS Twelve patients required reintervention owing to dysfunction of the RVOT replacement, which was caused by endocarditis (n = 4), degeneration (n = 2) or stricture at the proximal suture line (n = 6). For homografts, the incidence of reintervention was 1 in 150 patient years, compared with 1 in 36 patient years for stentless bioprostheses (P = 0.007). The median gradient was 15 mmHg for the homograft group and 24 mmHg for bioprosthesis (P < 0.0001). The incidence of gradients >40 mmHg was 10-fold higher in the bioprosthetic group. CONCLUSIONS Patients with bioprostheses in the RVOT position after the Ross procedure showed a significantly higher risk of reintervention or pulmonary valve dysfunction. The main problem, early development of a stricture at the proximal suture line, has to be solved to achieve satisfactory bioprosthetic function in the RVOT.

The CX3C chemokine fractalkine mediates platelet adhesion via the von Willebrand receptor glycoprotein Ib

The membrane-anchored CX3C chemokine fractalkine (FKN) is expressed on activated endothelium and is associated with the development of atherosclerosis. The potential of FKN in mediating platelet adhesion beyond platelet activation remains unexplored to date. A flow-based adhesion assay was used to study the adhesion of platelets to immobilized FKN under physiologic flow conditions. Platelet adhesion to von Willebrand factor (VWF) was increased in the presence of FKN at 600 inverse seconds. Additional platelet adhesion to FKN coimmobilized with VWF was dependent on the FKN receptor CX3CR1 and activation of glycoprotein (GP) IIb/IIIa. The number of platelets rolling on VWF was likewise enhanced in the presence of FKN. The enhancement of rolling on FKN and VWF was insensitive to anti-CX3CR1 antibody but was fully inhibited by neutralizing GPIbα function. The extracellular domain of GPIbα was covalently coupled to fluorescent microspheres, and microsphere binding was significantly higher in the presence of FKN. Platelet adhesion to activated endothelium in vitro and to intact human arteries was substantially increased in an FKN-dependent manner. These data demonstrate that endothelial expressed FKN activates platelets via its cognate receptor CX3CR1, whereas platelet adhesion is predominantly mediated by GPIbα and independent of CX3CR1.

Selenium and cardiovascular surgery: an overview.

Selenium is an essential nutritional element to mammalians necessary for the active function of different oxidant enzymes, as glutathione peroxidase (GPx), thioredoxin reductases (TrxR), and iodothyronine deiodinases (IDD). The anti-oxidative effect of selenium is pivotal for the human physiology. Oxidative stress is associated with various diseases, such as cardiovascular disease, diabetes mellitus or cancer, and is also associated with the majority of surgical procedures. Particularly, the use of cardiopulmonary bypass for open cardiac surgery with aortic clamping is always related to oxidative stress due to ischemia and reperfusion. Whereas myocardial protection with different temperatures and cardioplegic solutions has become more efficient, reperfusion is often followed by the activation of an injurious oxidative cascade. The pathogenesis of ischemia/reperfusion injury depends on many factors, among them, reactive nitrogen species (RNS) and reactive oxygen species (ROS) are considered as initiators of the injury. ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks. ROS production is physiologically controlled by free radical scavengers such as GPx and TrxR, and superoxide dismutase systems. GPx and TrxR are seleno-cysteine dependent enzymes, and their activity is known to be related to selenium availability. Furthermore, selenium has been reported to regulate gene expression of these selenoproteins as a cofactor and there is some evidence that selenium supplementation can attenuate the oxidative stress and decrease the complications after cardiac surgery. However, other clinical studies failed to demonstrate an association between selenium deficiency and cardiovascular outcomes. The aim of our review is to summarize the experimental and clinical evidence of preoperative selenium supplementation and therapy after cardiac surgery, focusing on the pathophysiology of oxidative stress and the clinical usage of selenium.

A 17-year, single-centre experience with the Ross procedure: fulfilling the promise of a durable option without anticoagulation?

OBJECTIVES For adult patients <60 years with aortic valve disease, the Ross procedure is an attractive alternative to a prosthetic aortic valve. The Ross procedure enables surgeons to achieve a haemodynamically ideal aortic valve replacement. A potential drawback may be long-term durability, which varies considerably between series. METHODS Between 1996 and 2014, 209 patients (mean age, 43 ± 10 years) underwent an elective Ross procedure in our department. In 78% (n = 161) of patients a bicuspid valve was found. Patients were examined clinically and with echocardiography during the follow-up. The mean follow-up was 7.9 ± 5 years and was 98% complete. RESULTS The 30-day mortality rate was 2.4% (n = 5). The Kaplan-Meier survival rates at 10 and 15 years were 91 and 85%, respectively. In 17 patients (8.3%) the pulmonary autograft had to be reoperated on: 12 of them could be repaired; only 5 patients finally underwent prosthetic valve replacement. The rate of freedom from reoperation for autograft failure was 93% and that from reoperation or moderate autograft regurgitation was 87% at 10 years. Thromboembolic events occurred in 9 patients (0.54%/patient-year) and were mostly related to atrial fibrillation. Endocarditis involving the pulmonary autograft was observed in 6 patients (0.36%/patient-year). CONCLUSIONS Pulmonary autograft aortic root replacement to treat patients with severe aortic valve dysfunction is a challenging procedure. The reoperation rate is higher compared with mechanical valve replacement; however, in the majority of patients with reoperations in our series the autograft could be saved. Other valve-related complications are rare.

Hepatocyte growth factor mobilizes non-bone marrow-derived circulating mesoangioblasts.

AIMS The identification of factors that mobilize subsets of endogenous progenitor cells may provide new therapeutic tools to enhance the repair of ischaemic tissue. We previously identified circulating mesenchymal cells that co-express endothelial markers (so-called circulating mesoangioblasts, cMABs) in children undergoing heart surgery with cardiopulmonary bypass (CPB). However, the mechanisms by which these cells are mobilized and their origin is unclear. METHODS AND RESULTS Circulating CD73(+)CD45(-)KDR(+) cMABs were analysed in adults undergoing heart surgery with (n = 21) or without CPB (n = 8). During surgery with CPB, cMABs are mobilized with a maximal response at the end of the operation. In contrast, off-pump heart surgery does not stimulate cMAB mobilization, indicating that the stress mediated by CPB induces the mobilization of cMAB. Circulating mesoangioblasts were enriched in blood obtained from the coronary sinus. Histologically, CD73(+) cells were detected around vessels in the heart, indicating that the heart is one of the niches of cMABs. Consistently, studies in gender mismatched bone marrow transplanted patients demonstrated that cMABs did not originate from the bone marrow. Cytokine profiling of serum samples revealed that hepatocyte growth factor (HGF) was profoundly increased at the time point of maximal mobilization of cMABs. Hepatocyte growth factor stimulated the migration of cMABs. Importantly, injection of recombinant HGF increased cMABs in rats. CONCLUSIONS Hepatocyte growth factor induces mobilization of non-haematopoietic progenitor cells with a cardiac repair capacity. This newly identified function together with the known pleiotrophic effects of HGF makes HGF an attractive therapeutic option for the treatment of ischaemic heart disease.

Modification of the David procedure for reconstruction of incompetent bicuspid aortic valves.

The David procedure was described primarily to treat tricuspid valves. The asymmetry of the bicuspid root asks for modifications to achieve a competent bicuspid valve. The most common feature of the bicuspid valve is the presence of left and right coronary rudimentary cusps. In this case usually the base of the noncoronary cusp is displaced toward the left ventricular outflow tract. The uneven plane of this type of bicuspid aortic annulus has to be compensated for when a rigid prosthesis is wrapped around the aortic root. We describe the modification of the David technique in 14 patients who underwent a valve-sparing aortic root replacement in presence of a bicuspid valve. This technique increases the coaptation surface and provides reliable early and mid-term competence of the reconstructed bicuspid aortic valves.

Platelets from flowing blood attach to the inflammatory chemokine CXCL16 expressed in the endothelium of the human vessel wall

Endothelial chemokine CXC motif ligand 16 (CXCL16) expression is associated with atherosclerosis, while platelets, particularly those attaching to atherosclerotic plaque, contribute to all stages of atherosclerotic disease. This investigation was designed to examine the role of CXCL16 in capturing platelets from flowing blood. CXCL16 was expressed in human atherosclerotic plaques, and lesion severity in human carotid endarterectomy specimens was positively correlated with CXCL16 levels. CXCL16 expression in plaques was co-localised with platelets deposited to the endothelium. Immobilised CXCL16 promoted CXCR6-dependent platelet adhesion to the human vessel wall, endothelial cells and von Willebrand factor during physiologic flow. At low shear, immobilised CXCL16 captured platelets from flowing blood. It also induced irreversible platelet aggregation and a rise in intra-platelet calcium levels. These results demonstrate that endothelial CXCL16s action on platelets is not only limited to platelet activation, but that immobilised CXCL16 also acts as a potent novel platelet adhesion ligand, inducing platelet adhesion to the human vessel wall.

Long-term results and cusp dynamics after aortic valve resuspension for aortic root aneurysms.

BACKGROUND This study reports our 10-year experience with the David technique and technical modifications to create neosinuses. METHODS From January 1996 to February 2009, the David procedure was performed in 151 consecutive patients in our department. Mean age was 59 ± 13 years (range, 22 to 78 years). All patients had ascending aortic aneurysm (mean diameter, 6.0 ± 1.1 cm); 59 patients had additional arch aneurysm. Fifty-four patients underwent the standard David procedure, with a pseudosinus created in 42 patients (28%) and neosinuses in 55 patients (36%) by plicating the base and sinotubular junction of the tube graft. Patients were followed up prospectively and had echocardiography studies before discharge and at follow-up. Mean follow-up was 5 years (584 patient-years). RESULTS There were 6 in-hospital and 16 late deaths. Reexploration for bleeding was necessary in 27 patients (17%). Three patients had perioperative neurologic events, and 2 patients experienced them during follow-up. Five patients required late aortic valve replacement. Cardiovascular events were the cause of late death in 6 patients. Valve gradients were low, with only 2 patients having significant valve incompetence remaining. Echocardiography results showed a more physiologic, reduced velocity of cusp movement in the neosinus group compared with the conventional technique. CONCLUSIONS Aortic valve resuspension is a durable procedure. Only 4.8% experienced a relevant valve dysfunction. Other valve-related complications were minimal, with three observed neurologic events and one endocarditis. Creation of the neosinus lead to more physiologic leaflet dynamics and facilitated geometric adaptation.

Mitral Valve Surgery in 6 Patients after Failed MitraClip Therapy

The MitraClip percutaneous mitral valve repair system, developed as an option for percutaneous mitral repair, was clinically introduced in 2007. From 2010 through 2012, 6 of our patients underwent mitral valve surgery after MitraClip failure. Their mean age was 75 ± 7.7 years (range, 62-87 yr). Three had undergone cardiac surgery previously. In 5 of the 6 patients, mitral regurgitation recurred after initially successful MitraClip deployment and was the indication for surgery. The mean interval between MitraClip implantation and surgery was 106 ± 86 days (range, 0-238 d). Mitral valve repair was feasible in 3 patients; the others underwent valve replacement. All the patients underwent additional cardiac procedures, because the MitraClip worsened existing conditions. Echocardiograms revealed sufficient valvular repairs. Two patients died during hospitalization, one of cerebral infarction and the other of bowel ischemia. Mitral valve repair after failed MitraClip therapy can be complex and a surgical challenge. Careful consideration should be given to appropriate patient selection for MitraClip therapy, because the MitraClip can cause existing pathologic valvular conditions to deteriorate substantially. The interval between MitraClip failure and corrective surgery should be as short as possible. The primary indication is an issue of ongoing discussion.

Long-Term Results Following Pericardial Patch Augmentation for Incompetent Bicuspid Aortic Valves: A Single Center Experience

BACKGROUND Many techniques for repair of bicuspid aortic valves have been described and long-term results differ considerably. The current study evaluates our institutional results using the pericardial patch augmentation technique with the aim of increasing coaptation height. METHODS From November 2002 through April 2015, 103 consecutive patients underwent aortic valve repair using pericardial patch augmentation for incompetent bicuspid aortic valve. Of them 26 were referred with an aortic valve regurgitation grade 1+ or 2+ and were excluded from the current report. The remaining 77 patients with a mean age of 42 ± 14 years and aortic valve regurgitation grade of 3+ or higher were included in this retrospective single-center study. The main step of operative technique is the partial correction of leaflet prolapse by leaflet plication and overcorrection of coaptation height augmenting the fused leaflet with an autologous pericardial patch. In 45 patients (58%) an isolated aortic valve repair was performed. The ascending aorta was dilated in 32 cases (42%), and the following procedures were used for correction: reduction aortoplasty (19 patients), the David procedure (11 patients), and ascending aortic replacement (2 patients). Long-term results were evaluated by echocardiography and standardized questionnaire. Mean follow-up was 4.9 ± 4.6 years. RESULTS There was no perioperative or 90-day mortality. Survival at 5 and 10 years was 96.1% and 93.5%, respectively. Freedom from reoperation at 5 and 10 years was 94.8% and 93.5%, respectively. At the latest echocardiographic follow-up, 94% of patients had none to trivial aortic regurgitation and 6% showed aortic regurgitation greater than or equal to 2°. Mean aortic gradients were 12.6 ± 9 mm Hg. One patients developed endocarditis 1 year after the procedure. There were no perioperative or long-term major neurologic events. CONCLUSIONS The pericardial patch augmentation technique provides reliable long-term competence of reconstructed bicuspid aortic valves and results in a low reoperation rate, with other valve related complications being rare.