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1.  Living-Engineered Valves for Transcatheter Venous Valve Repair 
Background: Chronic venous insufficiency (CVI) represents a major global health problem with increasing prevalence and morbidity. CVI is due to an incompetence of the venous valves, which causes venous reflux and distal venous hypertension. Several studies have focused on the replacement of diseased venous valves using xeno- and allogenic transplants, so far with moderate success due to immunologic and thromboembolic complications. Autologous cell-derived tissue-engineered venous valves (TEVVs) based on fully biodegradable scaffolds could overcome these limitations by providing non-immunogenic, non-thrombogenic constructs with remodeling and growth potential.
Methods: Tri- and bicuspid venous valves (n=27) based on polyglycolic acid–poly-4-hydroxybutyrate composite scaffolds, integrated into self-expandable nitinol stents, were engineered from autologous ovine bone-marrow-derived mesenchymal stem cells (BM-MSCs) and endothelialized. After in vitro conditioning in a (flow) pulse duplicator system, the TEVVs were crimped (n=18) and experimentally delivered (n=7). The effects of crimping on the tissue-engineered constructs were investigated using histology, immunohistochemistry, scanning electron microscopy, grating interferometry (GI), and planar fluorescence reflectance imaging. Results: The generated TEVVs showed layered tissue formation with increasing collagen and glycosaminoglycan levels dependent on the duration of in vitro conditioning. After crimping no effects were found on the MSC level in scanning electron microscopy analysis, GI, histology, and extracellular matrix analysis. However, substantial endothelial cell loss was detected after the crimping procedure, which could be reduced by increasing the static conditioning phase.
Conclusions: Autologous living small-diameter TEVVs can be successfully fabricated from ovine BM-MSCs using a (flow) pulse duplicator conditioning approach. These constructs hold the potential to overcome the limitations of currently used non-autologous replacement materials and may open new therapeutic concepts for the treatment of CVI in the future.
PMCID: PMC4026099  PMID: 24156382
2.  Pancreatic Stone Protein Predicts Postoperative Infection in Cardiac Surgery Patients Irrespective of Cardiopulmonary Bypass or Surgical Technique 
PLoS ONE  2015;10(3):e0120276.
We investigated the role of pancreatic stone protein (PSP) in predicting the occurrence of infection in the postoperative course of cardiac surgery patients. Several biomarkers indicating the presence of inflammation and infection are available in the clinical routine; yet, their utility in the postoperative course of patients following cardiac surgery remains uncertain. Moreover, cardiopulmonary bypass, also referred to as “on-pump surgery”, increases the susceptibility to an exaggerated inflammatory state. However, the impact of such extracorporeal circulation on circulating PSP levels remains poorly understood.
In a prospective cohort of unselected patients undergoing cardiac surgery, we set out to elucidate the diagnostic accuracy of serum PSP levels as opposed to canonical biomarkers (CRP, WBC) of inflammation to discriminate between the presence of infection and surgical trauma,. In addition, we investigated whether the biomarkers were influenced by the surgical technique employed, i.e. on-pump vs. off-pump and minimally invasive surgery vs. sternotomy. Levels of circulating PSP and routine inflammatory biomarkers (CRP, WBC) were measured in samples taken from 120 patients at baseline as well as at postoperative day 1–3.
Univariate analysis showed that among the biomarkers investigated, only PSP levels had discriminatory power to differentiate infection from surgical trauma in the postoperative course of the entire cohort of patients following cardiac surgery. With regard to cardiac surgical interventions, there was no significant association between the absence or presence of extracorporeal circulation and PSP levels. However, there was a significant difference in the slope of the rise of postoperative PSP between minimally invasive surgery as opposed to patients subjected to sternotomy.
In an unselected population of cardiac surgery patients, post-operative serum PSP levels were significantly associated with the presence of infection in both the on-pump and off-pump setting. Of note, the surgical technique employed (sternotomy vs. minimally invasive approach) had a significant impact on postoperative PSP levels.
PMCID: PMC4368752  PMID: 25793700
3.  Concept and first experimental results of a new ferromagnetic assist device for extra-aortic counterpulsation 
Based on a ferromagnetic silicone cuff for extra-aortic counterpulsation, a new assist device concept was developed. The driving force is generated by an external magnetic field, which leads to contraction of a soft magnetic cuff. The force generation capacity of the device was tested in a silicone aorta model.
Magnetic elastomers can be constructed through dispersion of micro- or nanoparticles in polymer matrices and were designed to act as soft actuators. Two magnetically active silicone cuffs were produced with a nanomagnet loading of 250 wt% (Cuff 1) and a micromagnet loading of 67 wt% (Cuff 2). The magnetic cuffs were applied on a silicone aorta model and contracted against hydrostatic pressure.
A full contraction of Cuff 1 was possible against a maximal hydrostatic pressure of 30 cmH2O (22 mmHg) at a magnetic flux density of 0.4 T (Tesla) and 65 cmH2O (48 mmHg) at a magnetic flux density of 1.2 T. A 50% contraction of Cuff 2 was possible against a maximal hydrostatic pressure of 80 cmH2O (59 mmHg) at a magnet-cuff-distance (MCD) of 0 cm. At MCDs of 1 and 2 cm a 50% contraction was possible against 33 cmH2O (24 mmHg) and 10 cmH2O (7 mmHg), respectively.
Combining the advantages of magnetic elastomers with the principle of extra-aortic counterpulsation in a new assist device concept avoids the need for anticoagulation (no contact with bloodstream). With regard to the magnetic principle of action, no intra- to extracorporeal connection is needed. More experimental work is needed to further increase the force generated by the silicone cuff and to transfer the device concept into an in vivo setting.
PMCID: PMC3867034  PMID: 24061069
Assist device; Heart failure; Extra-aortic counterpulsation
4.  Evaluation of calcium loss after transcatheter aortic valve implantation 
Aortic valve calcification and changes after transcatheter aortic valve implantation (TAVI) were specifically assessed by computed tomography (CT). The main difference between TAVI and the conventional technique is the compression of the cusps of the calcified native valve against the aortic wall before implantation. The objective of this study was to quantify the segmented calcification in the area of the basal annular plane before and after TAVI.
The CT scans of 20 patients (13 male and 7 female; mean age: 82.9 ± 8.1 years) were assessed. The aortic valve calcification was segmented; derived from this segmentation volume, mass and Hounsfield units (HU)/density of the calcifications on the annulus and cusps before and after TAVI were evaluated. Pre- and postoperative data were compared regarding potential calcification loss and calcification distances to the left and right coronary ostia.
Significantly lower postprocedural mean volumes and masses for all cusps (P < 0.001) were found. The mean differences in the volume for the non-coronary, right-coronary and left-coronary cusp were −156.8 ± 53.73, −155.5 ± 62.54 and −115 ± 57.53 mm3, respectively, and differences in mass were −88.78 ± 29.48, −95.2 ± 39.27 and −71.56 ± 35.62 mg, respectively. Over all cusps, mean HU increased after intervention [784.41 ± 92.5 HU (pre) and 818.63 ± 78.71 HU (post); P < 0.004]. In 80.03% of all cusps, calcification loss was found; all patients were affected. Significantly lower (P < 0.047) postprocedural mean distances were found from the left and right coronary ostia to the next calcification point.
Our results show a significant loss of calcification in all patients after TAVI, with a reduction in the calcification distances to the coronary ostia and the compression of calcification in the area of the device landing zone. The clinical implications of this finding need to be investigated further.
PMCID: PMC3867042  PMID: 24105864
Aortic root; Aortic valve repair; Aortic valve replacement; Valve calcification
5.  Diastolic Aorto–Right-Atrial Fistulation in Aortic and Tricuspid Valve Endocarditis 
Background Aorto–right-atrial fistula in native valve endocarditis is very rare.
Case Description A 45-year-old woman was referred with an endocarditis with a perforated right cusp of the aortic valve with at least moderate insufficiency and an affected tricuspid annulus with vegetations. In addition to this, an aorto-cavitary fistula from the aortic sinus to the right atrium with a holodiastolic left–right shunt had been detected. Streptococci viridans were found as underlying pathogen. Complete replacement of the aortic root and resection of the fistula were performed with good result.
Conclusion Endocarditis with fistula formation is rare and has to be treated aggressively.
PMCID: PMC4360693  PMID: 25798353
aortic valve and root; endocarditis; cardiovascular surgery
6.  The endovascular occlusion system for safe and immediate peripheral vessel occlusion during vascular interventions 
Endovascular occlusion of blood vessels is an important part of interventional therapy concepts. Here, we evaluate the feasibility, procedural safety and efficacy of the novel endovascular occlusion system (EOS) in the arterial system in a porcine model. Thirteen devices were deployed in the iliac and femoral arteries (diameter: 4–5 mm) of five adult swine. Post-deployment angiography was performed at 1, 5 and 10 min and 6 h. All devices (n = 13) could be successfully delivered without any complications, such as dissection, perforation or rupture. The devices could be easily advanced to the target vessel segment, deployed at the intended target location and produced immediate and complete vessel occlusion which was confirmed to be maintained after 6 h. No leaks, recanalization or device migration was observed. In this pilot study, we demonstrate the feasibility, safety and efficacy of immediate vessel occlusion with the EOS device in the peripheral arterial system in a porcine animal model. Our data indicate that this novel device allows precise delivery without the occurrence of cardiovascular complications. Owing to its long-term safety and efficacy the EOS may represent a promising and effective alternative to currently available devices for vessel occlusion during vascular interventions.
PMCID: PMC3805205  PMID: 23868605
Vessel occlusion; Endovascular; Occlusion device; Embolization
7.  HEARTSTRING enabled no-touch proximal anastomosis for off-pump coronary artery bypass grafting: current evidence and technique 
Surgical revascularization remains the standard of care for many patients. Off-pump coronary artery bypass grafting (OPCAB) without cardiopulmonary bypass (CPB) has evolved during the past 20 years, and as such can significantly reduce the occurrence of neurological complications. While avoiding the aortic cross-clamping required in conventional on-pump techniques, OPCAB results in a lower incidence of stroke. However, clamp-related risk of stroke remains if partial or side-biting clamps are applied for proximal anastomoses. Others and we have demonstrated that no-touch ‘anaortic’ approaches avoiding any clamping during off-pump procedures via complete in situ grafting result in significantly reduced stroke rates when compared with partial clamping. Therefore, OPCAB in situ grafting has been proposed as the ‘standard of care’ to reduce neurological complications. However, this technique may not be applicable to for every patient as the use of free grafts (arterial or venous) requiring proximal anastomosis is often still necessary to achieve complete revascularization. In these situations, proximal anastomosis can be performed without a partial clamp by using the HEARTSTRING device, and over the last few years, considerable evidence has arisen supporting the impact of HEARTSTRING-enabled anastomosis to significantly minimize atheroembolism and neurological complications when compared with partial- or side-bite clamping. This paper provides a systematic overview and technical information about the combination of OPCAB and clampless strategies using the HEARTSTRING for proximal anastomosis to reduce stroke to levels reported for percutaneous coronary intervention.
PMCID: PMC3745146  PMID: 23732260
Coronary artery bypass grafting; Coronary artery disease; Off-pump; Clampless; HEARTSTRING; No-touch; Stroke; Neurological complication
9.  Implantation of personalized, biocompatible mitral annuloplasty rings: feasibility study in an animal model 
Implantation of an annuloplasty ring is an essential component of a durable mitral valve repair. Currently available off-the-shelf rings still do not cover all the variations in mitral annulus anatomy and pathology from subject to subject. Computed tomography (CT) and echo imaging allow for 3-D segmentation of the mitral valve and mitral annulus. The concept of tailored annuloplasty rings has been proposed although, to date, no surgically applicable implementation of patient-specific annuloplasty rings has been seen. The objective of this trial was to prove the concept of surgical implantation of a model-guided, personalized mitral annuloplasty ring, manufactured based on individual CT-scan models.
ECG-gated CT angiography was performed in six healthy pigs under general anaesthesia. Based on the individual shape of the mitral annulus in systole, a customized solid ring with integrated suturing holes was designed and manufactured from a biocompatible titanium alloy by a rapid process using laser melting. The ring was implanted three days later and valve function was assessed by intraoperative echocardiography. The macroscopic annulus–annuloplasty match was assessed after heart explantation.
CT angiography provided good enough image quality in all animals to allow for segmentation of the mitral annulus. The individually tailored mitral rings were manufactured and successfully implanted in all pigs. In 50%, a perfect matching of the implanted ring and the mitral annulus was achieved. In one animal, a slight deviation of the ring shape from the circumference was seen postoperatively. The rings implanted in the first two animals were significantly oversized but the deviation did not affect valve competence.
CT image quality and accuracy of the dimensions of the mitral annulus were sufficient for digital modelling and rapid manufacturing of mitral rings. Implantation of individually tailored annuloplasty rings is feasible.
PMCID: PMC3598035  PMID: 23287589
Cardiac surgery; Animal feasibility study; Mitral valve repair; Personalized annuloplasty
10.  Chordae replacement versus leaflet resection in minimally invasive mitral valve repair 
Annals of Cardiothoracic Surgery  2013;2(6):809-813.
For many years, the quadrangular resection technique first proposed by Carpentier has become the gold standard for repair of posterior leaflet prolapse of the mitral valve (MV). Although this “resection” technique and its modifications are safe and very effective, they do not respect the anatomy of the MV and the physiological role of the posterior leaflet. Therefore some new techniques, aiming to preserve MV leaflets to a different extent, have been proposed. With the use of expanded polytetrafluoroethylene (ePTFE), neochordae leaflet preserving techniques for posterior MV prolapse treatment have emerged. The aim of these techniques is to support the free edge of the prolapsing segments and thereby restore the physiologic function of the MV. A simplified modification of this technique using premeasured ePTFE loops (“loop technique”) was successfully introduced to ease the implantation of neochordae, especially in the setting of minimally invasive MV surgery.
While “resection” techniques are associated with excellent long-term results, there is evolving evidence in favor of “non-resection” techniques supporting the concept of a “respect rather than resect” approach.
PMCID: PMC3856996  PMID: 24349986
Mitral valve repair (MVR); leaflet prolapse; leaflet resection; chordae replacement; loop technique; minimally invasive mitral surgery
11.  Epicardial left atrial appendage clip occlusion also provides the electrical isolation of the left atrial appendage 
The exclusion of the left atrial appendage (LAA) has been used to reduce the risk of stroke associated with atrial fibrillation (AF). While LAA exclusion has been associated with a reduced risk of stroke, the effect on the electrical activity of the LAA (a potential source of AF) remains unknown. As such, we sought to demonstrate whether surgical epicardial clip occlusion leads to the electrical isolation of the LAA.
From December 2010 until August 2011, 10 patients with paroxysmal AF underwent off-pump coronary artery bypass surgery with bilateral pulmonary vein isolation and an LAA clip occlusion with a new epicardial clip. Before and after the clip was placed, pacing manoeuvres were performed to assess the electrical exit and entry blocks from the LAA.
All clips were applied successfully. The mean procedure time for the clip application was 4 ± 1 min. No complications occurred related to clip application. Prior to the pericardial closure, 18 ± 3 min after the clip placement, the LAA stimulation and pacing manoeuvres demonstrated complete electrical isolation of the LAA in all cases.
Epicardial LAA clip occlusion leads to the acute electrical isolation of the LAA and may not only provide stroke prevention but also reduce the recurrence of AF.
PMCID: PMC3422917  PMID: 22647971
Atrial fibrillation; Left atrial appendage; Clip; Electrical isolation; Stroke; Occlusion; Maze; Ablation; Surgery
12.  Intramyocardial Transplantation and Tracking of Human Mesenchymal Stem Cells in a Novel Intra-Uterine Pre-Immune Fetal Sheep Myocardial Infarction Model: A Proof of Concept Study 
PLoS ONE  2013;8(3):e57759.
Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70–75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7–9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×105–5×105 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy.
PMCID: PMC3606388  PMID: 23533575
13.  Complete graft dehiscence 8 months after repair of acute type A aortic dissection 
Acute type A aortic dissection is a dreaded differential diagnosis of acute chest pain. Long-term outcome mainly depends on pre-existing comorbidities and post-operative complications. We present a patient with aortic graft dehiscence and subsequent severe aortic regurgitation due to fungal graft infection 8 months after repair of acute type A aortic dissection. Redo aortic surgery had to be delayed for 28 days due to intracerebral haemorrhage caused by septic embolism and clipping of a mycotic left middle cerebral artery aneurysm. Surgery revealed a circumferentially detached graft at the site of the proximal anastomosis thereby forming a massive pseudoaneurysm. The patient underwent successful aortic root replacement using a Freestyle porcine root bioprosthesis (25 mm), followed by re-anastomosis of the coronary arteries and partial replacement of the ascending aorta with a 28 mm Dacron graft. The patient was discharged on day 67 in stable cardiac condition with persistent neurological deficits. This case highlights the challenging management of patients with aortic graft infection and neurological dysfunction after redissection of the ascending aorta who require redo cardiac surgery.
PMCID: PMC3760577  PMID: 24062936
Acute type A aortic dissection; graft dehiscence; neurological dysfunction; redo surgery
14.  Interhospital transfer of seriously sick ARDS patients using veno-venous Extracorporeal Membrane Oxygenation (ECMO): Concept of an ECMO transport team 
Extracorporeal membrane oxygenation (ECMO) therapy constitutes the last option for patients with acute respiratory distress syndrome (ARDS) refractory to conservative treatment. Since primary care centers are unable to provide this therapy, such patients need a transfer to a tertiary care center, which may be life-threatening without extracorporeal support.
An ECMO transport team implanted an ECMO at the site of the primary care center with subsequent transport of the patient to the tertiary care center. Between September 2009 and March 2011, six patients with ARDS were treated by our ECMO transport team. Mean age was 39.5±12.0 years. All implantations were done percutaneously in a veno-venous configuration.
No complications occurred during the implant procedure and the subsequent transport. Four patients (67%) were successfully weaned from ECMO-therapy, and discharged from hospital.
With a specialized ECMO transport team, ECMO-implantation can be achieved successfully in a peripheral hospital, and patients can be transported safely.
PMCID: PMC3665119  PMID: 23724385
Acute respiratory distress syndrome; extracorporeal life support; extracorporeal membrane oxygenation; interhospital transfer
15.  Late pharmacologic conditioning with volatile anesthetics after cardiac surgery 
Critical Care  2012;16(5):R191.
The aim of this randomized controlled trial was to investigate whether volatile anesthetics used for postoperative sedation have any beneficial effects on myocardial injury in cardiac surgery patients after on-pump valve replacement.
Anesthesia was performed with propofol. After arrival in the intensive care unit (ICU), 117 patients were randomized to be sedated for at least 4 hours with either propofol or sevoflurane. Sevoflurane was administered by using the anesthetic-conserving device. Troponin T, creatine kinase, creatine kinase from heart muscle tissue, myoglobin, and oxygenation index were determined on arrival at the ICU, 4 hours after sedation, and in the morning of the first postoperative day (POD1). Primary end points were cardiac injury markers on POD1. As secondary end points oxygenation, postoperative pulmonary complications, and ICU and hospital stay were documented.
Fifty-six patients were analyzed in the propofol arm, and 46 patients in the sevoflurane arm. Treatment groups were comparable with regard to patient demographics and intraoperative characteristics. Concentration of troponin T as the most sensitive marker for myocardial injury at POD1 was significantly lower in the sevoflurane group compared with the propofol group (unadjusted difference, -0.4; 95% CI, -0.7 to -0.1; P < 0.01; adjusted difference, -0.2; 95% CI, -0.4 to -0.02; P = 0.03, respectively).
The data presented in this investigation indicate that late postconditioning with the volatile anesthetic sevoflurane might mediate cardiac protection, even with a late, brief, and low-dose application.
Trial registration NCT00924222.
PMCID: PMC3682293  PMID: 23062276
16.  Transapical aortic valve implantation with anatomically oriented prostheses 
Annals of Cardiothoracic Surgery  2012;1(2):176-181.
PMCID: PMC3741750  PMID: 23977490
17.  EH-myomesin splice isoform is a novel marker for dilated cardiomyopathy 
Basic Research in Cardiology  2010;106(2):233-247.
The M-band is the prominent cytoskeletal structure that cross-links the myosin and titin filaments in the middle of the sarcomere. To investigate M-band alterations in heart disease, we analyzed the expression of its main components, proteins of the myomesin family, in mouse and human cardiomyopathy. Cardiac function was assessed by echocardiography and compared to the expression pattern of myomesins evaluated with RT-PCR, Western blot, and immunofluorescent analysis. Disease progression in transgenic mouse models for dilated cardiomyopathy (DCM) was accompanied by specific M-band alterations. The dominant splice isoform in the embryonic heart, EH-myomesin, was strongly up-regulated in the failing heart and correlated with a decrease in cardiac function (R = −0.86). In addition, we have analyzed the expressions of myomesins in human myocardial biopsies (N = 40) obtained from DCM patients, DCM patients supported by a left ventricular assist device (LVAD), hypertrophic cardiomyopathy (HCM) patients and controls. Quantitative RT-PCR revealed that the EH-myomesin isoform was up-regulated 41-fold (P < 0.001) in the DCM patients compared to control patients. In DCM hearts supported by a LVAD and HCM hearts, the EH-myomesin expression was comparable to controls. Immunofluorescent analyses indicate that EH-myomesin was enhanced in a cell-specific manner, leading to a higher heterogeneity of the myocytes’ cytoskeleton through the myocardial wall. We suggest that the up-regulation of EH-myomesin denotes an adaptive remodeling of the sarcomere cytoskeleton in the dilated heart and might serve as a marker for DCM in mouse and human myocardium.
Electronic supplementary material
The online version of this article (doi:10.1007/s00395-010-0131-2) contains supplementary material, which is available to authorized users.
PMCID: PMC3032906  PMID: 21069531
Dilated cardiomyopathy; Heart failure; Sarcomere cytoskeleton; M-band; Myomesin
18.  Degenerative mitral valve regurgitation: best practice revolution 
European Heart Journal  2010;31(16):1958-1966.
Degenerative mitral valve disease often leads to leaflet prolapse due to chordal elongation or rupture, and resulting in mitral valve regurgitation. Guideline referral for surgical intervention centres primarily on symptoms and ventricular dysfunction. The recommended treatment for degenerative mitral valve disease is mitral valve reconstruction, as opposed to valve replacement with a bioprosthetic or mechanical valve, because valve repair is associated with improved event free survival. Recent studies have documented a significant number of patients are not referred in a timely fashion according to established guidelines, and when they are subjected to surgery, an alarming number of patients continue to undergo mitral valve replacement. The debate around appropriate timing of intervention for asymptomatic severe mitral valve regurgitation has put additional emphasis on targeted surgeon referral and the need to ensure a very high rate of mitral valve repair, particularly in the non-elderly population. Current clinical practice remains suboptimal for many patients, and this review explores the need for a ‘best practice revolution’ in the field of degenerative mitral valve regurgitation.
PMCID: PMC2921508  PMID: 20624767
Mitral valve; Valve repair
19.  Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis 
Objective To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease.
Design Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation.
Eligibility criteria for selecting studies A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease.
Data sources Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation.
Main outcome measure All cause mortality.
Results 100 trials in 93 553 patients with 262 090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment.
Conclusion Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment.
PMCID: PMC4066935  PMID: 24958153

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