Comparison of the function and structural integrity of cryopreserved pulmonary homografts versus decellularized pulmonary homografts after 180 days implantation in the juvenile ovine model.

Homograft availability and durability remain big challenges. Increasing the post-mortem ischaemic harvesting time beyond 24 h increases the potential donor pool. Cryopreservation, routinely used to preserve homografts, damages the extracellular matrix (ECM), contributing to valve degeneration. Decellularization might preserve the ECM, promoting host-cell infiltration and contributing towards better clinical outcomes. This study compared the performance of cryopreserved versus decellularized pulmonary homografts in the right ventricle outflow tract (RVOT) of a juvenile ovine model. Homografts (n = 10) were harvested from juvenile sheep, subjected to 48 h post-mortem cold ischaemia, cryopreserved or decellularized and implanted in the RVOT of juvenile sheep for 180 days. Valve performance was monitored echocardiographically. Explanted leaflet and wall tissue evaluated histologically, on electron microscopical appearance, mechanical properties and calcium content. In both groups the annulus diameter increased. Cryopreserved homografts developed significant (¾) pulmonary regurgitation, with trivial regurgitation (») in the decellularized group. Macroscopically, explanted cryopreserved valve leaflets retracted and thickened while decellularized leaflets remained thin and pliable with good coaptation. Cryopreserved leaflets and walls demonstrated loss of interstitial cells with collapsed collagen, and decellularized scaffolds extensive, uniform ingrowth of host-cells with an intact collagen network. Calcific deposits were shown only in leaflets and walls of cryopreserved explants. Young fibroblasts, with vacuoles and rough endoplasmic reticulum in the cytoplasm, repopulated the leaflets and walls of decellularized scaffolds. Young's modulus of wall tissue in both groups increased significantly. Cryopreserved valves deteriorate over time due to loss of cellularity and calcification, while decellularized scaffolds demonstrated host-cell repopulation, structural maintenance, tissue remodelling and growth potential.

Hybrid approach for percutaneous mitral valve repair (MitraClip®) followed by minimally invasive direct coronary artery bypass (MIDCAB) in a patient with a high risk constellation.

BACKGROUND: We present a 76-year-old poly-morbid male patient suffering from severe ischemic mitral valve regurgitation. A hybrid approach was suggested by the heart team to treat his multifaceted cardiac pathologies. METHODS: At first percutaneous mitral valve repair with the mitraclip device was performed to reduce surgical risk. This was then followed by minimally invasive direct coronary artery bypass (MIDCAB). RESULTS: At day 20 Post mitraclip intervention the patient suffered gastrointestinal bleeding which needed argon plasma coagulation (APC)-therapy and multiple blood transfusions. Stage II of the hybrid procedure was executed on post-intervention day 34 by minimally invasive direct coronary artery bypass (MIDCAB) to left anterior descending artery (LAD). Seven days later the patient was discharged. Up to two years of follow-up, the patient is in stable condition, without recurrent cardiac symptoms. CONCLUSION: Hybrid approach of percutaneous mitral valve repair followed by MIDCAB is an effective minimally invasive treatment for severe ischemic mitral valve regurgitation and coronary artery disease.

Surgical revision after percutaneous mitral valve repair by edge-to-edge device in high-risk patients.

BACKGROUND: Patients scheduled for surgery after unsuccessful MitraClip® intervention present increasingly with multiple comorbidities, and they are often referred to the heart team to suggest the most appropriate intervention. The publication of successful results of initial patient cohorts treated with the MitraClip device has resulted in recruitment of more seriously ill patients, who otherwise would have been denied catheter-based/surgical treatment. There has been increasingly reports on conventional surgery after failed mitral valve repair with the MitraClip device. However, data on such procedures remain scarce and mostly focused on individual case studies. The inevitable increase in use of MitraClip, however, will raise the number of patients in need of surgery post MitraClip, making it imperative for surgeons to understand challenges and outcome data related with surgery in this patient cohort. We present our long-term institutional experience with surgery after MitraClip intervention in highest risk patients. METHODS: Eighteen patients underwent surgery of the mitral valve at our Institution between January 2015 and June 2020. These patients developed recurrent mitral regurgitation grade more than 2° at various intervals after MitraClip. Mitral valve repair was performed where possible and gross examination Valve/MitraClip were intra-operatively documented. Implanted MitraClip devices were analyzed histopathologically to evaluate the healing process and rule out inflammation. Regular patient follow-up was performed. RESULTS: Mean patient age was 74 (±9 years) and MitraClip implantation was performed at various tertiary institutions. Sixteen out of eighteen (16/18) patients received mitral valve replacement, whereas the remaining two patients received mitral valve repair and extracorporal membrane oxygenation, respectively. Four patients died of sepsis and intractable multi organ failure in-hospital. The remaining patients were discharged alive out of hospital to different rehabilitation centers. Follow-up was complete in all patients. CONCLUSIONS: Surgery is demanding when patients require surgery for persistent or recurrent mitral regurgitation after MitraClip therapy and can be successfully implemented as a possible therapy option for selective cases as an interdisciplinary approach despite calculated high perioperative mortality risk. These patients should not be denied surgery outright.

Cadaver donation: structural integrity of pulmonary homografts harvested 48 h post mortem in the juvenile ovine model.

Cryopreserved pulmonary homograft (CPH) implantation remains the gold standard for reconstruction of the right ventricular outflow tract (RVOT). Harvesting homografts < 24-h post mortem is the international norm, thereby largely excluding cadaveric donors. This study examines the structural integrity and stability of ovine pulmonary homografts harvested after a 48-h post mortem period, cryopreserved and then implanted for up to 180 days. Fifteen ovine pulmonary homografts were harvested 48-h post mortem and cryopreserved. Five CPH served as a control group (group 1; n = 5). CPH were implanted in the RVOT of juvenile sheep and explanted after 14 days (group 2; n = 5) and 180 days (group 3; n = 5). Leaflet integrity was evaluated by strength analysis, using tensile strength (TS), Young's modulus (YM) and thermal denaturation temperature (Td), and morphology, including haematoxylin and eosin (H&E), Picrosirius red staining, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and von Kossa stains. Echocardiography confirmed normal function in all implants. In explants, no reduction in TS, YM or Td could be demonstrated and H&E showed mostly acellular leaflet tissue with no difference on Picrosirius red. TEM demonstrated consistent collagen disruption after cryopreservation in all three groups, with no morphological deterioration during the study period. von Kossa stains showed mild calcification in group 3. No deterioration of structural integrity could be demonstrated using strength or morphological evaluations between the controls and implant groups over the study period. Extending the post mortem harvesting time of homografts beyond 24 h did not appear to negatively affect the long-term performance of such transplanted valves in this study.

Initial Experience with Aortic Valve Replacement via a Minimally Invasive Approach: A Comparison of Stented, Stentless and Sutureless Valves.

BACKGROUND This study aimed to compare the short-term outcomes of MIS-AVR among 3 different types of biological heart valves. MATERIAL AND METHODS Complete data were obtained from 79 patients who underwent MIS-AVR between January 2010 and June 2015. Patients were divided into 3 groups: 27 patients (group A) received Medtronic 3f® (Medtronic Inc., Fridley, MN, USA), 36 patients (group B) received DokimosPlus® (LabCor Laboratórios Ltda., Belo Horizonte, Brazil) and 16 patients (group C) received Perceval® (Sorin Biomedica Cardio S.r.l., Saluggia VC, Italy) valves. Operative and postoperative parameters such as duration of operation, bypass time, duration of ventilation, morbidity, and mortality were statistically analyzed using the Kruskal-Wallis test. Hemodynamic assessment with transthoracic echocardiography was performed before discharge. RESULTS The EuroSCORE II ranged between 0.67 and 6.94 with no significant difference between the groups. The median operative time was 166 min (range 90-230 min) in total, with significantly shorter times in group C (120 min [range 90-200]). The median total ventilation time was significantly lower in group C and significantly higher in group A. Hemodynamic evaluation demonstrated a mean maximal velocity (vmax) over the aortic valve of 2.3 m/s (range 0.9-4.3 m/s) with average mean and peak pressure gradient values of 10 mmHg (range 3-24 mmHg) and 20 mmHg (range 5-42 mmHg), respectively. Group A showed the highest values for vmax (H>5.99). No significant difference was found regarding duration of hospitalization. Mortality was 3%. CONCLUSIONS In conclusion, all 3 valves showed good perioperative results, satisfying hemodynamic performance, and low complication rates.

Are Sutureless Aortic Valves Suitable for Severe High-Risk Patients Suffering from Active Infective Aortic Valve Endocarditis?

BACKGROUND Sutureless aortic valves were introduced to facilitate minimally invasive aortic valve surgery. Since sutureless aortic valves are a feasible procedure, we evaluated if any benefits could be identified in severe high-risk patients with active infective endocarditis of the aortic valve. MATERIAL AND METHODS Between April 2014 and April 2015, a total of 42 patients received a sutureless Perceval® aortic valve (Sorin Biomedica Cardio Srl, Saluggia, Italy) for different indications. Nine of these patients (median age 71 years, range 47-83 years) suffered from active infective endocarditis, including four patients with prosthetic aortic valve endocarditis. Five patients underwent prior cardiac surgery, including transcatheter aortic valve implantation (TAVI). The median EuroSCORE II was 29.5% (range 16.8-87.7%). Post-operatively, data regarding mortality, operative results, and early operative morbidity were collected. RESULTS There were no cases of 30-day mortality. Four patients needed abscess closure with pericardium. Three patients underwent left atrial appendix closure: one left ventricular thrombectomy, one bypass grafting, and one arch replacement. Median aortic cross-clamp and cardiopulmonary bypass time was 35 minutes (range 26-88 minutes) and 52 minutes (range 40-133 minutes), respectively. The median intubation time was 14 hours (range 1-9 hours). In these high-risk patients, no postoperative morbidity was found except for one re-intubation due to extensive delirium and one re-exploration. No pacemaker implantation was needed. Echocardiographic evaluation showed no central or para-valvular regurgitation, and a median discharge mean gradient of 5.5 mm Hg (range 2.5-10.0 mm Hg). CONCLUSIONS Sutureless aortic valve replacement in very high-risk patients suffering from active infection endocarditis seems to be an option with limited morbidity and appropriate echocardiographic results, however, further studies are needed.

Impedimetric Analysis of the Effect of Decellularized Porcine Heart Scaffold on Human Fibrosarcoma, Endothelial, and Cardiomyocyte Cell Lines.

BACKGROUND Experiments on porcine heart scaffold represent significant assays in development of immunoneutral materials for cardiac surgery. Characterization of cell-cell and cell-scaffold interactions is essential to understand the homing process of cardiac cells into the scaffolds. MATERIAL AND METHODS In the present study, the highly sensitive and real-time impedimetric technique of xCELLigence SP was used to monitor cell adhesion, which is the key process of recellularization in heart scaffolds. Our objectives were: (i) to characterize the effect of decellularized porcine heart scaffold on cell adhesion of human cardiovascular cells potentially used in the recellularization process; and (ii) to investigate cell-extracellular matrix element interactions for building artificial multi-layer systems, applied as cellular models of recellularization experiments. Human fibrosarcoma, endothelial, and cardiomyocyte cells were investigated and the effect of decellularized porcine heart scaffold (HS) and fibronectin on cell adhesion was examined. Adhesion was quantified as slope of curves. RESULTS Heart scaffold had neutral effect on cardiomyocytes as well as on endothelial cells. Adhesion of cardiomyocytes was increased by fibronectin (1.480±0.021) compared to control (0.745±0.029). The combination of fibronectin and HS induced stronger adhesion of cardiomyocytes (2.407±0.634) than fibronectin alone. Endothelial and fibrosarcoma cells showed similarly strong adhesion profiles with marked enhancer effect by fibronectin. CONCLUSIONS Decellularized porcine HS does not inhibit adhesion of human cardiovascular cells at the cell biological level, while fibronectin has strong cell adhesion-inducer effect, as well as an enhancer effect on activity of HS. Consequently, decellularized porcine hearts could be used as scaffolds for recellularization with cardiomyocytes and endothelial cells with fibronectin acting as a regulator, leading to construction of working bioartificial hearts.

Repair or Replacement for Isolated Tricuspid Valve Pathology? Insights from a Surgical Analysis on Long-Term Survival.

BACKGROUND Long-term follow-up data concerning isolated tricuspid valve pathology after replacement or reconstruction is limited. Current American Heart Association guidelines equally recommend repair and replacement when surgical intervention is indicated. Our aim was to investigate and compare operative mortality and long-term survival in patients undergoing isolated tricuspid valve repair surgery versus replacement. MATERIAL AND METHODS Between 1995 and 2011, 109 consecutive patients underwent surgical correction of tricuspid valve pathology at our institution for varying structural pathologies. A total of 41 (37.6%) patients underwent tricuspid annuloplasty/repair (TAP) with or without ring implantation, while 68 (62.3%) patients received tricuspid valve replacement (TVR) of whom 36 (53%) were mechanical and 32 (47%) were biological prostheses. RESULTS Early survival at 30 days after surgery was 97.6% in the TAP group and 91.1% in the TVR group. After 6 months, 89.1% in the TAP group and 87.8% in the TVR group were alive. In terms of long-term survival, there was no further mortality observed after one year post surgery in both groups (Log Rank p=0.919, Breslow p=0.834, Tarone-Ware p=0.880) in the Kaplan-Meier Survival analysis. The 1-, 5-, and 8-year survival rates were 85.8% for TAP and 87.8% for TVR group. CONCLUSIONS Surgical repair of the tricuspid valve does not show survival benefit when compared to replacement. Hence valve replacement should be considered generously in patients with reasonable suspicion that regurgitation after repair will reoccur.

Surgery for Infective Endocarditis: Outcomes and Predictors of Mortality in 360 Consecutive Patients.

BACKGROUND A retrospective analysis was conducted of the early and long-term outcomes after surgery for infective endocarditis (IE). MATERIAL AND METHODS We included 360 patients with IE operated upon between 1993 and 2012. The primary endpoint was overall cumulative postoperative survival at 30 days. Secondary endpoints were early postoperative outcomes and complication rates. Factors associated with 30-day mortality were analyzed. RESULTS Mean age was 58.7±14.7 years and 26.9% (n=97) were female. The mean follow-up was 4.41±4.53 years. Postoperative survival was 81.7% at 30 days, 69.4% at 1 year, 63.3% at 5 years, and 63.3% at 10 years. Non-survivors were significantly older (p=0.014), with higher NYHA Class (p=0.002), had higher rates of preoperative diabetes mellitus (p=0.005), renal failure (p=0.001), and hepatic disease (p=0.002). Furthermore, non-survivors had higher baseline alanine aminotransferase (ALT, p=0.048), aspartate transaminase (AST, p=0.027), bilirubin (p=0.013), white cell count (WCC, p=0.034), and CRP (p=0.049). Factors associated with 30-day mortality were longer duration of surgery, CPB, and aortic cross-clamping times (p<0.001, p<0.001, and p=0.003, respectively), as well as higher RBC, FFP, and platelet transfusion requirements (p<0.001, p=0.005, and p<0.001, respectively). Multivariate logistic regression analysis revealed liver cirrhosis (OR 4.583, 95-CI: 1.096-19.170, p=0.037) and longer CPB time (OR 1.025, 95-CI 1.008-1.042, p=0.004) as independent predictors of 30-day mortality. CONCLUSIONS Surgical treatment of IE shows satisfactory early, midterm, and long-term results. Multivariate logistic regression analysis revealed cirrhosis and longer CPB time as independent predictors of 30-day mortality.

Rapid molecular diagnosis of infective aortic valve endocarditis caused by Coxiella burnetii.

We describe a case of Q-fever endocarditis with severe destruction of the aortic valve with perivalvular abscess formation and cardiac failure. The patient needed urgent operative treatment and postoperative critical care. All specimens sent for microbiological examination were negative. Molecular analysis, including fluorescence in situ hybridization of aortic valve tissue combined with PCR and sequencing, led to the correct diagnosis and to appropriate anti-infective treatment. The patient subsequently recovered from complex cardiovascular surgery. This is the first report on Q-fever endocarditis that was rapidly diagnosed using these methods.