Ovine Biosynthetic Grafts for Aortoiliac Reconstructions in Nonsterile Operative Fields.

BACKGROUND: Prosthetic vascular grafts placed surgically or via endovascular techniques can be subject to the risk of life-threatening graft infections. The Omniflow II vascular prosthesis is a biosynthetic graft that was reported to have favorable properties in resisting infections. MATERIALS AND METHODS: We retrospectively reviewed our 3 years' experience of using the Omniflow II prostheses for aortoiliac reconstructions in patients considered to carry a substantial risk of subsequent prosthetic graft infections (prevention group) as well as in patients with actively infected prosthetic vascular grafts (treatment group). RESULTS: Aorto-bi-iliac (n = 4) and aortobifemoral (n = 12) vascular reconstructions were performed using bifurcated Omniflow II prostheses in nine patients in the prevention group and seven patients in the treatment group. During mean follow-up of 28.6 ± 17.2 months, there was one case of graft infection (6.3%) and graft thrombosis (6.3%) with subsequent successful thrombectomy. Early and late surgical revisions were required in eight (50%) and two (12.6%) patients, respectively. All graft prostheses were patent at last follow-up. CONCLUSION: Using bifurcated Omniflow II vascular prostheses in patients with or at a high risk of vascular graft infection is advisable, and is associated with acceptable reinfection and patency rates.

Minimizing Paravalvular Regurgitation With the Novel SAPIEN 3 Ultra TAVR Prosthesis: A Real-World Comparison Study.

Objectives: We investigated performance and outcome of the latest-generation balloon-expandable SAPIEN 3 Ultra prosthesis (S3U) compared to the established SAPIEN 3 prosthesis (S3) in a real-world cohort, with focus on paravalvular regurgitation (PVR). Background: PVR is an adverse prognostic indicator of short- and long-term survival after transcatheter aortic valve replacement (TAVR). The S3U has been designed to improve sealing. Methods: We enrolled 343 consecutive patients presenting with severe native aortic valve stenosis eligible for a balloon-expandable prosthesis. The established S3 was implanted in the first 200 patients, the following 143 patients received the novel S3U after introduction in our institution. Primary endpoint was PVR after TAVR. Furthermore, we investigated procedural parameters and in-hospital and 30-day outcome. Results: PVR was significantly lower in the S3U cohort compared to the S3 cohort. They differed in their rate of mild PVR (11.2 vs. 48.0%, p < 0.001), whereas at least moderate PVR was similarly low in both cohorts (0.7 vs. 0.5%, p = 0.811). A significant reduction of post-dilatation rate, fluoroscopy time, and amount of contrast was observed in patients treated with the novel S3U (p < 0.001). The rate of adverse events in the in-hospital course and at 30 days were similarly low. At 30 days more patients receiving S3U improved in NYHA class (improvement ≥2 grades 34.6 vs. 19.9%, p = 0.003). Conclusion: The current study provides evidence that the novel S3U strongly minimizes PVR, thereby demonstrating the efficacy of improved sealing. Further studies will have to address if the observed reduction of PVR with S3U has prognostic significance.

Minimally invasive coronary artery bypass grafting via a lower ministernotomy for left anterior descending artery myocardial bridging: mid-term results.

OBJECTIVES: Coronary artery bypass grafting or supra-arterial myotomy is now suggested as a better therapeutic option in myocardial bridging (MB) when medical treatment fails to control symptoms. For left anterior descending (LAD) MB, minimally invasive coronary artery bypass via a lower ministernotomy can be offered. METHODS: Forty-four consecutive patients who underwent elective minimally invasive coronary artery bypass surgery from 2005 to 2014 via an inferior sternotomy using the left internal mammary artery as a bypass graft for LAD MB were evaluated retrospectively. RESULTS: The mean age was 59.1 ± 13.1 years with 26 (59%) men and 18 (41%) women. The mean body mass index was 27.2 ± 3.9 and the mean EuroSCORE II was 1.6 ± 1.8. Routine coronary multislice computed tomography angiography on the 6th postoperative day revealed 97.7% graft patency. During the initial hospital stay, 1 patient (2.3%) underwent a reoperation for early graft failure. Forty patients (91%) could be followed up for a mean period of 64.4 ± 24.5 months after the procedure, during which 2 patients (4.5%) died of non-cardiac causes and 9 patients (20.5%) underwent postoperative coronary angiography with confirmed graft occlusion in only 1 case (2.3%). The improvement in the distribution of patients in the Canadian Cardiovascular Society class 0 was from 4 patients (9%) preoperatively to 37 patients (84%) at the end of the follow-up period (P-value 0.001). CONCLUSIONS: Minimally invasive coronary artery bypass surgery via a lower ministernotomy may be safe and efficient for treating LAD artery MB with acceptable complication rates, cosmetic benefits and patency rates.

"Unlucky punch": unexpected annular rupture during TAVR and successful treatment.

Although rare, annular rupture in TAVR is a feared and often unpredictable complication with relevant impact on in-hospital prognosis. Severe annular calcification is a common risk factor for annular rupture. We report on a case of annular rupture during TAVR with a balloon-expanded prosthesis in the absence of any annular calcification in the planning CT scan and illustrate the proposed pathomechanism as well as its successful immediate surgical management.

Concomitant tricuspid regurgitation severity and its secondary reduction determine long-term prognosis after transcatheter mitral valve edge-to-edge repair.

BACKGROUND: Concomitant tricuspid regurgitation (TR) is a common finding in mitral regurgitation (MR). Transcatheter repair (TMVR) is a favorable treatment option in patients at elevated surgical risk. To date, evidence on long-term prognosis and the prognostic impact of TR after TMVR is limited. METHODS: Long-term survival data of patients undergoing isolated edge-to-edge repair from June 2010 to March 2018 (combinations with other forms of TMVR or tricuspid valve therapy excluded) were analyzed in a retrospective monocentric study. TR severity was categorized and the impact of TR on survival was analysed. RESULTS: Overall, 606 patients [46.5% female, 56.4% functional MR (FMR)] were enrolled in this study. TR at baseline was categorized severe/medium/mild/no or trace in 23.2/34.3/36.3/6.3% of the cases. At 30-day follow-up, improvement of at least one TR-grade was documented in 34.9%. Severe TR at baseline was identified as predictor of 1-year survival [65.2% vs. 77.0%, p = 0.030; HR for death 1.68 (95% CI 1.12-2.54), p = 0.013] and in FMR-patients also regarding long-term prognosis [adjusted HR for long-term mortality 1.57 (95% CI 1.00-2.45), p = 0.049]. Missing post-interventional reduction of TR severity was predictive for poor prognosis, especially in the FMR-subgroup [1-year survival: 92.9% vs. 78.3%, p = 0.025; HR for death at 1-year follow-up 3.31 (95% CI 1.15-9.58), p = 0.027]. While BNP levels decreased in both subgroups, TR reduction was associated with improved symptomatic benefit (NYHA-class-reduction 78.6 vs. 65.9%, p = 0.021). CONCLUSION: In this large study, both, severe TR at baseline as well as missing secondary reduction were predictive for impaired long-term prognosis, especially in patients with FMR etiology. TR reduction was associated with increased symptomatic benefit.

Predictors of short- and long-term outcomes of patients undergoing transcatheter mitral valve edge-to-edge repair.

OBJECTIVES: Transcatheter mitral valve repair (TMVR) by edge-to-edge therapy is an established treatment for severe mitral valve regurgitation (MR). BACKGROUND: Symptomatic and prognostic benefit in functional MR has been shown recently; nevertheless, data on long-term outcomes are sparse. METHODS AND RESULTS: We analyzed survival of patients treated with isolated edge-to-edge repair from June 2010 to March 2018 (primarily combined edge-to-edge repair with other mitral valve interventions was excluded) in a retrospective monocentric study. Overall, 627 consecutive patients (47.0% females, 78.6 years in mean) were included. Leading etiology was functional MR (57.4%). Follow-up regarding survival was available in 97.0%. While 97.6% were discharged alive, 75.7% were alive after a 1-year, 54.5% after 3-year, 37.6% after 5-year and 21.7% after 7-year follow-up. Higher logistic Euroscores and comorbidities such as COPD and renal insufficiency were associated with higher in-hospital and 1-year mortality. Importantly, in-hospital survival increased over the years. CONCLUSIONS: With the present study we established high survival rates at discharge and after 1 year of patients treated with TMVR. This goes along with high implantation numbers, increased interventional experience and a better in-hospital survival over the years. Long-term mortality in turn was substantially influenced by comorbidities.

Influence of an Early Application of Mammalian Target of Rapamycin Inhibitors Everolimus and Sirolimus on Acute Vascular Inflammatory Responses After Ischemia-Reperfusion Injury.

OBJECTIVES: Ischemia-reperfusion injury is correlated with a substantial inflammatory response. Inflammation triggers the migration of cells through vessel endothelium and leads to serious tissue injury. Our hypothesis was that an early application of mammalian target of rapamycin inhibitors has an impact on human vessels after ischemia-reperfusion injury. MATERIALS AND METHODS: After exposure to ischemia for 5 hours, human vessels (veins and arteries) from 20 patients were reperfused for 120 minutes in an in vitro bioreactor with heparinized human blood after oxygenation and warming to 37 °C. The vessels were treated with mammalian target of rapamycin inhibitor everolimus (5 ng/mL, n = 7) or sirolimus (10 ng/mL, n = 6). As a control group, untreated human vessels were reperfused (n = 7). During the reperfusion period, blood samples were collected continuously (after 0, 15, 30, 60, 120 minutes); vessel biopsies were performed at the end. Oxygen consumption was measured during reperfusion to determine vessel viability. Inflammatory markers (interleukin 6, tumor necrosis factor α, vascular endothelial growth factor) were analyzed in blood samples. To quantify vascular inflammation, we investigated the expression of CD11 and CD31. RESULTS: Physiological oxygen consumption and pH values verified vessel viability. After reperfusion, interleukin 6 and vascular endothelial growth factor levels were significantly increased in the control group over time, whereas everolimus and sirolimus showed no significant differences. Furthermore, tumor necrosis factor α level increased significantly in the sirolimus group, whereas the everolimus and control groups showed constant values. A significant decrease of expression of CD11b and CD31 in both mammalian target of rapamycin inhibitor cohorts compared with control cohort was investigated. CONCLUSIONS: Early use of mammalian target of rapamycin inhibitors may limit an inflammatory rise of interleukin 6 and vascular endothelial growth factor after ischemia-reperfusion injury and could be associated with a restriction in vascular cell transmigration.

Feasibility of a MPR-based 3DTEE guidance protocol for transcatheter direct mitral valve annuloplasty.

OBJECTIVES: Several interventional approaches have been established for the treatment of severe mitral regurgitation (MR) in patients at elevated risk for surgery. Direct annuloplasty is a relatively novel option in transcatheter mitral valve repair dedicated to reverse pathology in specific subsets of MR. With regard to echocardiographic guidance, this procedure presents with higher efforts in comparison with edge-to-edge therapy to enable safe and exact positioning of the device's anchors; evidence on optimal peri-interventional imaging is sparse. We tested a specific 3D-echo-guidance protocol implementing single-beat multiplanar reconstruction (MPR) and evaluated its feasibility. METHODS: Overall, 16 patients consecutively treated with transcatheter direct annuloplasty for severe MR (87.5% functional/6.3% degenerative/6.3% mixed pathology) were entered in this monocentric analysis. Of these, two patients received a combined procedure including edge-to-edge repair. For all implantations, a 3D-echo-guidance protocol inheriting MPR was employed. RESULTS: Periprocedural device time decreased continuously (overall mean 140 ± 55.1 minutes, 213 ± 38 minutes in the first 4 vs 108 ± 33 minutes in the last 4 procedures, P = .018) using the MPR-based echo protocol, going along with reduced fluoroscopy times and doses. Technical success rate was high (93.8%) without any serious cardiac-related adverse events. MR could be relevantly improved. CONCLUSION: Echocardiographic guidance of transcatheter direct annuloplasty using a real time MPR-based protocol is feasible and safe. Optimized imaging might enable reduced implantation times and potentially increases safety.

Echocardiography-guided subxiphoidal transapical TAVR in a challenging anatomy: a case report.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) via an antegrade transapical access (TA-TAVR) is largely reserved to cases not amenable to transfemoral TAVR. Challenges resulting from unusual thoracic anatomies may require special considerations in terms of the surgical access. CASE PRESENTATION: We present a case of TA-TAVR through a subxiphoidal approach in a patient who had undergone extensive thoracic surgery 8 years previously. CONCLUSION: Our case demonstrates that unusual anatomic features should not discourage from TA-TAVR but may require unusual approaches designed on a case-to-case basis following careful interdisciplinary preparation and planning including adequate pre-operative diagnostics and imaging.

T-shaped Transseptal Approach for Mitral Valve Surgery.

We present a T-shaped transseptal approach for mitral valve surgery that makes adequate exposure possible under challenging anatomic and surgical circumstances, hence eliminating the need for forceful retraction on potentially fragile tissues. Particularly suited for patients with complex mitral pathology, it also facilitates juxta-annular transseptal right atrial anchoring, especially in cases of endocarditic anterior mitral annular destruction.

Effect of Rewarming on Leukocyte-Endothelial Interaction After Deep Hypothermic Preservation.

BACKGROUND The preservation of harvested organs plays an essential role in transplantation. Cold hypothermia is frequently applied but may lead to graft compromise resulting from reperfusion and rewarming injury. This study investigates the effect of deep hypothermia and posterior rewarming on leukocyte-endothelial interactions and junctional adhesion molecules. MATERIAL AND METHODS We established an in vitro model to investigate the transendothelial migration of leukocytes (TEM) during deep hypothermia (4°C) as well as during the post-hypothermic rewarming process. Additionally, leukocyte-endothelial interactions were analyzed by quantifying surface expression of the junctional adhesion molecules A (JAMA-A and JAM-B). RESULTS While deep hypothermia at 4°C was associated with reduced leukocyte infiltration, rewarming after hypothermic preservation resulted in a significant increase in TEM. This process is mainly triggered by activation of endothelial cells. Post-hypothermic rewarming caused a significant downregulation of JAM-A, whereas JAM-B was not altered through temperature modulation. CONCLUSIONS Hypothermia exerts a protective effect consisting of reduced leukocyte-endothelial interaction. Rewarming after hypothermic preservation, however, causes considerable upregulation of leukocyte infiltration. Downregulation of JAM-A may play a role in modulating TEM during hypothermia and rewarming. We conclude that the rewarming process is an essential but underestimated aspect during transplantation.

Early LVAD Implantation in a Patient with Left Ventricular Failure after Aortic Dissection with Left Main Stem Involvement.

BACKGROUND: Coronary involvement in aortic dissection heralds a poor outcome. Involvement of the left main stem may lead to left ventricular (LV) failure requiring mechanical circulatory support. CASE REPORT: A staged approach was applied in a 24-year-old female who suffered extensive infarction due to aortic dissection with left main stem involvement. After replacement of the ascending aorta and grafting of the left internal thoracic artery to the left anterior descending artery following a failed attempt at reconstruction of the left coronary ostium, she failed to wean from cardiopulmonary bypass (CPB) and underwent implantation of an extracorporeal life support (ECLS) system as a bridge to decision. Subsequent implantation of a left ventricular assist device (LVAD) as a bridge to recovery/transplantation was followed by an uneventful further course. CONCLUSIONS: Our experience suggests that early implantation of a ventricular assist device (VAD) as bridge to recovery/transplantation is an alternative to prolonged ECLS in patients who suffered extensive myocardial infarction in the course of aortic dissection.

Giant right atrial myxoma: A rare cause of cardiovascular collapse.

We report the case of a patient with a giant right atrial myxoma that remained clinically silent until it almost completely obliterated the right atrium, prolapsed into the right ventricle and obstructed the tricuspid valve inflow. This case illustrates the importance of rapid surgical intervention in the setting of acute heart failure caused by tumor masses obliterating heart valves or cardiac chambers.

Juxta-annular right atrial anchoring of prosthetic mitral valves in endocarditis with anterior annulus destruction†.

Destruction of the mitral annulus is associated with poor outcomes. We present the treatment of endocarditis using a technique that enables secure anchoring of prosthetic valves where the anterior part of the mitral annulus is severely disrupted. It was used in 5 patients. Follow-up at 10 ± 4 months showed the valves intact without recurrence of endocarditis. Mortality was limited to 1 patient who died of non-cardiac causes. We conclude that partial right atrial anchoring is a useful bail-out and enables favourable outcomes in patients with extensive loss of the (peri)annular tissue due to endocarditis.

A low threshold to ECG-gated repeat CTA reduces the risk of false-positive diagnosis of type A dissection in interhospital referrals: a case series study.

BACKGROUND: False-positive diagnosis of acute Stanford type A aortic dissection (AAD) on computed tomography angiography (CTA) is still an issue and may lead to substantial consequences. Given that electrocardiography (ECG)-gated CTA provides greater diagnostic safety, it may be assumed that interhospital referrals with a diagnosis of AAD based on non-ECG-gated pre-referral CTA carry an elevated risk of false-positive diagnosis. PATIENTS AND METHODS: We reviewed a series of patients in whom a diagnosis of AAD based on non-ECG-gated pre-referral CTA was subsequently proven false by ECG-gated CTA. The artifacts that gave rise to the misdiagnosis, as well as the diagnostic pathways followed and the consequences of false-positive diagnosis were investigated. RESULTS: In 5 patients, ECG-gated repeat CTA revealed artifacts in the pre-referral scans that had led to false-positive diagnosis and referral for emergent surgery. In the first case, the patient proceeded to surgery. In 4 subsequent cases, ECG-gated CTA was ordered because a false-positive diagnosis was suspected. We found that ECG-gated CTA rather than echocardiography provided sufficient information to rule out AAD in each of these cases. Comparison between pre-referral non-ECG-gated scans and ECG-gated repeat CTA demonstrated the wide range of artifacts that may give rise to a diagnosis of AAD. CONCLUSION: Patient condition permitting, the threshold to ECG-gated repeat CTA should be low when doubt arises with regard to a diagnosis of AAD based on non-ECG-gated CTA in interhospital referrals.

Repair of TEVAR-Associated Type A Dissection in the Elderly Is Possible With Reasonable Morbidity and Mortality.

BACKGROUND: Type A aortic dissection (AAD) is a devastating complication of thoracic endovascular repair (TEVAR). In elderly patients, surgery for AAD carries considerable morbidity and mortality. Repair of AAD after previous TEVAR is an even greater challenge as it usually requires the arch to be addressed and a preexisting stent graft to be included into the aortic repair. METHODS: A case series of 5 elderly patients who presented with acute AAD after previous TEVAR was reviewed. In 4 cases, there was retrograde AAD with involvement of the arch and stent graft. In 1 patient, intraoperative inspection showed no involvement of the arch. Three underwent ascending and subtotal arch replacement in moderate hypothermic circulatory arrest with selective cerebral perfusion. In 1 case, concomitant tricuspid valve repair was performed. The patient without involvement of the arch underwent emergent replacement of the ascending aorta in deep hypothermic circulatory arrest, and in the oldest, aged 88 years, surgery was limited to wrapping of the ascending aorta as an on-pump beating salvage procedure. RESULTS: Four (80%) of 5 patients survived and were discharged after an intensive care unit stay of 17.45 ± 15.98 days and a hospital stay of 26.0 ± 10.98 days. Mortality was 20%. All survivors were discharged with appropriate rehabilitation potential and without lasting neurological disabilities.

Acute heart failure due to giant left atrium: remote ECLS implantation for interhospital transfer and bridging to decision.

BACKGROUND: Remote extracorporeal life support (ECLS) implantation and mobile ECLS are increasingly applied to enable the treatment of patients with refractory heart failure at specialized care centers. Giant left atrium (GLA) is a rare cause but may lead to acute and devastating heart failure. CASE REPORT: Acute heart failure that gave rise to a prolonged period of out-of-hospital cardiopulmonary resuscitation in a patient who underwent remote ECLS implantation was found to have resulted from a GLA of impressive dimensions. There having no reasonable option for immediate surgical therapy, the patient was successfully bridged to recovery with a view to subsequent heart transplantation. CONCLUSIONS: The threshold to rapid institution of ECLS should be low in patients with acute refractory heart failure, including those with uncommon pathologies. Remote ECLS implantation and interhospital transfer on mobile ECLS increase the chances of survival in cases requiring treatment by specialized care centers.

Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients: Rescue by α-Ketoglutarate and TET-TDG Functional Reactivation.

RATIONALE: Human cardiac mesenchymal cells (CMSCs) are a therapeutically relevant primary cell population. Diabetes mellitus compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. OBJECTIVE: To investigate the role of α-ketoglutarate (αKG) in the epimetabolic control of DNA demethylation in CMSCs. METHODS AND RESULTS: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing, and gene-specific GC methylation detection revealed an accumulation of 5-methylcytosine, 5-hydroxymethylcytosine, and 5-formylcytosine in the genomic DNA of human CMSCs isolated from diabetic donors. Whole heart genomic DNA analysis revealed iterative oxidative cytosine modification accumulation in mice exposed to high-fat diet (HFD), injected with streptozotocin, or both in combination (streptozotocin/HFD). In this context, untargeted and targeted metabolomics indicated an intracellular reduction of αKG synthesis in diabetic CMSCs and in the whole heart of HFD mice. This observation was paralleled by a compromised TDG (thymine DNA glycosylase) and TET1 (ten-eleven translocation protein 1) association and function with TET1 relocating out of the nucleus. Molecular dynamics and mutational analyses showed that αKG binds TDG on Arg275 providing an enzymatic allosteric activation. As a consequence, the enzyme significantly increased its capacity to remove G/T nucleotide mismatches or 5-formylcytosine. Accordingly, an exogenous source of αKG restored the DNA demethylation cycle by promoting TDG function, TET1 nuclear localization, and TET/TDG association. TDG inactivation by CRISPR/Cas9 knockout or TET/TDG siRNA knockdown induced 5-formylcytosine accumulation, thus partially mimicking the diabetic epigenetic landscape in cells of nondiabetic origin. The novel compound (S)-2-[(2,6-dichlorobenzoyl)amino]succinic acid (AA6), identified as an inhibitor of αKG dehydrogenase, increased the αKG level in diabetic CMSCs and in the heart of HFD and streptozotocin mice eliciting, in HFD, DNA demethylation, glucose uptake, and insulin response. CONCLUSIONS: Restoring the epimetabolic control of DNA demethylation cycle promises beneficial effects on cells compromised by environmental metabolic changes.

Impact of T-cell-mediated immune response on xenogeneic heart valve transplantation: short-term success and mid-term failure.

OBJECTIVES: Allogeneic frozen cryopreserved heart valves (allografts or homografts) are commonly used in clinical practice. A major obstacle for their application is the limited availability in particular for paediatrics. Allogeneic large animal studies revealed that alternative ice-free cryopreservation (IFC) results in better matrix preservation and reduced immunogenicity. The objective of this study was to evaluate xenogeneic (porcine) compared with allogeneic (ovine) IFC heart valves in a large animal study. METHODS: IFC xenografts and allografts were transplanted in 12 juvenile merino sheep for 1-12 weeks. Immunohistochemistry, ex vivo computed tomography scans and transforming growth factor-ß release profiles were analysed to evaluate postimplantation immunopathology. In addition, near-infrared multiphoton imaging and Raman spectroscopy were employed to evaluate matrix integrity of the leaflets. RESULTS: Acellular leaflets were observed in both groups 1 week after implantation. Allogeneic leaflets remained acellular throughout the entire study. In contrast, xenogeneic valves were infiltrated with abundant T-cells and severely thickened over time. No collagen or elastin changes could be detected in either group using multiphoton imaging. Raman spectroscopy with principal component analysis focusing on matrix-specific peaks confirmed no significant differences for explanted allografts. However, xenografts demonstrated clear matrix changes, enabling detection of distinct inflammatory-driven changes but without variations in the level of transforming growth factor-ß. CONCLUSIONS: Despite short-term success, mid-term failure of xenogeneic IFC grafts due to a T-cell-mediated extracellular matrix-triggered immune response was shown.