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Background: The first coronary artery bypass operation (CABG) was performed on May 2, 1960. The first percutaneous coro - nary intervention (PCI) was performed almost 20 years later. Since then, the invasive treatment of coronary artery disease (CAD) has moved into the spotlight of cardiac medical care. Methods: We summarize the current status of medical and invasive CAD treatment through a selective review of the literature. Results: More than 800 000 patients currently undergo invasive diagnostic and therapeutic procedures for CAD in Germany each year. The number of coronary artery bypass grafting (CABG) procedures rose to 65 000/year by the turn of the millennium and has been declining since then. In contrast, the number of PCIs in Germany rose to approximately 350 000/year by 2017, and a beginning decline is being observed at present. This development occurred even though, for elective patients, a survival advantage from an invasive procedure compared to medical therapy has been shown in direct comparison only for CABG. Conclusion: Conservative treatment is always the baseline treatment and has undergone major advances in the last few decades. Moreover, non-invasive coronary evaluation with computed tomography, as well as non-invasive cardiac stress imaging studies, are increasingly replacing primary invasive coronary evaluations. In this review, we illustrate a mechanistic concept of the appropriate use of CABG and PCI that can improve patient care, while underscoring the importance of interdisciplinary and intersectoral collaboration. [ABSTRACT FROM AUTHOR]

The frozen elephant trunk is a standard treatment method for aortic arch pathologies extending into the descending aorta. We previously described the phenomenon of early postoperative intraluminal thrombosis within the frozen elephant trunk. We investigated the features and predictors of intraluminal thrombosis. A total of 281 patients (66% male, mean age 60 ± 12 years) underwent frozen elephant trunk implantation between May 2010 and November 2019. In 268 patients (95%), early postoperative computed tomography angiography was available to assess intraluminal thrombosis. The incidence of intraluminal thrombosis after frozen elephant trunk implantation was 8.2%. Intraluminal thrombosis was diagnosed early after the procedure (4.6 ± 2.9 days) and could be successfully treated with anticoagulation in 55% of patients. A total of 27% developed embolic complications. Mortality (27% vs 11%, P =.044) and morbidity were significantly higher in patients with intraluminal thrombosis. Our data showed a significant association of intraluminal thrombosis with prothrombotic medical conditions and anatomic slow flow features. The incidence of heparin-induced thrombopenia was higher in patients with intraluminal thrombosis (18% vs 3.3%, P =.011). Stent-graft diameter index, anticipated endoleak Ib, and degenerative aneurysm were significant independent predictors of intraluminal thrombosis. Therapeutic anticoagulation was a protective factor. Glomerular filtration rate, extracorporeal circulation time, postoperative rethoracotomy, and intraluminal thrombosis (odds ratio, 3.19, P =.047) were independent predictors of perioperative mortality. Intraluminal thrombosis is an underrecognized complication after frozen elephant trunk implantation. In patients with risk factors of intraluminal thrombosis indication for frozen elephant trunk should be carefully evaluated and postoperative anticoagulation considered. Early thoracic endovascular aortic repair extension should be considered in patients with intraluminal thrombosis to prevent embolic complications. Stent-graft designs should be improved to prevent intraluminal thrombosis after frozen elephant trunk implantation. [Display omitted] [ABSTRACT FROM AUTHOR]

To assess the mid-term clinical outcomes, hemodynamics, left ventricular (LV) mass regression, and structural valve deterioration (SVD) in patients implanted with the Perceval aortic sutureless valve across valve sizes. Data were obtained from a multicenter European trial and a US Investigational Device Exemption trial. Echocardiography data were analyzed by an echocardiography core lab. A mixed-effects regression model was used to assess relationships between hemodynamic outcomes, time from the procedure, and valve sizes. The Valve Academic Research Consortium (VARC)-3 definition for bioprosthetic valve failure was applied. A Perceval sutureless valve was implanted in 970 patients. The median patient age was 77.8 years, 57.2% were female, the median Society of Thoracic Surgeons predicated risk of mortality was 3.3% (range, 2.1%-6.2%), and 33.4% had a concomitant procedure. The median clinical follow-up was 45.7 months (range, 28.2-76.1 months). Small and medium valves were implanted more commonly in women than in men (16.9% vs 1.9% for small and 55.1% vs 19.5% for medium; P <.001). The mean aortic valve gradients decreased significantly postimplantation and remained stable across all valve sizes throughout the follow-up period. All patients were free from severe patient–prosthesis mismatch (with an effective orifice area/m2 of >0.8). Significant LV mass regression was documented regardless valve sizes, plateaued at -9.1% at 5 years. Freedom from SVD and reintervention were 95.2% and 96.3%, respectively, at 5 years and were independent of implanted valve size (P =.22). The VARC-3 stage 3 bioprosthetic valve failure rate was low, 2.8% at 5 years. The Perceval valve demonstrated low and stable mean gradients, significant LV mass regression, and low SVD and reintervention rates across all valve sizes. [Display omitted] [ABSTRACT FROM AUTHOR]

The "frozen elephant trunk" (FET) technique was developed by Karck et al., who modified Borst's ET technique by using a stent graft to secure the distal ET section. Working in collaboration with Vascutek Terumo, we in Hannover Medical School introduced the 4-branched hybrid FET graft In 2012 (Thoraflex Hybrid). However, the results after open aortic arch repair mainly depend on perioperative management and patient factors. Over the years, peri-operative management and operative techniques have evolved greatly contributing to better results. We describe our surgical technique of implantation of this hybrid graft in acute aortic dissection Stanford type A, DeBakey type I (AADA DeBakey I) patients. [ABSTRACT FROM AUTHOR]

The edge-to-edge mitral valve repair technique, invented by Alfieri and colleagues, introduced valve repair as a treatment option for patients with complex diseases where standard annuloplasty and related repair techniques are insufficient, due to annular calcification and patient frailty. We retrospectively evaluated the results of a transaortic edge-to-edge mitral valve repair (Alfieri stitch) in high-risk patients who were undergoing aortic valve replacement. From February, 2012 to December, 2017, 43 patients underwent transaortic edge-to-edge mitral valve repair with concomitant aortic valve replacement at a single institution. Preoperative and postoperative echocardiograms were compared. Home telephone follow up was conducted and postoperative morbidity was examined, including the need for reoperation, stroke and cardiac arrhythmia. 30-day and long-term survival rates were also determined. Mitral regurgitation (MR) was graded semi-quantitatively as 0 (trace and/or none), mild (1), moderate (2) or moderate to severe (3-4). The patients were 74 ± 7.8 years old. 65% of the patients were male. Mean cardiopulmonary bypass time was 115 ± 37 minutes and mean cross-clamp time was 71 ± 23 minutes. There was a significant improvement in preoperative vs postoperative median MR grade (2 (IQR 2-3) vs 0 (IQR 0-1); P = 0.05). Follow-up transthoracic echocardiograms in 29 patients obtained at a median of 9 months' (range 3 - 19 months') and in 16 patients at a median of 34 months' postoperatively (range 21 - 53 months') showed mild (1 (IQR 1-2)) grade of mitral regurgitation. 30-day survival was 98%. Long term survival at 12 and 24 months' were 88% and 81% respectively. Mitral valve reoperation was conducted in 1 patient (2%), who was suffering of endocarditis. Stroke occurred in 2 patients (7%). Cardiac arrhythmia was observed in 15 patients (35%). 8 patients (19%) suffered from atrial fibrillation and 7 patients (16%) displayed atrioventricular blockage. 10 patients (23%) could be treated conservatively and 5 patients (12%) needed implantation of a pacemaker. Transaortic edge-to-edge mitral valve repair can be safely performed during aortic valve replacement in high-risk patients and improves even long-term MR grade. Postoperative cardiac arrhythmia occurs frequently. 66% of them could be treated successfully by conservative procedures. [ABSTRACT FROM AUTHOR]

Venous-arterial extracorporeal membrane oxygenation (ECMO) is an established technique for intraoperative cardiopulmonary support in patients undergoing lung transplantation. Patients with pulmonary fibrosis have a higher risk to require it. The aim of this study was to identify risk factors for the need of intraoperative ECMO use. Records of patients undergoing lung transplantation for pulmonary fibrosis at our institution between January 2010 and May 2018 were retrospectively reviewed. Univariate logistic regression analysis was used for statistical identification of risk factors. There were 105 patients (34%) who required intraoperative ECMO support (ECMO+ group), and 203 (66%) did not (ECMO− group). Preoperative proof of pulmonary hypertension was identified as a risk factor for intraoperative ECMO support (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.2-6.5; P <.01). Revealed mean pulmonary arterial pressure values exceeding 50 mm Hg and pulmonary vascular resistance values exceeding 9.4 Wood units were identified as risk factors for the need of intraoperative ECMO use with a prediction probability of 70%. Increased recipient body surface area (OR, 0.2; 95% CI, 0.1-0.5; P <.01) emerged as a protective factor against intraoperative ECMO (Hosmer-Lemeshow statistic, P =.71) as well as higher cardiac output (OR, 0.7; 95% CI, 0.6-0.9; P <.01). The postoperative course was more complicated in the ECMO+ group, whereas survival at 5 years did not differ among groups (70% vs 69%, P =.79). Pulmonary hypertension with elevated pulmonary vascular resistance values predicts the need of intraoperative ECMO in patients receiving lung transplantation for pulmonary fibrosis. Although the postoperative course was more complicated in the ECMO+ group, long-term survival did not differ significantly. [ABSTRACT FROM AUTHOR]

Irreversible, end-stage biventricular heart failure is associated with mortality rates of up to 100%. Despite the increasing application of ventricular assist devices (VADs), many centers lack experience with total artificial heart (TAH) implantation techniques. We present a surgical technique consisting of the implantation of 2 HeartMate 3 VADs in the setting of a TAH as a bridge to transplantation strategy. [ABSTRACT FROM AUTHOR]

We report on a large series of patients treated at the S. Orsola Hospital, University of Bologna (Bologna, Italy) and Hannover Medical School (Hannover, Germany), with the aim to evaluate the early and midterm results. Between January 2007 and March 2017, 437 patients underwent total aortic arch replacement with the frozen elephant trunk technique. The frozen elephant trunk prostheses used were the custom-made Chavan-Haverich (Hanover, Germany) (n = 27, 6%), Jotec E-vita open (Jotec Inc, Hechingen, Germany) (n = 192, 44%), and Vascutek Thoraflex-Hybrid (Vascutek, Inchinnan, Scotland) (n = 218, 50%). The main indications were thoracic aortic aneurysm (n = 135, 31%), chronic aortic dissection (n = 182, 41.6%), and acute aortic dissection (n = 120, 27.5%). Overall in-hospital mortality was 14.9%, and permanent neurologic deficit and spinal cord injury were 10.8% and 5.5%, respectively. Patients with chronic aortic dissection presented a better in-hospital mortality rate than the thoracic aortic aneurysm and acute aortic dissection groups. Independent risk factors for mortality in the overall population were prolonged cardiopulmonary bypass time, age, urgent/emergency surgery, and Marfan syndrome. The median (p25, p75) follow-up time was 2.6 (1.4-4.4) years, and the mortality rate was 7.01 (95% confidence interval, 5.7-8.7) per 100 patient-years. A total of 86 patients (23.1%) required an additional procedure during the follow-up; 61 (16.3%) required endovascular extensions, and 25 (6.7%) required aortic surgery. The frozen elephant trunk technique is a treatment option for all complex pathologies of the thoracic aorta. Patients with thoracic aortic aneurysms presented a higher mortality rate, and in patients with acute aortic dissection, the malperfusion syndrome still remains a catastrophic complication. The midterm follow-up showed satisfactory results in terms of survival and freedom from reintervention. [ABSTRACT FROM AUTHOR]

Since its introduction in 1992, multiple variations of the aortic valve-sparing David procedure technique have been described. Here, we present the short- and midterm outcomes of 2 centers using the straight tube graft (David-I) and the Valsalva prosthesis in patients who underwent isolated David procedure. Between March 2002 and October 2015, 232 patients underwent the David procedure at 2 European centers. Patients received either a straight tube graft (David-I, group A, n = 103, 74% men) or Valsalva graft (group B, n = 129, 85% men). Mean age was 47 ± 17 years in group A and 48 ± 17 years in group B (P =.916). There were significantly more cusp repairs in group B (n=28, 22%) compared with group A (n = 4, 4%, P <.001). The 30-day mortality rate was 1% (n = 1) in group A and 2% (n = 2, P =.698) in group B. Postoperative echocardiography showed aortic insufficiency ≥II in 0% (n = 0) of group A and 17% (n = 21) of group B (P <.001). Follow-up comprised 1530 patient-years, and survival was comparable between the 2 groups (P =.799). Follow-up echocardiography showed aortic insufficiency ≥II in 22% (n = 15) of group A and 39% (n = 33) of group B (P <.026). The rates for aortic valve-related reoperation were 8% (n = 8) in group A and 13% (n = 16) in group B (P =.241). Logistic Cox regression analysis identified bicuspid aortic valve (odds ratio, 3.435; 95% confidence interval, 1.459-8.083, P =.005) and postoperative aortic insufficiency ≥II (odds ratio, 5.988; 95% confidence interval, 2.545-14.088, P <.001) as risk factors for aortic valve-related reoperation. The aortic valve-sparing David procedure has acceptable midterm results. Our results show that the David-I procedure with straight tube graft is not inferior to those performed with Valsalva prosthesis. [ABSTRACT FROM AUTHOR]

Background: Nearly 1000 permanent ventricular assist devices (VADs) are implanted in patients with severe congestive heart failure in Germany each year. VADs are miniaturized centrifugal pumps that generate continuous blood flow; they are powered and controlled through a cable that passes through the skin. Para-corporeal systems are only rarely implanted, usually in children. Methods: In this selective review of the literature, including guidelines and registry data, we discuss the indications, therapeutic effects, and complications of permanently implantable cardiac support systems. Results: The optimal time for VAD implantation cannot be precisely defined. A comparative assessment of the various available systems is not possible, as no randomized trials have been performed on this topic. Registry data indicate that 69% to 81% of patients survive one year after VAD implantation, which is significantly better than the natural course of (conservatively treated) severe congestive heart failure. The distance patients are able to walk is 129 to 220 m longer at six months, depending on the system implanted. Scores on the EQ-5D health status questionnaire are 28 to 37 points better at six months. The potential severe complications include infection, right-heart failure, hemorrhage, pump thrombosis, stroke, and death. Conclusion: A VAD system can be implanted as an alternative to cardiac transplantation or as a bridging treatment until the patient can be listed for transplantation and receive the transplant. Because of the organ shortage in Germany, only a minority of VAD patients ever receive a transplant. [ABSTRACT FROM AUTHOR]

Donor lung use for transplantation is the lowest among solid organ tranplants because of several complex and multifactorial reasons; one area that could have a substantial role is the limited capabilities of cold ischaemic storage. The aim of the EXPAND trial was to evaluate the efficacy of normothermic portable Organ Care System (OCS) Lung perfusion and ventilation on donor lung use from extended-criteria donors and donors after circulatory death, which are rarely used. In this single-arm, pivotal trial done in eight institutions across the USA, Germany, and Belgium, lungs from extended-criteria donors were included if fulfilling one or more of the following criteria: a ratio of partial pressure of arterial oxygen (PaO 2) to fractional concentration of oxygen inspired air (FiO 2) in the donor lung of 300 mm Hg or less; expected ischaemic time longer than 6 h; donor age 55 years or older; or lungs from donors after circulatory death that were recruited and assessed using OCS Lung. Lungs were transplanted if they showed stability of OCS Lung variables, PaO 2 :FiO 2 was more than 300 mm Hg, and they were accepted by the transplanting surgeon. Patients were adult bilateral lung transplant recipients. The primary efficacy endpoint was a composite of patient survival at day 30 post-transplant and absence of The International Society for Heart & Lung Tranplantation primary-graft dysfunction grade 3 (PGD3) within 72 h post-transplantation, with a prespecified objective performance goal of 65%. The primary analysis population was all transplanted recipients. This trial is registered with ClinicalTrials.gov , number NCT01963780 , and is now complete. Between Jan 23, 2014, and Oct 23, 2016, 93 lung pairs were perfused, ventilated, and assessed on the OCS Lung. 12 lungs did not meet OCS transplantation criteria so 81 lungs were suitable for transplantation. Two lungs were excluded for logistical reasons, hence 79 (87%) of eligible lungs were transplanted. The primary endpoint was achieved in 43 (54%) of 79 patients and did not meet the objective performance goal. 35 (44%) of 79 patients had PGD3 within the initial 72 h. 78 (99%) of 79 patients had survived at 30 days post-transplant. The mean number of lung graft-related serious adverse events (respiratory failure and major pulmonary-related infection) was 0·3 events per patient (SD 0·5). Despite missing the objective primary endpoint, the portable OCS Lung resulted in 87% donor lung use for transplantation with excellent clinical outcomes. Many lungs declined by other transplant centres were successfully transplanted using this new technology, which implies its use has the potential to increase the number of lung transplants performed worldwide. Whether similar outcomes could be obtained if these lungs were preserved on ice is unknown and remains an area for future research. TransMedics Inc. [ABSTRACT FROM AUTHOR]

The generation of small-caliber vascular grafts remains a significant challenge within the field of tissue engineering. In pursuit of this objective, fibrin has emerged as a promising scaffold material. However, its lack of biomechanical strength has limited its utility in the construction of tissue engineered vascular grafts. We have previously reported about the implementation of centrifugal casting molding to generate compacted fibrin tubes with a highly increased biomechanical strength. In this study, we conducted a structural analysis of compacted fibrin tubes using the open-source software Fiji/BoneJ. The primary aim was to validate the hypothesis that the compaction of fibrin leads to a more complex structure characterized by increased crosslinking of fibrin fibers. Structural analysis revealed a strong correlation between fibrin's structure and its biomechanical strength. Moreover, we enhanced fibrin compaction in a subsequent dehydration process, leading to a significant increase of biomechanical strength. Thus, the presented method in combination with an adequate imaging, e.g., micro-CT, has substantial potential as a powerful tool for quality assurance in the development of fibrin-based vascular grafts. To validate this concept, acellular highly compacted fibrin tubes were implanted as substitutes of a segment of the carotid artery in a sheep model (n = 4). After 6 months explanted segments exhibited distinct remodeling, transitioning into newly formed arteries. [Display omitted] • Rotational molding leads to a significant compaction of fibrin. • Compaction of fibrin results in a significantly more complex and crosslinked fibrin structure. • Further dehydration improves fibrin's structure and biomechanical strength. [ABSTRACT FROM AUTHOR]

We present our 25-year experience with valve-sparing aortic root replacement using a straight tube graft (David-I). From 1993 to 2019, 677 patients (median age, 56.0 years; range, 42-65) underwent the David-I procedure with a straight tube graft. A total of 24 different surgeons performed these operations. Marfan syndrome was present in 111 patients (16.4%), and bicuspid aortic valve was present in 71 patients (10.5%). Aortic root aneurysm was present in 544 patients (80.4%), and acute dissection was present in 133 patients (19.6%). Ministernotomy was used in 57 patients (8.4%). Additional cusp plasty was performed in 84 patients (12.4%). Concomitant procedures were coronary artery bypass grafting (n = 122, 18.0%), mitral valve surgery (n = 34, 5%), proximal arch replacement (n = 125, 18.4%), subtotal arch replacement (n = 43, 6.4%), and total arch replacement (n = 102, 15.1%). Overall in-hospital mortality was 4.0% (n = 27), and perioperative stroke occurred in 26 patients (3.8%). Postoperative echocardiography showed aortic insufficiency less than I° in 600 of 623 (96.3%). The 1-, 5-, 10-, 15-, and 20-year survivals were 97%, 92%, 79%, 68%, and 50%, respectively. The rates for freedom from aortic valve-related reoperation at 1, 5, 10, 15, and 20 years were 97%, 92%, 87%, 84%, and 80%, respectively. Multivariate Cox regression analysis identified age (odds ratio, 0.974; 95% confidence interval, 0.957-0.992; P =.004), senior surgeon (odds ratio, 0.546; 95% confidence interval, 0.305-0.979; P =.042), and residual postoperative aortic insufficiency (odds ratio, 4.864; 95% confidence interval, 1.124-21.052; P =.034) as independent risk factors for aortic valve-related reoperation. The aortic valve-sparing David-I procedure can be performed with very low perioperative morbidity and mortality. The short- and long-term results are excellent. The straight tube graft does not lead to increased leaflet erosion. This procedure is reproducible by multiple surgeons. [Display omitted] [ABSTRACT FROM AUTHOR]

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Unlike the vast amount of animal data available on the recellularization of allogenic decellularized heart valves (DHVs), there have only been sporadic histologic reports on such grafts in humans. Two experienced cardiac pathologists independently evaluated human specimens obtained during reoperation between December 2010 and April 2017 DHVs in seven categories after automated staining (scores: 0 to 6) in comparison with published data. An optimal result of 42 points was classified as 100%. We found that 364 DHVs, 236 decellularized pulmonary homografts (DPHs), and 128 decellularized aortic homografts (DAHs) were implanted, and freedom from explantation was 96.1% (DAH) and 98.7% (DPH). Reoperations were because of (suspected) endocarditis in 5 of 11 patients, stenosis at the subvalvular or valvular or supravalvular level in 3 of 11 patients, planned staged reoperation in 2 of 11 patients, and 1 heart transplantation. Good reader agreement was reflected by an interagreement weighted κ of 0.783 (95% confidence interval: 0.707 to 0.859). The relative histologic score in nonendocarditis specimens was 76% ± 4.3% (maximum 81%). Intracellular procollagen type 1 production was found in recipient mesenchymal cells within the transplanted grafts. In endocarditis specimens the histologic score was significantly lower with 48% ± 7.3% (minimum 41%, p = 0.0004) because of leucocyte infiltration and matrix degradation. One DPH showed immune system-mediated graft failure. Grafts obtained during the first 12 months after implantation were not evenly repopulated with less recellularization in the inner parts; no difference was found between DAH and DPH with respect to extent of recellularization. Substantial in vivo recellularization with noninflammatory cells was observed in this study. Spontaneous recellularization appears to require multiple months, which correspondingly has an impact on size selection for growing patients. [ABSTRACT FROM AUTHOR]

Chronic lung allograft dysfunction (CLAD) is a severe complication of lung transplantation limiting long-term survival. We studied correlations between CLAD after clinical lung transplantation and leukocyte-mediated development of transplant arteriosclerosis (TA) in a humanized mouse model. The pericardiophrenic artery was procured from surplus tissue of donor lungs (n = 22) transplanted in our clinical program and was implanted into the abdominal aorta of immune-deficient mice. Allogeneic human peripheral blood mononuclear cells (PBMCs) had been procured 1 day after lung transplantation from the respective recipients with or without enriching for CD4+CD25high T cells were used. TA was assessed in mice 28 days later by histology. The respective clinical lung recipients were later divided into 2 groups. Eight patients (36.3%) had developed CLAD 23 ± 5 months after lung transplantation, whereas the remaining 14 (63.6%) did not develop CLAD within 25 ± 5 months. In the PBMC CLAD+ group of mouse experiments, TA was significantly more severe than in the PBMC CLAD– group (39.9% ± 13% vs 14.9% ± 4% intimal thickening; P =.0081). Then, intimal thickening was significantly inhibited in the PBMC+ regulatory T cells CLAD+ group compared with the PBMC CLAD+ group (0.4% ± 4% vs 39.9% ± 13%; P =.003). In the experiments using PBMCs from lung recipients without CLAD, enriching regulatory T cells also suppressed the development of TA (0.9% ± 3% PBMC CLAD– vs 14.9% ± 4% PBMC+ regulatory T cells CLAD–; P =.001). Lung transplant recipients who later develop CLAD have peripheral leukocytes already at the time of transplant that transfer proinflammatory properties leading to TA in a humanized mouse model. TA remains sensitive to inhibition by autologous regulatory T cells, suggesting a cell therapy-based approach for the prevention of CLAD after lung transplantation. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To evaluate the feasibility of multiparametric magnetic resonance imaging (MRI) of the lungs to detect impaired organ function in a porcine model of ischemic injury within an ex-vivo lung perfusion system (EVLP) prior to transplantation.Materials and Methods: Twelve pigs were anesthetized, and left lungs were clamped to induce warm ischemia for 3 hours. Right lungs remained perfused as controls. Lungs were removed and installed in an EVLP for 12 hours. Lungs in the EVLP were imaged repeatedly using computed tomography, proton MRI (1H-MRI) and fluorine MRI (19F-MRI). Dynamic contrast-enhanced derived parenchymal blood volume, oxygen washout times, and 19F washout times were calculated. PaO2 was measured for ischemic and normal lungs, wet/dry ratio was determined, histologic samples were assessed, and cytokines in the lung tissue were analyzed. Statistical analysis was performed using nonparametric testing.Results: Eleven pigs were included in the final analysis. Ischemic lungs showed significantly higher wet/dry ratios (p = 0.024), as well as IL-8 tissue levels (p = 0.0098). Histologic assessment as well as morphologic scoring of computed tomography and 1H-MRI did not reveal significant differences between ischemic and control lungs. 19F washout (p = 0.966) and parenchymal blood flow (p = 0.32) were not significantly different. Oxygen washout was significantly prolonged in ischemic lungs compared to normal control lungs at the beginning (p = 0.018) and further prolonged at the end of the EVLP run (p = 0.005).Conclusion: Multiparametric pulmonary MRI is feasible in lung allografts within an EVLP system. Oxygen-enhanced imaging seems to be a promising marker for ischemic injury, enabling detection of affected lung segments prior to transplantation. [ABSTRACT FROM AUTHOR]

Background: The Heartmate 3 (HM3) is a Conformiteé Européenne mark-approved left ventricular (LV) assist device (LVAD) with fully magnetically levitated rotor and features consisting of a wide range operational speeds, wide flow paths, and artificial pulse. We performed a hemodynamic-echocardiographic speed optimization evaluation in HM3-implanted patients to achieve optimal LV- and right ventricular (RV) shape.Methods and Results: Sixteen HM3 patients underwent pump speed ramp tests with right heart catheterization. Three-dimensional echocardiographic (3DE) LV and RV datasets (Philips) were acquired, and volumetric (Tomtec) and shape (custom software) analyses were performed (LV: sphericity, conicity; RV: septal and free-wall curvatures). Data were recorded at up to 13 speed settings. Speed changes were in 100-rpm steps, starting at 4600 rpm and ramping up to 6200 rpm. 3DE was feasible in 50% of the patients. Mean original speed was 5306 ± 148 rpm. LV end-diastolic (ED) diameter (-0.15 ± 0.09 cm/100 rpm) and volumes (ED: 269 ± 109 mL to 175 ± 90 mL; end-systolic [ES]: 234 ± 111 mL to 146 ± 81 mL) progressively decreased as the shape became less spherical and more conical; RV volumes initially remained stable, but at higher speeds increased (ED: from 148 ± 64 mL to 181 ± 92 mL; ES: 113 ± 63 mL to 130 ± 69 mL). On average, the RV septum became less convex (bulging toward the LV) at the highest speeds.Conclusions: LV and RV shape changes were noted in HM3-supported patients. Although a LV volumetric decrease and shape improvement was consistently noted, RV volumes grew in response to increase in speed above a certain point. A next concern would be whether understanding of morphologic and function changes in LV and RV during LVAD speed change assessed with the use of 3DE helps to optimize LVAD speed settings and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Background The HeartMate 3 (HM3; Abbott Laboratories, Lake Forest, Ill) left ventricular assist device (LVAD) received its Conformité Européenne mark for Europe in October 2015 and is currently under investigation of the Food and Drug Administration to gain approval in the United States. Within this study, we present the first real-world experiences, 1-year outcomes, and adverse events of a single-center cohort treated with the HM3. Methods We prospectively studied midterm results of 27 consecutive patients receiving the HM3 at a single institution. After HM 3 implantation, survival, causes of death, and complications were recorded for all patients. Follow up was 100% complete. Results Twenty-seven patients were enrolled into the study. Within 1 year after HM3 implantation, 3 patients underwent heart transplantation and 3 patients died. Thirty-day survival was 88.9%, 6-month 85.2%, and 1-year survival 85.2%. No pump thrombosis and no strokes were observed within the study group. One incident of gastrointestinal bleeding was observed (3.7%). Right heart failure was diagnosed in 1 patient after HM3 implantation (3.7%). No technical complications of the pump were documented. No pump exchanges were necessary. The main complication was LVAD-related infection (22.2%). Conclusions The novel LVAD HM3 has already shown excellent Conformité Européenne mark trial results. Within this cohort, 1-year survival after HM3 implantation was 85%. The HM3 showed excellent midterm results with 0% stroke and 0% pump thrombosis rates 1 year after implantation. [ABSTRACT FROM AUTHOR]

Despite great advances in technology and medical care, device infection and pump thrombosis remain major difficulties in the therapy with left ventricular assist devices. When medical treatment fails, operative left ventricular assist devices exchange is the only curative option. We present a step by step guide to the conventional exchange procedure via lateral thoracotomy as well as a guide to the exchange from an older to a new generation device. [ABSTRACT FROM AUTHOR]

The decellularization of biological tissues decreases immunogenicity, allows repopulation with cells, and may lead to improved long-term performance after implantation. Freeze drying these tissues would ensure off-the-shelf availability, save storage costs, and facilitates easy transport. This study evaluates the in vivo performance of freeze-dried decellularized heart valves in juvenile sheep. TritonX-100 and sodium dodecylsulfate decellularized ovine and porcine pulmonary valves (PV) were freeze-dried in a lyoprotectant sucrose solution. After rehydration for 24 h, valves were implanted into the PV position in sheep as allografts (fdOPV) and xenografts (fdPPV), while fresh dezellularized ovine grafts (frOPV) were implanted as controls. Functional assessment was performed by transesophageal echocardiography at implantation and at explantation six months later. Explanted grafts were analysed histologically to assess the matrix, and immunofluorescence stains were used to identify the repopulating cells. Although the graft diameters and orifice areas increased, good function was maintained, except for one insufficient, strongly deteriorated frOPV. Cells which were positive for either endothelial or interstitial markers were found in all grafts. In fdPPV, immune-reactive cells were also found. Our findings suggest that freeze-drying does not alter the early hemodynamic performance and repopulation potential of decellularized grafts in vivo , even in the challenging xenogeneic situation. Despite evidence of an immunological reaction for the xenogenic valves, good early functionalities were achieved. Statement of Significance Decellularized allogeneic heart valves show excellent results as evident from large animal experiments and clinical trials. However, a long-term storing method is needed for an optimal use of this limited resource in the clinical setting, where an optimized matching of graft and recipient is requested. As demonstrated in this study, freeze-dried and freshly decellularized grafts reveal equally good results after implantation in the juvenile sheep concerning function and repopulation with recipients’ cells. Thus, freeze-drying arises as a promising method to extend the shelf-life of valvular grafts compared to those stored in antibiotic-solution as currently practised. [ABSTRACT FROM AUTHOR]

For several years, the standard implantation strategy of ventricular assist devices has involved a full sternotomy approach. However, less invasive implantation techniques are now becoming increasingly popular as they are associated with reduction of trauma, blood loss, and arrhythmogenic complications, as well as a decreased duration of intensive care unit and in-hospital stay. Thus, due to miniaturization and increasing technical improvement of ventricular assist devices, less invasive strategies for implantation, explantation, exchange, and concomitant cardiac procedures are on the rise. In this review article, we report on the state of the art of less invasive techniques for implantation, explantation, exchange, and combined cardiac procedures of ventricular assist devices. [ABSTRACT FROM AUTHOR]

Background We present our results after elective, isolated David I procedures over the past 20 years. Methods Between 1993 and 2015, 197 patients (mean age 46 ± 17 years, 73% men) underwent isolated aortic valve reimplantation using straight tube grafts (David I procedure). Sixty patients (31%) had Marfan syndrome, and 24 (12%) had a bicuspid aortic valve. Twenty-four patients (12%) were operated through upper mini-sternotomy. Results There were no perioperative deaths. Stroke rate was 1% (2 of 197). Discharge echocardiography showed none to trivial aortic regurgitation (AR) in 71% (139 of 197 patients) and mild AR in 26% (51 of 197 patients). Thirty-two patients (16%) died during follow-up (9.0 ± 5.5 years after operation). One death was aortic valve related. Twenty-six patients (13%) underwent aortic valve reoperations during follow-up (5.5 ± 5.0 years after operation). Late endocarditis occurred in 2 patients (1.0%). More than trivial AR at discharge predicted a higher reoperation rate. In 144 non-reoperated survivors, echocardiography showed none to trivial AR in 56 (39%), mild AR in 53 (37%), moderate AR in 19 (6.3%), and severe AR in 4 (2.7%) of the patients after 12 ± 5.3 years. Conclusions The valve-sparing David I procedure has excellent short- and long-term results. Erosion due to supposed leaflet contact with the straight tube graft was not observed in any patient, proving that using a straight graft has no negative impact on the leaflets. The “spared valve” (being native living tissue) seems to be more resistant to infection than prosthetic valves. [ABSTRACT FROM AUTHOR]

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Objectives Atherosclerosis is a hallmark of cardiovascular disease. Shear stress on endothelial cells has been linked to atherogenesis and to fibrous cap thinning and rupture. Pericytes reside in the sub-endothelial space of vessels and have vasoprotective effects. They are subjected to shear stress when endothelial cell integrity is disrupted. The aim was to investigate the susceptibility and response of pericytes to shear stress. Methods Endothelial cells and pericytes were seeded in two dimensional monocultures and co-cultures, and in a novel three dimensional co-culture system and were subjected to no, low and high shear stress (0, 10, 30 dyne/cm 2 ) for 48 h. The morphological response to flow was assessed by histology and the expression of extracellular matrix proteins was analysed using quantitative polymerase chain reaction, immunoblotting, and ELISA. Results While endothelial cells aligned into flow direction, pericytes aligned perpendicularly ( p < .001), indicating that they must be capable of sensing flow. When pericytes were embedded into a 3D matrix they showed similar alignment and pericytes built long processes towards the lumen. Under shear stress endothelial cells upregulated “a disintegrin and metalloproteinase with thrombospondin motif 1” (ADAMTS-1) ( p < .01) and pericytes upregulated “tissue inhibitor of matrix metalloproteinase” (TIMP) 3 ( p < .05), an inhibitor of ADAMTS-1, meanwhile differential expression of extracellular matrix (ECM) proteins could be detected in co-cultures of both cells. For TIMP3 expression direct cell–cell contact between endothelial cells and pericytes was required. Conclusion The experiments highlight that pericytes are able to sense direct flow thereby regulating ECM proteins known to be involved in vascular remodelling. Furthermore, pericytes counter-regulate endothelial ADAMTS-1 by protective TIMP3 expression to prevent matrix degradation and maintain vascular stability. For this protective effect direct cell contact was necessary. This observation might represent an adaptive, protective mechanism of pericytes to counteract endothelial damage in the onset of atherosclerosis. [ABSTRACT FROM AUTHOR]