Reciprocal interferences of the left ventricular assist device and the aortic valve competence.

Patients suffering from end-stage heart failure tend to have high mortality rates. With growing numbers of patients progressing into severe heart failure, the shortage of available donors is a growing concern, with less than 10% of patients undergoing cardiac transplantation (CTx). Fortunately, the use of left ventricular assist devices (LVADs), a variant of mechanical circulatory support has been on the rise in recent years. The expansion of LVADs has led them to be incorporated into a variety of clinical settings, based on the goals of therapy for patients ailing from heart failure. However, with an increase in the use of LVADs, there are a host of complications that arise with it. One such complication is the development and progression of aortic regurgitation (AR) which is noted to adversely influence patient outcomes and compromise pump benefits leading to increased morbidity and mortality. The underlying mechanisms are likely multifactorial and involve the aortic root-aortic valve (AV) complex, as well as the LVAD device, patient, and other factors, all of them alter the physiological mechanics of the heart resulting in AV dysfunction. Thus, it is imperative to screen patients before LVAD implantation for AR, as moderate or greater AR requires a concurrent intervention at the time of LVADs implantation. No current strict guidelines were identified in the literature search on how to actively manage and limit the development and/or progression of AR, due to the limited information. However, some recommendations include medical management by targeting fluid overload and arterial blood pressure, along with adjusting the settings of the LVADs device itself. Surgical interventions are to be considered depending on patient factors, goals of care, and the underlying pathology. These interventions include the closure of the AV, replacement of the valve, and percutaneous approach via percutaneous occluding device or transcatheter aortic valve implantation. In the present review, we describe the interaction between AV and LVAD placement, in terms of patient management and prognosis. Also it is provided a comprehensive echocardiographic strategy for the precise assessment of AV regurgitation severity.

Outcomes of heart transplantation in patients bridged with Impella 5.0: Comparison with native chest transplanted patients without preoperative mechanical circulatory support.

The Impella (Abiomed, Danvers, MA, USA) has become an important adjunct treatment modality in bridging patients with end-stage heart failure to recovery or orthotopic heart transplantation (HTx). We compared the outcome of patients directly bridged to HTx with the Impella 5.0 versus patients without mechanical circulatory support (MCS). Patients with no previous sternotomy or MCS, who were transplanted between September 2014 and March 2019 were included in this retrospective analysis. Impella 5.0 was implanted using surgical access and transesophageal echocardiography guidance. Forty-two out of 155 transplanted patients fulfilled the insertion criteria. Eight (19%) were bridged with Impella 5.0 to HTx. Recipient and donor baseline characteristics were comparable in both groups. There were no significant differences in survival between the groups at 30-day (94% no MCS vs. 87.5% Impella group, P = .47) or 6 months (94% vs. 87.5%, P = .51). Patients on Impella 5.0 showed a significant recovery of hemodynamic parameters and end-organ function. Average duration of support to HTx was 16 ± 17 days. Impella 5.0, when used in suitable patients in a timely fashion can be a good strategy for bridging patients to HTx. The axillary approach allows for early extubation and mobilization. Outcomes of patients bridged to HTx with Impella 5.0 in acute cardiogenic shock are comparable to those of patients with no MCS.

Suicidal hanging donors for lung transplantation: Is this chapter still closed? Midterm experience from a single center in United Kingdom.

In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group.Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed.No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P < .001, P = .022 and P = .0042, respectively). Recipient preoperative and perioperative characteristics were comparable. Postoperatively in group 1 there was a higher incidence of extracorporeal life support (27.3 vs 9.1%, P = .019). There were no significant differences in chronic lung allograft dysfunction-free survival between group 1 and 2: 92.3 vs 94% at 1 year and 65.9 vs 75.5% at 3 years (P = .99). The estimated cumulative survival rate was also similar between groups: 68.2 vs 83.2% at 1 year and 68.2% versus 72% at 3 years (P = .3758).Hanging as a donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation.

Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury.

RATIONALE: Primary graft dysfunction in lung transplant recipients derives from the initial, largely leukocyte-dependent, ischaemia-reperfusion injury. Intravascular lung-marginated monocytes have been shown to play key roles in experimental acute lung injury, but their contribution to lung ischaemia-reperfusion injury post transplantation is unknown. OBJECTIVE: To define the role of donor intravascular monocytes in lung transplant-related acute lung injury and primary graft dysfunction. METHODS: Isolated perfused C57BL/6 murine lungs were subjected to warm ischaemia (2 hours) and reperfusion (2 hours) under normoxic conditions. Monocyte retention, activation phenotype and the effects of their depletion by intravenous clodronate-liposome treatment on lung inflammation and injury were determined. In human donor lung transplant samples, the presence and activation phenotype of monocytic cells (low side scatter, 27E10+, CD14+, HLA-DR+, CCR2+) were evaluated by flow cytometry and compared with post-implantation lung function. RESULTS: In mouse lungs following ischaemia-reperfusion, substantial numbers of lung-marginated monocytes remained within the pulmonary microvasculature, with reduced L-selectin and increased CD86 expression indicating their activation. Monocyte depletion resulted in reductions in lung wet:dry ratios, bronchoalveolar lavage fluid protein, and perfusate levels of RAGE, MIP-2 and KC, while monocyte repletion resulted in a partial restoration of the injury. In human lungs, correlations were observed between pre-implantation donor monocyte numbers/their CD86 and TREM-1 expression and post-implantation lung dysfunction at 48 and 72 hours. CONCLUSIONS: These results indicate that lung-marginated intravascular monocytes are retained as a 'passenger' leukocyte population during lung transplantation, and play a key role in the development of transplant-associated ischaemia-reperfusion injury.

Use of taurolidine in lung transplantation for cystic fibrosis and impact on bacterial colonization.

OBJECTIVES: The presence of bacterial colonization that causes chronic pulmonary infections in cystic fibrosis (CF) patients remains a key issue before lung transplantation. We sought to assess the impact of intraoperative taurolidine lavage on bacterial colonization and long-term outcomes following lung transplantation in CF patients. METHODS: Between 2007 and 2013, 114 CF patients underwent lung transplantation at our institute, and taurolidine 2% bronchial lavage was applied in a substantial proportion of patients (n = 42). A detailed analysis of donor and recipient bacterial colonization status in treatment and control groups and their impact on outcome was performed. RESULTS: The proportion of recipients colonized with Pseudomonas aeruginosa was lower in the taurolidine group at 3 months (P < 0.001) and at 1 year (P = 0.053) postoperatively, despite no differences before transplant (P = 1.000). Moreover, a complete eradication of Burkholderia cepacia and Stenotrophomonas maltophilias colonizations could be achieved in the taurolidine group, whereas in the non-taurolidine group, persistent B. cepacia and S. maltophilias colonizations were observed. Early outcome in the taurolidine group was superior regarding fraction of expired volume in 1 s at 3 and 6 months after surgery with 74.5 ± 14.6 vs 60.4 ± 17.5 (P < 0.001) and 80.6 ± 16.9 vs 67.2 ± 19.4 (P = 0.005) percent of predicted values, respectively. In terms of long-term overall survival (P = 0.277) and freedom from bronchiolitis obliterans syndrome (P = 0.979), both groups were comparable. CONCLUSIONS: Taurolidine might be associated with a reduced proportion of CF patients colonized with multiresistant pathogens, particularly with P. aeruginosa. Long-term results should be further assessed in larger multicentre trials.

Does postoperative blood pressure influence development of aortic regurgitation following continuous-flow left ventricular assist device implantation?†.

OBJECTIVES: The true impact of postoperative blood pressure (BP) control on development of aortic regurgitation (AR) following continuous-flow left ventricular assist device (CF-LVAD) implantation remains uncertain. This study examines the influence of BP in patients with de novo AR following CF-LVAD implantation. METHODS: All patients with no or

Preoperative predictors and outcomes of right ventricular assist device implantation after continuous-flow left ventricular assist device implantation.

OBJECTIVE: The outcomes of ventricular assist device therapy remain limited by right ventricular failure. We sought to define the predictors and evaluate the outcomes of right ventricular failure requiring right ventricular assist device support after long-term continuous-flow left ventricular assist device implantation. METHODS: Records of all continuous-flow left ventricular assist device recipients for the last 10 years were analyzed, including patients on preoperative intra-aortic balloon pump, extracorporeal membrane oxygenation, and short-term ventricular assist device support. Perioperative clinical, echocardiographic, hemodynamic, and laboratory data of continuous-flow left ventricular assist device recipients requiring right ventricular assist device support (right ventricular assist device group) were compared with the rest of the patient cohort (control group). RESULTS: Between July 2003 and June 2013, 152 patients underwent continuous-flow left ventricular assist device implantation as a bridge to transplantation. The overall postoperative incidence of right ventricular assist device support was 23.02% (n = 35). Right ventricular assist device implantation did not significantly affect eventual transplantation (P = .784) or longer-term survival (P = .870). Preoperative right ventricular diameter (P < .001), tricuspid annular plane systolic excursion (P < .001), previous sternotomy (P = .002), preoperative short-term mechanical support (P = .005), left atrial diameter (P = .014), female gender (P = .020), age (P = .027), and preoperative bilirubin levels (P = .031) were univariate predictors of right ventricular assist device implantation. Multivariate analysis revealed lesser tricuspid annular plane systolic excursion (P = .013; odds ratio, 0.613; 95% confidence interval, 0.417-0.901) and smaller left atrial diameter (P = .007; odds ratio, 0.818; 95% confidence interval, 0.707-0.947) as independent predictors of right ventricular assist device implantation. Receiver operating characteristic curve of tricuspid annular plane systolic excursion yielded an area under the curve of 0.85 (95% confidence interval, 0.781-0.923), with cutoff tricuspid annular plane systolic excursion less than 12.5 mm having 84% sensitivity and 75% specificity. CONCLUSIONS: Lesser tricuspid annular plane systolic excursion and smaller left atrial diameter are independent predictors of the need for right ventricular assist device support after continuous-flow left ventricular assist device implantation. Right ventricular assist device implantation does not adversely affect eventual transplantation or survival after continuous-flow left ventricular assist device implantation.

Perfusion-Decellularization of Porcine Lung and Trachea for Respiratory Bioengineering.

Decellularization of native organs may provide an acellular tissue platform for organ regeneration. However, decellularization involves a trade-off between removal of immunogenic cellular elements and preservation of biomechanical integrity. We sought to develop a bioartificial scaffold for respiratory tissue engineering by decellularization of porcine lungs and trachea while preserving organ architecture and vasculature. Lung-trachea preparations from 25 German Landrace pigs were perfused in a modified Langendorff circuit and decellularized by an SDC (sodium deoxycholate)-based perfusion protocol. Decellularization was evaluated by histology and fluorescence microscopy, and residual DNA quantified spectrophotometrically and compared with controls. Airway compliance was evaluated by endotracheal intubation and mechanical ventilation to simulate physiological breathing-induced stretch. Structural integrity was evaluated by bronchoscopy and biomechanical stress/strain analysis by measuring passive tensile strength, all compared with controls. Decellularized lungs and trachea lacked intracellular components but retained specific collagen fibers and elastin. Quantitative DNA analysis demonstrated a significant reduction of DNA compared with controls (32.8 ± 12.4 µg DNA/mg tissue vs. 179.7 ± 35.8 µg DNA/mg tissue, P < 0.05). Lungs and trachea decellularized by our perfusion protocol demonstrated increased airway compliance but preserved biomechanical integrity as compared with native tissue. Whole porcine lungs-tracheae can be successfully decellularized to create an acellular scaffold that preserves extracellular matrix and retains structral integrity and three-dimensional architecture to provide a bioartifical platform for respiratory tissue engineering.

Bioartificial heart: a human-sized porcine model--the way ahead.

BACKGROUND: A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Native hearts decellularized with preserved architecture and vasculature may provide an acellular tissue platform for organ regeneration. We sought to develop a tissue-engineered whole-heart neoscaffold in human-sized porcine hearts. METHODS: We decellularized porcine hearts (n = 10) by coronary perfusion with ionic detergents in a modified Langendorff circuit. We confirmed decellularization by histology, transmission electron microscopy and fluorescence microscopy, quantified residual DNA by spectrophotometry, and evaluated biomechanical stability with ex-vivo left-ventricular pressure/volume studies, all compared to controls. We then mounted the decellularized porcine hearts in a bioreactor and reseeded them with murine neonatal cardiac cells and human umbilical cord derived endothelial cells (HUVEC) under simulated physiological conditions. RESULTS: Decellularized hearts lacked intracellular components but retained specific collagen fibers, proteoglycan, elastin and mechanical integrity; quantitative DNA analysis demonstrated a significant reduction of DNA compared to controls (82.6±3.2 ng DNA/mg tissue vs. 473.2±13.4 ng DNA/mg tissue, p<0.05). Recellularized porcine whole-heart neoscaffolds demonstrated re-endothelialization of coronary vasculature and measurable intrinsic myocardial electrical activity at 10 days, with perfused organ culture maintained for up to 3 weeks. CONCLUSIONS: Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure.

De novo aortic regurgitation after continuous-flow left ventricular assist device implantation.

BACKGROUND: Significant aortic regurgitation (AR) after continuous-flow left ventricular assist device (cf-LVAD) placement affects device performance and patient outcomes. This study examined the development of AR and long-term results after implantation of cf-LVADs. METHODS: The study included all patients with no or less than mild AR who underwent HeartMate II (58 [62%]; Thoratec Corp, Pleasanton, CA) or HeartWare (35 [38%]; HeartWare International, Framingham, MA) implantation at our institute from July 2006 to July 2012. Serial echocardiograms were obtained preoperatively, at 1, 3 and 6 months postoperatively, and then at a minimum of 4-month intervals in patients with longer-term support. Kaplan-Meier estimates for freedom from moderate or greater AR were generated. Logistic regression analysis was used to define independent predictors of AR after cf-LVAD implantation. RESULTS: Median duration of LVAD support was 527 days (25(th), 75(th): 289, 907; range, 60 to 2,433 days). Mild AR developed in 48 patients (51.6%) over a median duration of 126 days, with progression to moderate AR in 13 (14%) over 493 days and to severe AR in 2 (2.1%) over 1,231 days. The incidence of mild or greater AR was 43.1% in HeartMate II vs 65.7% in HeartWare recipients (p = 0.035). Overall freedom from moderate or greater AR was 94.7% ± 2.6% at 1 year, 86.9% ± 4.5% at 2 years, 82.8% ± 5.9% at 3 years, and 31% ± 16.9% at 4 years. Independent predictors of AR were duration of support (odds ratio, 1.002; 95% confidence interval, 1.000 to 1.004; p = 0.017) and a persistently closed aortic valve (odds ratio, 0.193; 95% confidence interval, 0.097 to 0.382; p < 0.001). CONCLUSIONS: AR is associated with longer cf-LVAD support duration and persistent aortic valve closure. Incidence of moderate or greater AR after cf-LVAD implantation increases significantly after 3 years. The clinical implications of these data may warrant consideration of prophylactic aortic valve replacement at the time of cf-LVAD implantation, particularly with expected longer duration of support and in patients with preexisting AR that is more than mild.

Surgical treatment of infective endocarditis in active intravenous drug users: a justified procedure?

BACKGROUND: Infective endocarditis is a life threatening complication of intravenous drug abuse, which continues to be a major burden with inadequately characterised long-term outcomes. We reviewed our institutional experience of surgical treatment of infective endocarditis in active intravenous drug abusers with the aim of identifying the determinants long-term outcome of this distinct subgroup of infective endocarditis patients. METHODS: A total of 451 patients underwent surgery for infective endocarditis between January 1993 and July 2013 at the University Hospital of Heidelberg. Of these patients, 20 (7 female, mean age 35 ± 7.7 years) underwent surgery for infective endocarditis with a history of active intravenous drug abuse. Mean follow-up was 2504 ± 1842 days. RESULTS: Staphylococcus aureus was the most common pathogen detected in preoperative blood cultures. Two patients (10%) died before postoperative day 30. Survival at 1, 5 and 10 years was 90%, 85% and 85%, respectively. Freedom from reoperation was 100%. Higher NYHA functional class, higher EuroSCORE II, HIV infection, longer operating time, postoperative fever and higher requirement for red blood cell transfusion were associated with 90-day mortality. CONCLUSIONS: In active intravenous drug abusers, surgical treatment for infective endocarditis should be performed as extensively as possible and be followed by an aggressive postoperative antibiotic therapy to avoid high mortality. Early surgical intervention is advisable in patients with precipitous cardiac deterioration and under conditions of staphylococcal endocarditis. However, larger studies are necessary to confirm our preliminary results.