Disparities in donor heart acceptance between the USA and Europe: clinical implications.

BACKGROUND AND AIMS: Given limited evidence and lack of consensus on donor acceptance for heart transplant (HT), selection practices vary widely across HT centres in the USA. Similar variation likely exists on a broader scale-across countries and HT systems-but remains largely unexplored. This study characterized differences in heart donor populations and selection practices between the USA and Eurotransplant-a consortium of eight European countries-and their implications for system-wide outcomes. METHODS: Characteristics of adult reported heart donors and their utilization (the percentage of reported donors accepted for HT) were compared between Eurotransplant (n = 8714) and the USA (n = 60 882) from 2010 to 2020. Predictors of donor acceptance were identified using multivariable logistic regression. Additional analyses estimated the impact of achieving Eurotransplant-level utilization in the USA amongst donors of matched quality, using probability of acceptance as a marker of quality. RESULTS: Eurotransplant reported donors were older with more cardiovascular risk factors but with higher utilization than in the USA (70% vs. 44%). Donor age, smoking history, and diabetes mellitus predicted non-acceptance in the USA and, by a lesser magnitude, in Eurotransplant; donor obesity and hypertension predicted non-acceptance in the USA only. Achieving Eurotransplant-level utilization amongst the top 30%-50% of donors (by quality) would produce an additional 506-930 US HTs annually. CONCLUSIONS: Eurotransplant countries exhibit more liberal donor heart acceptance practices than the USA. Adopting similar acceptance practices could help alleviate the scarcity of donor hearts and reduce waitlist morbidity in the USA.

Soluble urokinase plasminogen activator receptor and survival in elective cardiac surgery.

BACKGROUND: The study investigated the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in patients undergoing cardiac surgery and calculated a simplified biomarker score comprising suPAR, N-terminal pro B-type natriuretic peptide (NT-proBNP) and age. METHODS AND RESULTS: Biomarkers were assessed in a cohort of 478 patients undergoing elective cardiac surgery. After a median follow-up of 4.2 years, a total of 72 (15.1%) patients died. SuPAR, NT-proBNP and age were independent prognosticators of mortality in a multivariable Cox regression model after adjustment for EuroScoreII. We then calculated a simplified biomarker score comprising age, suPAR and NT-proBNP, which had a superior prognostic value compared to EuroScoreII (Harrel's C of 0.76 vs. 0.72; P for difference = 0.02). Besides long-term mortality, the biomarker score had an excellent performance predicting one-year mortality and hospitalization due to heart failure. CONCLUSION: The biomarker suPAR and NT-proBNP were strongly and independently associated with mortality in patients undergoing cardiac surgery. A simplified biomarker score comprising only three variables (age, suPAR and NT-proBNP) performed better than the established EuroScoreII with respect to intermediate and long-term outcome as well as hospitalization due to heart failure. As such, integration of established and upcoming biomarkers in clinical practice may provide improved decision support in cardiac surgery.

Nose-shaped mass in the ascending aorta.

A 79-year-old man was referred for urgent coronary artery bypass grafting. Contrast-enhanced computed tomography revealed an atypically nose-shaped contrast defect, which intraoperatively turned out to be an atheromatous plaque. Its preoperative detection allowed us to prevent an adverse cerebral event. This case highlights that a thorough preoperative work-up should ideally include a CT angiography, in patients where atherosclerotic changes are to be expected.

Observed versus predicted mortality after isolated tricuspid valve surgery.

BACKGROUND: Aim of this study is to analyse the performances of Clinical Risk Score (CRS) and European System for Cardiac Operative Risk Evaluation (EuroSCORE)-II in isolated tricuspid surgery. METHODS: Three hundred and eighty-three patients (54 ± 16 year; 54% female) were enrolled. Receiver operating characteristic analysis was performed to evaluate the relationship between the true positive fraction of test results and the false-positive fraction for a procedure. RESULTS: Considering the 30-day mortality the area under the curve was 0.6 (95% confidence interval [CI] 0.50-0.72) for EuroSCORE II and 0.7 (95% CI 0.56-0.84) for CRS-score. The ratio of expected/observed mortality showed underestimation when considering EuroSCORE-II (min. 0.46-max. 0.6). At multivariate analysis, the CRS score (p = .005) was predictor of late cardiac death. CONCLUSION: We suggest using both scores to obtain a range of expected mortality. CRS to speculate on late survival.

Telocytes in the human ascending aorta: Characterization and exosome-related KLF-4/VEGF-A expression.

Telocytes (TCs), a novel interstitial cell entity promoting tissue regeneration, have been described in various tissues. Their role in inter-cellular signalling and tissue remodelling has been reported in almost all human tissues. This study hypothesizes that TC also contributes to tissue remodelling and regeneration of the human thoracic aorta (HTA). The understanding of tissue homeostasis and regenerative potential of the HTA is of high clinical interest as it plays a crucial role in pathogenesis from aortic dilatation to lethal dissection. Therefore, we obtained twenty-five aortic specimens of heart donors during transplantation. The presence of TCs was detected in different layers of aortic tissue and characterized by immunofluorescence and transmission electron microscopy. Further, we cultivated and isolated TCs in highly differentiated form identified by positive staining for CD34 and c-kit. Aortic-derived TC was characterized by the expression of PDGFR-α, PDGFR-ß, CD29/integrin ß-1 and αSMA and the stem cell markers Nanog and KLF-4. Moreover, TC exosomes were isolated and characterized for soluble angiogenic factors by Western blot. CD34+ /c-kit+ TCs shed exosomes containing the soluble factors VEGF-A, KLF-4 and PDGF-A. In summary, TC occurs in the aortic wall. Correspondingly, exosomes, derived from aortic TCs, contain vasculogenesis-relevant proteins. Understanding the regulation of TC-mediated aortic remodelling may be a crucial step towards designing strategies to promote aortic repair and prevent adverse remodelling.

Awake Implementation of Extracorporeal Life Support in Refractory Cardiogenic Shock.

Background and objectives: Extracorporeal life support (ECLS) is a widely accepted and effective strategy for use in patients presenting with refractory cardiogenic shock. Implantation in awake and non-intubated patients allows for optimized evaluation of further therapy options while avoiding potential side effects associated with the need for sedation and intubation. The aim of the study was the assessment of safety and feasibility of awake ECLS implementation and of outcomes in patients treated with this concept. Materials and Methods: We retrospectively reviewed the concept of awake ECLS implantation in 16 consecutive patients (mean age 58 ± 8 years; male: 88%; ischemic cardiomyopathy: 50%) from 02/2017 to 01/2021. Study endpoints were survival to weaning or bridging to durable support or organ replacement and development of end-organ function and hemodynamic parameters on ECLS. Results: Fourteen patients (88%) were able to be successfully transitioned to definite therapy options. ECLS support stabilized end-organ function, led to a decrease in mean lactate levels (5.3 ± 3.7 mmol/L at baseline to 1.9 ± 1.3 mmol/L 12 h after ECLS start; p = 0.01) and improved hemodynamics (median central venous pressure 20 ± 5 mmHg vs. 10 ± 2 mmHg, p = 0.001) over a median duration of two days (1-8 days IQR). Two patients (13%) died on ECLS support due to multi-organ dysfunction syndrome. Survival to discharge of initially successfully bridged or weaned patients was 64%. Conclusions: Awake ECLS implantation is feasible and safe with the key advantage of omitting or delaying general anesthesia and intubation, with their associated risks in cardiogenic-shock patients, facilitating further decision making.

Molecular-level HLA mismatch is associated with rejection and worsened graft survival in heart transplant recipients - a retrospective study.

The aim was to evaluate the association of molecular-level human leukocyte antigen (HLA) mismatching with post-transplant graft survival, rejection, and cardiac allograft vasculopathy (CAV). We retrospectively analyzed all primary cardiac transplant recipients between 01/1984-06/2016. 1167 patients fulfilled inclusion criteria and had HLA typing information available. In 312 donor-recipient pairs, typing at serological split antigen level was available. We used the Epitope MisMatch Algorithm to calculate the number of amino acid differences in antibody-verified HLA eplets (amino acid mismatch load (AAMM)) between donor and recipient. Patients with a higher HLA-DR AAMM load had inferior 1-year graft survival (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.01-1.28). The HLA-AB AAMM load showed no impact on graft survival. In the subgroup with available split-level information, we observed an inferior graft survival for a higher HLA-DR AAMM load 3 months after transplantation (HR, 1.22; 95% CI, 1.04-1.44) and a higher risk for rejection for an increasing HLA-AB (HR, 1.70; 95% CI, 1.29-2.24) and HLA-DR (HR, 1.32; 95% CI, 1.09-1.61) AAMM load. No impact on the development of CAV was found. Molecular-level HLA mismatch analysis could serve as a tool for risk stratification after heart transplantation and might take us one step further into precision medicine.

Off-Pump Tricuspid Annuloplasty through a Direct Transatrial Approach: Early Results.

Severe tricuspid regurgitation constitutes a growing disease burden. Conventional surgery for tricuspid valve disease has an increased risk while several interventional procedures are currently under clinical investigation, yet do not offer comprehensive solutions. We investigated a novel surgical approach for off-pump beating-heart tricuspid annuloplasty in circulating blood through a single port in the right atrium. Early feasibility results in preclinical porcine in vivo studies encourage further development of this approach, combining the proven concept of surgical annuloplasty with the benefits of minimally invasive off-pump procedures in a hybrid setting.

Early Antibiotic Prophylaxis Prior to Bypass Surgery Improves Tissue Penetration.

BACKGROUND: We previously identified preparation of the internal mammary artery as a risk factor significantly impairing antibiotic tissue penetration into the presternal subcutaneous tissue. We, therefore, adapted our dosing schema regarding preoperative timing to overcome this risk factor. METHODS: Eight patients who underwent coronary artery bypass grafting with a left internal mammary artery and vein grafts were included in this clinical trial. Cefazolin (4 g) was administered twice (3 hours and 1 hour) prior to skin incision and once during skin closure (2 g). Antibiotic concentrations were measured with subcutaneous microdialysis probes on both sternal sides. Results were directly compared with the previously published patient cohort receiving the standard schema (4 g cefazolin prior to skin incision and 2 g during closure). RESULTS: All patients (7 male, 1 female, 69 ± 7 years, 26.3 ± 3.9 kg/m2) survived the perioperative period. Mean area under the curve on the right and left sternal side was 117.0 ± 92.5 µg/mL and 114.5 ± 83.2 µg/mL, respectively (p = 0.95). This was well above the previously measured mean peak tissue concentrations without early preoperative antibiotic administration on the side of mammary artery harvesting (52.4 ± 48.5 µg/mL vs. 13.1 ± 5.8 µg/mL; p = 0.039). The %fT > minimal inhibitory concentration (MIC) for Staphylococcus epidermidis and Staphylococcus aureus during the first 10 hours in presternal tissue was ≥ 70% but did not differ compared with standard schema. CONCLUSIONS: Early, additional preoperative administration of cefazolin was able to significantly increase peak tissue concentrations during surgery compared with the standard protocol. No difference, however, could be achieved in the percentage of time during which the concentration exceeded the MIC.

Thoracic endovascular repair for acute complicated type B aortic dissections.

OBJECTIVE: This study retrospectively assessed in-hospital mortality and long-term results of emergency thoracic endovascular aortic repair (TEVAR) for patients with life-threatening acute complicated type B aortic dissection (acTBD). METHODS: Between March 2001 and December 2016, there were 55 patients (40 male; median age, 52 ± 13 years) with an acTBD who were treated with TEVAR for malperfusion (58%), aortic rupture (18%), or persistent untreatable pain with true lumen reduction or rapid aortic diameter enlargement (24%) as a sign of disease progression. The patients were categorized according to clinical appearance into two groups: group A, malperfusion, pending rupture, or rupture; and group B, persistent ongoing pain, rapid enlargement of aortic diameter, or significant changes in the true to false lumen ratio. Four patients (7%) had undergone previous aortic surgery. RESULTS: Technical success (coverage of the primary intimal tear) was achieved in 50 patients (91%). The overall in-hospital mortality rate was 9% (n = 5), and there was a statistically significant difference in early mortality between group A and group B (7% vs 2%; P < .02). Causes of in-hospital death were all aorta related, including a rupture during the procedure and on the first postinterventional day in two patients and redissection (ascending aorta, n = 2; descending aorta, n = 1) with a consequent aortic rupture after TEVAR in the remaining three. Permanent neurologic dysfunction occurred in five patients (stroke, n = 2; paraplegia, n = 3). Overall, 19 patients (34%) developed early endoleaks (type IA, n = 5; type IB, n = 11; type II, n = 2; type IB plus type II, n = 1). Therefore, 5 patients needed early (within 30 days) endovascular intervention because of a type IA (n = 2), type IB (n = 3), or type II endoleak (n = 1) and the rapid progression of aortic diameter, persistent signs of ischemia (n = 2), or rupture (n = 1), whereas the remaining 14 patients were treated conservatively and followed up by computed tomography angiography. Seven patients with early endoleaks needed an endovascular intervention (n = 3) or conventional surgery (n = 4) because of aortic progression in the follow-up period (mean interval after procedure, 92 ± 56 months). The actual survival rates were 87%, 85%, and 75% at 1 year, 2 years, and 5 years, respectively, and freedom from aorta-related death was 87%, 87%, and 77% at 1 year, 2 years, and 5 years, respectively. Freedom from reintervention for any cause using a Kaplan-Meier analysis was 70%, 68%, 68%, and 63% at 6 months, 1 year, 2 years, and 5 years, respectively. CONCLUSIONS: TEVAR of acTBD has been proven to be an excellent treatment modality in this cohort of high-risk patients, with promising midterm and long-term results.

Intravenous Heme Arginate Induces HO-1 (Heme Oxygenase-1) in the Human Heart.

Objective- HO-1 (heme oxygenase-1) induction may prevent or reduce ischemia-reperfusion injury. We previously evaluated its in vivo induction after a single systemic administration of heme arginate in peripheral blood mononuclear cells. The current trial was designed to assess the pharmacological tissue induction of HO-1 in the human heart with heme arginate in vivo. Approach and Results- Patients planned for conventional aortic valve replacement received placebo (n=8), 1 mg/kg (n=7) or 3 mg/kg (n=9) heme arginate infused intravenously 24 hours before surgery. A biopsy of the right ventricle was performed directly before aortic cross-clamping and after cross-clamp release. In addition, the right atrial appendage was partially removed for analysis. HO-1 protein and mRNA concentrations were measured in tissue samples and in peripheral blood mononuclear cells before to and up to 72 hours after surgery. No study medication-related adverse events occurred. A strong, dose-dependent effect on myocardial HO-1 mRNA levels was observed (right ventricle: 7.9±5.0 versus 88.6±49.1 versus 203.6±148.7; P=0.002 and right atrium: 10.8±8.8 versus 229.8±173.1 versus 392.7±195.7; P=0.001). This was paralleled by a profound increase of HO-1 protein concentration in atrial tissue (8401±3889 versus 28 585±10 692 versus 29 022±8583; P<0.001). Surgery and heme arginate infusion significantly increased HO-1 mRNA concentration in peripheral blood mononuclear cells ( P<0.001). HO-1 induction led to a significant increase of postoperative carboxyhemoglobin (1.7% versus 1.4%; P=0.041). No effect on plasma HO-1 protein levels could be detected. Conclusions- Myocardial HO-1 mRNA and protein can be dose-dependently induced by heme arginate. Protective effects of this therapeutic strategy should be evaluated in upcoming clinical trials. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02314780.

A rare case of quadruple valve surgery with bioprosthetic pulmonary valve replacement in an octogenarian for degenerative valvular disease: Technical aspects.

Quadruple valve surgery represents a complex and rare surgical procedure, requiring a systematic and standardized approach. In this intervention, pulmonary valve replacement (PVR) in patients without pre-existing congenital heart disease represents a challenge and no large data have been reported yet. We hereby report a case of bioprosthetic PVR in an octogenarian within a quadruple valve procedure, illustrating our preferred technique of PVR with bioprosthetic implantation and right ventricular outflow tract reconstruction.

Strong Signs for a Weak Wall in Tricuspid Aortic Valve Associated Aneurysms and a Role for Osteopontin in Bicuspid Aortic Valve Associated Aneurysms.

Central processes in the pathogenesis of TAV- (tricuspid aortic valve) and BAV- (bicuspid aortic valve) associated ascending thoracic aortic aneurysm (ATAA) development are still unknown. To gain new insights, we have collected aortic tissue and isolated smooth muscle cells of aneurysmal tissue and subjected them to in situ and in vitro analyses. We analyzed aortic tissue from 78 patients (31 controls, 28 TAV-ATAAs, and 19 BAV-ATAAs) and established 30 primary smooth muscle cell cultures. Analyses included histochemistry, immuno-, auto-fluorescence-based image analyses, and cellular analyses including smooth muscle cell contraction studies. With regard to TAV associated aneurysms, we observed a strong impairment of the vascular wall, which appears on different levels-structure and dimension of the layers (reduced media thickness, increased intima thickness, atherosclerotic changes, degeneration of aortic media, decrease of collagen, and increase of elastic fiber free area) as well as on the cellular level (accumulation of fibroblasts/myofibroblasts, and increase in the number of smooth muscle cells with a reduced alpha smooth muscle actin (α-SM actin) content per cell). The pathological changes in the aortic wall of BAV patients were much less pronounced-apart from an increased expression of osteopontin (OPN) in the vascular wall which stem from smooth muscle cells, we observed a trend towards increased calcification of the aortic wall (increase significantly associated with age). These observations provide strong evidence for different pathological processes and different disease mechanisms to occur in BAV- and TAV-associated aneurysms.

Diminished impact of cytomegalovirus infection on graft vasculopathy development in the antiviral prophylaxis era - a retrospective study.

Evidence concerning an association between cytomegalovirus (CMV) infection and accelerated cardiac allograft vasculopathy (CAV) is inconclusive. Data were analyzed retrospectively from 297 consecutive heart transplants between 1.1.2002 and 31.12.2012. Patients ≤18 years of age, survival, and follow-up ≤1-year post-transplant and patients with early CAV were excluded. CMV-infection was diagnosed and monitored closely in the first year. CAV was diagnosed by coronary angiography via left heart catheterization, and results were categorized according to the International Society of Heart and Lung Transplantation (ISHLT) scoring system. Risk factors for CAV were tested in a multivariable model. Median follow-up was 7.5 years (IQR: 5.6-10.3). CMV infection in the first year after transplantation occurred in 26% of patients (n = 78), CMV disease in 5% (n = 15). CAV ≥1 ISHLT was detected in 36% (n = 108). Incidence of CAV >1 ISHLT and severity of CAV increased over time. No statistically significant association between CMV infection and disease within the first year and risk of CAV after 1-year post-HTx was detected in the univariate (P = 0.16) and multivariable [hazard ratio (HR), 1.36; confidence interval (CI), 0.89-2.07; P = 0.16] Cox regression. In the multivariable Cox regression, donor age (HR, 1.04; 95% CI, 1.02-1.06; P < 0.01) and acute cellular rejection (ACR) ≥2R in the first year after HTx (HR, 1.77; 95% CI, 1.06-2.95; P = 0.03) were independent risk factors for CAV development. In our cohort, CMV infection and disease in the first year after transplantation did not significantly influence the risk of CAV in the long-term follow-up.

Lung allocation score: the Eurotransplant model versus the revised US model - a cross-sectional study.

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.

Bridging the gap in heart transplantation.

PURPOSE OF REVIEW: Countries in Europe and in the USA are proclaiming their need for an objective allocation system that can cope with distribution of a scarce resource in a changing environment of an older donor and recipient population and of an increased number of patients on mechanical circulatory support, whose prospects are increasing. RECENT FINDINGS: The current heart allocation systems in Eurotransplant, France and the USA are all urgency tier systems, where within the same tier a first-come, first-served principle is applied. Both Eurotransplant and France are developing new heart allocation schemes that hinge on a benefit principle, thereby combining the prospects of patients after transplantation with their expected clinical course while on the waiting list. In the USA, a different approach has been chosen for their new allocation scheme, as the medical urgency of the patient is the driving force behind the proposal. SUMMARY: Policies to ensure a fair, efficient, and medically optimal matching of donor organs and recipients are continually evaluated and refined. The ethical cornerstone of each organ allocation policy in the described countries is the effort of balancing justice and utility.

Primary preventive cardioverter-defibrillator implantation (Pro-ICD) in patients awaiting heart transplantation. A prospective, randomized, controlled 12-year follow-up study.

The aim of this study was to evaluate whether short-term primary preventive cardioverter-defibrillator (ICD) implantation as bridge to heart transplantation (HTX) provides any survival benefit. Thirty-three patients awaiting HTX were randomized to either conventional therapy (control group) or primary preventive ICD implantation (ICD group). Fourteen patients had ischemic cardiomyopathy (ICM) and 19 patients had dilated cardiomyopathy (DCM). Sixteen patients were randomized to the ICD group and 17 patients were randomized to the control group. Twenty patients (61%) were transplanted after a waiting time of 10 ± 9 months. The remaining 13 patients (39%) were not transplanted because of clinical improvement (n = 5), cerebral hemorrhage (n = 3), or death (n = 5). On the waiting list, 3 ICD patients with DCM developed slow VTs without ICD intervention, two patients with ICM (6%) had fast VT terminated by the ICD, and no arrhythmic death was observed. After 11.9 years (median), 13 of 20 HTX patients (65%) and 5 of 13 non-HTX patients (38%) were alive. Survivors had a higher LVEF (22 ± 6 vs. 17 ± 4%, P = 0.0092) and a better exercise capacity (75 ± 29 vs. 57 ± 24 Watt, P = 0.0566) at baseline as compared to nonsurvivors. This study may not support the general use of primary preventive ICDs as a short-term bridge to heart transplantation.

Pediatric heart allocation and transplantation in Eurotransplant.

Pediatric heart allocation in Eurotransplant (ET) has evolved over the past decades to better serve patients and improve utilization. Pediatric heart transplants (HT) account for 6% of the annual transplant volume in ET. Death rates on the pediatric heart transplant waiting list have decreased over the years, from 25% in 1997 to 18% in 2011. Within the first year after listing, 32% of all infants (<12 months), 20% of all children aged 1-10 years, and 15% of all children aged 11-15 years died without having received a heart transplant. Survival after transplantation improved over the years, and in almost a decade, the 1-year survival went from 83% to 89%, and the 3-year rates increased from 81% to 85%. Improved medical management of heart failure patients and the availability of mechanical support for children have significantly improved the prospects for children on the heart transplant waiting list.