Right Axillary Artery Cannulation for Veno-Arterial Extracorporeal Membrane Oxygenation in Postcardiotomy Patients: A Single-Center Experience.

Background and Objectives: To analyze the patient outcome and complication rate of axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients who could not be weaned from cardiopulmonary bypass after cardiothoracic surgery. Materials and Methods: We analyzed the data of 179 patients who were supported with VA-ECMO with femoral-axillary access (FA VA-ECMO) after cardiothoracic surgery between January 2014 and January 2019 in our department. Patients requiring central aortic cannulation and patients with respiratory failure requiring veno-venous ECMO were excluded. Primary outcomes were in-hospital mortality and 1-year survival rate of patients who were weaned from VA-ECMO support. Secondary outcomes were cannulation-related complications at the axillary site, VA-ECMO-related complications, and systemic complications. Results: In our cohort, 60 (33.5%) patients were female. Mean age was 67.0 ± 10.9 years. Overall, 78 (43.5%) patients were operated upon electively, 37 (20.7%) patients underwent urgent surgery, and 64 (35.8%) patients underwent emergency surgical treatment. Sixty-seven patients (37.4%) were resuscitated preoperatively. The mean duration of VA-ECMO support was 8.4 ± 5.1 days. Weaning from VA-ECMO was successful in 87 (48.6%) patients; 62 (34.6%) patients survived the hospital stay. The 1-year survival rate was 74%. Subclavian bleeding occurred in 24 (13.4%) patients, femoral bleeding in 4 (2.2%) patients, ischemia of the upper limb in 11 (6.1%) patients, intracerebral bleeding in 9 (5%) patients, and stroke in 19 (10.6%) patients. Conclusions: In patients with acute LV dysfunction after cardiothoracic surgery who cannot be weaned from cardiopulmonary bypass, right axillary artery cannulation is a safe and reliable method for VA-ECMO support with an acceptable complication rate.

Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation.

Marfan syndrome (MFS) is a connective tissue disorder that results in aortic root aneurysm formation. Reactive oxygen species (ROS) seem to play a role in aortic wall remodelling in MFS, although the mechanism remains unknown. MFS Fbn1C1039G/+ mouse root/ascending (AS) and descending (DES) aortic samples were examined using DHE staining, lucigenin-enhanced chemiluminescence (LGCL), Verhoeff's elastin-Van Gieson staining (elastin breakdown) and in situ zymography for protease activity. Fbn1C1039G/+ AS- or DES-derived smooth muscle cells (SMC) were treated with anti-TGF-ß antibody, angiotensin II (AngII), anti-TGF-ß antibody + AngII, or isotype control. ROS were detected during early aneurysm formation in the Fbn1C1039G/+ AS aorta, but absent in normal-sized DES aorta. Fbn1C1039G/+ mice treated with the unspecific NADPH oxidase inhibitor, apocynin reduced AS aneurysm formation, with attenuated elastin fragmentation. In situ zymography revealed apocynin treatment decreased protease activity. In vitro SMC studies showed Fbn1C1039G/+ -derived AS SMC had increased NADPH activity compared to DES-derived SMC. AS SMC NADPH activity increased with AngII treatment and appeared TGF-ß dependent. In conclusion, ROS play a role in MFS aneurysm development and correspond anatomically with aneurysmal aortic segments. ROS inhibition via apocynin treatment attenuates MFS aneurysm progression. AngII enhances ROS production in MFS AS SMCs and is likely TGF-ß dependent.

Ischemic Cardiomyopathy Affects the Thioredoxin System in the Human Myocardium.

BACKGROUND: Oxidative stress due to reactive oxygen species (ROS) production is a key factor in the development of heart failure (HF). This study investigated the thioredoxin (Trx) system, which plays a major role in antioxidant defense, in patients suffering from ischemic (ICM) or dilated (DCM) cardiomyopathy. METHODS AND RESULTS: Myocardial tissue from ICM (n = 13) and DCM (n = 13) patients, as well as septal tissue of patients with aortic stenosis but without diagnosed hypertrophic cardiomyopathy or subaortic stenosis (control; n = 12), was analyzed for Trx1, Trx-interacting protein (TXNIP) and E3 ligase ITCH (E3 ubiquitin-protein ligase Itchy homolog) expression. Trx-reductase 1 (TXNRD1) amount and activity, cytosolic cytochrome C content, and apoptosis markers were quantified by means of enzyme-linked immunosorbent assay and multiplexing. Compared with control samples, ITCH and Trx1 expression, TXNRD1 amount and activity were reduced and TXNIP expression was increased in ICM (ITCH: P = .013; Trx1: P = .028; TXNRD1 amount: P = .035; TXNRD1 activity: P = .005; TXNIP: P = .014) but not in DCM samples. A higher level of the downstream apoptosis marker caspase-9 (ICM: 582 ± 262 MFI [P = .995]; DCM: 1251 ± 548 MFI [P = .002], control: 561 ± 214 MFI) was detected in DCM tissue. A higher expression of Bcl-2 was found in DCM (P = .011). CONCLUSION: The Trx system was impaired in ICM but not in DCM. ITCH appeared to be responsible for the down-regulation of the Trx system. ROS-induced mitochondrial instability appeared to play a role in DCM.

Acute Effect of Mitral Valve Repair on Mitral Valve Geometry.

BACKGROUND: The aim of this study was to quantify acute mitral valve (MV) geometry dynamic changes throughout the cardiac cycle using three-dimensional transesophageal echocardiography (3D TEE) in patients undergoing surgical MV repair (MVR) with ring annuloplasty and optional neochord implantation. METHODS: Twenty-nine patients (63 ± 10 years) with severe primary mitral regurgitation underwent surgical MVR using ring annuloplasty with or without neochord implantation. We recorded 3D TEE data throughout the cardiac cycle before and after MVR. Dynamic changes (4D) in the MV annulus geometry and anatomical MV orifice area (AMVOA) were measured using a novel semiautomated software (Auto Valve, Siemens Healthcare). RESULTS: MVR significantly reduces the anteroposterior diameter by up to 38% at end-systole (36.8-22.7 mm; p < 0.001) and the lateromedial diameter by up to 31% (42.7-30.3 mm; p < 0.001). Moreover, the annular circumference was reduced by up to 31% at end-systole (129.6-87.6 mm, p < 0.001), and the annular area was significantly decreased by up to 52% (12.8-5.7 cm2; p < 0.001). Finally, the AMVOA experienced the largest change, decreasing from 1.1 to 0.2 cm2 during systole (at midsystole; p < 0.001) and from 4.1 to 3.2 cm2 (p < 0.001) during diastole. CONCLUSIONS: MVR reduces the annular dimension and the AMVOA, contributing to mitral competency, but the use of annuloplasty rings reduces annular contractility after the procedure. Surgeons can use 4D imaging technology to assess MV function dynamically, detecting the acute morphological changes of the mitral annulus and leaflets before and after the procedure.

The Ubiquitin Proteasome System in Ischemic and Dilated Cardiomyopathy.

Dilated (DCM) and ischemic cardiomyopathies (ICM) are associated with cardiac remodeling, where the ubiquitin-proteasome system (UPS) holds a central role. Little is known about the UPS and its alterations in patients suffering from DCM or ICM. The aim of this study is to characterize the UPS activity in human heart tissue from cardiomyopathy patients. Myocardial tissue from ICM (n = 23), DCM (n = 28), and control (n = 14) patients were used to quantify ubiquitinylated proteins, E3-ubiquitin-ligases muscle-atrophy-F-box (MAFbx)/atrogin-1, muscle-RING-finger-1 (MuRF1), and eukaryotic-translation-initiation-factor-4E (eIF4E), by Western blot. Furthermore, the proteasomal chymotrypsin-like and trypsin-like peptidase activities were determined fluorometrically. Enzyme activity of NAD(P)H oxidase was assessed as an index of reactive oxygen species production. The chymotrypsin- (p = 0.71) and caspase-like proteasomal activity (p = 0.93) was similar between the groups. Trypsin-like proteasomal activity was lower in ICM (0.78 ± 0.11 µU/mg) compared to DCM (1.06 ± 0.08 µU/mg) and control (1.00 ± 0.06 µU/mg; p = 0.06) samples. Decreased ubiquitin expression in both cardiomyopathy groups (ICM vs. control: p < 0.001; DCM vs. control: p < 0.001), as well as less ubiquitin-positive deposits in ICM-damaged tissue (ICM: 4.19% ± 0.60%, control: 6.28% ± 0.40%, p = 0.022), were detected. E3-ligase MuRF1 protein expression (p = 0.62), NADPH-oxidase activity (p = 0.63), and AIF-positive cells (p = 0.50). Statistical trends were detected for reduced MAFbx protein expression in the DCM-group (p = 0.07). Different levels of UPS components, E3 ligases, and UPS activation markers were observed in myocardial tissue from patients affected by DCM and ICM, suggesting differential involvement of the UPS in the underlying pathologies.

Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus.

RATIONALE: Accelerated arterial stiffening is a major complication of diabetes mellitus with no specific therapy available to date. OBJECTIVE: The present study investigates the role of the osteogenic transcription factor runt-related transcription factor 2 (Runx2) as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes mellitus. METHODS AND RESULTS: Using a murine model of type 2 diabetes mellitus (db/db mice), we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae, as well as in thoracic aortic samples from patients with type 2 diabetes mellitus. Vascular smooth muscle cell-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that expression of Runx2 in diabetes mellitus is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter. CONCLUSIONS: In conclusion, this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes mellitus, promoting arterial stiffness irrespective of calcification.

Preoperative Predictors and Outcome of Triple Valve Surgery in 487 Consecutive Patients.

Background Triple valve surgery (TVS) is associated with an elevated risk for operative mortality and thus remains a surgical challenge. We report our experience and results of TVS procedures, especially with respect to identification of preoperative risk factors, to improve patient selection. Methods Between December 1994 and January 2013, 487 consecutive patients (240 male, 247 female) underwent TVS at the Heart Center Leipzig, University of Leipzig. The data were prospectively collected and retrospectively analyzed. Univariate and multivariable regression analyses were performed to identify risk factors. Results The 30-day mortality was 16.1% and the long-term survival at 1 year and 5 years was 71.8% and 54.6%, respectively. Multivariable logistic regression analysis identified previous myocardial infarction to be the only significant predictor for early mortality. Age, New York Heart Association functional class IV, previous myocardial infarction, dialysis, and liver dysfunction were identified as preoperative predictors for late mortality. Furthermore, an increase of operative risk, given for each year, was observed during the study period. In contrast, 30-day mortality decreased during the observation time. Conclusion TVS is associated with a high surgical risk. Long-term survival is decreased, but acceptable for these high-risk patients. The series demonstrates that increasing surgical risk, age, and comorbidities are the future challenges in TVS.

Segmental aortic stiffening contributes to experimental abdominal aortic aneurysm development.

BACKGROUND: Stiffening of the aortic wall is a phenomenon consistently observed in age and in abdominal aortic aneurysm (AAA). However, its role in AAA pathophysiology is largely undefined. METHODS AND RESULTS: Using an established murine elastase-induced AAA model, we demonstrate that segmental aortic stiffening precedes aneurysm growth. Finite-element analysis reveals that early stiffening of the aneurysm-prone aortic segment leads to axial (longitudinal) wall stress generated by cyclic (systolic) tethering of adjacent, more compliant wall segments. Interventional stiffening of AAA-adjacent aortic segments (via external application of surgical adhesive) significantly reduces aneurysm growth. These changes correlate with the reduced segmental stiffness of the AAA-prone aorta (attributable to equalized stiffness in adjacent segments), reduced axial wall stress, decreased production of reactive oxygen species, attenuated elastin breakdown, and decreased expression of inflammatory cytokines and macrophage infiltration, and attenuated apoptosis within the aortic wall, as well. Cyclic pressurization of segmentally stiffened aortic segments ex vivo increases the expression of genes related to inflammation and extracellular matrix remodeling. Finally, human ultrasound studies reveal that aging, a significant AAA risk factor, is accompanied by segmental infrarenal aortic stiffening. CONCLUSIONS: The present study introduces the novel concept of segmental aortic stiffening as an early pathomechanism generating aortic wall stress and triggering aneurysmal growth, thereby delineating potential underlying molecular mechanisms and therapeutic targets. In addition, monitoring segmental aortic stiffening may aid the identification of patients at risk for AAA.

Enhanced caspase activity contributes to aortic wall remodeling and early aneurysm development in a murine model of Marfan syndrome.

OBJECTIVE: Rupture and dissection of aortic root aneurysms remain the leading causes of death in patients with the Marfan syndrome, a hereditary connective tissue disorder that affects 1 in 5000 individuals worldwide. In the present study, we use a Marfan mouse model (Fbn1(C1039G/+)) to investigate the biological importance of apoptosis during aneurysm development in Marfan syndrome. APPROACH AND RESULTS: Using in vivo single-photon emission computed tomographic-imaging and ex vivo autoradiography for Tc99m-annexin, we discovered increased apoptosis in the Fbn1(C1039G/+) ascending aorta during early aneurysm development peaking at 4 weeks. Immunofluorescence colocalization studies identified smooth muscle cells (SMCs) as the apoptotic cell population. As biological proof of concept that early aortic wall apoptosis plays a role in aneurysm development in Marfan syndrome, Fbn1(C1039G/+) mice were treated daily from 2 to 6 weeks with either (1) a pan-caspase inhibitor, Q-VD-OPh (20 mg/kg), or (2) vehicle control intraperitoneally. Q-VD-OPh treatment led to a significant reduction in aneurysm size and decreased extracellular matrix degradation in the aortic wall compared with control mice. In vitro studies using Fbn1(C1039G/+) ascending SMCs showed that apoptotic SMCs have increased elastolytic potential compared with viable cells, mostly because of caspase activity. Moreover, in vitro (1) cell membrane isolation, (2) immunofluorescence staining, and (3) scanning electron microscopy studies illustrate that caspases are expressed on the exterior cell surface of apoptotic SMCs. CONCLUSIONS: Caspase inhibition attenuates aneurysm development in an Fbn1(C1039G/+) Marfan mouse model. Mechanistically, during apoptosis, caspases are expressed on the cell surface of SMCs and likely contribute to elastin degradation and aneurysm development in Marfan syndrome.

Improved integration of single-cell transcriptome data demonstrates common and unique signatures of heart failure in mice and humans.

BACKGROUND: Cardiovascular research heavily relies on mouse (Mus musculus) models to study disease mechanisms and to test novel biomarkers and medications. Yet, applying these results to patients remains a major challenge and often results in noneffective drugs. Therefore, it is an open challenge of translational science to develop models with high similarities and predictive value. This requires a comparison of disease models in mice with diseased tissue derived from humans. RESULTS: To compare the transcriptional signatures at single-cell resolution, we implemented an integration pipeline called OrthoIntegrate, which uniquely assigns orthologs and therewith merges single-cell RNA sequencing (scRNA-seq) RNA of different species. The pipeline has been designed to be as easy to use and is fully integrable in the standard Seurat workflow.We applied OrthoIntegrate on scRNA-seq from cardiac tissue of heart failure patients with reduced ejection fraction (HFrEF) and scRNA-seq from the mice after chronic infarction, which is a commonly used mouse model to mimic HFrEF. We discovered shared and distinct regulatory pathways between human HFrEF patients and the corresponding mouse model. Overall, 54% of genes were commonly regulated, including major changes in cardiomyocyte energy metabolism. However, several regulatory pathways (e.g., angiogenesis) were specifically regulated in humans. CONCLUSIONS: The demonstration of unique pathways occurring in humans indicates limitations on the comparability between mice models and human HFrEF and shows that results from the mice model should be validated carefully. OrthoIntegrate is publicly accessible (https://github.com/MarianoRuzJurado/OrthoIntegrate) and can be used to integrate other large datasets to provide a general comparison of models with patient data.

Angiotensin Receptor-Neprilysin Inhibition (Sacubitril/Valsartan) Reduces Structural Arterial Stiffness in Middle-Aged Mice.

BACKGROUND: Increasing arterial stiffness is a prominent feature of the aging cardiovascular system. Arterial stiffening leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function resulting in significant morbidity and death, and specific therapies to address the underlying age-related structural arterial remodeling remain elusive. The present study investigates the potential of the recently clinically available dual angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) to counteract age-related arterial fibrotic remodeling and stiffening in 1-year-old mice. METHODS AND RESULTS: Treatment of in 1-year-old mice with ARNI (sacubitril/valsartan), in contrast to angiotensin receptor blocker monotherapy (valsartan) and vehicle treatment (controls), significantly decreases structural aortic stiffness (as measured by in vivo pulse-wave velocity and ex vivo aortic pressure myography). This phenomenon appears, at least partly, independent of (indirect) blood pressure effects and may be related to a direct antifibrotic interference with aortic smooth muscle cell collagen production. Furthermore, we find aortic remodeling and destiffening due to ARNI treatment to be associated with improved parameters of cardiac diastolic function in aged mice. CONCLUSIONS: This study provides preclinical mechanistic evidence indicating that ARNI-based interventions may counteract age-related arterial stiffening and may therefore be further investigated as a promising strategy to improve cardiovascular outcomes in the elderly.

Cerebral protection during controlled hypoperfusion in a piglet model: comparison of moderate (25°C) versus deep (18°C) hypothermia at various flow rates using intraoperative measurements and ex vivo investigation.

BACKGROUND: During surgical correction of complex cardiac anomalies, some degree of hypoperfusion may be required. The aim of this study was to evaluate the effectiveness and safety of controlled cerebral hypoperfusion at moderate (25°C) versus deep (18°C) hypothermia. METHODS: In this study, 56 female piglets (9.4 ± 0.8 kg, 3-4 weeks old) received cardiopulmonary bypass (CPB) at 25, 50, or 100% of the standard flow rate for 60 minutes of cardioplegic cardiac arrest. Body temperature was kept at 18, 25, and 37°C. Routine hemodynamic and functional parameters were measured online until 4 hours of reperfusion. Immunohistology was used to quantify heat shock protein 70 (HSP70) and nitrotyrosine (NO-Tyr) levels in the hippocampus; high-performance liquid chromatography was used to quantify jugular venous blood malondialdehyde (MDA) levels. RESULTS: Reduced CPB flow led to significant reduction of mean arterial pressure by 79%, reduction of jugular venous oxygen saturation (SvO2) by 47%, reduction of carotid blood flow by 92%, and increase of serum lactate by 350%. All these changes were significantly enhanced in the 37°C versus the 25 and the 18°C groups. Regional oxygen saturation (rSO2) was significantly reduced in the 37°C low flow groups. HSP70, NO-Tyr, and MDA were increased in the 25 and 50% flow groups (p < 0.05). There was a significant correlation between rSO2 and SvO2 (r = 0.61) and between SvO2 and HSP70 (r = - 0.72). CONCLUSIONS: Reduction in global blood flow during CPB leads to comparable biochemical changes in the hippocampus at 25 and 18°C. Regional oxygenation saturation, SvO2, and HSP70 are important parameters to evaluate the efficacy of further anti-ischemic therapies during surgical corrections.

Correction: Hlavicka et al. Long-Term Outcomes after Aortic Valve and Root Replacement in a Very High-Risk Population. J. Cardiovasc. Dev. Dis. 2022, 9, 197.

The authors would like to make the following corrections to the published paper [...].

Ablation of palladin in adult heart causes dilated cardiomyopathy associated with intercalated disc abnormalities.

Palladin (PALLD) belongs to the PALLD/myopalladin (MYPN)/myotilin family of actin-associated immunoglobulin-containing proteins in the sarcomeric Z-line. PALLD is ubiquitously expressed in several isoforms, and its longest 200 kDa isoform, predominantly expressed in striated muscle, shows high structural homology to MYPN. MYPN gene mutations are associated with human cardiomyopathies, whereas the role of PALLD in the heart has remained unknown, partly due to embryonic lethality of PALLD knockout mice. In a yeast two-hybrid screening, CARP/Ankrd1 and FHOD1 were identified as novel interaction partners of PALLD's N-terminal region. To study the role of PALLD in the heart, we generated conditional (cPKO) and inducible (cPKOi) cardiomyocyte-specific PALLD knockout mice. While cPKO mice exhibited no pathological phenotype, ablation of PALLD in adult cPKOi mice caused progressive cardiac dilation and systolic dysfunction, associated with reduced cardiomyocyte contractility, intercalated disc abnormalities, and fibrosis, demonstrating that PALLD is essential for normal cardiac function. Double cPKO and MYPN knockout (MKO) mice exhibited a similar phenotype as MKO mice, suggesting that MYPN does not compensate for the loss of PALLD in cPKO mice. Altered transcript levels of MYPN and PALLD isoforms were found in myocardial tissue from human dilated and ischemic cardiomyopathy patients, whereas their protein expression levels were unaltered.

Single-nuclear transcriptome profiling identifies persistent fibroblast activation in hypertrophic and failing human hearts of patients with longstanding disease.

AIMS: Cardiac fibrosis drives the progression of heart failure in ischaemic and hypertrophic cardiomyopathy. Therefore, the development of specific anti-fibrotic treatment regimens to counteract cardiac fibrosis is of high clinical relevance. Hence, this study examined the presence of persistent fibroblast activation during longstanding human heart disease at a single-cell resolution to identify putative therapeutic targets to counteract pathological cardiac fibrosis in patients. METHODS AND RESULTS: We used single-nuclei RNA sequencing with human tissues from two samples of one healthy donor, and five hypertrophic and two failing hearts. Unsupervised sub-clustering of 7110 nuclei led to the identification of 7 distinct fibroblast clusters. De-convolution of cardiac fibroblast heterogeneity revealed a distinct population of human cardiac fibroblasts with a molecular signature of persistent fibroblast activation and a transcriptional switch towards a pro-fibrotic extra-cellular matrix composition in patients with established cardiac hypertrophy and heart failure. This sub-cluster was characterized by high expression of POSTN, RUNX1, CILP, and a target gene adipocyte enhancer-binding protein 1 (AEBP1) (all P < 0.001). Strikingly, elevated circulating AEBP1 blood level were also detected in a validation cohort of patients with confirmed cardiac fibrosis and hypertrophic cardiomyopathy by cardiac magnetic resonance imaging (P < 0.01). Since endogenous AEBP1 expression was increased in patients with established cardiac hypertrophy and heart failure, we assessed the functional consequence of siRNA-mediated AEBP1 silencing in human cardiac fibroblasts. Indeed, AEBP1 silencing reduced proliferation, migration, and fibroblast contractile capacity and α-SMA gene expression, which is a hallmark of fibroblast activation (all P < 0.05). Mechanistically, the anti-fibrotic effects of AEBP1 silencing were linked to transforming growth factor-beta pathway modulation. CONCLUSION: Together, this study identifies persistent fibroblast activation in patients with longstanding heart disease, which might be detected by circulating AEBP1 and therapeutically modulated by its targeted silencing in human cardiac fibroblasts.

Temporary Mechanical Circulatory Support in Cardiogenic Shock Patients after Cardiac Procedures: Selection Algorithm and Weaning Strategies.

Mechanical circulatory support has proven effective in managing postcardiotomy cardiogenic shock by stabilizing patients' hemodynamics and ensuring adequate organ perfusion. Among the available device modalities, the combination of extracorporeal life support and a microaxial flow pump for left ventricular unloading has emerged as a valuable tool in the surgical armamentarium. In this publication, we provide recommendations for the application and weaning of temporary mechanical circulatory support in cardiogenic shock patients, derived from a consensus among leading cardiac centers in German-speaking countries.

Long-Term Outcomes after Aortic Valve and Root Replacement in a Very High-Risk Population.

Background: Aortic valve and root replacement (AVRR) is a standardised procedure to treat patients with aortic valve and root disease. In centres with a well-established aortic valve and root repair program (valve repairs and Ross operations), only patients with very complex conditions receive AVRR; this procedure uses a mechanical or biological composite valve graft (modified Bentall-de Bono procedure). The aim of the study was to evaluate the short- and long-term results after AVRR in a high-risk population with complex pathologies. Methods: Between 2005 and 2018, a total of 273 consecutive patients (mean age 64 ± 12.8 years; 23% female) received AVRR. The indication for surgery was an acute type A aortic dissection in 18%, infective endocarditis in 36% and other pathologies in 46% patients; 39% were redo procedures. The median EuroSCORE II was 11.65% (range 1.48-95.63%). Concomitant surgery was required in 157 patients (58%). Results: The follow-up extended to 5.2 years (range 0.1-15 years) and it was complete in 96% of the patients. The 30-day mortality was 17%. The overall estimated survival at 5 and 10 years was 65% ± 3% and 49% ± 4%, respectively. Univariate and multivariate logistic regression analyses revealed the following risk factors for survival: perioperative neurological dysfunction (OR 5.45), peripheral artery disease (OR 4.4) and re-exploration for bleeding (OR 3.37). Conclusions: AVRR can be performed with acceptable short- and long-term results in a sick patient population. The Bentall-De Bono procedure may be determined to be suitable for only elderly or high-risk patients. Any other patients should receive an AV repair or the Ross procedure in well-established centres.