The impact of socio-demographic factors on health-related quality of life after coronary artery bypass surgery.

OBJECTIVES: To achieve a beneficial impact on long-term outcome after coronary artery bypass grafting (CABG), the goal of the present study was the early identification of patients at risk of impaired postoperative health-related quality of life (HRQoL), particularly evaluating the significance of socio-demographic variables. METHODS: In this prospective, single-centre cohort study of patients having an isolated CABG (January 2004-December 2014), preoperative socio-demographic (preSOC) and preoperative medical variables as well as 6-month follow-up data including the Nottingham Health Profile were analysed in 3,237 patients. RESULTS: All preSOC (gender, age, marriage and employment) and follow-up (chest pain, dyspnoea) variables proved to have significant influence on HRQoL (P < 0.001), male patients below 60 years being particularly impaired. The effects of marriage and employment on HRQoL are modulated by age and gender. The significance of the predictors of reduced HRQoL differs between the 6 Nottingham Health Profile domains. Multivariable regression analyses revealed explained proportions of variance amounting to 7% for preSOC and 4% for preoperative medical variables. CONCLUSIONS: The identification of patients at risk of impaired postoperative HRQoL is decisive for providing additional support. This study reveals that the assessment of 4 preoperative socio-demographic characteristics (age, gender, marriage, employment) is more predictive of HRQoL after CABG than are multiple medical variables.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

Degeneration of biological heart valve grafts in a rat model of superoxide dismutase-3 deficiency.

While oxidative stress is known as key element in the pathogenesis of atherosclerosis and calcific aortic valve disease, its role in the degeneration of biological cardiovascular grafts has not been clarified yet. Therefore, the present study aimed to examine the impact of oxidative stress on the degeneration of biological cardiovascular allografts in a standardized chronic implantation model realized in rats exhibiting superoxide dismutase 3 deficiency (SOD3(-) ). Rats with SOD3 loss-of-function mutation (n = 24) underwent infrarenal implantation of cryopreserved valved aortic conduits, while SOD3-competent recipients served as controls (n = 28). After a follow-up period of 4 or 12 weeks, comparative analyses addressed degenerative processes, hemodynamics, and evaluation of the oxidative stress model. SOD3(-) rats presented decreased circulating SOD activity (p = .0079). After 12 weeks, 58% of the implant valves in SOD3(-) rats showed regurgitation (vs. 31% in controls, p = .2377). Intima hyperplasia and chondro-osteogenic transformation contributed to progressive graft calcification (p = .0024). At 12 weeks, hydroxyapatite deposition (p = .0198) and the gene expression of runt-related transcription factor-2 (Runx2) (p = .0093) were significantly enhanced in group SOD3(-) . This study provides the first in vivo evidence that impaired systemic antioxidant activity contributes to biological cardiovascular graft degeneration.

Bilateral Internal Thoracic Artery Minimally Invasive CABG Management in COPD.

Background Off-pump multi-arterial minimally invasive coronary surgery via anterolateral mini-thoracotomy has become a feasible and safe procedure. Case Description We report on a 61-year-old patient with a coronary one-vessel disease with severely stenotic left anterior descending artery and diagonal branch, additionally suffering from chronic obstructive pulmonary disease with severely impaired lung function. Using a fan technique allowing for double lung ventilation, the patient was successfully operated grafting both internal thoracic arteries via a left anterolateral mini-thoracotomy. Conclusion Anaortic, minimally invasive off-pump coronary artery bypass grafting is an excellent technique to achieve myocardial revascularization with both internal thoracic arteries even in patients with impaired lung function.

Coronary artery bypass grafting under sole Impella 5.0 support for patients with severely depressed left ventricular function.

Selection of the ideal surgical procedure for coronary revascularization in patients with severe cardiac dysfunction at times may represent a challenge. In recent years, with the advent of surgical large microaxial pumps, e.g., Impella 5.0 (Abiomed Inc., Boston, USA), specific support and effective unloading of the left ventricle has become available. In the interventional field, good results have been achieved with smaller microaxial pumps in the setting of so-called protected percutaneous coronary intervention. In this study, we would like to share our early experience with surgical coronary revascularization under the sole support of Impella 5.0, omitting the use of heart-lung machine in three cases of severe cardiac dysfunction due to complex ischemic heart disease. Effective circulatory support intraoperatively and postoperatively speaks in favor of this technique in selected patients.

Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure -A clinical practice Guideline Level 3.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements. Conclusions This first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated.

Impact of PPAR-gamma activation on the durability of biological heart valve prostheses in hypercholesterolaemic rats.

OBJECTIVES: Hypercholesterolaemia and obesity are risk factors for the development of calcified aortic valve disease and common comorbidities in respective patients. Peroxisome proliferator-activated receptor gamma activation has been shown to reduce the progression of native aortic valve sclerosis, while its effect on bioprosthetic valve degeneration is yet unknown. This project aims to analyse the impact of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the degeneration of biological aortic valve conduits in an implantation model in obese and hypercholesterolaemic rats. METHODS: Cryopreserved allogenic rat aortic valve conduits (n = 40) were infrarenally implanted into Wistar rats on high-fat (34.6%) diet. One cohort was treated with pioglitazone (75 mg/kg chow; n = 20, group PIO) and compared to untreated rats (n = 20, group control). After 4 or 12 weeks, conduits were explanted and analysed by (immuno-)histology and real-time polymerase chain reaction. RESULTS: A significantly decreased intima hyperplasia occurred in group PIO compared to control after 4 (P = 0.014) and 12 weeks (P = 0.045). Calcification of the intima was significantly decreased in PIO versus control at 12 weeks (P = 0.0001). No significant inter-group differences were shown for media calcification after 4 and 12 weeks. Echocardiographically, significantly lower regurgitation through the implanted aortic valve conduit was observed in PIO compared to control after 4 (P = 0.018) and 12 weeks (P = 0.0004). Inflammatory activity was comparable between both groups. CONCLUSIONS: Systemic peroxisome proliferator-activated receptor gamma activation decreases intima hyperplasia and subsequent intima calcification of cryopreserved allografts in obese, hypercholesterolaemic recipients. Additionally, it seems to inhibit functional impairment of the implanted aortic valve. Further preclinical studies are required to determine the long-term impact of peroxisome proliferator-activated receptor gamma agonists on graft durability.

A Role for Peroxisome Proliferator-Activated Receptor Gamma Agonists in Counteracting the Degeneration of Cardiovascular Grafts.

ABSTRACT: Aortic valve replacement for severe stenosis is a standard procedure in cardiovascular medicine. However, the use of biological prostheses has limitations especially in young patients because of calcifying degeneration, resulting in implant failure. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, was shown to decrease the degeneration of native aortic valves. In this study, we aim to examine the impact of pioglitazone on inflammation and calcification of aortic valve conduits (AoC) in a rat model. Cryopreserved AoC (n = 40) were infrarenally implanted into Wistar rats treated with pioglitazone (75 mg/kg chow; n = 20, PIO) or untreated (n = 20, controls). After 4 or 12 weeks, AoC were explanted and analyzed by histology, immunohistology, and polymerase chain reaction. Pioglitazone significantly decreased the expression of inflammatory markers and reduced the macrophage-mediated inflammation in PIO compared with controls after 4 (P = 0.03) and 12 weeks (P = 0.012). Chondrogenic transformation was significantly decreased in PIO after 12 weeks (P = 0.001). Calcification of the intima and media was significantly reduced after 12 weeks in PIO versus controls (intima: P = 0.008; media: P = 0.025). Moreover, echocardiography revealed significantly better functional outcome of the AoC in PIO after 12 weeks compared with control. Interestingly, significantly increased intima hyperplasia could be observed in PIO compared with controls after 12 weeks (P = 0.017). Systemic PPAR-gamma activation prevents inflammation as well as intima and media calcification in AoC and seems to inhibit functional impairment of the implanted aortic valve. To further elucidate the therapeutic role of PPAR-gamma regulation for graft durability, translational studies and long-term follow-up data should be striven for.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

Initial experience covering 50 consecutive cases of large Impella implantation at a single heart centre.

AIMS: Pre-operative or post-operative heart failure (HF) and cardiogenic shock of various natures frequently remain refractory to conservative treatment and require mechanical circulatory support. We report our clinical experience with large Impella systems (5.0 or 5.5; i.e. Impella 5+) (Abiomed Inc., Boston, USA) and evaluate the parameters that determined patient outcome. METHODS AND RESULTS: The initial 50 cases of Impella 5+ implanted for acute HF between November 2018 and August 2020 at a single centre were enrolled in this study. Data, including preoperative characteristics, perioperative clinical course information, and post-operative outcomes, were retrospectively collected from the hospital data management and quality assurance system. Descriptive and univariate analyses were performed. Among the 49 patients in this study, 28 (56.0%) survived in the first 30 days post-operatively, and 3 died of non-cardiac reasons later. In-hospital mortality was significantly higher in patients with biventricular failure [P < 0.01, odds ratio (OR) 5.63] or dilated cardiomyopathy (DCM) (P = 0.02, OR 15.8), whereas ischaemic cardiomyopathy (ICM) was associated with lower mortality (P = 0.03, OR 0.24). Interestingly, the mortality was comparable between the 'solo' Impella group and the veno-arterial extracorporal membrane oxygenation (va-ECMO) plus Impella (ECMELLA) group, despite the severity of the patients' profile in the ECMELLA group ('solo' vs. ECMELLA; 55.6% vs. 52.6%, P = 1.00). All patients who received an additional temporary right ventricular assist device (tRVAD) were successfully weaned from va-ECMO. CONCLUSIONS: Our results suggest that biventricular failure and DCM are predictors of higher mortality in patients with Impella. Considering the pathophysiology of HF, implantation of a large Impella system seems to be promising, especially for ICM patients. The large Impella system might be more effective for better prognosis of patients under va-ECMO, and combination therapy with tRVAD seems to be a promising strategy for early weaning from va-ECMO.

Dichloroacetate inhibits the degeneration of decellularized cardiovascular implants.

OBJECTIVES: Intima hyperplasia is a major issue of biological cardiovascular grafts resulting in progressive in vivo degeneration that particularly decreases the durability of coronary and peripheral vascular bypasses. Previously, dichloroacetate (DCA) has been reported to prevent the formation of hyperplastic intima in injured arteries. In this study, the effect of DCA on the neointima formation and degeneration of decellularized small-caliber implants was investigated in a rat model. METHODS: Donor rat aortic grafts (n = 22) were decellularized by a detergent-based technique, surface-coated with fibronectin (50 µl ml-1, 24 h incubation) and implanted via anastomoses to the infrarenal aorta of the recipients. Rats in the DCA group (n = 12) received DCA via drinking water during the whole follow-up period (0.75 g l-1), while rats without DCA treatment served as controls (n = 10). At 2 (n = 6 + 5) and 8 (n = 6 + 5) weeks, the grafts were explanted and examined by histology and immunofluorescence. RESULTS: Systemic DCA treatment inhibited neointima hyperplasia, resulting in a significantly reduced intima-to-media ratio (median 0.78 [interquartile range, 0.51-1.27] vs 1.49 [0.67-2.39] without DCA, P < 0.001). At 8 weeks, neointima calcification, as assessed by an established von Kossa staining-based score, was significantly decreased in the DCA group (0 [0-0.25] vs 0.63 [0.06-1.44] without DCA, P < 0.001). At 8 weeks, explanted grafts in both groups were luminally completely covered by an endothelial cell layer. In both groups, inflammatory cell markers (CD3, CD68) proved negative. CONCLUSIONS: Systemic DCA treatment reduces adverse neointima hyperplasia in decellularized small-caliber arterial grafts, while allowing for rapid re-endothelialization. Furthermore, DCA inhibits calcification of the implants.

Health-related quality of life after heart surgery - Identification of high-risk patients: A cohort study.

BACKGROUND: This cohort study evaluated factors, which have been shown to be relevant for Health-Related Quality of Live (HRQL) after cardiac surgery and investigated the combinatory impact on HRQL. Additionally, the aim was to introduce a first attempt to developing a risk estimation model which could identify patients at risk for impaired HRQL. METHODS: For this single-centre cohort study, 6099 cardiac surgical patients (60% isolated coronary bypass surgery) filled in the Nottingham Health Profile (NHP) for the evaluation of HRQL six months after surgery and provided information regarding their medical and socio-demographic status. For the NHP scores the deviation to the matched normative data of a healthy sample was calculated. A robust linear regression examined factors that influence HRQL. As a next step, based on the regression model, a risk estimation model was developed which is a first attempt to classify patients into risk categories. RESULTS: Male gender, age below 60 or between 60 and 74 years, living alone, no occupation, bypass surgery, NYHA status II, III or IV and chest pain were identified as risk factors to determine impaired HRQL. The model explains 29.13% of the variance. Based on the risk estimation model 27.4% were classified as medium or high risk. CONCLUSIONS: For the first time a multilevel method was applied to evaluate HRQL after heart surgery showing that socio-demographic variables are important co-factors to dyspnea and chest pain. We take a first attempt in developing a new approach that should encourage further research in this field to frame a screening tool that may help identifying patients at risk in the future.

Computational investigation of hemodynamics in hardshell venous reservoirs: A comparative study.

Extracorporeal circulation using heart-lung-machines is associated with a profound activation of corpuscular and plasmatic components of circulating blood, which can also lead to deleterious events such as systemic inflammatory response and hemolysis. Individual components used to install the extracorporeal circulation have an impact on the level of activation, most predominantly membrane oxygenators and hardshell venous reservoirs as used in extracorporeal systems. The blood flows in two different hardshell reservoirs are computationally investigated. A special emphasis is placed on the prediction of an onset of transition and turbulence generation. Reynolds-averaged numerical simulations (RANS) based on a transitional turbulence model, as well as large eddy simulations (LES) are applied to achieve an accurate prediction. In the LES analysis, the non-Newtonian behavior of the blood is considered via the Carreau model. Blood damage potential is quantified applying the Modified Index of Hemolysis (MIH) based on the predicted flow fields. The results indicate that the flows in both reservoirs remain predominantly laminar. For one of the reservoirs, considerable turbulence generation is observed near the exit site, caused by the specific design for the connection with the drainage tube. This difference causes the MIH of this reservoir to be nearly twice as large as compared to the alternative design. However, a substantial improvement of these performance criteria can be expected by a local geometry modification.

Controlled autologous recellularization and inhibited degeneration of decellularized vascular implants by side-specific coating with stromal cell-derived factor 1α and fibronectin.

Optimized biocompatibility is crucial for the durability of cardiovascular implants. Previously, a combined coating with fibronectin (FN) and stromal cell-derived factor 1α (SDF1α) has been shown to accelerate the in vivo cellularization of synthetic vascular grafts and to reduce the calcification of biological pulmonary root grafts. In this study, we evaluate the effect of side-specific luminal SDF1α coating and adventitial FN coating on the in vivo cellularization and degeneration of decellularized rat aortic implants. Aortic arch vascular donor grafts were detergent-decellularized. The luminal graft surface was coated with SDF1α, while the adventitial surface was coated with FN. SDF1α-coated and uncoated grafts were infrarenally implanted (n = 20) in rats and followed up for up to eight weeks. Cellular intima population was accelerated by luminal SDF1α coating at two weeks (92.4 ± 2.95% versus 61.1 ± 6.51% in controls, p < 0.001). SDF1α coating inhibited neo-intimal hyperplasia, resulting in a significantly decreased intima-to-media ratio after eight weeks (0.62 ± 0.15 versus 1.35 ± 0.26 in controls, p < 0.05). Furthermore, at eight weeks, media calcification was significantly decreased in the SDF1α group as compared to the control group (area of calcification in proximal arch region 1092 ± 517 µm2 versus 11 814 ± 1883 µm2, p < 0.01). Luminal coating with SDF1α promotes early autologous intima recellularization in vivo and attenuates neo-intima hyperplasia as well as calcification of decellularized vascular grafts.

Influence of Laminin Coating on the Autologous In Vivo Recellularization of Decellularized Vascular Protheses.

Decellularization of non-autologous biological implants reduces the immune response against foreign tissue. Striving for in vivo repopulation of aortic prostheses with autologous cells, thereby improving the graft biocompatibility, we examined surface coating with laminin in a standardized rat implantation model. Detergent-decellularized aortic grafts from donor rats (n = 37) were coated with laminin and systemically implanted into Wistar rats. Uncoated implants served as controls. Implant re-colonization and remodeling were examined by scanning electron microscopy (n = 10), histology and immunohistology (n = 18). Laminin coating persisted over eight weeks. Two weeks after implantation, no relevant neoendothelium formation was observed, whereas it was covering the whole grafts after eight weeks, with a significant acceleration in the laminin group (p = 0.0048). Remarkably, the intima-to-media ratio, indicating adverse hyperplasia, was significantly diminished in the laminin group (p = 0.0149). No intergroup difference was detected in terms of medial recellularization (p = 0.2577). Alpha-smooth muscle actin-positive cells originating from the adventitial surface invaded the media in both groups to a similar extent. The amount of calcifying hydroxyapatite deposition in the intima and the media did not differ between the groups. Inflammatory cell markers (CD3 and CD68) proved negative in coated as well as uncoated decellularized implants. The coating of decellularized aortic implants with bioactive laminin caused an acceleration of the autologous recellularization and a reduction of the intima hyperplasia. Thereby, laminin coating seems to be a promising strategy to enhance the biocompatibility of tissue-engineered vascular implants.

Muscular Mitral Chord Contribution to Left Ventricular Outflow Tract Obstruction in HOCM.

Papillary muscle anomaly with a muscular chord directly attached to the anterior mitral leaflet is a rare mitral valve disease. A 62-year-old man with systolic anterior motion of the anterior mitral leaflet and hypertrophic obstructive cardiomyopathy presented to surgical intervention after unsuccessful transcoronary ablation of septal hypertrophy with alcohol. Intraoperative findings revealed a primarily not detected anomalous muscular mitral chord (0.8 × 2.2 cm) connecting the base of the A1 segment to the anterolateral papillary muscle. Resection of this chord and additional septal myectomy treated systolic anterior motion and obstruction of the outflow tract. In spite of the infrequent occurrence, anomalies of the subvalvular apparatus, such as muscular chords, should be ruled out by thorough transesophageal echocardiography imaging before decision on the therapeutical strategy.