RESUMO
One of the most important medical interventions for individuals with heart valvular disease is heart valve replacement, which is not without substantial challenges, particularly for pediatric patients. Due to their biological properties and biocompatibility, natural tissue-originated scaffolds derived from human or animal sources are one type of scaffold that is widely used in tissue engineering. However, they are known for their high potential for immunogenicity. Being free of cells and genetic material, decellularized xenografts, consequently, have low immunogenicity and, thus, are expected to be tolerated by the recipient's immune system. The scaffold ultrastructure and ECM composition can be affected by cell removal agents. Therefore, applying an appropriate method that preserves intact the structure of the ECM plays a critical role in the final result. So far, there has not been an effective decellularization technique that preserves the integrity of the heart valve's ultrastructure while securing the least amount of genetic material left. This study demonstrates a new protocol with untraceable cells and residual DNA, thereby maximally reducing any chance of immunogenicity. The mechanical and biochemical properties of the ECM resemble those of native heart valves. Results from this study strongly indicate that different critical factors, such as ionic detergent omission, the substitution of Triton X-100 with Tergitol, and using a lower concentration of trypsin and a higher concentration of DNase and RNase, play a significant role in maintaining intact the ultrastructure and function of the ECM.
Assuntos
Bioprótese , Próteses Valvulares Cardíacas , Animais , Suínos , Humanos , Criança , Xenoenxertos , Transplante Heterólogo , Engenharia TecidualRESUMO
BACKGROUND: Transcatheter aortic valve implantation (TAVI) can either be conducted as an elective (scheduled in advance) or a non-elective procedure performed during an unplanned hospital admission. The objective of this study was to compare the outcomes of elective and non-elective TAVI patients. METHODS: This single-centre study included 512 patients undergoing transfemoral TAVI between October 2018 and December 2020; 378 (73.8%) were admitted for elective TAVI, 134 (26.2%) underwent a non-elective procedure. Our TAVI programme entails an optimized fast-track concept aimed at minimizing the total length of stay to ≤ 5 days for elective patients which in the German healthcare system is currently defined as the minimal time period to safely perform TAVI. Clinical characteristics and survival rates at 30 days and 1 year were analysed. RESULTS: Patients who underwent non-elective TAVI had a significantly higher comorbidity burden. Median duration from admission to discharge was 6 days (elective group 6 days versus non-elective group 15 days; p < 0.001), including a median postprocedural stay of 5 days (elective 4 days versus non-elective 7 days; p < 0.001). All-cause mortality at 30 days was 1.1% for the elective group and 3.7% for non-elective patients (p = 0.030). At 1 year, all-cause mortality among elective TAVI patients was disproportionately lower than in non-elective patients (5.0% versus 18.7%, p < 0.001). In the elective group, 54.5% of patients could not be discharged early due to comorbidities or procedural complications. Factors associated with a failure of achieving a total length of stay of ≤ 5 days comprised frailty syndrome, renal impairment as well as new permanent pacemaker implantation, new bundle branch block or atrial fibrillation, life-threatening bleeding, and the use of self-expanding valves. After multivariate adjustment, new permanent pacemaker implantation (odds ratio 6.44; 95% CI 2.59-16.00), life-threatening bleeding (odds ratio 4.19; 95% confidence interval 1.82-9.66) and frailty syndrome (odds ratio 5.15; 95% confidence interval 2.40-11.09; all p < 0.001, respectively) were confirmed as significant factors. CONCLUSIONS: While non-elective patients had acceptable periprocedural outcomes, mortality rates at 1 year were significantly higher compared to elective patients. Approximately only half of elective patients could be discharged early. Improvements in periprocedural care, follow-up strategies and optimized treatment of both elective and non-elective TAVI patients are needed.
Assuntos
Estenose da Valva Aórtica , Fibrilação Atrial , Fragilidade , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Idoso , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Idoso Fragilizado , Universidades , Bloqueio de Ramo/etiologia , Fibrilação Atrial/etiologia , Resultado do Tratamento , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Fatores de Risco , Próteses Valvulares Cardíacas/efeitos adversosRESUMO
Transcatheter aortic valve replacement (TAVR) is routinely performed via the transfemoral or transapical route. Subclavian, transcarotid, and transaortic access are described as alternative routes for TAVR. The small intercostal approach can be used for a safe TAVR without touching the ribs and sternum.
Assuntos
Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Fatores de RiscoRESUMO
Transcatheter pulmonary valve replacement is a minimally-invasive alternative treatment for right ventricular outflow tract dysfunction and has been rapidly evolving over the past years. Heart valve prostheses currently available still have major limitations. Therefore, one of the significant challenges for the future is the roll out of transcatheter tissue engineered pulmonary valve replacement to more patients. In the present study, biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds in the form of a 3D leaflet matrix were successfully seeded with human endothelial colony-forming cells (ECFCs), human induced pluripotent stem cell-derived MSCs (hMSCs), and porcine MSCs (pMSCs) for three weeks for the generation of 3D tissue-engineered tri-leaflet valved stent grafts. The cell adhesion, proliferation, and distribution of these 3D heart leaflets was analyzed using fluorescence microscopy and scanning electron microscopy (SEM). All cell lineages were able to increase the overgrown leaflet area within the three-week timeframe. While hMSCs showed a consistent growth rate over the course of three weeks, ECFSs showed almost no increase between days 7 and 14 until a growth spurt appeared between days 14 and 21. More than 90% of heart valve leaflets were covered with cells after the full three-week culturing cycle in nearly all leaflet areas, regardless of which cell type was used. This study shows that seeded biodegradable PCL nanofiber scaffolds incorporated in nitinol or biodegradable stents will offer a new therapeutic option in the future.
Assuntos
Células-Tronco Pluripotentes Induzidas , Poliésteres , Humanos , Animais , Suínos , Poliésteres/farmacologia , Engenharia Tecidual , Alicerces Teciduais , StentsRESUMO
BACKGROUND: Mitral valved stents tend to migrate or to develop paravalvular leakage due to high-left ventricular pressure in this cavity. Thus, this study describes a newly developed mitral valved stent anchoring technology. METHODS: Based on an existing mitral valved stent, four anchoring units with curved surgical needles were designed and fabricated using three-dimensional (3D) software and print technology. Mitral nitinol stents assembled with four anchoring units were successively fixed on 10 porcine annuli. Mechanical tests were performed with a tensile force test system and recorded the tension forces of the 10 nitinol stents on the annulus. RESULTS: The average maximum force was 28.3 ± 5.21 N, the lowest was 21.7 N, and the highest was 38.6 N until the stent lost contact with the annulus; for the break force (zero movement of stent from annulus), the average value was 18.5 ± 6.7 N with a maximum value of 26.9 N and a minimum value of 6.07 N. It was additionally observed that the puncture needles of the anchoring units passed into the mitral annulus in all 10 hearts and further penetrated the myocardium in only one additional heart. The anchoring units enhanced the tightness of the mitral valved stent and did not destroy the circumflex coronary artery, coronary sinus, right atrium, aortic root, or the left ventricular outflow tract. CONCLUSION: The new anchoring units for mitral nitinol stents were produced with 3D software and printing technology; with this new type of anchoring technology, the mitral valved stent can be tightly fixed toward the mitral annulus.
Assuntos
Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral , Animais , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Stents , Suínos , Tecnologia , Resultado do TratamentoRESUMO
Clinically used heart valve prostheses, despite their progress, are still associated with limitations. Biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds, as a matrix, were seeded with human endothelial colony-forming cells (ECFCs) and human induced-pluripotent stem cells-derived MSCs (iMSCs) for the generation of tissue-engineered heart valves. Cell adhesion, proliferation, and distribution, as well as the effects of coating PCL nanofibers, were analyzed by fluorescence microscopy and SEM. Mechanical properties of seeded PCL scaffolds were investigated under uniaxial loading. iPSCs were used to differentiate into iMSCs via mesoderm. The obtained iMSCs exhibited a comparable phenotype and surface marker expression to adult human MSCs and were capable of multilineage differentiation. EFCFs and MSCs showed good adhesion and distribution on PCL fibers, forming a closed cell cover. Coating of the fibers resulted in an increased cell number only at an early time point; from day 7 of colonization, there was no difference between cell numbers on coated and uncoated PCL fibers. The mechanical properties of PCL scaffolds under uniaxial loading were compared with native porcine pulmonary valve leaflets. The Young's modulus and mean elongation at Fmax of unseeded PCL scaffolds were comparable to those of native leaflets (p = ns.). Colonization of PCL scaffolds with human ECFCs or iMSCs did not alter these properties (p = ns.). However, the native heart valves exhibited a maximum tensile stress at a force of 1.2 ± 0.5 N, whereas it was lower in the unseeded PCL scaffolds (0.6 ± 0.0 N, p < 0.05). A closed cell layer on PCL tissues did not change the values of Fmax (ECFCs: 0.6 ± 0.1 N; iMSCs: 0.7 ± 0.1 N). Here, a successful two-phase protocol, based on the timed use of differentiation factors for efficient differentiation of human iPSCs into iMSCs, was developed. Furthermore, we demonstrated the successful colonization of a biodegradable PCL nanofiber matrix with human ECFCs and iMSCs suitable for the generation of tissue-engineered heart valves. A closed cell cover was already evident after 14 days for ECFCs and 21 days for MSCs. The PCL tissue did not show major mechanical differences compared to native heart valves, which was not altered by short-term surface colonization with human cells in the absence of an extracellular matrix.
Assuntos
Biopolímeros/química , Caproatos/química , Células Progenitoras Endoteliais/citologia , Valvas Cardíacas , Células-Tronco Pluripotentes Induzidas/citologia , Lactonas/química , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual , Alicerces Teciduais , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Matriz Extracelular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Nanofibras , Suínos , Alicerces Teciduais/químicaRESUMO
Patients with the complex congenital heart disease (CHD) are usually associated with right ventricular outflow tract dysfunction and typically require multiple surgical interventions during their lives to relieve the right ventricular outflow tract abnormality. Transcatheter pulmonary valve replacement was used as a non-surgical, less invasive alternative treatment for right ventricular outflow tract dysfunction and has been rapidly developing over the past years. Despite the current favorable results of transcatheter pulmonary valve replacement, many patients eligible for pulmonary valve replacement are still not candidates for transcatheter pulmonary valve replacement. Therefore, one of the significant future challenges is to expand transcatheter pulmonary valve replacement to a broader patient population. This review describes the limitations and problems of existing techniques and focuses on decellularized tissue engineering for pulmonary valve stenting.
Assuntos
Implante de Prótese de Valva Cardíaca/métodos , Valva Pulmonar/cirurgia , Stents , Engenharia Tecidual , Animais , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/normas , Ventrículos do Coração/fisiopatologia , Humanos , Prognóstico , Engenharia Tecidual/métodos , Resultado do Tratamento , Função VentricularRESUMO
BACKGROUND: Chronic kidney disease as well as acute kidney injury are associated with adverse outcomes after transcatheter aortic valve replacement (TAVR). However, little is known about the prognostic implications of an improvement in renal function after TAVR. METHODS: Renal improvement (RI) was defined as a decrease in postprocedural creatinine in µmol/l of ≥1% compared to its preprocedural baseline value. A propensity score representing the likelihood of RI was calculated to define patient groups which were comparable regarding potential confounders (age, sex, BMI, NYHA classification, STS score, log. EuroSCORE, history of atrial fibrillation/atrial flutter, pulmonary disease, previous stroke, CRP, creatinine, hsTNT and NT-proBNP). The cohort was stratified into 5 quintiles according to this propensity score and the survival time after TAVR was compared within each subgroup. RESULTS: Patients in quintile 5 (n = 93) had the highest likelihood for RI. They were characterized by higher creatinine, lower eGFR, higher NYHA class, higher NT-proBNP, being mostly female and having shorter overall survival time. Within quintile 5, patients without RI had significantly shorter survival compared to patients with RI (p = 0.002, HR = 0.32, 95% CI = [0.15-0.69]). There was no survival time difference between patients with and without RI in the whole cohort (p = 0.12) and in quintiles 1 to 4 (all p > 0.16). Analyses of specific subgroups showed that among patients with NYHA class IV, those with RI also had a significant survival time benefit (p < 0.001, HR = 0.15; 95%-CI = [0.05-0.44]) compared to patients without RI. CONCLUSIONS: We here describe a propensity score-derived specific subgroup of patients in which RI after TAVR correlated with a significant survival benefit.
Assuntos
Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Síndrome Cardiorrenal/fisiopatologia , Rim/fisiopatologia , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/mortalidade , Síndrome Cardiorrenal/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , Pontuação de Propensão , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The impact of patient-prosthesis mismatch (PPM) after aortic valve replacement (AVR) on long-term survival and quality of life (QoL) remains controversial. The objective of this study was to evaluate the impact of PPM on long-term survival and QoL in a large cohort of patients treated with isolated stented biological AVR in a single-center experience. METHODS: We analyzed data of 632 consecutive patients following isolated stented biological AVR between 2007 and 2012 at our institution. We evaluated the QoL (393 evaluable patients) using the Short Form 12-item Health Survey (SF-12) questionnaire via telephone call and the impact of PPM on long-term survival (533 evaluable patients) by Kaplan-Meier's estimate. RESULTS: Severe PPM (<0.65 cm2/m2) had a negative impact on physical component summary (PCS) score (SF-12) compared with patients with moderate or no PPM (p = 0.014), while the mental component summary (MCS) score (SF-12) was not affected by the degree of PPM (p = 0.133). Long-term survival was not different among the three different PPM groups investigated (p = 0.75). CONCLUSION: Severity of PPM demonstrated no influence on long-term survival and MCS score (SF-12), but it was associated with a lower PCS score (SF-12) in patients with severe PPM.
Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
In this feasibility study, a novel catheter prototype for laser thrombolysis under the guidance of optical coherence tomography (OCT) was designed and evaluated in a preclinical model. Human arteries and veins were integrated into a physiological flow model and occluded with thrombi made from the Chandler Loop. There were four experimental groups: placebo, 20 mg alteplase, laser, 20 mg alteplase + laser. The extent of thrombolysis was analyzed by weighing, OCT imaging and relative thrombus size. In the alteplase group, thrombus size decreased to 0.250 ± 0.036 g (p < 0.0001) and 14.495 ± 0.526 mm2 (p < 0.0001) at 60 min. The relative thrombus size decreased to 73.6 ± 4.1% at 60 min (p < 0.0001). In the laser group, thrombus size decreased significantly to 0.145 ± 0.028 g (p < 0.0001) and 11.559 ± 1.034 mm2 (p < 0.0001). In the alteplase + laser group, thrombus size decreased significantly (0.051 ± 0.026 g; p < 0.0001; 9.622 ± 0.582 mm2; p < 0.0001; 47.4 ± 6.1%; p < 0.0001) in contrast to sole alteplase and laser application. The reproducibility and accuracy of the OCT imaging was high (SD <10%). Histological examination showed no relevant destruction of the vascular layers after laser ablation (arteries: 745.8 ± 5.5 µm; p = 0.69; veins: 448.3 ± 4.5 µm; p = 0.27). Thus, laser ablation and OCT imaging are feasible with the novel catheter and thrombolysis combining alteplase with laser irradiation appears highly efficient.
Assuntos
Catéteres/normas , Terapia a Laser , Trombólise Mecânica/métodos , Tomografia de Coerência Óptica/normas , Fibrinolíticos/uso terapêutico , Humanos , Modelos Biológicos , Reprodutibilidade dos Testes , Trombose/patologia , Trombose/terapia , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
Transcatheter mitral interventions has been developed to address an unmet clinical need and may be an alternative therapeutic option to surgery with the intent to provide symptomatic and prognostic benefit. Beyond MitraClip therapy, alternative repair technologies are being developed to expand the transcatheter intervention armamentarium. Recently, the feasibility of transcatheter mitral valve implantation in native non-calcified valves has been reported in very high-risk patients. Acknowledging the lack of scientific evidence to date, it is difficult to predict what the ultimate future role of transcatheter mitral valve interventions will be. The purpose of the present report is to review the current state-of-the-art of mitral valve intervention, and to identify the potential future scenarios, which might benefit most from the transcatheter repair and replacement devices under development.
Assuntos
Cateterismo Cardíaco/métodos , Implante de Prótese de Valva Cardíaca/métodos , Anuloplastia da Valva Mitral/métodos , Insuficiência da Valva Mitral/cirurgia , Anticoagulantes/uso terapêutico , Bioprótese , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/tendências , Ecocardiografia , Desenho de Equipamento , Fluoroscopia , Previsões , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/tendências , Humanos , Valva Mitral/fisiologia , Anuloplastia da Valva Mitral/instrumentação , Anuloplastia da Valva Mitral/tendências , Insuficiência da Valva Mitral/fisiopatologia , Função Ventricular Esquerda/fisiologiaRESUMO
OBJECTIVES: The impact of patient-prosthesis mismatch (PPM) after aortic valve replacement (AVR) on short-term and long-term mortality remains controversial. The objective of this study was to evaluate the incidence and severity of PPM and its impact on short-term survival in a large cohort of patients treated with isolated stented biological AVR in a single institution. METHODS: We analyzed retrospectively data of 632 consecutive patients with aortic stenosis undergoing isolated stented biological AVR between January 2007 and February 2012 at our institution. PPM was defined as an indexed effective orifice area ≤ 0.85 cm(2)/m(2). Statistical analyses were performed to identify influencing variables on valve size implanted. RESULTS: Of the 632 patients investigated, 46% were females and mean age was 71.9 ± 10.4 years. PPM was observed in 93.8% (593 of 632 patients). In 71% of the patients, moderate (0.65-0.85 cm(2)/m(2)) PPM was present and in 22.8% severe (< 0.65 cm(2)/m(2)) PPM was present. The 30-day mortality was 1.4% (9 of 632 patients) with all being females. PPM was not associated with increased 30-day mortality. Multiple regression analyses demonstrated the usefulness of sex, height, body mass index, and body surface area as simultaneous predictors of the valve size implanted (R(2)= 0.39). CONCLUSION: PPM had no discernable impact on short-term survival, although it was present in 93.8% of our patients following isolated stented biological AVR.
Assuntos
Valva Aórtica/cirurgia , Bioprótese , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Desenho de Prótese , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/fisiopatologia , Feminino , Alemanha , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/mortalidade , Doenças das Valvas Cardíacas/fisiopatologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Hemodinâmica , Humanos , Masculino , Seleção de Pacientes , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Introduction: Transcatheter mitral valve replacement (TMVR) is a valuable treatment option in patients with severe mitral regurgitation. Prior transapical transcatheter aortic valve replacement (TA-TAVR) may complicate the procedure and is therefore considered a relative contraindication. In this case report, the authors describe the successful TMVR as a tertiary cardiac surgery and transapical redo procedure. Case Summary: An 83-year-old male patient, suffering from dyspnoea and angina, was diagnosed with severe mitral valve regurgitation (MR). He had already undergone cardiac surgery in the form of coronary artery bypass grafting at the age of 64 and TA-TAVR at 79 years. After a failed attempt at mitral valve transcatheter edge-to-edge repair, he opted for TMVR. Pre-TMVR computed tomography simulation was used to analyse possible interactions between the prostheses and to predict the neo-left ventricular outflow tract (neo-LVOT). The operation was carried out without complications. There was no bleeding and the LV function remained unchanged. On MRI, the valves were perfectly aligned without any signs of paravalvular leakage or LVOT obstruction. The patient was discharged seven days postoperatively. At the one-year follow up, there was no need for rehospitalisation and the patient had clinically improved (from NYHA IV to II). Echocardiography demonstrated a mean transvalvular gradient of under 5 mmHg and no residual MR. Conclusion: A redo transapical access for TMVR as a tertiary cardiac operation can be easily performed. Pre-operative CT suggested good alignment of the aortic and mitral valved stent which was confirmed postoperatively.
RESUMO
BACKGROUND: TAVI indications expand not only to low-risk patients but also to patients with a more complex anatomy and comorbidities. Transfemoral retrograde access is recognized as the first preferred approach according to the current guidelines. However, this approach is not suitable in up to 10-15% of patients, for whom an alternative non-femoral access route is required. CASE PRESENTATION: An 83-year-old male patient with known aortic isthmus stenosis presented with severe symptomatic aortic stenosis. Computed tomography revealed a subtotal isthmus stenosis, directly after left subclavian artery origin, with many collaterals extending toward the axillary and subclavian arteries. Duplex ultrasound verified the proximal diameter of the left brachial artery to be 5.5 mm. A successful surgical cutdown trans-brachial TAVI with an Evolut prosthetic valve with a size of 29 mm was performed. On the fourth postoperative day, the patient was discharged, and the three-month follow-up was uneventful. CONCLUSION: In patients with aortic isthmus stenosis, the brachial artery could be a feasible alternative, as a less invasive access site, which can be determined after careful assessment of the vessel diameter. More data are required to evaluate the safety and efficacy of this access route and to achieve more technical improvements to increase operator familiarity with it.
RESUMO
BACKGROUND: The etiology of transcatheter aortic valve (TAV) degeneration is poorly understood, particularly noncalcific mechanisms. OBJECTIVES: The authors sought to investigate noncalcific and calcific mechanisms of TAV degeneration and evaluate their impact on leaflet function by bench testing, imaging, and histology. METHODS: TAV explants were obtained from the EXPLANT THV registry and clinical institutions. Hydrodynamic assessment was performed using a heart valve pulse duplicator system under physiological conditions. Micro-computed tomography, high-resolution photography, high speed video, and hematoxylin and eosin staining were used to evaluate the morphological appearance, leaflet kinematics, and calcium burden of TAVs. RESULTS: A total of 14 explants were evaluated: 10 self-expanding CoreValve/Evolut TAVs (Medtronic), 3 balloon-expandable SAPIEN 3 TAVs (Edwards Lifesciences), and 1 mechanically expandable Lotus TAV (Boston Scientific). The median patient age at explantation was 73.0 years (Q1-Q3: 64.5-80.0 years), with a time to explantation of 4 years 1 month (1 year 5 months to 4 years 11 months). Six TAV explants were found to have leaflet calcification (162.4 mm3; 58.8-603.0 mm3), and 8 had no calcification detectable by micro-computed tomography and histology. All samples had impaired leaflet kinematics. There was no significant difference in the hydrodynamic mean gradient between calcified (47.2 mm Hg; 26.6-74.1 mm Hg) and noncalcified (27.6 mm Hg; 15.2-36.7 mm Hg; P = 0.28) TAVs. Leaflet calcification had a weak but nonsignificant association with the hydrodynamic mean gradient (r = 0.42; P = 0.14). CONCLUSIONS: TAV function can be severely impacted by noncalcific and calcific mechanisms of tissue degeneration. Importantly, functional stenosis can occur in TAVs in the absence of obvious and significant calcification.
Assuntos
Valva Aórtica , Calcinose , Próteses Valvulares Cardíacas , Hidrodinâmica , Desenho de Prótese , Falha de Prótese , Sistema de Registros , Substituição da Valva Aórtica Transcateter , Microtomografia por Raio-X , Humanos , Idoso , Valva Aórtica/fisiopatologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Valva Aórtica/patologia , Calcinose/fisiopatologia , Calcinose/diagnóstico por imagem , Calcinose/patologia , Calcinose/cirurgia , Feminino , Idoso de 80 Anos ou mais , Masculino , Substituição da Valva Aórtica Transcateter/instrumentação , Substituição da Valva Aórtica Transcateter/efeitos adversos , Pessoa de Meia-Idade , Fatores de Tempo , Remoção de Dispositivo , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Hemodinâmica , Fenômenos Biomecânicos , Teste de Materiais , Gravação em VídeoRESUMO
Background. The significance of concomitant tricuspid regurgitation (TR) in the context of transcatheter aortic valve replacement (TAVR) remains unclear. This study aimed to analyze the severity of TR before and after TAVR with regard to short- and long-term survival and to analyze the influencing factors. Methods. In our retrospective analysis, TR before and after TAVR was examined and patients were classified into groups accordingly. Special attention was paid to patients with post-interventional changes in TR. Mortality after TAVR was considered the primary endpoint of the analysis and major complications according to the Valve Academic Research Consortium 3 (VARC3) were compared. Moreover, biomarkers and risk factors for worsening or improvement of TR through TAVR were analyzed. Results. Among 775 patients who underwent TAVR in our center between January 2009 and December 2019, 686 patients (89%) featured low- and 89 patients (11%) high-grade TR. High-grade pre-TAVR TR was associated with worse short- (30-day), mid- (2-year) and long-term survival up to 8 years. Even though in nearly half of the patients with high-grade TR the regurgitation improved within seven days after TAVR (n = 42/89), this did not result in a survival benefit for this subgroup. On the other hand, a worsening of low-grade TR was seen in more than 10% of the patients (n = 73/686), which was also associated with a worse prognosis. Predictors of worsening of TR after TAVR were adipositas, impaired right ventricular function and the presence of mild TR. Age, atrial fibrillation, COPD, impaired renal function and elevated cardiac biomarkers were risk factors for mortality after TAVR independent from the grade of TR. Conclusions. Not only pre-interventional, but also post-TAVR high-grade TR is associated with a worse prognosis after TAVR. TAVR can change concomitant tricuspid regurgitation, but improvement does not have any impact on short- and long-term survival. Worsening of TR after TAVR is possible and impairs the prognosis.
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Rupture or dissection of thoracic aortic aneurysms is still the leading cause of death for patients diagnosed with Marfan syndrome. Inflammation and matrix digestion regulated by matrix metalloproteases (MMPs) play a major role in the pathological remodeling of the aortic media. Regnase-1 is an endoribonuclease shown to cleave the mRNA of proinflammatory cytokines, such as interleukin-6. Considering the major anti-inflammatory effects of regnase-1, here, we aimed to determine whether adeno-associated virus (AAV)-mediated vascular overexpression of the protein could provide protection from the development and progression of aortic aneurysms in Marfan syndrome. The overexpression of regnase-1 resulted in a marked decrease in inflammatory parameters and elastin degradation in aortic smooth muscle cells in vitro. Intravenous injection of a vascular-targeted AAV vector resulted in the efficient transduction of the aortic wall and overexpression of regnase-1 in a murine model of Marfan syndrome, associated with lower circulating levels of proinflammatory cytokines and decreased MMP expression and activity. Regnase-1 overexpression strongly improved elastin architecture in the media and reduced aortic diameter at distinct locations. Therefore, AAV-mediated regnase-1 overexpression may represent a novel gene therapy approach for inhibiting aortic aneurysms in Marfan syndrome.
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BACKGROUND: It is still controversial as to which cannulation strategy for acute type A aortic dissection (AAD) is optimal. Antegrade perfusion to diminish further organ malperfusion and ischemia is preferable. METHODS: We retrospectively analyzed a total of 420 patients who underwent AAD surgery from January 2001 to December 2020. Group A included 229 patients with a transatrial cannulation; group B included 191 patients with all other additionally used cannulation sites. A retrospective analysis was conducted at 30 days and according to clinical outcome and midterm mortality. Risk factors for probability of death were analyzed by multifactorial logistic regression. RESULTS: The calculated risk scores and demographic preoperative variables were comparable except for hyperlipoproteinemia (P = .011) and redo operation in group B (P < .001) and more pericardial tamponade in group A (P = .006). In addition, fewer patients with postoperative new onset of renal failure were observed in group A (P = .039), although new onset of dialysis was not different between the groups (P = .878). Patients in group A were discharged from the hospital significantly earlier (P = .004). Nevertheless, although significantly more total arch surgery was performed in group A, shorter operation times (P < .001) and lower transfusion rates were observed in group A. Patients' follow-up after a median time of 3.6 (0.6-7.6) years showed no difference in 30-day, 1-year, and long-term mortality. Multivariate logistic regression revealed aortic valve stenosis (P = .041), coronary artery bypass graft surgical procedures (P = .014), preoperative cardiopulmonary resuscitation (P < .001), and length of surgery (P = .032) as the strongest risk factors for mortality. CONCLUSIONS: Transatrial cannulation for AAD operation was safe and successfully performed under emergent conditions. Although no benefit in mortality was achieved, clinical benefits of shorter operation times, less transfusion, better kidney preservation, and earlier discharge of the patient were observed.
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Dissecção Aórtica , Ventrículos do Coração , Humanos , Estudos Retrospectivos , Seguimentos , Cateterismo/métodos , Dissecção Aórtica/cirurgiaRESUMO
OBJECTIVE: Outcomes after surgical aortic root replacement using different valved conduits are rarely reported. The present study shows the experience of a single center with the use of the partially biological LABCOR (LC) conduit and the fully biological BioIntegral (BI) conduit. Special attention was paid to preoperative endocarditis. METHODS: All 266 patients who underwent aortic root replacement by an LC conduit (n = 193) or a BI conduit (n = 73) between 01/01/2014 and 31/12/2020 were studied retrospectively. Dependency on an extracorporeal life support system preoperatively and congenital heart disease were exclusion criteria. For patients with (n = 67) and without (n = 199) preoperative endocarditis subanalyses were made. RESULTS: Patients treated with a BI conduit were more likely to have diabetes mellitus (21.9 vs. 6.7%, p < 0.001), previous cardiac surgery (86.3 vs. 16.6%; p < 0.001), permanent pacemaker (21.9 vs. 2.1%; p < 0.001), and had a higher EuroSCORE II (14.9 vs. 4.1%; p < 0.001). The BI conduit was used more frequently for prosthetic endocarditis (75.3 vs. 3.6%; <0.001), and the LC conduit was used predominantly for ascending aortic aneurysms (80.3 vs. 41.1%; <0.001) and Stanford type A aortic dissections (24.9 vs. 9.6%; p = 0.006). The LC conduit was used more often for elective (61.7 vs. 47.9%; p = 0.043) and emergency (27.5 vs. 15.1%; p = 0-035) surgeries, and the BI conduit for urgent surgeries (37.0 vs. 10.9%; p < 0.001). Conduit sizes did not differ significantly, with a median of 25 mm in each case. Surgical times were longer in the BI group. In the LC group, coronary artery bypass grafting and proximal or total replacement of the aortic arch were combined more frequently, whereas in the BI group, partial replacement of the aortic arch were combined. In the BI group, ICU length of stay and duration of ventilation were longer, and rates of tracheostomy and atrioventricular block, pacemaker dependence, dialysis, and 30-day mortality were higher. Atrial fibrillation occurred more frequently in the LC group. Follow-up time was longer and rates of stroke and cardiac death were less frequent in the LC group. Postoperative echocardiographic findings at follow-up were not significantly different between conduits. Survival of LC patients was better than that of BI patients. In the subanalysis of patients with preoperative endocarditis, significant differences between the used conduits were found with respect to previous cardiac surgery, EuroSCORE II, aortic valve and prosthesis endocarditis, elective operation, duration of operation, and proximal aortic arch replacement. For patients without preoperative endocarditis, significant differences were observed concerning previous cardiac surgery, pacemaker implantation history, duration of procedure, and bypass time. The Kaplan-Meier curves for the subanalyses showed no significant differences between the used conduits. CONCLUSIONS: Both biological conduits studied here are equally suitable in principle for complete replacement of the aortic root in all aortic root pathologies. The BI conduit is often used in bail-out situations, especially in severe endocarditis, without being able to show a clinical advantage over the LC conduit in this context.
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Introduction: Unilateral pulmonary edema (UPE) is a potential complication after mitral valve surgery (MVS), and its cause is not yet fully understood. Definitions are inconsistent, and previous studies have reported wide variance in the incidence of UPE. This research aims at the evaluation of the Radiographic Assessment of Lung Edema (RALE) score concerning assessment of UPE after MVS in order to provide an accurate and consistent definition of this pathology. Methods and Results: Postoperative chest X-ray images of 676 patients after MVS (minimally invasive MVS, n = 434; conventional MVS, n = 242) were retrospectively analyzed concerning presence of UPE. UPE was diagnosed only after exclusion of other pathologies up until the eighth postoperative day. RALE values were calculated for each patient. ROC analysis was performed to assess diagnostic performance. UPE was diagnosed in 18 patients (2.8%). UPE occurred significantly more often in the MI-MVS group (p = 0.045; MI-MVS n = 15; C-MVS n = 3). Postoperative RALE values for the right hemithorax (Q1 + Q2) > 12 and the right-to-left RALE difference ((Q1 + Q2) - (Q3 + Q4)) > 13 provide a sensitivity of up to 100% and 94.4% and a specificity of up to 88.4% and 94.2% for UPE detection. Conclusion: The RALE score is a practical tool for assessment of chest X-ray images after MVS with regard to UPE and provides a clear definition of UPE. In addition, it enables objective comparability when assessing of the postoperative course. The given score thresholds provide a sensitivity and specificity of up to 94%. Further, UPE after MVS seems to be a rather rare pathology with an incidence of 2.6%.