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1.
N Engl J Med ; 382(2): 111-119, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31733181

RESUMO

BACKGROUND: The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial. METHODS: In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up. RESULTS: In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years. CONCLUSIONS: Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Tratamento Conservador , Idoso , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/terapia , Doenças Assintomáticas/terapia , Doenças Cardiovasculares/mortalidade , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Complicações Pós-Operatórias/mortalidade
2.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(10): 806-813, 2019 Oct 24.
Artigo em Chinês | MEDLINE | ID: mdl-31648463

RESUMO

Objective: To analyze the clinical features and summarize the experience on the diagnosis and treatment of aortic stenosis caused by Takayasu arteritis in pediatric patients. Methods: This study was a retrospective study. Five pediatric patients diagnosed as aortic stenosis caused by Takayasu arteritis in Fuwai Hospital of Chinese Academy of Medical Sciences from January 2016 to August 2018 were included. The clinical features, methods of examination, treatment and outcome were analyzed. Results: There were 2 male and 3 female patients in this cohort. The age of onset ranged from 10 to 13 years. The main clinical symptoms were as follows: intermittent claudication and hypertension (5 patients), heart failure (3 patients). Three patients with heart failure were misdiagnosed with dilated cardiomyopathy in other hospitals. Except 1 patient died due to disease aggravation before operation, the other 4 patients received interventional therapy for severe heart failure or refractory hypertension on the basis of hormone anti-inflammatory treatment, including 2 patients treated with aortic balloon dilatation and 2 patients treated with aortic balloon dilatation and stent implantation. In post-operational follow-up, clinical symptoms and laboratory examination values of the 4 patients treated with interventional therapy were significantly improved. Conclusions: The clinical symptoms of pediatric patients with aortic stenosis caused by Takayasu arteritis mainly present with intermittent claudication, hypertension and heart failure. Aortic intervention strategy should be applied for pediatric patients with severe heart failure or refractory hypertension as early as possible.


Assuntos
Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/terapia , Arterite de Takayasu/complicações , Adolescente , Estenose da Valva Aórtica/etiologia , Criança , Feminino , Humanos , Hipertensão , Masculino , Estudos Retrospectivos
3.
Int. j. cardiovasc. sci. (Impr.) ; 32(5): 492-504, Sept-Oct. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1040093

RESUMO

Transcatheter aortic valve implantation (TAVI) has become a therapeutic option for high-risk or non-operable patients with severe symptomatic aortic stenosis. Atrioventricular conduction disturbances requiring permanent pacemaker (PPM) are a common and clinically important complication. Objectives: To evaluate the incidence of conduction disorders (CDs) after TAVI and the need for subsequent PPM implantation. To identify the predictors of postoperative PPM implantation. Methods: Retrospective study. All patients who underwent TAVI in a public hospital from December/2011 to June/2016 were included. Multivariate analysis was conducted to establish the predictor of permanent pacemaker implantation. Survival curves were constructed by the Kaplan-Meyer method. Statistically significant variables were those with p value < 0.05. Results: 64 patients with AS underwent TAVI. Eleven patients were excluded. TAVI induced a new CD in 40 (77%) of the remaining 53 patients. The most common new CDs were 3rd degree AV block (32%) and left bundle branch block (30%). Sixteen patients (30,2%) underwent PPM implantation during the index hospitalization. On univariate analysis the risk factors for PPM implantation were CoreValve® use (OR: 1,76; P = 0,005), larger prosthesis implantation (P = 0,015), presence of a QRS ≥ 120 ms (OR: 5,62; P = 0,012), and 1st degree AV block (OR: 13; P = 0.008). On multivariate analysis the presence of 1st degree AV block predicted the need for PPM. Conclusion: TAVI induced CDs requiring PPM in 30% of the patients. The presence of 1st degree AV block predicted the need for PPM


Assuntos
Humanos , Masculino , Feminino , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/terapia , Marca-Passo Artificial , Bloqueio de Ramo , Substituição da Valva Aórtica Transcateter/métodos , Valva Aórtica , Volume Sistólico , Ecocardiografia/métodos , Análise Estatística , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Bloqueio Atrioventricular
4.
An Sist Sanit Navar ; 42(2): 199-208, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31317953

RESUMO

Aortic stenosis is one of the most common heart valve diseases, as well as one of the most common causes of heart failure in the elderly. Currently, there are no medical therapies to prevent or slow the progression of the disease. When symptoms develop alongside severe aortic stenosis, there is a poor prognosis unless aortic valve replacement is performed. Aortic stenosis is a heterogeneous disease with a complex pathophysiology involving structural and biological changes of the valve, as well as adaptive and maladaptive compensatory changes in the myocardium and vasculature in response to chronic pressure overload. Galectin-3 serves important functions in numerous biological activities including cell growth, apoptosis, differentiation, inflammation and fibrosis. With evidence emerging to support the function of Galectin-3, the current review aims to summarize the latest literature regarding the potential of Galectin-3 as therapeutic target in aortic valve and cardiovascular alterations associated with aortic stenosis.


Assuntos
Estenose da Valva Aórtica/terapia , Galectina 3/metabolismo , Idoso , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/fisiopatologia , Progressão da Doença , Insuficiência Cardíaca/etiologia , Humanos , Prognóstico , Índice de Gravidade de Doença
5.
Heart Lung Circ ; 28(9): 1310-1319, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31266725

RESUMO

Degenerative or fibrocalcific aortic stenosis (AS) is now the most common native valvular heart disease assessed and managed by cardiologists in developed countries. Transthoracic echocardiography remains the quintessential imaging modality for the non-invasive characterisation of AS due to its widespread availability, superior assessment of flow haemodynamics, and a wealth of prognostic data accumulated over decades of clinical utility and research applications. With expanding technologies and increasing availability of treatment options such as transcatheter aortic valve replacements, in addition to conventional surgical approaches, accurate and precise assessment of AS severity is critical to guide decisions for and timing of interventions. Despite clear guideline echocardiographic parameters demarcating severe AS, discrepancies between transvalvular velocities, gradients, and calculated valve areas are commonly encountered in clinical practice. This often results in diagnostically challenging cases with significant implications. Greater emphasis must be placed on the quality of performance of basic two dimensional (2D) and Doppler measurements (attention to detail ensuring accuracy and precision), incorporating ancillary haemodynamic surrogates, understanding study- or patient-specific confounders, and recognising the role and limitations of stress echocardiography in the subgroups of low-flow low-gradient AS. A multiparametric approach, along with the incorporation of multimodality imaging (cardiac computed tomography or magnetic resonance imaging) in certain scenarios, is now mandatory to avoid incorrect misclassification of severe AS. This is essential to ensure appropriate selection of patients who would most benefit from interventions on the aortic valve to relieve the afterload mismatch resulting from truly severe valvular stenosis.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Valva Aórtica/patologia , Calcinose/diagnóstico por imagem , Calcinose/fisiopatologia , Ecocardiografia sob Estresse , Ecocardiografia , Hemodinâmica , Imagem Multimodal , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/prevenção & controle , Estenose da Valva Aórtica/terapia , Calcinose/prevenção & controle , Calcinose/terapia , Humanos , Substituição da Valva Aórtica Transcateter
6.
Dtsch Med Wochenschr ; 144(11): 734-738, 2019 06.
Artigo em Alemão | MEDLINE | ID: mdl-31163471

RESUMO

There is growing understanding to recognize the aorta as complex system and treat aortic diseases in an integrated fashion.The indication for interventional aortic valve replacement (TAVR) comprises patients with moderate and high perioperative risk and symptomatic, high grade aortic valve stenosis. In contrast "low risk" patients receive conventional therapy. Ongoing randomised trials analyse the expansion of indication towards low risk patients for interventional approaches. A final rating is owing, but first data support the assumption that both therapeutic options may be equivalent. Moreover, the interventional therapy of low flow, low gradient aortic valve stenosis has been revalued and interventional valve-in-valve therapy has been integrated into clinical routine as invidualised decision of the heart team.Aortic diseases include several entities which require specialised diagnostic and therapeutic tools. Studies to evaluate evidence of follow up options need to be performed in future to enable for surveillance tailored to suit medical need.


Assuntos
Doenças da Aorta , Estenose da Valva Aórtica , Aorta/fisiopatologia , Doenças da Aorta/diagnóstico , Doenças da Aorta/fisiopatologia , Doenças da Aorta/terapia , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/terapia , Humanos
7.
Bratisl Lek Listy ; 120(6): 462-467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223028

RESUMO

BACKGROUND: The purpose of this study is to report our experience in performing transapical (TA) TAVR with a balloon-expandable valve only by cardiac surgeons, with on site interventional cardiology support. METHODS: A retrospective review of 97 consecutive patients that underwent TA TAVR due to severe symptomatic aortic stenosis was performed from 2012 to 2016. Median follow-up time was 20.5 months. Preoperative risk factors and postoperative outcomes were evaluated using Valve Academic Research Consortium-2 definitions. RESULTS: All patients were high risk with a mean Euroscore of 7.28±7.77. Five year and 30-day mortality were 9.3 % and 1.1 %, respectively. Ninty six (98.9 %) of the patients had no or mild paravalvular leak seen by transesophageal echocardiography after implantation. Device success was 91.8%. Postoperatively there was a significant increase of the ejection fraction (50.8±7.1 % preoperatively vs 53.1±7.7 % postoperatively, p=0.009) and reverse remodeling of the left ventricle (left ventricular end-diastolic diameter preoperatively 50.8±7.1 mm vs 49.2±8.1 mm postoperatively, p=0.031). CONCLUSION: Our experience demonstrates that TA TAVR can be performed only by cardiac surgeons, with on site interventional cardiology support safely and successfully with low and comparable postoperative mortality and rate of complications (Tab. 4, Fig. 1, Ref. 26).


Assuntos
Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Estenose da Valva Aórtica/terapia , Cateterismo Cardíaco , Humanos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
8.
EuroIntervention ; 15(6): e500-e507, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31113766

RESUMO

AIMS: The aim of this study was to compare the risk of prosthetic valve endocarditis (PVE) in patients with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). METHODS AND RESULTS: The FinnValve registry included data from 6,463 consecutive patients who underwent TAVR (n=2,130) or SAVR (n=4,333) with a bioprosthesis from 2008 to 2017. PVE was defined according to the modified Duke criteria. In this study, the incidence of PVE was 3.4/1,000 person-years after TAVR, and 2.9/1,000 person-years after SAVR. In competing risk analysis there was no significant difference in the risk of PVE between patients with TAVR and SAVR over an eight-year observational period. Male gender (HR 1.73, 95% CI: 1.04-2.89) and deep sternal wound infection or vascular access-site infection (HR 5.45, 95% CI: 2.24-13.2) were positively associated with PVE, but not type of procedure (HR 1.09, 95% CI: 0.59-2.01) in multivariate analysis. The mortality rate was 37.7% at one month and increased to 52.5% at one year. Surgical treatment was independently associated with decreased in-hospital mortality (HR 0.34, 95% CI: 0.21-0.61). CONCLUSIONS: PVE is rare, and its risk is similar after TAVR and SAVR. ClinicalTrials.gov Identifier: NCT03385915. https://clinicaltrials.gov/ct2/show/NCT03385915.


Assuntos
Estenose da Valva Aórtica/terapia , Valva Aórtica/cirurgia , Bioprótese , Endocardite/etiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Substituição da Valva Aórtica Transcateter , Estenose da Valva Aórtica/fisiopatologia , Endocardite/epidemiologia , Humanos , Masculino , Sistema de Registros , Resultado do Tratamento
9.
Int Heart J ; 60(3): 768-771, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31019171

RESUMO

A 91-year-old woman was admitted to our hospital for treatment of congestive heart failure with severe aortic stenosis. After admission, she developed a high fever due to pneumonia and worsened heart failure. We could not perform transcatheter aortic valve implantation (TAVI) because of active infection; therefore, retrograde balloon aortic valvuloplasty (BAV) was urgently performed. A complete atrioventricular block and severe functional mitral regurgitation appeared suddenly after BAV in the absence of mechanical disorders. Her condition improved after several days in our intensive care unit. Pacemaker implantation and TAVI were then performed, and the patient was discharged from our hospital. MR could sometimes exacerbate after BAV in clinical practice; therefore, we set out to report this case.


Assuntos
Estenose da Valva Aórtica/complicações , Bloqueio Atrioventricular/diagnóstico , Valvuloplastia com Balão/efeitos adversos , Insuficiência da Valva Mitral/diagnóstico , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/terapia , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/fisiopatologia , Feminino , Humanos , Insuficiência da Valva Mitral/etiologia , Marca-Passo Artificial/normas , Substituição da Valva Aórtica Transcateter/métodos , Resultado do Tratamento
10.
Rev. chil. cardiol ; 38(1): 64-67, abr. 2019. ilus
Artigo em Espanhol | LILACS | ID: biblio-1003639

RESUMO

Abstracts: Successful treatment following percutaneous angioplasty (PTCA) and percutaneous trans aortic valve aortic valve stenosis and critical obstruction of the main left coronary artery is presented. Due to a very high estimated surgical risk the patient underwent PTCA of the main left trunk followed, a week later, by trans catheter implantation of an aortic valve (TAVI). The procedure was uneventful, and the clinical condition of the patient was excellent at one year (Functional class I).


Assuntos
Humanos , Masculino , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/terapia , Intervenção Coronária Percutânea/métodos , Substituição da Valva Aórtica Transcateter , Valva Aórtica/transplante , Próteses Valvulares Cardíacas , Stents , Implante de Prótese de Valva Cardíaca
11.
Cardiovasc Interv Ther ; 34(4): 352-357, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30847654

RESUMO

This study aimed to investigate the efficacy of percutaneous transcatheter aortic valvuloplasty (PTAV) performed prior to non-cardiac surgery and the safety of non-cardiac surgery after PTAV in elderly Japanese patients. Between March 2012 and August 2018, 14 patients who underwent PTAVs prior to non-cardiac surgery were enrolled. The mean age was 82.2 ± 7.0 years. A total of 9 patients (64.3%) were women. A retrograde approach was selected for 57.1% of the patients. More than 75% of the procedures were performed using echocardiographic imaging. Echocardiographic data including the aortic valve area (AVA), peak aortic valve blood velocity flow (AVF), peak aortic valve pressure gradient (AVPG), and mean AVPG significantly improved after PTAV (AVA; from 0.54 ± 0.11 to 0.80 ± 0.13 cm2, peak AVF; from 4.6 ± 0.8 to 3.8 ± 0.7 m/s, peak AVG; from 87.9 ± 28.0 to 62.2 ± 19.9 mmHg, mean AVG; from 49.8 ± 18.9 to 35.7 ± 11.6 mmHg; p < 0.001, p < 0.001, p < 0.001, p = 0.0012, respectively). Neither complications related to the PTAV procedure nor procedural mortality were noted. Non-cardiac surgery after PTAV was safely performed; there were no significant adverse events during non-cardiac surgery and no in-hospital mortality occurred after non-cardiac surgery. PTAV prior to non-cardiac surgery in elderly Japanese patients with severe aortic stenosis is safe and effective. In addition, non-cardiac surgery after PTAV can be safety performed without adverse events.


Assuntos
Estenose da Valva Aórtica/terapia , Valvuloplastia com Balão/métodos , Procedimentos Cirúrgicos Operatórios , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Ecocardiografia , Feminino , Humanos , Japão , Masculino , Cuidados Pré-Operatórios , Ultrassonografia de Intervenção
12.
JACC Cardiovasc Imaging ; 12(2): 236-248, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30732719

RESUMO

OBJECTIVES: This study sought to build a patient-patient similarity network using multiple features of left ventricular (LV) structure and function in patients with aortic stenosis (AS). The study further validated the observations in an experimental murine model of AS. BACKGROUND: The LV response in AS is variable and results in heterogeneous phenotypic presentations. METHODS: The patient similarity network was developed using topological data analysis (TDA) from cross-sectional echocardiographic data collected from 246 patients with AS. Multivariate features of AS were represented on the map, and the network topology was compared with that of a murine AS model by imaging 155 animals at 3, 6, 9, or 12 months of age. RESULTS: The topological map formed a loop in which patients with mild and severe AS were aggregated on the right and left sides, respectively (p < 0.001). These 2 regions were linked through moderate AS; with upper arm of the loop showing patients with predominantly reduced ejection fractions (EFs), and the lower arm showing patients with preserved EFs (p < 0.001). The region of severe AS showed >3 times the increased risk of balloon valvuloplasty, and transcatheter or surgical aortic valve replacement (hazard ratio: 3.88; p < 0.001) compared with the remaining patients in the map. Following aortic valve replacement, patients recovered and moved toward the zone of mild and moderate AS. Topological data analysis in mice showed a similar distribution, with 1 side of the loop corresponding to higher peak aortic velocities than the opposite side (p < 0.0001). The validity of the cross-sectional data that revealed a path of AS progression was confirmed by comparing the locations occupied by 2 groups of mice that were serially imaged. LV systolic and diastolic dysfunction were frequently identified even during moderate AS in both humans and mice. CONCLUSIONS: Multifeature assessments of patient similarity by machine-learning processes may allow precise phenotypic recognition of the pattern of LV responses during the progression of AS.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Idoso , Idoso de 80 Anos ou mais , Animais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/terapia , Valvuloplastia com Balão , Estudos Transversais , Modelos Animais de Doenças , Progressão da Doença , Feminino , Implante de Prótese de Valva Cardíaca , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo , Função Ventricular Esquerda
13.
Trends Pharmacol Sci ; 40(3): 212-225, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30732864

RESUMO

Interest in lipoprotein (a) [Lp(a)] has exploded over the past decade with the emergence of genetic and epidemiological studies pinpointing elevated levels of this unique lipoprotein as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). This review summarizes the most recent discoveries regarding therapeutic approaches to lower Lp(a) and presents these findings in the context of an emerging, although far from complete, understanding of the biosynthesis and catabolism of Lp(a). Application of Lp(a)-specific lowering agents to outcome trials will be the key to opening this new frontier in the battle against CVD.


Assuntos
Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/terapia , Valva Aórtica/patologia , Aterosclerose/sangue , Aterosclerose/terapia , Calcinose/sangue , Calcinose/terapia , Lipoproteína(a)/sangue , Animais , Valva Aórtica/efeitos dos fármacos , Estenose da Valva Aórtica/genética , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Calcinose/genética , Humanos , Lipoproteína(a)/genética , Terapia de Alvo Molecular
14.
Circ Res ; 124(3): 405-415, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30702993

RESUMO

The prevalence of calcific aortic valve disease is increasing with aging of the population. Current treatment options for advanced or symptomatic aortic stenosis are limited to traditional surgical or percutaneous aortic valve replacement. Medical therapies that impact the progression of calcific aortic valve disease do not currently exist. New pathophysiological insights suggest that the processes leading to calcific aortic valve disease are metabolically active for many years before and during the clinical expression of disease. The identification of genetic and potentially causal mediators of calcific aortic valve disease allows opportunities for therapies that may slow progression to the point where aortic valve replacement can be avoided. Recent studies suggest that approximately one-third of aortic stenosis cases are associated with highly elevated lipoprotein(a) [Lp(a)] and pathways related to the metabolism of procalcifying oxidized phospholipids. Oxidized phospholipids can be carried by Lp(a) into valve leaflets but can also be formed in situ from cell membranes, lipoproteins, and apoptotic cells. This review will summarize the clinical data implicating the potential causality of Lp(a)/oxidized phospholipids, describe emerging therapeutic agents, and propose clinical trial designs to test the hypothesis that lowering Lp(a) will reduce progression aortic stenosis and the need for aortic valve replacement.


Assuntos
Estenose da Valva Aórtica/terapia , Calcinose/terapia , Hiperlipoproteinemias/complicações , Lipoproteína(a) , Fosfolipídeos/metabolismo , Estenose da Valva Aórtica/etiologia , Calcinose/etiologia , Causalidade , Ensaios Clínicos como Assunto , Implante de Prótese de Valva Cardíaca , Humanos , Oxirredução , Fatores de Risco
15.
Biomed Mater ; 14(3): 035014, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30769335

RESUMO

INTRODUCTION: Calcific aortic valve disease (CAVD) is the most common acquired heart valve disease with complex underlying pathomechanisms that are yet not fully understood. Three-dimensional (3D) cell culture models as opposed to conventional two-dimensional (2D) techniques may reveal new aspects of CAVD and serve as a transitional platform between conventional 2D cell culture and in vivo experiments. METHODS: Here we report on fabrication and characterization of a novel 3D hydrogel derived from cell-free native aortic valves. A detailed analysis containing protein composition, rheological behavior, cytotoxic and proliferative effects as well as results of 3D cell culture experiments are presented. Moreover, this aortic valve derived hydrogel (AVdH) is compared to commercially available biological extracellular matrix (ECM) components to evaluate and classify AVdH with respect to other currently used ECM solutions, i.e. Collagen type I and Matrigel®. RESULTS: On the biochemical level, a complex composition of native proteins was detected. Using different techniques, including mass spectrometry with Gene Ontology network and enrichment analysis, different fundamental biological functions of AVdH were identified, including peptidase-, peptidase inhibitor-, growth- and binding activity. No cytotoxic effects were detected and AVdH showed positive effects on cell growth and proliferation in vitro when compared to Collagen type I and Matrigel®. CONCLUSION: These results suggest AVdH as an organotypic ECM supporting sophisticated 3D cell culture model studies, while mimicking the native environment of the aortic valve to a greater level for enhanced in vitro analyses.


Assuntos
Valva Aórtica/fisiologia , Materiais Biomiméticos , Técnicas de Cultura de Células , Hidrogéis/química , Engenharia Tecidual/métodos , Animais , Valva Aórtica/patologia , Estenose da Valva Aórtica/terapia , Calcinose/terapia , Proliferação de Células , Sistema Livre de Células , Colágeno/química , Combinação de Medicamentos , Matriz Extracelular/química , Doenças das Valvas Cardíacas/terapia , Cinética , Laminina/química , Proteoglicanas/química , Reologia , Ovinos , Software
16.
JACC Cardiovasc Imaging ; 12(1): 163-171, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30621988

RESUMO

Left ventricular (LV) systolic dysfunction is an adverse consequence of the pressure overload of severe aortic stenosis (AS). The enlargement of the interstitial space with reactive fibrosis and subsequently with replacement fibrosis and cell death has been suggested to be the main driver of the transition to symptoms, heart failure, and adverse cardiovascular events even after aortic valve replacement (AVR). Early and accurate recognition of myocardial dysfunction offers the potential to optimize the timing of intervention in severe AS. In the asymptomatic patient, an LV ejection fraction (EF) cutpoint of <50% has been used for this purpose. However, in most asymptomatic patients, an LVEF <50% is uncommon, and patients with an LVEF of 50% to 59% fare almost as badly. Moreover, the presence of a small LV cavity, the reliability and automation of the global longitudinal strain (GLS) signal, and the independent prognostic role of GLS are reasons why GLS could be expected to be a better marker of subclinical LV dysfunction in these patients. This review seeks to define whether the existing EF cutoff in AS should be modified or whether GLS should replace it as the marker of subclinical LV dysfunction.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Idoso , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/terapia , Doenças Assintomáticas , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Sístole , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia
17.
JACC Cardiovasc Imaging ; 12(1): 172-184, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30621989

RESUMO

Clinical management of patients with only moderate aortic stenosis (AS) but symptoms of heart failure with a reduced left ventricular ejection fraction (HFrEF) is challenging. Current guidelines recommend clinical surveillance with multimodality imaging; aortic valve replacement (AVR) is deferred until the stenosis becomes severe. Given the known benefits of afterload reduction in management of patients with HFrEF, it has been hypothesized that AVR may be beneficial in patients with only moderate AS who present with HFrEF. In this article, we first review the current approach for management of patients with moderate AS and HFrEF based on close clinical and imaging surveillance with AVR delayed until AS is severe. We then discuss the case for transcatheter AVR (TAVR) earlier in the disease course, when AS is moderate, based on stress echocardiographic data. We conclude with a detailed summary of the TAVR UNLOAD (Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure) trial, in which patients with moderate AS and HFrEF are randomized to guideline-directed heart failure therapy alone versus guideline-directed heart failure therapy plus TAVR.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Tomada de Decisão Clínica , Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Volume Sistólico , Tomografia Computadorizada por Raios X , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/terapia , Ecocardiografia Doppler , Ecocardiografia sob Estresse , Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Imagem por Ressonância Magnética , Imagem Multimodal , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia
18.
JACC Cardiovasc Imaging ; 12(1): 185-197, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30621990

RESUMO

Aortic stenosis represents a growing health care burden in high-income countries. Currently, the only definitive treatment is surgical or transcatheter valve intervention at the end stages of disease. As the understanding of the underlying pathophysiology evolves, many promising therapies are being investigated. These seek to both slow disease progression in the valve and delay the transition from hypertrophy to heart failure in the myocardium, with the ultimate aim of avoiding the need for valve replacement in the elderly patients afflicted by this condition. Noninvasive imaging has played a pivotal role in enhancing our understanding of the complex pathophysiology underlying aortic stenosis, as well as disease progression in both the valve and myocardium. In this review, the authors discuss the means by which contemporary imaging may be used to assess disease progression and how these approaches may be utilized, both in clinical practice and research trials exploring the clinical efficacy of novel therapies.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/terapia , Tomada de Decisão Clínica , Progressão da Doença , Hemodinâmica , Humanos , Imagem Multimodal , Seleção de Pacientes , Valor Preditivo dos Testes
20.
JACC Cardiovasc Imaging ; 12(1): 84-92, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30621997

RESUMO

OBJECTIVES: In this individual participant data meta-analysis on left ventricular global longitudinal strain (LVGLS), our objective was to: 1) describe its distribution; 2) identify the most predictive cutoff values; and 3) assess its impact on mortality in asymptomatic patients with significant aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF). BACKGROUND: The evidence supporting the prognostic role of LVGLS in asymptomatic patients with AS has been obtained from several relatively small studies. METHODS: A literature search was performed for studies published between 2005 and 2017 without language restriction according to the following criteria: "aortic stenosis" AND "longitudinal strain." The corresponding authors of selected studies were contacted and invited to share their data that we computerized in a specific database. The primary endpoint was all-cause mortality. RESULTS: Among the 10 studies included, 1,067 asymptomatic patients with significant AS and LVEF >50% were analyzed. The median of LVGLS was 16.2% (from 5.6% to 30.1%). There were 91 deaths reported during follow-up with median of 1.8 (0.9 to 2.8) years, resulting in a pooled crude mortality rate of 8.5%. The LVGLS performed well in the prediction of death (area under the curve: 0.68). The best cutoff value identified was LVGLS of 14.7% (sensitivity, 60%; specificity, 70%). Using random effects model, the risk of death for patients with LVGLS <14.7% is multiplied by >2.5 (hazard ratio: 2.62; 95% confidence interval: 1.66 to 4.13; p < 0.0001), without significant heterogeneity between studies (I2 = 18.3%; p = 0.275). The relationship between LVGLS and mortality remained significant in patients with LVEF ≥60% (p = 0.001). CONCLUSIONS: This individual participant data meta-analysis demonstrates that in asymptomatic patients with significant AS and normal LVEF, impaired LVGLS is associated with reduced survival. These data emphasize the potential usefulness of LVGLS for risk stratification and management of these patients.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Contração Miocárdica , Volume Sistólico , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/terapia , Doenças Assintomáticas , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Estresse Mecânico
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