Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.198
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
Circulation ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101203

RESUMO

BACKGROUND: Previous transcatheter valve therapy registry analyses of transcatheter mitral valve in valve (MViV) replacement of degenerated bioprosthesis reported early experience in the United States. Given recent increases in transseptal MViV volumes and introduction of the SAPIEN 3 Ultra valve, it is important to determine contemporary outcomes for patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV replacement. METHODS: The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry was used to extract data for all patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV from 2015 to September 2022. Primary efficacy outcome was 1-year all-cause mortality. Secondary end points included 30-day mortality, functional class, quality of life, and mitral valve performance. Primary safety outcomes were device success and in-hospital complications. RESULTS: A total of 4243 patients with a mean STS score of 9.2±7.7 underwent transseptal MViV at 455 sites. The rate of Mitral Valve Academic Research Consortium technical (96.6%) success was high, and procedural complications were low. All-cause in-hospital, 30-day, and 1-year mortality rates were 3.2%, 4.3%, and 13.4%, respectively. Significant improvements in New York Heart Association class (New York Heart Association I/II, 18% to 87%) and quality of life (Kansas City Cardiomyopathy Questionnaire score, 38 to 78) were noted at 1 year (P<0.0001 for both) after MViV. Upon stratifying by STS scores, it was observed that the low-risk group (STS<4) had a significantly lower in-hospital mortality rate of 0.4%, whereas the intermediate-risk group (STS, 4-8) had an in-hospital mortality rate of 1.9%. From 2015 to 2022, the number of transseptal MViV cases/year increased significantly, whereas procedure times, length of stay, and intensive care unit hours shortened significantly. At the same time, there was a significant trend toward reduced in-hospital (P=0.0005), 30-day (P=0.004), and 1-year mortality rates (P=0.01). CONCLUSIONS: This multicenter, prospective study reports excellent procedural outcomes, 1-year mortality rates, and a significant improvement in quality of life for patients undergoing transseptal MViV in the contemporary era. Patients in the low-risk and intermediate-risk STS score categories had significantly better outcomes compared with those in the high-risk category. MViV is a reasonable therapy for the majority of patients with degenerated bioprosthetic mitral valves, who are anatomical candidates.

2.
Circulation ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39129623

RESUMO

BACKGROUND: Diagnosis of mitral regurgitation (MR) requires careful evaluation by echocardiography with Doppler imaging. This study presents the development and validation of a fully automated deep learning pipeline for identifying apical 4-chamber view videos with color Doppler echocardiography and detecting clinically significant (moderate or severe) MR from transthoracic echocardiograms. METHODS: A total of 58 614 transthoracic echocardiograms (2 587 538 videos) from Cedars-Sinai Medical Center were used to develop and test an automated pipeline to identify apical 4-chamber view videos with color Doppler across the mitral valve and then assess MR severity. The model was tested internally on a test set of 1800 studies (80 833 videos) from Cedars-Sinai Medical Center and externally evaluated in a geographically distinct cohort of 915 studies (46 890 videos) from Stanford Healthcare. RESULTS: In the held-out Cedars-Sinai Medical Center test set, the view classifier demonstrated an area under the curve (AUC) of 0.998 (0.998-0.999) and correctly identified 3452 of 3539 echocardiography videos as having color Doppler information across the mitral valve (sensitivity of 0.975 [0.968-0.982] and specificity of 0.999 [0.999-0.999] compared with manually curated videos). In the external test cohort from Stanford Healthcare, the view classifier correctly identified 1051 of 1055 manually curated videos with color Doppler information across the mitral valve (sensitivity of 0.996 [0.990-1.000] and specificity of 0.999 [0.999-0.999]). In the Cedars-Sinai Medical Center test cohort, MR moderate or greater in severity was detected with an AUC of 0.916 (0.899-0.932) and severe MR was detected with an AUC of 0.934 (0.913-0.953). In the Stanford Healthcare test cohort, the model detected MR moderate or greater in severity with an AUC of 0.951 (0.924-0.973) and severe MR with an AUC of 0.969 (0.946-0.987). CONCLUSIONS: In this study, a novel automated pipeline for identifying clinically significant MR from full transthoracic echocardiography studies demonstrated excellent performance across large numbers of studies and across multiple institutions. Such an approach has the potential for automated screening and surveillance of MR.

3.
Circulation ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38881496

RESUMO

BACKGROUND: Artificial intelligence, particularly deep learning (DL), has immense potential to improve the interpretation of transthoracic echocardiography (TTE). Mitral regurgitation (MR) is the most common valvular heart disease and presents unique challenges for DL, including the integration of multiple video-level assessments into a final study-level classification. METHODS: A novel DL system was developed to intake complete TTEs, identify color MR Doppler videos, and determine MR severity on a 4-step ordinal scale (none/trace, mild, moderate, and severe) using the reading cardiologist as a reference standard. This DL system was tested in internal and external test sets with performance assessed by agreement with the reading cardiologist, weighted κ, and area under the receiver-operating characteristic curve for binary classification of both moderate or greater and severe MR. In addition to the primary 4-step model, a 6-step MR assessment model was studied with the addition of the intermediate MR classes of mild-moderate and moderate-severe with performance assessed by both exact agreement and ±1 step agreement with the clinical MR interpretation. RESULTS: A total of 61 689 TTEs were split into train (n=43 811), validation (n=8891), and internal test (n=8987) sets with an additional external test set of 8208 TTEs. The model had high performance in MR classification in internal (exact accuracy, 82%; κ=0.84; area under the receiver-operating characteristic curve, 0.98 for moderate/severe MR) and external test sets (exact accuracy, 79%; κ=0.80; area under the receiver-operating characteristic curve, 0.98 for moderate or greater MR). Most (63% internal and 66% external) misclassification disagreements were between none/trace and mild MR. MR classification accuracy was slightly higher using multiple TTE views (accuracy, 82%) than with only apical 4-chamber views (accuracy, 80%). In subset analyses, the model was accurate in the classification of both primary and secondary MR with slightly lower performance in cases of eccentric MR. In the analysis of the 6-step classification system, the exact accuracy was 80% and 76% with a ±1 step agreement of 99% and 98% in the internal and external test set, respectively. CONCLUSIONS: This end-to-end DL system can intake entire echocardiogram studies to accurately classify MR severity and may be useful in helping clinicians refine MR assessments.

4.
Circulation ; 149(24): 1865-1874, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38690659

RESUMO

BACKGROUND: The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. METHODS: The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). CONCLUSIONS: Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Insuficiência Cardíaca , Insuficiência da Valva Mitral , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Insuficiência da Valva Mitral/tratamento farmacológico , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Masculino , Feminino , Idoso , Método Duplo-Cego , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Fragmentos de Peptídeos/sangue , Função Ventricular Esquerda/efeitos dos fármacos , Peptídeo Natriurético Encefálico
5.
Circulation ; 150(6): e109-e128, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38881493

RESUMO

Valvular heart disease is a common cause of morbidity and mortality worldwide and has no effective medical therapy. Severe disease is managed with valve replacement procedures, which entail high health care-related costs and postprocedural morbidity and mortality. Robust ongoing research programs have elucidated many important molecular pathways contributing to primary valvular heart disease. However, there remain several key challenges inherent in translating research on valvular heart disease to viable molecular targets that can progress through the clinical trials pathway and effectively prevent or modify the course of these common conditions. In this scientific statement, we review the basic cellular structures of the human heart valves and discuss how these structures change in primary valvular heart disease. We focus on the most common primary valvular heart diseases, including calcific aortic stenosis, bicuspid aortic valves, mitral valve prolapse, and rheumatic heart disease, and outline the fundamental molecular discoveries contributing to each. We further outline potential therapeutic molecular targets for primary valvular heart disease and discuss key knowledge gaps that might serve as future research priorities.


Assuntos
American Heart Association , Doenças das Valvas Cardíacas , Humanos , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/metabolismo , Estados Unidos , Animais
6.
Circ Res ; 133(6): 463-480, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37555328

RESUMO

BACKGROUND: Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known. METHODS: We used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from Prox1ΔVEC mice in which Prox1 was conditionally deleted from VECs. Isolated valve endothelial cells and valve interstitial cells were used to identify the molecular mechanisms in vitro, which were tested in vivo by RNAScope, additional mouse models, and pharmacological approaches. The significance of our findings was tested by evaluation of human samples of mitral valve prolapse and aortic valve insufficiency. RESULTS: Histological analysis revealed that the aortic and mitral valves of Prox1ΔVEC mice become progressively thick and myxomatous. Echocardiography revealed that the aortic valves of Prox1ΔVEC mice are stenotic. FOXC2 was downregulated and PDGF-B (platelet-derived growth factor-B) was upregulated in the VECs of Prox1ΔVEC mice. Conditional knockdown of FOXC2 and conditional overexpression of PDGF-B in VECs recapitulated the phenotype of Prox1ΔVEC mice. PDGF-B was also increased in mice lacking FOXC2 and in human mitral valve prolapse and insufficient aortic valve samples. Pharmacological inhibition of PDGF-B signaling with imatinib partially ameliorated the valve defects of Prox1ΔVEC mice. CONCLUSIONS: PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.


Assuntos
Doenças das Valvas Cardíacas , Prolapso da Valva Mitral , Animais , Humanos , Camundongos , Células Endoteliais/metabolismo , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/prevenção & controle , Doenças das Valvas Cardíacas/metabolismo , Valva Mitral/metabolismo , Prolapso da Valva Mitral/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Proto-Oncogênicas c-sis/metabolismo
7.
Arterioscler Thromb Vasc Biol ; 44(7): 1540-1554, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38660802

RESUMO

BACKGROUND: Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan syndrome includes valve leaflet thickening and progressive valve degeneration. However, the underlying mechanisms by which the disease progresses remain undefined. METHODS: Mice with Fibrillin 1 gene variant Fbn1C1039G/+ recapitulate histopathologic features of Marfan syndrome, and Wnt (Wingless-related integration site) signaling activity was detected in TCF/Lef-lacZ (T-cell factor/lymphoid enhancer factor-ß-galactosidase) reporter mice. Single-cell RNA sequencing was performed from mitral valves of wild-type and Fbn1C1039G/+ mice at 1 month of age. Inhibition of Wnt signaling was achieved by conditional induction of the secreted Wnt inhibitor Dkk1 (Dickkopf-1) expression in periostin-expressing valve interstitial cells of Periostin-Cre; tetO-Dkk1; R26rtTA; TCF/Lef-lacZ; Fbn1C1039G/+ mice. Dietary doxycycline was administered for 1 month beginning with MVD initiation (1-month-old) or MVD progression (2-month-old). Histological evaluation and immunofluorescence for ECM (extracellular matrix) and immune cells were performed. RESULTS: Wnt signaling is activated early in mitral valve disease progression, before immune cell infiltration in Fbn1C1039G/+ mice. Single-cell transcriptomics revealed similar mitral valve cell heterogeneity between wild-type and Fbn1C1039G/+ mice at 1 month of age. Wnt pathway genes were predominantly expressed in valve interstitial cells and valve endothelial cells of Fbn1C1039G/+ mice. Inhibition of Wnt signaling in Fbn1C1039G/+ mice at 1 month of age prevented the initiation of MVD as indicated by improved ECM remodeling and reduced valve leaflet thickness with decreased infiltrating macrophages. However, later, Wnt inhibition starting at 2 months did not prevent the progression of MVD. CONCLUSIONS: Wnt signaling is involved in the initiation of mitral valve abnormalities and inflammation but is not responsible for later-stage valve disease progression once it has been initiated. Thus, Wnt signaling contributes to MVD progression in a time-dependent manner and provides a promising therapeutic target for the early treatment of congenital MVD in Marfan syndrome.


Assuntos
Modelos Animais de Doenças , Progressão da Doença , Fibrilina-1 , Valva Mitral , Via de Sinalização Wnt , Animais , Fibrilina-1/genética , Fibrilina-1/metabolismo , Valva Mitral/metabolismo , Valva Mitral/patologia , Valva Mitral/efeitos dos fármacos , Camundongos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos Transgênicos , Síndrome de Marfan/genética , Síndrome de Marfan/complicações , Síndrome de Marfan/metabolismo , Síndrome de Marfan/patologia , Insuficiência da Valva Mitral/patologia , Insuficiência da Valva Mitral/metabolismo , Insuficiência da Valva Mitral/prevenção & controle , Insuficiência da Valva Mitral/genética , Camundongos Endogâmicos C57BL , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Inflamação/genética , Masculino , Feminino , Moléculas de Adesão Celular , Adipocinas
8.
Arterioscler Thromb Vasc Biol ; 44(9): 1944-1959, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38989578

RESUMO

BACKGROUND: Mitral valve (MV) disease including myxomatous degeneration is the most common form of valvular heart disease with an age-dependent frequency. Genetic evidence indicates that mutations of the human transcription factor FOXC1 are associated with MV defects, including MV regurgitation. In this study, we sought to determine whether murine Foxc1 and its closely related factor, Foxc2, are required in valvular endothelial cells (VECs) for the maintenance of MV leaflets, including VEC junctions and the stratified trilaminar ECM (extracellular matrix). METHODS: Adult mice carrying tamoxifen-inducible, vascular endothelial cell (EC), and lymphatic EC-specific, compound Foxc1;Foxc2 mutations (ie, EC-Foxc-DKO and lymphatic EC-Foxc-DKO mice, respectively) were used to study the function of Foxc1 and Foxc2 in the maintenance of MVs. The EC and lymphatic EC mutations of Foxc1/c2 were induced at 7 to 8 weeks of age by tamoxifen treatment, and abnormalities in the MVs of these mutant mice were assessed via whole-mount immunostaining, immunohistochemistry/RNAscope, Movat pentachrome/Masson Trichrome staining, and Evans blue injection. RESULTS: EC deletions of Foxc1 and Foxc2 in mice resulted in abnormally extended and thicker MVs by causing defects in the regulation of ECM organization with increased proteoglycan and decreased collagen. Notably, reticular adherens junctions were found in VECs of control MV leaflets, and these reticular structures were severely disrupted in EC-Foxc-DKO mice. PROX1 (prospero homeobox protein 1), a key regulator in a subset of VECs on the fibrosa side of MVs, was downregulated in EC-Foxc1/c2 mutant VECs. Furthermore, we determined the precise location of lymphatic vessels in murine MVs, and these lymphatic vessels were aberrantly expanded and dysfunctional in EC-Foxc1/c2 mutant MVs. Lymphatic EC deletion of Foxc1/c2 also resulted in similar structural/ECM abnormalities as seen in EC-Foxc1/c2 mutant MVs. CONCLUSIONS: Our results indicate that Foxc1 and Foxc2 are required for maintaining the integrity of the MV, including VEC junctions, ECM organization, and lymphatic vessel formation/function to prevent myxomatous MV degeneration.


Assuntos
Modelos Animais de Doenças , Células Endoteliais , Fatores de Transcrição Forkhead , Linfangiogênese , Vasos Linfáticos , Camundongos Knockout , Animais , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Valva Mitral/metabolismo , Valva Mitral/patologia , Mutação , Camundongos , Junções Intercelulares/metabolismo , Junções Intercelulares/patologia , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/genética , Fenótipo , Camundongos Endogâmicos C57BL , Prolapso da Valva Mitral/metabolismo , Prolapso da Valva Mitral/genética , Prolapso da Valva Mitral/patologia , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia
9.
Eur Heart J ; 45(11): 940-949, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38243821

RESUMO

BACKGROUND AND AIMS: Mitral valve surgery and, more recently, mitral transcatheter edge-to-edge repair (TEER) are the two treatments of severe mitral regurgitation in eligible patients. Clinical comparison of both therapies remains limited by the number of patients analysed. The objective of this study was to analyse the outcomes of mitral TEER vs. isolated mitral valve surgery at a nationwide level in France. METHODS: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients treated for mitral regurgitation with isolated TEER or isolated mitral valve surgery between 2012 and 2022. Propensity score matching was used for the analysis of outcomes. RESULTS: A total of 57 030 patients were found in the database. After matching on baseline characteristics, 2160 patients were analysed in each arm. At 3-year follow-up, TEER was associated with significantly lower incidence of cardiovascular death (hazard ratio 0.685, 95% confidence interval 0.563-0.832; P = .0001), pacemaker implantation, and stroke. Non-cardiovascular death (hazard ratio 1.562, 95% confidence interval 1.238-1.971; P = .0002), recurrent pulmonary oedema, and cardiac arrest were more frequent after TEER. No significant differences between the two groups were observed regarding all-cause death (hazard ratio 0.967, 95% confidence interval 0.835-1.118; P = .65), endocarditis, major bleeding, atrial fibrillation, and myocardial infarction. CONCLUSIONS: Our results suggest that TEER for severe mitral regurgitation was associated with lower cardiovascular mortality than mitral surgery at long-term follow-up. Pacemaker implantation and stroke were less frequently observed after TEER.


Assuntos
Fibrilação Atrial , Endocardite , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Acidente Vascular Cerebral , Humanos , Insuficiência da Valva Mitral/epidemiologia , Insuficiência da Valva Mitral/cirurgia , Acidente Vascular Cerebral/epidemiologia , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Bases de Dados Factuais , Resultado do Tratamento
10.
Eur Heart J ; 45(26): 2306-2316, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38751052

RESUMO

BACKGROUND AND AIMS: Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. METHODS: In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. RESULTS: At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27-1.65), P < .001] but was higher in females [SMR 2.00 (1.67-2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04-1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14-2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02-1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16-1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85-0.99), P = .036]. CONCLUSIONS: Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.


Assuntos
Insuficiência da Valva Mitral , Humanos , Feminino , Masculino , Insuficiência da Valva Mitral/mortalidade , Insuficiência da Valva Mitral/cirurgia , Idoso , Fatores Sexuais , Pessoa de Meia-Idade , Ecocardiografia , Sistema de Registros , Resultado do Tratamento , Tratamento Conservador , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/etiologia , Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem
11.
Eur Heart J ; 45(20): 1831-1839, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38740526

RESUMO

BACKGROUND AND AIMS: Arrhythmic mitral valve prolapse (AMVP) is linked to life-threatening ventricular arrhythmias (VAs), and young women are considered at high risk. Cases of AMVP in women with malignant VA during pregnancy have emerged, but the arrhythmic risk during pregnancy is unknown. The authors aimed to describe features of women with high-risk AMVP who developed malignant VA during the perinatal period and to assess if pregnancy and the postpartum period were associated with a higher risk of malignant VA. METHODS: This retrospective international multi-centre case series included high-risk women with AMVP who experienced malignant VA and at least one pregnancy. Malignant VA included ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock from an implantable cardioverter defibrillator. The authors compared the incidence of malignant VA in non-pregnant periods and perinatal period; the latter defined as occurring during pregnancy and within 6 months after delivery. RESULTS: The authors included 18 women with AMVP from 11 centres. During 7.5 (interquartile range 5.8-16.6) years of follow-up, 37 malignant VAs occurred, of which 18 were pregnancy related occurring in 13 (72%) unique patients. Pregnancy and 6 months after delivery showed increased incidence rate of malignant VA compared to the non-pregnancy period (univariate incidence rate ratio 2.66, 95% confidence interval 1.23-5.76). CONCLUSIONS: The perinatal period could impose increased risk of malignant VA in women with high-risk AMVP. The data may provide general guidance for pre-conception counselling and for nuanced shared decision-making between patients and clinicians.


Assuntos
Prolapso da Valva Mitral , Complicações Cardiovasculares na Gravidez , Humanos , Feminino , Gravidez , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/epidemiologia , Estudos Retrospectivos , Adulto , Complicações Cardiovasculares na Gravidez/epidemiologia , Fatores de Risco , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologia , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/etiologia , Transtornos Puerperais/epidemiologia , Transtornos Puerperais/etiologia , Desfibriladores Implantáveis , Incidência , Fibrilação Ventricular/epidemiologia , Fibrilação Ventricular/etiologia , Período Pós-Parto
12.
J Mol Cell Cardiol ; 186: 16-30, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37935281

RESUMO

Epicardial-derived cells (EPDCs) are involved in the regulation of myocardial growth and coronary vascularization and are critically important for proper development of the atrioventricular (AV) valves. SOX9 is a transcription factor expressed in a variety of epithelial and mesenchymal cells in the developing heart, including EPDCs. To determine the role of SOX9 in epicardial development, an epicardial-specific Sox9 knockout mouse model was generated. Deleting Sox9 from the epicardial cell lineage impairs the ability of EPDCs to invade both the ventricular myocardium and the developing AV valves. After birth, the mitral valves of these mice become myxomatous with associated abnormalities in extracellular matrix organization. This phenotype is reminiscent of that seen in humans with myxomatous mitral valve disease (MVD). An RNA-seq analysis was conducted in an effort to identify genes associated with this myxomatous degeneration. From this experiment, Cd109 was identified as a gene associated with myxomatous valve pathogenesis in this model. Cd109 has never been described in the context of heart development or valve disease. This study highlights the importance of SOX9 in the regulation of epicardial cell invasion-emphasizing the importance of EPDCs in regulating AV valve development and homeostasis-and reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.


Assuntos
Doenças das Valvas Cardíacas , Valva Mitral , Humanos , Camundongos , Animais , Valva Mitral/metabolismo , Doenças das Valvas Cardíacas/patologia , Ventrículos do Coração/metabolismo , Miocárdio/metabolismo , Camundongos Knockout , Fatores de Transcrição/metabolismo
13.
Circulation ; 147(10): 798-811, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36573420

RESUMO

BACKGROUND: Mitral valve prolapse (MVP) is responsible for a considerable disease burden but is widely heterogeneous. The lack of a comprehensive prognostic instrument covering the entire MVP spectrum, encompassing the quantified consequent degenerative mitral regurgitation (DMR), hinders clinical management and therapeutic trials. METHODS: The new Mitral Regurgitation International Database Quantitative (MIDA-Q) registry enrolled 8187 consecutive patients (ages 63±16 years, 47% women, follow-up 5.5±3.3 years) first diagnosed with isolated MVP, without or with DMR quantified prospectively (measuring effective regurgitant orifice [ERO] and regurgitant volume) in routine practice of 5 tertiary care centers from North America, Europe, and the Middle East. The MIDA-Q score ranges from 0 to 15 by accumulating guideline-based risk factors and DMR severity. Long-term survival under medical management was the primary outcome end point. RESULTS: MVP was associated with DMR absent/mild (ERO <20 mm2) in 50%, moderate (ERO 20-40 mm2) in 25%, and severe or higher (ERO ≥40 mm2) in 25%, with mean ERO 24±24 mm2, regurgitant volume 37±35 mL. Median MIDA-Q score was 4 with a wide distribution (10%-90% range, 0-9). MIDA-Q score was higher in patients with EuroScore II ≥1% versus <1% (median, 7 versus 3; P < 0.0001) but with wide overlap (10%-90% range, 4-11 versus 0-7) and mediocre correlation (R2 0.18). Five-year survival under medical management was strongly associated with MIDA-Q score, 97±1% with score 0, 95±1% with score 1 to 2, 82±1% with score 3 to 4, 67±1% with score 5 to 6, 60±1% with score 7 to 8, 44±1% with score 9 to 10, 35±1% with score 11 to 12, and 5±4% with MIDA-Q score ≥13, with hazard ratio 1.31 [1.29-1.33] per 1-point increment. Excess mortality with higher MIDA-Q scores persisted after adjustment for age, sex, and EuroScore II (adjusted hazard ratio, 1.13 [1.11-1.15] per 1-point increment). Subgroup analysis showed persistent association of MIDA-Q score with mortality in all possible subsets, in particular, with EuroScore II<1% (hazard ratio, 1.08 [1.02-1.14]) or ≥1% (hazard ratio, 1.11 [1.08-1.13]) and with no/mild DMR (hazard ratio, 1.14 [1.10-1.19]) or moderate/severe DMR (hazard ratio, 1.13 [1.10-1.16], all per 1-point increment with P<0.0001). Nested-model and bootstrapping analyses demonstrated incremental prognostic power of MIDA-Q score (all P<0.0001). CONCLUSIONS: This large, international cohort of isolated MVP, with prospective DMR quantification in routine practice, demonstrates the wide range of risk factor accumulation and considerable heterogeneity of outcomes after MVP diagnosis. The MIDA-Q score is strongly, independently, and incrementally associated with long-term survival after MVP diagnosis, irrespective of presentation, and is therefore a crucial prognostic instrument for risk stratification, clinical trials, and management of patients diagnosed with all forms of MVP.


Assuntos
Insuficiência da Valva Mitral , Prolapso da Valva Mitral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Prolapso da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/complicações , Prognóstico , Estudos Prospectivos , Fatores de Risco
14.
Br J Haematol ; 204(6): 2453-2457, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38594875

RESUMO

ACTN1-related thrombocytopenia is a rare disorder caused by heterozygous variants in the ACTN1 gene characterized by macrothrombocytopenia and mild bleeding tendency. We describe for the first time two patients affected with ACTN1-RT caused by a homozygous variant in ACTN1 (c.982G>A) with mild heart valve defects unexplained by any other genetic variants investigated by WES. Within the reported family, the homozygous sisters have moderate thrombocytopenia and marked platelet macrocytosis with giant platelets, revealing a more severe haematological phenotype compared to their heterozygous relatives and highlighting a significant effect of allelic burden on platelet size. Moreover, we hypothesize that some ACTN1 variants, especially when present in the homozygous state, may also contribute to the cardiac abnormalities.


Assuntos
Actinina , Homozigoto , Fenótipo , Trombocitopenia , Humanos , Trombocitopenia/genética , Actinina/genética , Feminino , Masculino , Linhagem , Mutação , Adulto
15.
Artigo em Inglês | MEDLINE | ID: mdl-39118252

RESUMO

OBJECTIVES: This study aims to investigate the occurrence, type and correlation of early and late atrial arrhythmias following mitral valve repair in patients with no preoperative history of atrial arrhythmias. METHODS: Patients undergoing mitral valve (MV) repair for degenerative disease were included. Early and late postoperative electrocardiograms were evaluated for the incidence and type of atrial arrhythmia (atrial fibrillation [AF] or atrial tachycardia [AT]). RESULTS: The 192 patients were included. Early atrial arrhythmias occurred in 100/192 (52.1%) patients; AF in 61 (31.8%) patients, early AT in 15 (7.8%) and both in 24 (12.5%). In total 89% of patients were discharged in sinus rhythm. During a follow-up time of 7.3 years, 14 patients (7.3%) died and 49 (25.5%) patients developed late atrial arrhythmias. At 10 years, the cumulative incidence of any late atrial arrhythmia, with death as competing risk, was 64% (95% confidence interval [CI] = 55%-72%). On Fine-Gray model analysis, only early postoperative AF lasting >24 h was related to the development of late AF (hazard ratio 5.99, 95% CI = 1.78%-20.10%, p = .004). Early postoperative ATs were related to the development of late tachycardias, independent of their duration (<24 h hazard ratio 4.25, 95% CI = 1.89-9.57, p = .001 and >24 h hazard ratio 3.51, 95% CI = 1.65-7.46, p = .001). CONCLUSIONS: Early and late atrial arrhythmias were common after MV repair surgery. Only early postoperative AF lasting >24 h was a risk factor for the occurrence of late AF. Conversely, any postoperative AT was correlated to the development of late ATs.

16.
J Cardiovasc Electrophysiol ; 35(2): 290-300, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38098308

RESUMO

INTRODUCTION: Mitral valve prolapse (MVP) is a common clinical condition in the general population. A subgroup of patients with MVP may experience ventricular arrhythmias and sudden cardiac death ("arrhythmic mitral valve prolapse" [AMVP]) but how to stratify arrhythmic risk is still unclear. Our meta-analysis aims to identify predictive factors for arrhythmic risk in patients with MVP. METHODS: We systematically searched Medline, Cochrane, Journals@Ovid, Scopus electronic databases for studies published up to December 28, 2022 and comparing AMVP and nonarrhythmic mitral valve prolapse (NAMVP) for what concerns history, electrocardiographic, echocardiographic and cardiac magnetic resonance features. The effect size was estimated using a random-effect model as odds ratio (OR) and mean difference (MD). RESULTS: A total of 10 studies enrolling 1715 patients were included. Late gadolinium enhancement (LGE) (OR: 16.67; p = .005), T-wave inversion (TWI) (OR: 2.63; p < .0001), bileaflet MVP (OR: 1.92; p < .0001) and mitral anulus disjunction (MAD) (OR: 2.60; p < .0001) were more represented among patients with AMVP than in NAMVP. Patients with AMVP were shown to have longer anterior mitral leaflet (AML) (MD: 2.63 mm; p < .0001), posterior mitral leaflet (MD: 2.96 mm; p < .0001), thicker AML (MD: 0.49 mm; p < .0001), longer MAD length (MD: 1.24 mm; p < .0001) and higher amount of LGE (MD: 1.41%; p < .0001) than NAMVP. AMVP showed increased mechanical dispersion (MD: 8.04 ms; 95% confidence interval: 5.13-10.96; p < .0001) compared with NAMVP. CONCLUSIONS: Our meta-analysis proved that LGE, TWI, bileaflet MVP, and MAD are predictive factors for arrhythmic risk in MVP patients.


Assuntos
Prolapso da Valva Mitral , Prolapso da Valva Mitral/fisiopatologia , Prolapso da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/diagnóstico , Humanos , Medição de Risco , Fatores de Risco , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Prognóstico , Adulto , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/epidemiologia , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Frequência Cardíaca , Potenciais de Ação
17.
J Anat ; 245(2): 201-216, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38629319

RESUMO

Despite centuries of investigation, certain aspects of left ventricular anatomy remain either controversial or uncertain. We make no claims to have resolved these issues, but our review, based on our current knowledge of development, hopefully identifies the issues requiring further investigation. When first formed, the left ventricle had only inlet and apical components. With the expansion of the atrioventricular canal, the developing ventricle cedes part of its inlet to the right ventricle whilst retaining the larger parts of the cushions dividing the atrioventricular canal. Further remodelling of the interventricular communication provides the ventricle with its outlet, with the aortic root being transferred to the left ventricle along with the newly formed myocardium supporting its leaflets. The definitive ventricle possesses inlet, apical and outlet parts. The inlet component is guarded by the mitral valve, with its leaflets, in the normal heart, supported by papillary muscles located infero-septally and supero-laterally. There is but a solitary zone of apposition between the leaflets, which we suggest are best described as being aortic and mural. The trabeculated component extends beyond the inlet to the apex and is confluent with the outlet part, which supports the aortic root. The leaflets of the aortic valve are supported in semilunar fashion within the root, with the ventricular cavity extending to the sinutubular junction. The myocardial-arterial junction, however, stops well short of the sinutubular junction, with myocardium found only at the bases of the sinuses, giving rise to the coronary arteries. We argue that the relationships between the various components should now be described using attitudinally appropriate terms rather than describing them as if the heart is removed from the body and positioned on its apex.


Assuntos
Ventrículos do Coração , Humanos , Ventrículos do Coração/anatomia & histologia , Animais
18.
Heart Fail Rev ; 29(1): 65-77, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37735319

RESUMO

Cardiac amyloidosis (CA) is an underdiagnosed condition caused by the deposition of misfolded proteins, namely immunoglobulin light chains and transthyretin, in the extracellular spaces of the heart. Any cardiovascular structure can be affected by amyloid infiltration, including the valves. Amyloid accumulation within the cardiac valves may lead to their structural and functional impairment, with a profound impact on patients' prognosis and quality of life. The most common forms of valvular disease in CA are aortic stenosis (AS), mitral regurgitation (MR), and tricuspid regurgitation (TR). CA and AS share similar risk factors, disease mechanisms, and remodeling patterns, which make their diagnosis particularly challenging. Patients with both CA and AS experience worse outcomes than CA or AS alone, and transcatheter aortic valve replacement may represent a useful therapeutic strategy in this population. Data on MR and TR are quite limited and mainly coming from case reports or small series. This review paper will summarize our current understanding on the epidemiology, disease mechanisms, echocardiographic features, clinical implications, and therapeutic options of AS, MR, and TR in patients with CA.


Assuntos
Amiloidose , Estenose da Valva Aórtica , Doenças das Valvas Cardíacas , Insuficiência da Valva Mitral , Insuficiência da Valva Tricúspide , Humanos , Qualidade de Vida , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/cirurgia , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/cirurgia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Amiloidose/complicações
19.
Heart Fail Rev ; 29(1): 227-234, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37950833

RESUMO

As the survival after heart transplantation (HTx) is steadily improving, an increasing number of patients with late cardiac pathologies such as valvular disease is expected to rise. Nevertheless, no guidelines for indication of redo cardiac surgery after HTx exists. The aim of the present systematic review is to describe the results reported in the literature of surgical management of severe aortic and/or mitral valve disease. A systematic review was conducted including studies reporting on adult patients with severe mitral or aortic valve pathology needing surgery after their previous HTx. Exclusion criteria consisted in surgery with no left heart valve surgery, concomitant valve surgery during heart transplant, transcatheter interventions, and heterotopic HTx. A total of 35 papers met our inclusion criteria out of 2755 potentially eligible studies with 44 mitral valve surgery patients and 20 aortic valve surgery patients. In the entire population, the mean time from HTx to reintervention was 6.19 ± 5.22 years. After a mean follow-up of 2.78 ± 3.54 years and 1.53 ± 2.26 years from reintervention, 65.6% mitral and 86.7% aortic patients were reported as alive, respectively. As guidelines on cardiac surgery after HTx are currently lacking, left-sided valvular cardiac reinterventions can be considered a possible therapeutic approach in carefully selected patients. These interventions may not only improve the patient's functional status and survival, but may ultimately reduce the need for re-transplantation due to the chronic shortage of donor hearts. However, the support of more robust data is warranted.


Assuntos
Cardiopatias , Transplante de Coração , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Adulto , Humanos , Transplante de Coração/efeitos adversos , Resultado do Tratamento , Doadores de Tecidos , Doenças das Valvas Cardíacas/cirurgia , Valva Mitral/cirurgia , Implante de Prótese de Valva Cardíaca/métodos
20.
Histopathology ; 84(6): 960-966, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38233105

RESUMO

AIMS: Mitral valve prolapse (MVP) is an accepted cause of sudden cardiac death (SCD) in most autopsy series. Diagnosis at autopsy relies upon subjective assessment with no established objective pathological criteria. This study set out to establish objective measurements to help pathologists dealing with SCD. METHODS: We diagnosed 120 (1.5%) cases of MVP in 8108 cases of SCD. We measured the mitral annulus, anterior and posterior leaflets, rough zone and mitral annular disjunction (MAD) in 27 MVP cases and compared them to 54 age- and sex-matched normal mitral valves. RESULTS: Age of death was 39 ± 16 years, with 59 females and 61 males. History of mild MV disease was present in 19 (16%). Eleven (9%) died associated with exertion. Left ventricular hypertrophy was present in nine (15%) females and 10 (16%) males. Both MV leaflets showed thickening and ballooning in all individuals. MVP showed highly significantly increased annular circumference, elongation and thickening of both leaflets as well as increased MAD (all P < 0.001). Left ventricular fibrosis was present in 108 (90%), with interstitial fibrosis in the posterolateral wall and papillary muscle in 88 (81%) and coexisting replacement fibrosis in 40 (37%). CONCLUSION: This is the largest MVP associated with SCD series highlighting a young cohort with equal representation of males and females. There is involvement of both leaflets with significant annular dilatation, elongation and thickening of both leaflets with MAD. Left ventricular fibrosis explains arrhythmia. Our quantitative measurements should serve as a reference for pathologists assessing post-mortem hearts for MVP.


Assuntos
Prolapso da Valva Mitral , Valva Mitral , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Valva Mitral/patologia , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/patologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/patologia , Músculos Papilares/patologia , Fibrose
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA