RESUMO
Calcific aortic valve disease (CAVD) is the most common heart valve disease requiring intervention. Most research on CAVD has focused on inflammation, ossification, and cellular phenotype transformation. To gain a broader picture into the wide range of cellular and molecular mechanisms involved in this disease, we compared the total protein profiles between calcified and non-calcified areas from 5 human valves resected during surgery. The 1413 positively identified proteins were filtered down to 248 proteins present in both calcified and non-calcified segments of at least 3 of the 5 valves, which were then analyzed using Ingenuity Pathway Analysis. Concurrently, the top 40 differentially abundant proteins were grouped according to their biological functions and shown in interactive networks. Finally, the abundance of selected osteogenic proteins (osteopontin, osteonectin, osteocalcin, osteoprotegerin, and RANK) was quantified using ELISA and/or immunohistochemistry. The top pathways identified were complement system, acute phase response signaling, metabolism, LXR/RXR and FXR/RXR activation, actin cytoskeleton, mineral binding, nucleic acid interaction, structural extracellular matrix (ECM), and angiogenesis. There was a greater abundance of osteopontin, osteonectin, osteocalcin, osteoprotegerin, and RANK in the calcified regions than the non-calcified ones. The osteogenic proteins also formed key connections between the biological signaling pathways in the network model. In conclusion, this proteomic analysis demonstrated the involvement of multiple signaling pathways in CAVD. The interconnectedness of these pathways provides new insights for the treatment of this disease.
Assuntos
Estenose da Valva Aórtica , Calcinose , Valva Aórtica/metabolismo , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/cirurgia , Calcinose/metabolismo , Humanos , Osteogênese/fisiologia , Proteoma/metabolismo , ProteômicaRESUMO
PURPOSE OF REVIEW: Mitral repair is the best treatment for degenerative mitral regurgitation. Many patients are referred too late for optimal outcomes. The US repair vs. replacement rate is only 60-80%, at a time when the inferiority of replacement has been established. Therefore, widely used traditional techniques of repair are being reappraised. RECENT FINDINGS: Identification of risk factors predictive of poor early and late outcome have improved timing for surgical referral. Composite risk scores have been developed. Novel echocardiographic, cardiac MRI, and molecular level risk factors could improve timing. Analysis of factors contributing to low repair rates is also of critical importance. The role of institutional and surgeon volumes have been identified. More detailed data on the importance of dynamic function of the mitral valve have led to improved repair techniques such as intraoperative simulation of end diastole and early systole, use of expanded polytetrafluoroethylene neochords instead of leaflet resection, and dynamic instead of rigid annuloplasty. SUMMARY: Our perception of mitral regurgitation has changed from a seemingly simple condition to one of considerable complexity at multiple levels. National guidelines should be studied and followed.
Assuntos
Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/cirurgia , Politetrafluoretileno , Técnicas de Sutura , Resultado do TratamentoAssuntos
Líquido Extracelular/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Líquido Extracelular/fisiologia , Feminino , Fibrose/diagnóstico por imagem , Fibrose/fisiopatologia , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/fisiopatologia , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: Calcification in atherosclerotic plaques has been viewed as a marker of plaque stability, but whether calcification accumulates in specific anatomic sites in the carotid artery is unknown. We determined the burden and distribution of calcified plaque in carotid endarterectomy (CEA) tissues. METHODS: A total of 22 CEA tissues were imaged with high-resolution micro-computed tomography (micro-CT). Total plaque burden and total calcium score using the Agatston method were quantified. The Agatston score (AS) was also normalized for tissue size. Plaque and calcium distribution were analyzed separately for three CEA regions: common segment (CS), bulb segment (BS), and internal/external segments (IES). RESULTS: The average CEA tissue length was 40.83 (interquartile range [IQR] 33.31-42.41) mm with total plaque burden of 103.45 (IQR: 78.84-156.81) mm(3) and total AS of 38.58 (IQR 11.59-89.97). Total plaque volume was 21.02 (IQR: 14.47-25.42) mm(3) in the CS, 37.89 (22.59-48.32) mm(3) in the BS, and 54.05 (36.87-74.52) mm(3) in the IES. Of the 22 tissues, 15 had no calcium in the CS compared with three in the bulb and two in the IES. Normalized calcified plaque was most prevalent in the BS, the IES and was least prevalent in the CS. The overall correlation of calcification between histology sections and matched micro-CT images was 0.86 (p<0.001). CONCLUSIONS: Calcified plaque is heterogeneously distributed in CEA tissues with most in the bulb and IES regions. The amount of calcification in micro-CT slices shows a high correlation with matched histology sections.
Assuntos
Calcinose/diagnóstico por imagem , Calcinose/patologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Biópsia por Agulha , Estenose das Carótidas/cirurgia , Estudos de Coortes , Endarterectomia das Carótidas/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Masculino , Variações Dependentes do Observador , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Técnicas de Cultura de Tecidos , Microtomografia por Raio-X/métodosAssuntos
Aneurisma Aórtico , Síndrome de Marfan , Seio Aórtico , Adulto , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/patologia , Feminino , Humanos , Síndrome de Marfan/diagnóstico por imagem , Síndrome de Marfan/patologia , Seio Aórtico/diagnóstico por imagem , Seio Aórtico/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Tricuspid valve prolapse (TVP) is an uncertain diagnosis with unknown clinical significance because of a scarcity of published data. OBJECTIVES: In this study, cardiac magnetic resonance was used to: 1) propose diagnostic criteria for TVP; 2) evaluate the prevalence of TVP in patients with primary mitral regurgitation (MR); and 3) identify the clinical implications of TVP with regard to tricuspid regurgitation (TR). METHODS: Forty-one healthy volunteers were analyzed to identify normal tricuspid leaflet displacement and propose criteria for TVP. A total of 465 consecutive patients with primary MR (263 with mitral valve prolapse [MVP] and 202 with nondegenerative mitral valve disease [non-MVP]) were phenotyped for the presence and clinical significance of TVP. RESULTS: The proposed TVP criteria included right atrial displacement of ≥2 mm for the anterior and posterior tricuspid leaflets and ≥3 mm for the septal leaflet. Thirty-one (24%) subjects with single-leaflet MVP and 63 (47%) with bileaflet MVP met the proposed criteria for TVP. TVP was not evident in the non-MVP cohort. Patients with TVP were more likely to have severe MR (38.3% vs 18.9%; P < 0.001) and advanced TR (23.4% of patients with TVP demonstrated moderate or severe TR vs 6.2% of patients without TVP; P < 0.001), independent of right ventricular systolic function. CONCLUSIONS: TR in subjects with MVP should not be routinely considered functional, as TVP is a prevalent finding associated with MVP and more often associated with advanced TR compared with patients with primary MR without TVP. A comprehensive assessment of tricuspid anatomy should be an important component of the preoperative evaluation for mitral valve surgery.
RESUMO
Cor triatriatum dexter is a rare congenital heart defect with a varied clinical presentation ranging from asymptomatic to right heart failure. Accurate diagnosis is imperative as it may affect clinical decision making. We present a multimodality imaging assessment of cor triatriatum dexter in a 70-year-old woman with severe tricuspid regurgitation.
Assuntos
Coração Triatriado , Cardiopatias Congênitas , Insuficiência da Valva Tricúspide , Idoso , Coração Triatriado/diagnóstico por imagem , Coração Triatriado/cirurgia , Feminino , Humanos , Imagem MultimodalRESUMO
Spontaneous coronary sinus thrombosis (CST) is an extremely rare occurrence. Most cases are iatrogenic and related to right heart instrumentation, due to either central line placement or electrophysiology procedures such as pacemaker insertion that causes direct damage to the endothelial lining. The course can be insidious and may result in a fatal outcome. Diagnosis of CST is challenging, and the syndrome often goes unrecognized. However, in the current era of multimodality imaging, it is possible that this condition will be recognized in more patients. Herein, we present a patient with spontaneous coronary sinus thrombosis that was diagnosed using multimodality imaging and thereafter successfully managed.
Assuntos
Seio Coronário , Trombose Coronária , Anomalias dos Vasos Coronários , Trombose dos Seios Intracranianos , Cateterismo Cardíaco , Seio Coronário/diagnóstico por imagem , Trombose Coronária/complicações , Trombose Coronária/diagnóstico por imagem , Anomalias dos Vasos Coronários/complicações , Humanos , Trombose dos Seios Intracranianos/complicaçõesRESUMO
The treatment of drug-refractory chronic ventricular tachycardia (VT) has undergone a revolution over the last 50 years. We now have automatic implantable cardioverter defibrillator therapy with pace-terminating capabilities, and catheter ablation of VT has refined mapping and improved methods of lesion generation. Between 1980 and 1993, Houston Methodist Hospital became a leader in the diagnosis and surgical ablation of VT and other arrhythmias. This is a brief account of that period and some of the experiences and lessons that have led to significant advances used today.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Frequência Cardíaca , Taquicardia Ventricular/cirurgia , Potenciais de Ação , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/história , Difusão de Inovações , Técnicas Eletrofisiológicas Cardíacas , História do Século XX , História do Século XXI , Humanos , Complicações Pós-Operatórias/etiologia , Recidiva , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/história , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: We studied the results of a dynamic mitral repair technique that preserves normal mitral valve function by avoiding leaflet resection and rigid and semirigid annuloplasty rings. METHODS: In previous reports we demonstrated that intraoperative simulation of mitral valve locking and isovolumic systole by rapid left ventricular inflation with pressurized saline accurately simulates mitral annular and leaflet shape and position, and left ventricular outflow tract dimensions. Length of polytetrafluoroethylene neochordae and size of fully flexible adjustable annuloplasty ring can be adjusted in three dimensions for accurate apposition of zones of leaflet coaptation, premarked with dots. We followed 1068 consecutive patients after repairs performed between 2001 and 2018. RESULTS: Of the 1068 patients, 674 were men (63.1%). Mean age was 62.25 ± 13 years. Leaflet repaired was anterior in 118 patients (11.05%), posterior in 564 (52.81%), both in 55 (5.15%), and neither in 123 (11.5%). Barlow's disease was present in 208 patients (19.48%). Repair was isolated in 82.5% (881 of 1068). Reparability was 100%. Perioperative mortality overall was 1.59% (17 of 1068): isolated repair, 1.14% (10 of 881); and isolated posterior leaflet, 0.85% (4 of 472). Leaflet systolic anterior motion occurred in 1.7% (18 of 1068), and was significant in 0.4% (4 of 1068). Survival at 10 years by Kaplan-Meier analysis was 74.65%, freedom from reoperation was 96.01%, and freedom from severe mitral regurgitation was 94%. The only predictor of reoperation (Cox analysis) was being male (P = .001). CONCLUSIONS: Use of intraoperative simulation of mitral dynamics led to 100% reparability for degenerative valves with minimal systolic anterior motion, despite no leaflet resection. Long-term durability has been good and similar for all leaflets.
Assuntos
Anuloplastia da Valva Mitral/métodos , Prolapso da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Feminino , Próteses Valvulares Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of this study was to assess mitral valve (MV) remodeling and strain in patients with secondary mitral regurgitation (SMR) compared with primary MR (PMR) and normal valves. BACKGROUND: A paucity of data exists on MV strain during the cardiac cycle in humans. Real-time 3-dimensional (3D) echocardiography allows for dynamic MV imaging, enabling computerized modeling of MV function in normal and disease states. METHODS: Three-dimensional transesophageal echocardiography (TEE) was performed in a total of 106 subjects: 36 with SMR, 38 with PMR, and 32 with normal valves; MR severity was at least moderate in both MR groups. Valve geometric parameters were quantitated and patient-specific 3D MV models generated in systole using a dedicated software. Global and regional peak systolic MV strain was computed using a proprietary software. RESULTS: MV annular area was larger in both the SMR and PMR groups (12.7 ± 0.7 and 13.3 ± 0.7 cm2, respectively) compared with normal subjects (9.9 ± 0.3 cm2; p < 0.05). The leaflets also had significant remodeling, with total MV leaflet area larger in both SMR (16.2 ± 0.9 cm2) and PMR (15.6 ± 0.8 cm2) versus normal subjects (11.6 ± 0.4 cm2). Leaflets in SMR were thicker than those in normal subjects but slightly less than those with PMR posteriorly. Posterior leaflet strain was significantly higher than anterior leaflet strain in all 3 groups. Despite MV remodeling, strain in SMR (8.8 ± 0.3%) was overall similar to normal subjects (8.5 ± 0.2%), and both were lower than in PMR (12 ± 0.4%; p < 0.0001). Valve thickness, severity of MR, and primary etiology of MR were correlates of strain, with leaflet thickness being the multivariable parameter significantly associated with MV strain. In patients with less severe MR, anterior leaflet strain in SMR was lower than normal, whereas strain in PMR remained higher than normal. CONCLUSIONS: The MV in secondary MR remodels significantly and similarly to PMR with a resultant larger annular area, leaflet surface area, and leaflet thickness compared with that of normal subjects. Despite these changes, MV strain remains close to or in some instances lower than normal and is significantly lower than that of PMR. Strain determination has the potential to improve characterization of MV mechano-biologic properties in humans and to evaluate its prognostic impact in patients with MR, with or without valve interventions.
Assuntos
Ecocardiografia Tridimensional , Insuficiência da Valva Mitral , Ecocardiografia Transesofagiana , Humanos , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Valor Preditivo dos TestesRESUMO
OBJECTIVES: The aim of this study was to quantitate patient-specific mitral valve (MV) strain in normal valves and in patients with mitral valve prolapse with and without significant mitral regurgitation (MR) and assess the determinants of MV strain. BACKGROUND: Few data exist on MV deformation during systole in humans. Three-dimensional echocardiography allows for dynamic MV imaging, enabling digital modeling of MV function in health and disease. METHODS: Three-dimensional transesophageal echocardiography was performed in 82 patients, 32 with normal MV and 50 with mitral valve prolapse (MVP): 12 with mild mitral regurgitation or less (MVP - MR) and 38 with moderate MR or greater (MVP + MR). Three-dimensional MV models were generated, and the peak systolic strain of MV leaflets was computed on proprietary software. RESULTS: Left ventricular ejection fraction was normal in all groups. MV annular dimensions were largest in MVP + MR (annular area: 13.8 ± 0.7 cm2) and comparable in MVP - MR (10.6 ± 1 cm2) and normal valves (10.5 ± 0.3 cm2; analysis of variance: p < 0.001). Similarly, MV leaflet areas were largest in MVP + MR, particularly the posterior leaflet (8.7 ± 0.5 cm2); intermediate in MVP - MR (6.5 ± 0.7 cm2); and smallest in normal valves (5.5 ± 0.2 cm2; p < 0.0001). Strain was overall highest in MVP + MR and lowest in normal valves. Patients with MVP - MR had intermediate strain values that were higher than normal valves in the posterior leaflet (p = 0.001). On multivariable analysis, after adjustment for clinical and MV geometric parameters, leaflet thickness was the only parameter that was retained as being significantly correlated with mean MV strain (r = 0.34; p = 0.008). CONCLUSIONS: MVs that exhibit prolapse have higher strain compared to normal valves, particularly in the posterior leaflet. Although higher strain is observed with worsening MR and larger valves and annuli, mitral valve leaflet thickness-and, thus, underlying MV pathology-is the most significant independent determinant of valve deformation. Future studies are needed to assess the impact of MV strain determination on clinical outcome.
Assuntos
Prolapso da Valva Mitral , Humanos , Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/diagnóstico por imagem , Valor Preditivo dos Testes , Prolapso , Volume Sistólico , Função Ventricular EsquerdaRESUMO
OBJECTIVES: This study hypothesized that left ventricular (LV) enlargement in Barlow disease can be explained by accounting for the total volume load that consists of transvalvular mitral regurgitation (MR) and the prolapse volume. BACKGROUND: Barlow disease is characterized by long prolapsing mitral leaflets that can harbor a significant amount of blood-the prolapse volume-at end-systole. The LV in Barlow disease can be disproportionately enlarged relative to MR severity, leading to speculation of Barlow cardiomyopathy. METHODS: Cardiac magnetic resonance (CMR) was used to compare MR, prolapse volume, and heart chambers remodeling in patients with Barlow disease (bileaflet prolapse [BLP]) and in single leaflet prolapse (SLP). RESULTS: A total of 157 patients (81 with BLP, 76 with SLP) were included. Patients with SLP were older and more had hypertension. Patients with BLP had more heart failure. Indexed LV end-diastolic volume was larger in BLP despite similar transvalvular MR. However, the prolapse volume was larger in BLP, which led to larger total volume load compared with SLP. Increasing tertiles of prolapse volume and MR both led to an incremental increase in LV end-diastolic volume in BLP. Using the total volume load improved the correlation with indexed LV end-diastolic volume in the BLP group, which closely matched that of SLP. A multivariable model that incorporated the prolapse volume explained left heart chamber enlargement better than a MR-based model, independent of prolapse category. CONCLUSIONS: The prolapse volume is part of the total volume load exerted on the LV during the cardiac cycle and could help explain the disproportionate LV enlargement relative to MR severity noted in Barlow disease.
Assuntos
Insuficiência da Valva Mitral , Prolapso da Valva Mitral , Ventrículos do Coração , Humanos , Espectroscopia de Ressonância Magnética , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Prolapso da Valva Mitral/diagnóstico por imagem , Valor Preditivo dos TestesRESUMO
OBJECTIVES: This study used cardiovascular magnetic resonance (CMR) to evaluate whether elevated extracellular volume (ECV) was associated with mitral valve prolapse (MVP) or if elevated ECV was a consequence of remodeling independent of primary mitral regurgitation (MR) etiology. BACKGROUND: Replacement fibrosis in primary MR is more prevalent in MVP; however, data on ECV as a surrogate for diffuse interstitial fibrosis in primary MR are limited. METHODS: Patients with chronic primary MR underwent comprehensive CMR phenotyping and were stratified into an MVP cohort (>2 mm leaflet displacement on a 3-chamber cine CMR) and a non-MVP cohort. Factors associated with ECV and replacement fibrosis were assessed. The association of ECV and symptoms related to MR and clinical events (mitral surgery and cardiovascular death) was ascertained. RESULTS: A total of 424 patients with primary MR (229 with MVP and 195 non-MVP) were enrolled. Replacement fibrosis was more prevalent in the MVP cohort (34.1% vs. 6.7%; p < 0.001), with bi-leaflet MVP having the strongest association with replacement fibrosis (odds ratio: 10.5; p < 0.001). ECV increased with MR severity in a similar fashion for both MVP and non-MVP cohorts and was associated with MR severity but not MVP on multivariable analysis. Elevated ECV was independently associated with symptoms related to MR and clinical events. CONCLUSIONS: Although replacement fibrosis was more prevalent in MVP, diffuse interstitial fibrosis as inferred by ECV was associated with MR severity, regardless of primary MR etiology. ECV was independently associated with symptoms related to MR and clinical events. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823).
Assuntos
Insuficiência da Valva Mitral , Humanos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Valor Preditivo dos TestesRESUMO
BACKGROUND: Recent studies reported left ventricular (LV) fibrosis in patients with primary mitral regurgitation (MR) thought to be principally due to mitral valve prolapse (MVP). OBJECTIVES: This study sought to evaluate the prevalence, characteristics, and prognostic implications of LV fibrosis in a large cohort of primary MR patients with and without MVP using cardiovascular magnetic resonance (CMR). METHODS: Patients referred for contrast CMR assessment of chronic primary MR were enrolled and underwent comprehensive assessment of cardiac remodeling, severity of MR, and LV replacement fibrosis. Primary MR patients were stratified into: an MVP group if there was >2 mm mitral leaflet displacement on cine-CMR, or a non-MVP group. Patients were followed for arrhythmic events (sudden cardiac death, aborted sudden cardiac arrest, and sustained or inducible ventricular arrhythmia). RESULTS: A total of 356 primary MR patients (177 MVP and 179 non-MVP) were enrolled. LV fibrosis was more prevalent in the MVP group than the non-MVP group (36.7% vs. 6.7%; p < 0.001). The presence of MVP had the strongest association (odds ratio: 6.82; p < 0.001) with LV fibrosis even after adjustment for clinical variables, measures of cardiac remodeling, and MR severity. During follow-up (median 1,354 days), MVP patients with LV fibrosis had the highest event rate for arrhythmic events. CONCLUSIONS: In primary MR patients, LV fibrosis is more prevalent in MVP than non-MVP, suggesting a unique pathophysiology beyond volume overload in MVP. LV fibrosis in primary MR may represent a risk marker of arrhythmic events.
Assuntos
Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/epidemiologia , Prolapso da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/epidemiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Fibrose/diagnóstico por imagem , Fibrose/epidemiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a central role in arterial wall remodeling, affecting stability of fibrous caps covering atherosclerotic plaques. The objective of this study was to determine the spatial distribution of TIMP mass and MMP mass and activity of carotid endarterectomy (CEA) tissues and relate it to the distribution of atherosclerotic lesions. METHODS AND RESULTS: Fresh CEA tissues were imaged by multicontrast MRI to generate 3D reconstructions. Tissue segments were cut transversely from the common, bifurcation, internal, and external regions. Segments were subjected to total protein extractions and analyzed by ELISA for MMP-2 and -9 and TIMP-1 and -2 mass and by zymography for gelatinase activity. Segments at or near the bifurcation with highly calcified lesions contained higher MMP levels and activity than segments distant from the bifurcation; highly fibrotic or necrotic plaque contained lower MMP levels and activity and higher TIMP levels. Fatty streak, fibroatheroma with hemorrhage and calcification, and fully occluded lesions were enriched in MMP-2, MMP-9, and TIMP-1 and TIMP-2, respectively. CONCLUSIONS: The spatial distribution of MMPs and TIMPs in carotid atherosclerotic lesions is highly heterogeneous, reflecting lesion location, size, and composition. This study provides the first semi-quantitative maps of differential distribution of MMPs and TIMPs over atherosclerotic plaques.