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1.
Elife ; 92020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33320094

RESUMO

Over 1.6 million Americans suffer from significant tricuspid valve leakage. In most cases this leakage is designated as secondary. Thus, valve dysfunction is assumed to be due to valve-extrinsic factors. We challenge this paradigm and hypothesize that the tricuspid valve maladapts in those patients rendering the valve at least partially culpable for its dysfunction. As a first step in testing this hypothesis, we set out to demonstrate that the tricuspid valve maladapts in disease. To this end, we induced biventricular heart failure in sheep that developed tricuspid valve leakage. In the anterior leaflets of those animals, we investigated maladaptation on multiple scales. We demonstrated alterations on the protein and cell-level, leading to tissue growth, thickening, and stiffening. These data provide a new perspective on a poorly understood, yet highly prevalent disease. Our findings may motivate novel therapy options for many currently untreated patients with leaky tricuspid valves.


Assuntos
Matriz Extracelular/metabolismo , Insuficiência Cardíaca/complicações , Hemodinâmica , Insuficiência da Valva Tricúspide/etiologia , Valva Tricúspide/metabolismo , Função Ventricular Esquerda , Função Ventricular Direita , Adaptação Fisiológica , Animais , Modelos Animais de Doenças , Metabolismo Energético , Matriz Extracelular/genética , Matriz Extracelular/patologia , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Regulação da Expressão Gênica , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Masculino , Carneiro Doméstico , Transdução de Sinais , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/fisiopatologia , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/metabolismo , Insuficiência da Valva Tricúspide/fisiopatologia
2.
Haematologica ; 97(2): 193-200, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21993671

RESUMO

BACKGROUND: Patients with Chuvash polycythemia, (homozygosity for the R200W mutation in the von Hippel Lindau gene (VHL)), have elevated levels of hypoxia inducible factors HIF-1 and HIF-2, often become iron-deficient secondary to phlebotomy, and have elevated estimated pulmonary artery pressure by echocardiography. The objectives of this study were to provide a comprehensive echocardiographic assessment of cardiovascular physiology and to identify clinical, hematologic and cardiovascular risk factors for elevation of tricuspid regurgitation velocity in children and adults with Chuvash polycythemia. DESIGN AND METHODS: This cross-sectional observational study of 120 adult and pediatric VHL(R200W) homozygotes and 31 controls at outpatient facilities in Chuvashia, Russian Federation included echocardiography assessment of pulmonary artery pressure (tricuspid regurgitation velocity), cardiac volume, and systolic and diastolic function, as well as hematologic and clinical parameters. We determined the prevalence and risk factors for elevation of tricuspid regurgitation velocity in this population and its relationship to phlebotomy. RESULTS: The age-adjusted mean ± SE tricuspid regurgitation velocity was higher in VHL(R200W) homozygotes than controls with normal VHL alleles (2.5±0.03 vs. 2.3±0.05 m/sec, P=0.005). The age-adjusted left ventricular diastolic diameter (4.8±0.05 vs. 4.5±0.09 cm, P=0.005) and left atrial diameter (3.4±0.04 vs. 3.2±0.08 cm, P=0.011) were also greater in the VHL(R200W) homozygotes, consistent with increased blood volume, but the elevation in tricuspid regurgitation velocity persisted after adjustment for these variables. Among VHL(R200W) homozygotes, phlebotomy therapy was associated with lower serum ferritin concentration, and low ferritin independently predicted higher tricuspid regurgitation velocity (standardized beta=0.29; P=0.009). CONCLUSIONS: Children and adults with Chuvash polycythemia have higher estimated right ventricular systolic pressure, even after adjustment for echocardiography estimates of blood volume. Lower ferritin concentration, which is associated with phlebotomy, independently predicts higher tricuspid regurgitation velocity (www.clinicaltrials.gov identifier NCT00495638).


Assuntos
Anemia Ferropriva/genética , Hipóxia/genética , Policitemia/genética , Pressão Propulsora Pulmonar/fisiologia , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adolescente , Adulto , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/metabolismo , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Homozigoto , Humanos , Hipóxia/epidemiologia , Hipóxia/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Policitemia/epidemiologia , Policitemia/metabolismo , Federação Russa/epidemiologia , Insuficiência da Valva Tricúspide/epidemiologia , Insuficiência da Valva Tricúspide/genética , Insuficiência da Valva Tricúspide/metabolismo , Regulação para Cima/fisiologia , Função Ventricular Esquerda/fisiologia
3.
Int J Cardiol ; 151(3): 323-7, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20580447

RESUMO

BACKGROUND: Most of the atrial cardiomyocytes with positive terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labelling (TUNEL) reaction are not apoptotic in patients with mitral and tricuspid valve diseases. The TUNEL-positive myocytes with expression of spliceosome assembly factor SC-35, an indicator of increased RNA synthesis, should be living cardiomyocytes. METHODS: This study analyzed twenty-three patients with significant mitral and tricuspid regurgitation. Fifteen patients had persistent atrial fibrillation, and eight had sinus rhythm. Atrial appendageal tissues were obtained during surgery. Immunohistochemical study was performed. RESULTS: Immunohistochemical study of fibrillating right atrial myocardium demonstrated that 44.8 ± 24.6% of myocytes had TUNEL-positive nuclei whereas 39.4 ± 21.4% of myocytes had TUNEL-positive nuclei in sinus right atrial myocardium (p=0.682). However, most (81.6%) nuclei of TUNEL-positive myocytes in the fibrillating right atria also expressed proliferating cell nuclear antigen (PCNA), an indicator of DNA replication and repair, and most nuclei (91.8%) of TUNEL-positive myocytes also expressed SC-35. In fibrillating left atria, most (88.1%) nuclei of TUNEL-positive myocytes also expressed SC-35. Similarly, in sinus right atrial myocardium, most (78.0%) nuclei of TUNEL-positive myocytes expressed PCNA, and most (91.4%) nuclei of TUNEL-positive myocytes also expressed SC-35, but none expressed Ki-67, a replication-associated antigen. Additionally, the percentage of TUNEL-positive myocytes in the right atria significantly and positively correlated with the percentage of PCNA-positive myocytes (r=0.826, p<0.001) and SC-35 positive myocytes (r=0.713, p<0.001). CONCLUSIONS: Most TUNEL-positive atrial cardiomyocytes in patients with mitral and tricuspid regurgitation are living cardiomyocytes.


Assuntos
Regulação da Expressão Gênica , Marcação In Situ das Extremidades Cortadas/métodos , Miócitos Cardíacos/metabolismo , Proteínas Nucleares/biossíntese , Ribonucleoproteínas/biossíntese , Spliceossomos/metabolismo , Insuficiência da Valva Tricúspide/metabolismo , Adulto , Idoso , Apêndice Atrial/metabolismo , Apêndice Atrial/patologia , Sobrevivência Celular/fisiologia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/patologia , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Antígeno Nuclear de Célula em Proliferação/biossíntese , Ribonucleoproteínas/genética , Fatores de Processamento de Serina-Arginina , Insuficiência da Valva Tricúspide/genética , Insuficiência da Valva Tricúspide/patologia
4.
Kardiol Pol ; 67(4): 378-83, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19492250

RESUMO

BACKGROUND: Although surgical treatment for tetralogy of Fallot (TOF) has been used with considerable success, right ventricular function may remain altered after repair. The NT-proBNP assessment has been shown to be a reliable parameter for the heart failure assessment. AIM: To determine NT-proBNP values in assessment of right ventricular function in children after TOF correction. METHODS: In 20 patients after TOF correction aged from 10 to 17 years (follow-up period ranged from 7 to 16 years) NT-proBNP level at rest and after exertion, treadmill test and echocardiography were performed. In the control healthy children NT-proBNP level at rest was assessed. RESULTS: The mean values of NT-proBNP level in the TOF patients were significantly higher than in controls (11.0 +/- 12.0 fmol/l and 5.4 +/- 7.5 fmol/l, p < 0.05). In patients repaired with a transannular patch the mean value of NT-proBNP level was higher than in children operated on without a transannular patch (18.3 +/- 16.5 vs. 6.8 +/- 7.9 fmol/l, p < 0.05). In children in whom physiological shortening of QRS complex during treadmill test was observed, NT-proBNP level was lower (mean values at rest 5.0 +/- 4.8 fmol/l and after exertion 7.3 +/- 6.3 fmol/l) compared to patients with prolongation of QRS duration (mean values at rest 17.7 +/- 15.6 fmol/l and after exertion 20.3 +/- 17.8 fmol/l) (p < 0.05). Significant differences in NT-proBNP levels between children with severe pulmonary regurgitation and mild/moderate pulmonary regurgitation were detected (mean values at rest 18.6 +/- 15.0 vs. 4.2 +/- 3.9 fmol/l and after exertion 20.0 +/- 18.6 vs. 5.7 +/- 4.6 fmol/l) (p < 0.05). The NT-proBNP levels were also higher in children with severe tricuspid valve insufficiency compared to children with mild/moderate tricuspid valve regurgitation (mean values at rest 19.5 +/- 15.0 vs. 4.9 +/- 3.7 fmol/l and after exertion 22.5 +/- 17.1 vs. 7.0 +/- 4.6 fmol/l). CONCLUSIONS: The NT-proBNP level in patients after TOF correction is higher than in healthy children. The NT-proBNP level is higher and exertion tolerance is lower in children repaired with rather than without transannular patch. In patients with severe pulmonary regurgitation and/or severe tricuspid valve insufficiency NT-proBNP level is higher than in patients without right ventricular volume overload. The measurement of NT-proBNP level might be helpful in order to separate those patients after TOF correction who are at increased risk of heart failure and arrhythmia.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Tetralogia de Fallot/cirurgia , Disfunção Ventricular Direita/diagnóstico , Adolescente , Biomarcadores/metabolismo , Criança , Ecocardiografia , Teste de Esforço , Feminino , Humanos , Masculino , Insuficiência da Valva Pulmonar/diagnóstico , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/metabolismo , Estenose da Valva Pulmonar/diagnóstico , Estenose da Valva Pulmonar/etiologia , Estenose da Valva Pulmonar/metabolismo , Tetralogia de Fallot/complicações , Insuficiência da Valva Tricúspide/diagnóstico , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/metabolismo , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/metabolismo
5.
J Cardiol ; 27 Suppl 2: 31-7; discussion 38, 1996.
Artigo em Japonês | MEDLINE | ID: mdl-9067815

RESUMO

Cardiac amyloidosis is associated with amyloid deposits in cardiac valves which also show the thickening of leaflets and cusps. This study examined amyloid deposits on cardiac valves to investigate the possible involvement in echocardiographic valvular abnormalities in 17 patients with systemic amyloidosis (12 males and 5 females aged 44 to 82, mean 66.4 years) in the autopsy files of the National Cardiovascular Center between 1980 and 1993. All four cardiac valves were examined histologically using hematoxylin-eosin and Congo red stains with polarization. All cusps and leaflets were divided into six segments and all segments of each cusp and leaflet were scored for the proportional area of amyloid deposit (from 0 to 3). The immunohistochemical types of amyloid proteins were immunoglobulin light chain-related (AL) amyloidosis in 16 cases, and amyloid A-related (AA) amyloidosis in one case. Twelve of 16 cases with AL amyloidosis were subclassified as AL lambda type and 4 were subclassified as AL kappa type. In the atrioventricular valve leaflets, the atrial side of basal portion showed the most remarkable amyloid deposits among the six segments. In the semilunar valves, amyloid deposits were mild in the tip and middle portions. Among the patients with AL amyloidosis, those with AL lambda type amyloid appeared to have greater deposits than those with AL kappa type amyloid. Mitral valves appearing abnormal by echocardiography had greater amyloid deposits. However, considering other factors affecting valvular function, the relationship between the localization or the degree of amyloid deposition and endocardiographic valvular abnormalities was unclear.


Assuntos
Amiloide/metabolismo , Amiloidose/patologia , Cardiomiopatias/patologia , Valvas Cardíacas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/metabolismo , Cardiomiopatias/metabolismo , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/metabolismo , Insuficiência da Valva Mitral/patologia , Insuficiência da Valva Tricúspide/metabolismo , Insuficiência da Valva Tricúspide/patologia
7.
Arch Inst Cardiol Mex ; 50(4): 461-9, 1980.
Artigo em Espanhol | MEDLINE | ID: mdl-7469590

RESUMO

It is presented a case with mitral and tricuspid rheumatic valvulopathy and refractory chronic congestive heart failure, which developed two episodes of severe hyponatremia and hyperkalemia, accompanied in at least one occasion of hyperpreninemia and hyperaldosteronism, after administration of 50 and 100 mg of sprionolactone for 2 and 3 weeks. It is believed that this severe effect of spironolactone was due to the presence of an alteration of aldosterone receptors acquired during the large period of congestive failure suffered by the patient. In as much as we have studied 4 similar cases in the last few months, a note of warning is done in the use of this drug in the treatment of this type of cardiac condition.


Assuntos
Aldosterona/biossíntese , Insuficiência Cardíaca/metabolismo , Espironolactona/metabolismo , Idoso , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hiperaldosteronismo/induzido quimicamente , Hiperaldosteronismo/metabolismo , Masculino , Espironolactona/efeitos adversos , Espironolactona/uso terapêutico , Insuficiência da Valva Tricúspide/tratamento farmacológico , Insuficiência da Valva Tricúspide/metabolismo
8.
Am J Cardiol ; 40(3): 458-62, 1977 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-900044

RESUMO

A man evaluated for disabling chest pain was found to have isolated anatomically corrected transposition of the great vessels. Angiography demonstrated right and left atrioventricular (A-V) valve prolapse and normal coronary arteries. Atrial pacing produced chest pain, ischemic electrocardiographic changes, abnormal myocardial lactate metabolism and marked elevation of the left ventricular end-diastolic pressure; all of these changes returned to normal on termination of pacing. The association of corrected transposition and bilateral A-V valve prolapse and the possible causes of myocardial ischemia in this patient are discussed.


Assuntos
Dor/etiologia , Transposição dos Grandes Vasos/complicações , Insuficiência da Valva Tricúspide/complicações , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Lactatos/metabolismo , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Marca-Passo Artificial , Prolapso , Radiografia , Tórax , Transposição dos Grandes Vasos/metabolismo , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/metabolismo
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