RESUMEN
Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-B-type natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.
Asunto(s)
Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/genética , Cardiopatías/diagnóstico , Cardiopatías/genética , Mutación/genética , Prealbúmina/genética , Adulto , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Bundle Sheath Defective 2, BSD2, is a stroma-targeted protein initially identified as a factor required for the biogenesis of ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) in maize. Plants and algae universally have a homologous gene for BSD2 and its deficiency causes a RuBisCO-less phenotype. As RuBisCO can be the rate-limiting step in CO2 assimilation, the overexpression of BSD2 might improve photosynthesis and productivity through the accumulation of RuBisCO. To examine this hypothesis, we produced BSD2 overexpression lines in Arabidopsis. Compared with wild type, the BSD2 overexpression lines BSD2ox-2 and BSD2ox-3 expressed 4.8-fold and 8.8-fold higher BSD2 mRNA, respectively, whereas the empty-vector (EV) harbouring plants had a comparable expression level. The overexpression lines showed a significantly higher CO2 assimilation rate per available CO2 and productivity than EV plants. The maximum carboxylation rate per total catalytic site was accelerated in the overexpression lines, while the number of total catalytic sites and RuBisCO content were unaffected. We then isolated recombinant BSD2 (rBSD2) from E. coli and found that rBSD2 reduces disulfide bonds using reductants present in vivo, for example glutathione, and that rBSD2 has the ability to reactivate RuBisCO that has been inactivated by oxidants. Furthermore, 15% of RuBisCO freshly isolated from leaves of EV was oxidatively inactivated, as compared with 0% in BSD2-overexpression lines, suggesting that the overexpression of BSD2 maintains RuBisCO to be in the reduced active form in vivo. Our results demonstrated that the overexpression of BSD2 improves photosynthetic efficiency in Arabidopsis and we conclude that it is involved in mediating RuBisCO activation.
Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Fotosíntesis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Arabidopsis/fisiología , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiología , Escherichia coli , Regulación de la Expresión Génica de las Plantas , Proteínas Recombinantes , Ribulosa-Bifosfato Carboxilasa/metabolismoRESUMEN
Sarcoidosis is a systemic inflammatory disease characterized by the formation of noncaseating epithelioid granulomas. Multiple organs, including the lung, eyes, and skin, are involved in this disorder, and cardiac involvement is a major cause of morbidity and mortality in patients with this disorder. We present the case history of a 22-year-old man with neurosarcoidosis complicated by abrupt onset of cardiac tamponade. Cardiac tamponade is a rare but potentially fatal manifestation of sarcoidosis, which is treatable with glucocorticoid therapy. Including the present case, previously reported cases of sarcoidosis with cardiac tamponade are reviewed to delineate its clinical characteristics.
Asunto(s)
Taponamiento Cardíaco/etiología , Enfermedades del Sistema Nervioso Central/complicaciones , Derrame Pericárdico/cirugía , Pericardiocentesis/métodos , Sarcoidosis/complicaciones , Bloqueo de Rama/diagnóstico , Bloqueo de Rama/etiología , Taponamiento Cardíaco/diagnóstico , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/patología , Disnea/diagnóstico , Disnea/etiología , Electrocardiografía/métodos , Humanos , Masculino , Limitación de la Movilidad , Enfermedades Musculares/etiología , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/etiología , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/patología , Esteroides/administración & dosificación , Esteroides/uso terapéutico , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Although the benefit of updated therapeutic regimens, including bortezomib, on the survival of immunoglobulin light chain (AL) amyloidosis patients with heart failure (HF) has been reported, predictors of mortality in the patients treated with the updated therapy remain unclear. We retrospectively enrolled AL amyloidosis patients who had severe HF at the time of diagnosis and received the updated therapy, including bortezomib (n = 19, 61 ± 6 years old, 68% male). Severe HF was defined as the presence of both NYHA functional class III or IV and BNP > 200 pg/ml or NT-pro-BNP > 900 pg/ml. One-year mortality rate during follow-up after commencement of the treatment was 37%. Left ventricular morphological parameters and indexes of left ventricular diastolic function on admission were similar in the non-survivors and survivors. However, non-survivors had higher incidences of atrial fibrillation and ventricular tachycardia, higher serum total bilirubin levels (1.34 ± 0.55 vs. 0.61 ± 0.29 mg/dl), higher right atrial volume index (RAVI 49.7 ± 29.9 vs. 27.3 ± 6.8 ml/m2), lower tricuspid annular peak velocities during systole (RVs' 8.0 ± 1.8 vs. 11.6 ± 3.7 cm/sec) and late diastole (RVa' 3.4 ± 0.9 vs. 11.4 ± 5.3 cm/sec), and larger inferior vena cava dimension (22.7 ± 6.4 vs. 16.3 ± 4.9 mm) than those in survivors. Kaplan-Meier curve analyses showed that larger RAVI and lower RVs' and RVa', but not left ventricular systolic/diastolic dysfunction, predicted higher mortality during 1-year follow-up. The present results suggest that the presence of right-sided heart abnormality on admission is associated with high 1-year mortality in AL amyloidosis patients with severe HF under the updated therapeutic regimens.
Asunto(s)
Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Disfunción Ventricular Derecha/fisiopatología , Anciano , Fibrilación Atrial/etiología , Bilirrubina/sangre , Bortezomib/uso terapéutico , Ecocardiografía , Electrocardiografía , Femenino , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/fisiopatología , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico , Análisis de Regresión , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
Which combination of clinical parameters improves the prediction of prognosis in patients with pulmonary arterial hypertension (PAH) remains unclear. We examined whether combined assessment of pulmonary vascular resistance and right ventricular function by echocardiography is useful for classifying risks in PAH. In 41 consecutive patients with PAH (mean age of 48.9 ± 17.3 years, 31 females), a 6-min walk test, pulmonary function test, and echocardiography were performed at baseline and during PAH-specific therapies. The study endpoint was defined as a composite of cardiovascular death and hospitalization for PAH and/or right ventricular failure. During a follow-up period of 9.2 ± 8.7 months, 18 patients reached the endpoint. Multivariate regression analysis showed that the ratio of tricuspid regurgitation pressure gradient to the time-velocity integral of the right ventricular outflow tract (TRPG/TVI) and tricuspid annular plane systolic excursion (TAPSE) during PAH-specific treatment were independent prognostic predictors of the endpoint. Using cutoff values indicated by receiver operating characteristic analysis, the patients were divided into four subsets. Multivariate analyses by Cox's proportional hazards model adjusted for age, sex and body mass index indicated that subset 4 (TRPG/TVI ≥ 3.89 and TAPSE ≤ 18.9 mm) had a significantly higher event risk than did subset 1 (TRPG/TVI < 3.89 and TAPSE > 18.9 mm): HR = 25.49, 95% CI 4.70-476.97, p < 0.0001. Combined assessment of TRPG/TVI and TAPSE during adequate PAH-specific therapies enables classification of risks for death and/or progressive right heart failure in PAH.
Asunto(s)
Ecocardiografía/métodos , Hipertensión Arterial Pulmonar/epidemiología , Arteria Pulmonar/fisiopatología , Presión Esfenoidal Pulmonar/fisiología , Medición de Riesgo , Resistencia Vascular/fisiología , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Hipertensión Arterial Pulmonar/clasificación , Hipertensión Arterial Pulmonar/fisiopatología , Arteria Pulmonar/diagnóstico por imagen , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Sístole , Función Ventricular Izquierda/fisiología , Función Ventricular Derecha/fisiologíaRESUMEN
BACKGROUND: Fatty acid-binding protein 4 (FABP4), which is expressed in both adipocytes and macrophages, is secreted from the cells and acts as an adipokine. An elevated circulating FABP4 level is associated with insulin resistance and atherosclerosis.MethodsâandâResults:We investigated the causative association between FABP4 level and progression of atherosclerosis in subjects of the Tanno-Sobetsu Study, a population-based cohort. In 281 subjects without medication (male/female: 109/172) in the year 2010 or 2013, the carotid intima-media thickness (CIMT) assessed using carotid ultrasonography was significantly correlated with age, adiposity, blood pressure, renal dysfunction and levels of cholesterol, triglycerides, fasting glucose, HbA1c and FABP4 (r=0.331, P<0.001). Multiple regression analysis demonstrated that age, sex and FABP4 concentration were independent predictors of CIMT. A total of 78 (male/female: 29/49) of the 156 subjects in 2010 underwent carotid ultrasonography again in 2013. The change in CIMT each year during that 3-year period (mean±SD: 3.8±22.3 µm/year) was positively correlated with basal levels of high-sensitivity C-reactive protein (hsCRP) (r=0.231, P=0.046) and FABP4 (r=0.267, P=0.018) in 2010. After adjustment for age, sex and hsCRP level, the basal FABP4 level was independently associated with the change in CIMT per year. CONCLUSIONS: FABP4 concentration is an independent predictor of the progression of carotid atherosclerosis.
Asunto(s)
Enfermedades de las Arterias Carótidas/epidemiología , Progresión de la Enfermedad , Proteínas de Unión a Ácidos Grasos/sangre , Adipoquinas/sangre , Anciano , Aterosclerosis/sangre , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
A 64-year-old man was diagnosed with chronic-phase chronic myelogenous leukemia(CML)in May 2009. He was treated with imatinib and achieved complete cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed interstitial pneumonia and became intolerant to imatinib. He was then switched to nilotinib from October of the same year. In June 2013, he was diagnosed with drug-induced pericarditis resulting from nilotinib use, and thus, nilotinib was discontinued. Subsequently, he was followed up without specific treatment for CML. In January 2014, he was admitted to the Dept. of Cardiovascular, Renal and Metabolic Medicine at our hospital because of heart failure. After examinations of cardiac function, he was diagnosed with constrictive pericarditis. Therefore, pericardiolysis was performed by the Dept. of Cardiovascular Surgery at our hospital. Pathologic findings showed hyaline-like fibrous tissue proliferation in the pericardium, which was diagnosed as fibrous pericarditis induced by nilotinib. We report a case of chronic myelogenous leukemia that developed fibrous pericarditis owing to nilotinib use.
Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Pericarditis/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Análisis Citogenético , Fibrosis , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Masculino , Persona de Mediana Edad , Pericarditis/patología , Pericarditis/cirugía , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéuticoRESUMEN
BACKGROUND: Activity of mTOR complex 1 (mTORC1) has been shown to be up-regulated in animal models of heart failure. Here, we investigated the change and role of mTORC1 in human nonischemic dilated cardiomyopathy (NICM). METHODS: Endomyocardial biopsy specimens were obtained from patients with NICM (n=52) and from Brugada syndrome patients with normal LVEF as controls (n=10). The specimens were stained for phospho-ribosomal protein S6 (p-Rps6) and phospho-p70S6K (p-p70S6K), and the area with p-Rps6 signal was used as an index of mTORC1 activity. Using median mTORC1 activity, patients were divided into a high mTORC1 activity (H-mTOR) group and a low mTORC1 activity (L-mTOR) group. RESULTS: The ratio of p-Rps6-positive area in biopsy samples was 10-fold larger in patients with NICM than in controls (2.0±2.2% vs. 0.2±0.2%, p<0.01). p-p70S6K signal level was higher in the H-mTOR group than in the L-mTOR group. The proportion of patients with a family history of cardiomyopathy was higher and the proportion of patients on ACE inhibitors or angiotensin receptor blockers was lower in the H-mTOR group than in the L-mTOR group. The p-Rps6-positive area was correlated with extent of myocardial fibrosis (r=0.46, p<0.01). The cardiac event-free survival rate during a 5-year follow-up period tended to be lower in the H-mTOR group than in the L-mTOR group (52.9% vs. 81.6%, P=0.10). CONCLUSION: Aberrant activation of mTORC1 in cardiomyocytes was associated with myocardial fibrosis and a trend for worse prognosis in patients with NICM, indicating that persistently activated mTORC1 contributes to progression of human heart failure.
Asunto(s)
Síndrome de Brugada/genética , Cardiomiopatía Dilatada/genética , Insuficiencia Cardíaca/genética , Complejos Multiproteicos/metabolismo , Miocardio/enzimología , Serina-Treonina Quinasas TOR/metabolismo , Adulto , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Biopsia , Síndrome de Brugada/tratamiento farmacológico , Síndrome de Brugada/mortalidad , Síndrome de Brugada/patología , Cardiomiopatía Dilatada/tratamiento farmacológico , Cardiomiopatía Dilatada/mortalidad , Cardiomiopatía Dilatada/patología , Progresión de la Enfermedad , Endocardio/efectos de los fármacos , Endocardio/enzimología , Endocardio/patología , Activación Enzimática , Femenino , Fibrosis , Expresión Génica , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/patología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/enzimología , Ventrículos Cardíacos/patología , Humanos , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina , Persona de Mediana Edad , Complejos Multiproteicos/agonistas , Complejos Multiproteicos/genética , Miocardio/patología , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Estudios Retrospectivos , Proteínas Quinasas S6 Ribosómicas/genética , Proteínas Quinasas S6 Ribosómicas/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Análisis de Supervivencia , Serina-Treonina Quinasas TOR/genéticaRESUMEN
Whether different patterns of ventricular ballooning in takotsubo cardiomyopathy (TCM) reflect differences in trigger mechanisms or clinical outcomes is unclear. Here we examined differences in the clinical characteristics of typical and atypical forms of TCM. TCM patients (n = 251) in the BOREAS Registry were enrolled for comparison of TCM with apical ballooning (type A, n = 217) and TCM with non-apical ballooning (type non-A, n = 34). The percentage of females was significantly lower in the type non-A group (58.8 vs. 75.6 %), while other demographic parameters and triggers of TCM were similar in the two groups. Rate of mid-ventricular obstruction (MVO) was lower (2.9 vs. 14.3 %) in the type non-A group than in the type A group, though left ventricular ejection fractions in the two groups were comparable. During a follow-up period of 2.6 ± 2.8 years, TCM recurred in 2.9 % of the patients and cardiac death occurred in 4.0 %. Cox proportional hazard analysis indicated that body mass index (hazard ratio [HR]: 0.75, 95 % confidence interval [CI] 0.54-0.99) and MVO (HR: 14.71, CI 1.87-304.66) were determinants of TCM recurrence and that advanced age (HR: 1.09, CI 1.02-1.17) and cardiogenic shock (HR: 4.27, CI 1.07-18.93) were significantly associated with cardiac death. In conclusion, approximately 20 % of TCM patients show non-apical left ventricular ballooning, and female sex and MVO are less frequent in this type than in apical ballooning type TCM. Low body mass index and MVO are risk factors of recurrence, and advanced age and cardiogenic shock are risk factors of cardiac death in TCM.
Asunto(s)
Muerte , Ventrículos Cardíacos/fisiopatología , Choque Cardiogénico/mortalidad , Cardiomiopatía de Takotsubo/fisiopatología , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Comorbilidad , Electrocardiografía , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Recurrencia , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Whether an intervendor discordance of myocardial velocities determined by tissue Doppler echocardiography (TDE) can be generalized remains unclear. We compared intervendor variabilities of left ventricular (LV) and right ventricular (RV) myocardial velocities among three TDE systems. METHODS: Examinations with TDE were performed in 41 healthy subjects and 11 patients with cardiovascular risk factors (CVR) using α-7 (V1, Hitachi Aloka Medical), Artida (V2, Toshiba Medical Systems), and Vivid E9 (V3, GE Healthcare) on the same day. Peak systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities at medial and lateral sites of the mitral annulus and lateral site of the tricuspid annulus were measured using both pulsed-wave TDE and color TDE. Intra-observer and inter-observer variabilities were determined in 10 subjects and test-retest variability in 14 subjects. RESULTS: As for test-retest variability, reproducibilities of LV and RV myocardial velocities determined by pulsed-wave TDE and color TDE were relatively low but comparable between V1, V2, and V3. Myocardial velocities in healthy subjects determined by both pulsed-wave TDE and color TDE were significantly different among the three TDE systems. Myocardial velocities by pulsed-wave TDE in V3 were 2-12% lower (P < 0.05) than those by V2 and 5-14% lower (P < 0.05) than those by V1. Similar differences in myocardial velocities determined by both pulsed-wave TDE and color TDE were found in patients with CVR. CONCLUSIONS: LV and RV myocardial velocities determined by both pulsed-wave TDE and color TDE are vendor dependent, and reproducibility of the myocardial velocities determined by both TDE systems is relatively low.
Asunto(s)
Diagnóstico por Imagen de Elasticidad/instrumentación , Volumen Sistólico , Disfunción Ventricular/diagnóstico por imagen , Disfunción Ventricular/fisiopatología , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Fatty acid-binding protein 4 (FABP4) is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, hypertension, and atherosclerosis. However, little is known about role of FABP4 in cardiac function. METHODS: From the database of the Tanno-Sobetsu Study, data for 190 subjects (male/female: 82/108) who were not treated with any medication and underwent echocardiography in 2011 or 2012 were retrieved for analyses of relationships between serum FABP4 concentration, metabolic markers and parameters of echocardiography. RESULTS: Serum FABP4 level was positively correlated with age, body mass index (BMI), blood pressure (BP), LDL cholesterol, HOMA-R and mean left ventricular (LV) wall thickness (LVWT, males: r = 0.315, females: r = 0.401, p < 0.01) and was negatively correlated with HDL cholesterol, estimated glomerular filtration rate (eGFR) and peak myocardial velocity during early diastole (e'; males: r = -0.434, females: r = -0.353, p < 0.01), an index of LV diastolic function. However, no significant correlation was found between FABP4 level and LV end-diastolic dimension, LV ejection fraction or LV mass index. There were significant correlations of e' with age, BMI, BP, eGFR, brain natriuretic peptide (BNP), FABP4, metabolic markers and LVWT. Multivariate regression analysis adjusted by HOMA-R, BMI, eGFR, BNP or LVWT in addition to age, gender and BP revealed that serum FABP4 concentration was independently correlated with e'. CONCLUSIONS: Elevation of circulating FABP4 may contribute to LV diastolic dysfunction in a general population.
Asunto(s)
Proteínas de Unión a Ácidos Grasos/sangre , Vigilancia de la Población , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/diagnóstico , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodosRESUMEN
BACKGROUND: Inter-vendor discordance in three-dimensional speckle-tracking echocardiography (3DS) remains uncharacterized. We aimed to examine inter-vendor discordance of left ventricular (LV) volumes, and functional parameters and their reproducibilities between two commercially available 3DS systems. METHODS: Echocardiographic examinations with 3DS were performed in 26 healthy subjects (age 34 ± 13 years, 85% men) using a Vivid E9 system (V1) with 4V probe (GE Health Care) and Artida (V2) with PST-25SX probe (Toshiba Medical Systems) on the same day. LV variables and global LV longitudinal, circumferential, radial, and area strains were measured by vendor-specific softwares, 4D strain EchoPAC BT11 (for V1) and 3D WMT (for V2), respectively. Reproducibility of data was assessed by an intra-class correlation coefficient (ICC). RESULTS: The mean time required for 3DS analysis was 5.4 ± 1.5 min for V1, being 21% less than that for V2 (6.8 ± 1.9 min, P < 0.01). Reproducibilities of all LV strains were comparable between V1 (ICC 0.50-0.82) and V2 (ICC 0.51-0.76), except for intra-observer and inter-observer reproducibilities of radial strain being lower in V2 (ICC for V1 0.82 and 0.82 and ICC for V2 0.44 and 0.40, respectively). LV strains in all directions and area were significantly different between V1 and V2, though LV volumes and ejection fraction were comparable. CONCLUSIONS: Global longitudinal, circumferential, and area LV strains are reproducible in both 3DS vendors. However, values of three-dimensional LV strains by 3DS are highly vendor-dependent.
Asunto(s)
Algoritmos , Ecocardiografía Tridimensional/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Función Ventricular Izquierda/fisiología , Adulto , Estudios Transversales , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
AIMS: The role of necroptosis in dilated cardiomyopathy (DCM) remains unclear. Here, we examined whether phosphorylation of mixed lineage kinase domain-like protein (MLKL), an indispensable event for execution of necroptosis, is associated with the progression of DCM. METHODS AND RESULTS: Patients with DCM (n = 56, 56 ± 15 years of age; 68% male) were enrolled for immunohistochemical analyses of biopsies. Adverse events were defined as a composite of death or admission for heart failure or ventricular arrhythmia. Compared with the normal myocardium, increased signals of MLKL phosphorylation were detected in the nuclei, cytoplasm, and intercalated discs of cardiomyocytes in biopsy samples from DCM patients. The phosphorylated MLKL (p-MLKL) signal was increased in enlarged nuclei or nuclei with bizarre shapes in hypertrophied cardiomyocytes. Nuclear p-MLKL level was correlated negatively with septal peak myocardial velocity during early diastole (r = -0.327, P = 0.019) and was correlated positively with tricuspid regurgitation pressure gradient (r = 0.339, P = 0.023), while p-MLKL level in intercalated discs was negatively correlated with mean left ventricular wall thickness (r = -0.360, P = 0.014). During a median follow-up period of 3.5 years, 10 patients (18%) had adverse events. To examine the difference in event rates according to p-MLKL expression levels, patients were divided into two groups by using the median value of nuclear p-MLKL or intercalated disc p-MLKL. A group with high nuclear p-MLKL level (H-nucMLKL group) had a higher adverse event rate than did a group with low nuclear p-MLKL level (L-nucMLKL group) (32% vs. 4%, P = 0.012), and Kaplan-Meier survival curves showed that the adverse event-free survival rate was lower in the H-nucMLKL group than in the L-nucMLKL group (P = 0.019 by the log-rank test). Such differences were not detected between groups divided by a median value of intercalated disc p-MLKL. In δ-sarcoglycan-deficient (Sgcd-/- ) mice, a model of DCM, total p-MLKL and nuclear p-MLKL levels were higher than in wild-type mice. CONCLUSION: The results suggest that increased localization of nuclear p-MLKL in cardiomyocytes is associated with left ventricular diastolic dysfunction and future adverse events in DCM.
Asunto(s)
Cardiomiopatía Dilatada , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Animales , Femenino , Masculino , Ratones , Ventrículos Cardíacos , Miocardio/patología , Proteínas Quinasas , Persona de Mediana Edad , AncianoRESUMEN
A 56-year-old postmenopausal woman with out-of-hospital cardiac arrest caused by acute myocardial infraction was successfully resuscitated by intensive treatments and recovered without any neurological disability. She was diagnosed as having familial hypercholesterolemia (FH) based on a markedly elevated low-density lipoprotein cholesterol (LDL-C) level and family history of premature coronary artery disease. Genetic testing in her family members showed that a variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (c.2004Cï¼A, p.S668R), which had been previously reported as having uncertain significance, was associated with FH, indicating that the variant is a potential candidate for the FH phenotype. Next-generation sequencing analysis for the proband also showed that there was a heterozygous mutation of the ATP-binding cassette sub-family G member 5 ( ABCG5) gene (c.1166Gï¼A, R389H), which has been reported to increase LDL-C level and the risk of cardiovascular disease. She was also diagnosed as having type 1 CD36 deficiency based on a lack of myocardial uptake of 123I-labeled 15-(p-iodophenyl)-3-R,S-methyl-pentadecanoic acid in scintigraphy and the absence of CD36 antigen in both monocytes and platelets in flow cytometry. She had a homozygous mutation of the CD36 gene (c.1126-5_1127delTTTAGAT), which occurs in a canonical splice site (acceptor) and is predicted to disrupt or distort the normal gene product. To our knowledge, this is the first report of a heterozygous FH phenotype caused by possibly oligogenic variants of the PCSK9 and ABCG5 genes complicated with type I CD36 deficiency caused by a novel homozygous mutation. Both FH phenotype and CD36 deficiency might have caused extensive atherosclerosis, leading to acute myocardial infarction in the present case.
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Hiperlipoproteinemia Tipo II , Infarto del Miocardio , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/genética , Trastornos de las Plaquetas Sanguíneas , Femenino , Enfermedades Genéticas Congénitas , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/genética , Lipoproteínas/genética , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/genética , Fenotipo , Proproteína Convertasa 9/genética , Receptores de LDL/genéticaRESUMEN
BACKGROUND: Two-dimensional speckle tracking imaging (2DS) enables quantitative measurement of left ventricular strain. However, application of 2DS for measurement of circumferential carotid arterial strain (CAS) is not fully elucidated. We investigated the feasibility and reproducibility of measuring CAS by 2DS and determinants of CAS in healthy subjects. METHODS: Fifty-one healthy subjects (20 men and 31 women) with a mean age of 29 ± 11 years were enrolled. Ultrasound examination of bilateral common carotid arteries (CCAs) was performed and short axial views were recorded. The mean intima-media thickness (IMT) of bilateral CCAs was measured using semiautomated edge-detection software. Bilateral peak CAS at systole and time to peak CAS in each region were measured by 2DS. Stiffness parameter ß of bilateral CCAs was measured and bilateral cardio-ankle vascular index (CAVI) was recorded. Intraobserver and interobserver variabilities for mean CAS were calculated in 15 subjects. RESULTS: Of the 612 regions, 577 (94%) had adequate waveforms for measurement of CAS. The mean value of CAS was 6.7 ± 2.1%. Required time for CAS analysis was 128 ± 12 seconds per subject. Multiple regression analysis identified age (P < 0.001) and pulse pressure (P < 0.05) as independent significant determinants of mean CAS. Corrected CAS, which was calculated as mean CAS/pulse pressure, correlated with age, mean IMT, and stiffness parameter ß and systolic pressure (P < 0.001), age (P < 0.01), and stiffness parameter ß (P = 0.02) were identified as independent significant determinants of corrected CAS. Coefficient of variance (CV) of intraobserver and interobserver variabilities for mean CAS were 8.8% and 5.9%, respectively. CONCLUSIONS: 2DS in the CCAs is simply and quickly performed with high feasibility and excellent reproducibility. In healthy subjects, age and pulse pressure are the most important determinants of mean CAS.
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Arteria Carótida Común/diagnóstico por imagen , Adulto , Índice Tobillo Braquial , Arteria Carótida Común/fisiología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Reproducibilidad de los Resultados , Ultrasonografía , Adulto JovenRESUMEN
Background: Takayasu arteritis (TA) is a large vessel vasculitis of unknown etiology characterized by chronic inflammatory changes of the aorta and its major branches. Complications such as anastomotic aneurysm and valve detachment have been reported in active TA patients who received aortic valve replacement and graft replacement of aorta. Case Summary:A 61-year-old man with a history of emergency aortic valve replacement and patch closure of the noncoronary sinus of Valsalva due to acute heart failure induced by acute aortic regurgitation and ruptured sinus of Valsalva 4 years ago was referred for exertional dyspnea. Dilatation of the sinus of Valsalva together with protrusion of the right sinus of Valsalva and ostial stenosis of the left coronary artery were newly found by computed tomography (CT). A Bentall operation with concomitant coronary artery bypass grafting was successfully performed with a composite graft. Diagnosis of TA was made on the basis of histological analyses of the resected sinus of Valsalva, though other arterial manifestations were not detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography. Three months later, a follow-up study revealed left coronary ostial pseudoaneurysm at the anastomotic site together with strong 18F-FDG uptake, leading to commencement of steroid therapy. Eight months later, disappearance of left coronary ostial pseudoaneurysm was found by a follow-up CT scan. Conclusion: This is a rare TA case in whom spontaneous resolution of coronary anastomotic aneurysm by steroid therapy was found without reconstructive surgery.
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BACKGROUND: There are a lot of reports of the renal failure and heart failure due to coarctation of the aorta. However, there are no case reports in which revascularization dramatically improved left ventricular function in patients with progressive decline in left ventricular function. Herein, we present a rare case in which the left ventricular function was dramatically improved by surgical treatment for progressive left ventricular dysfunction due to atypical coarctation of the aorta. CASE PRESENTATION: A 58-year-old man underwent left axillary artery-bilateral femoral artery bypass at another hospital for atypical coarctation of the aorta due to Takayasu's arteritis. Approximately 10 years later, he was re-hospitalized for heart failure, and the left ventricular ejection fraction gradually decreased to 28%. Computed tomography showed severe calcification and stenosis at the same site from the peripheral thoracic descending aorta to the lower abdominal aorta of the renal artery, and aortography showed delayed bilateral renal artery blood flow. An increase in plasma renin activity was also observed. Despite the administration of multiple antihypertensive drugs, blood pressure control was insufficient. We decided to perform surgical treatment to improve progressive cardiac dysfunction due to increased afterload and activated plasma renin activity. Descending thoracic aorta-abdominal aorta bypass and revascularization of the bilateral renal arteries via the great saphenous vein grafts were performed. Postoperative blood pressure control was improved, and the dose of antihypertensive drugs could be reduced. Plasma renin activity decreased, and transthoracic echocardiography 1.5 years later showed an improvement in contractility with a left ventricular ejection fraction of 58%. CONCLUSION: In atypical coarctation of the aorta in patients with decreased bilateral renal blood flow, heart failure due to renal hypertension, and progressive decrease in left ventricular contractility, descending thoracic aorta-abdominal aortic bypass and bilateral renal artery recirculation can be extremely effective.
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Aorta Abdominal , Coartación Aórtica , Insuficiencia Cardíaca , Arteritis de Takayasu , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/cirugía , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Coartación Aórtica/complicaciones , Coartación Aórtica/diagnóstico por imagen , Coartación Aórtica/cirugía , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/cirugía , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Circulación Renal , Volumen Sistólico , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/cirugía , Función Ventricular IzquierdaRESUMEN
BACKGROUND: The 6-min walk test (6MWT) provides prognostic information for patients with interstitial lung disease (ILD). Parameter determined by Doppler echocardiography after the 6MWT (6 MW stress echocardiography) is shown to be a predictor of future development of pulmonary hypertension in patients with connective tissue disease. However, the clinical utility of 6 MW stress echocardiography in predicting cardiopulmonary events in patients with ILD remains unknown. We examined whether parameters determined by 6 MW stress echocardiography independent predictors of adverse events in patients with ILD. METHODS: Echocardiographic examinations were performed in 68 consecutively enrolled patients with ILD (age, 65 ± 10 years, 65% men). A pressure gradient of tricuspid regurgitation (TRPG) and pulmonary vascular resistance (PVRecho) calculated using the following formula [PVRecho = (peak velocity of TR × 10/time-velocity integral of right ventricular outflow (RVOT-VTI)) + 0.16] were measured at baseline and at post 6MWT. Data for parameters of pulmonary functional tests and for 6MWT were collected. RESULTS: During a mean follow-up period of 22 ± 12 months, 22 patients experienced cardiopulmonary events. In univariate analysis, %VC, TRPG, PVRecho, TRPG post 6MWT, and PVRecho post 6MWT were significantly associated with cardiopulmonary events. Multivariate analysis using the Cox proportional hazards model indicated that %VC [hazard ratio (HR): 0.97, p = 0.009] and PVRecho post 6MWT (HR: 1.77, p = 0.004) were independent predictors of cardiopulmonary events in patients with ILD. CONCLUSIONS: In addition to parameters of pulmonary function tests, increased PVRecho post 6MWT is a significant predictor of cardiopulmonary events in patients with ILD. A 6 MW stress echocardiography is useful in assessing the risk of adverse events in patients with ILD.
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Hipertensión Pulmonar , Enfermedades Pulmonares Intersticiales , Anciano , Ecocardiografía de Estrés , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pronóstico , CaminataRESUMEN
Nonalcoholic fatty liver disease has been reported to be potentially linked to cardiovascular disease. Fatty liver index (FLI) is a noninvasive and simple predictor of nonalcoholic fatty liver disease. However, little is known about the relationship between FLI and cardiac function, especially in a general population. We investigated the relationships of FLI with echocardiographic parameters in 185 subjects (men/women: 79/106) of the Tanno-Sobetsu Study, a population-based cohort, who were not being treated with any medication and who underwent echocardiography. FLI was negatively correlated with high-density lipoprotein cholesterol and peak myocardial velocity during early diastole (e'; r = -0.342, p <0.001), an index of left ventricular (LV) diastolic function, and ratio of peak mitral velocities during early and late diastole (E/A) and was positively correlated with age, systolic and diastolic blood pressures, creatinine, uric acid, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, ratio of mitral to myocardial early diastolic peak velocity (E/e'), left atrial volume index and LV mass index. No significant correlation was found between FLI and LV ejection fraction. Stepwise multivariable regression analysis showed that FLI was independently and negatively associated with e' after adjustment of age, gender, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, and high-sensitivity C-reactive protein. Conversely, e' was independently and negatively associated with FLI after adjustment of age, gender, systolic blood pressure, and LV ejection fraction. In conclusion, elevated FLI is independently associated with LV diastolic dysfunction in a general population without medication. FLI would be a novel marker of LV diastolic dysfunction as an early sign of myocardial injury.
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Hígado Graso/diagnóstico , Disfunción Ventricular Izquierda/diagnóstico , Anciano , Velocidad del Flujo Sanguíneo , Índice de Masa Corporal , Estudios de Cohortes , Ecocardiografía , Hígado Graso/sangre , Hígado Graso/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos/sangre , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/fisiopatología , Circunferencia de la Cintura , gamma-Glutamiltransferasa/sangreRESUMEN
A 14-year-old girl with cardiopulmonary arrest was referred to our hospital. She had received an injection of inactivated influenza vaccine 7 days before the referral. Her cardiac rhythm was pulseless wide QRS tachycardia, and mechanical circulatory support was immediately begun. Results of endomyocardial biopsy showed that there was massive infiltration of CD3- and CD68-positive cells and various degrees of cardiomyocyte necrosis in all of 3 endomyocardial specimens, whereas infiltration of eosinophils or giant cells was not observed. A histologic diagnosis of lymphocytic myocarditis was made. Acute myocarditis is a rare but potentially fatal complication of the influenza vaccination.