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AIMS: A comprehensive description of transcatheter heart valve (THV) failure has not been performed. We undertook a systematic review to investigate the aetiology, diagnosis, management, and outcomes of THV failure. METHODS AND RESULTS: The systematic review was performed in accordance with the PRISMA guidelines using EMBASE, MEDLINE, and Scopus. Between December 2002 and March 2014, 70 publications reported 87 individual cases of transcatheter aortic valve implantation (TAVI) failure. Similar to surgical bioprosthetic heart valve failure, we observed cases of prosthetic valve endocarditis (PVE) (n = 34), structural valve failure (n = 13), and THV thrombosis (n = 15). The microbiological profile of THV PVE was similar to surgical PVE, though one-quarter had satellite mitral valve endocarditis, and surgical intervention was required in 40% (75% survival). Structural valve failure occurred most frequently due to leaflet calcification and was predominantly treated by redo-THV (60%). Transcatheter heart valve thrombosis occurred at a mean 9 ± 7 months post-implantation and was successfully treated by prolonged anticoagulation in three-quarters of cases. Two novel causes of THV failure were identified: late THV embolization (n = 18); and THV compression (n = 7) following cardiopulmonary resuscitation (CPR). These failure modes have not been reported in the surgical literature. Potential risk factors for late THV embolization include low prosthesis implantation, THV undersizing/underexpansion, bicuspid, and non-calcified anatomy. Transcatheter heart valve embolization mandated surgery in 80% of patients. Transcatheter heart valve compression was noted at post-mortem in most cases. CONCLUSION: Transcatheter heart valves are susceptible to failure modes typical to those of surgical bioprostheses and unique to their specific design. Transcatheter heart valve compression and late embolization represent complications previously unreported in the surgical literature.
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Estenosis de la Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas , Falla de Prótesis/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Embolia/etiología , Endocarditis/tratamiento farmacológico , Endocarditis/etiología , Endocarditis/prevención & control , Femenino , Oclusión de Injerto Vascular/etiología , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Histoplasmosis/diagnóstico , Histoplasmosis/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity. METHODS: In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and galectin 3 (gal-3). We determined if biomarker increases were associated with cardiotoxicity at the same visit and the subsequent visit over the entire course of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation Criteria; alternative definitions were also considered. RESULTS: Across the entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15 months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at the same visit [MPO hazard ratio 1.38 (95% CI 1.10-1.71), P = 0.02; PlGF 3.78 (1.30-11.0), P = 0.047; GDF-15 1.71 (1.15-2.55), P = 0.01] and the subsequent visit. MPO was robust to alternative outcome definitions. CONCLUSIONS: Increases in MPO are associated with cardiotoxicity over the entire course of doxorubicin and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value. These findings motivate validation studies in additional cohorts.
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Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Cardiotoxicidad/diagnóstico , Cardiotoxinas/efectos adversos , Doxorrubicina/efectos adversos , Corazón/efectos de los fármacos , Trastuzumab/efectos adversos , Adulto , Biomarcadores/análisis , Mama/efectos de los fármacos , Proteína C-Reactiva/análisis , Cardiotoxicidad/etiología , Femenino , Galectina 3/análisis , Factor 15 de Diferenciación de Crecimiento/análisis , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Péptido Natriurético Encefálico/análisis , Fragmentos de Péptidos/análisis , Pronóstico , Troponina I/análisis , Receptor 1 de Factores de Crecimiento Endotelial Vascular/análisisRESUMEN
Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0µg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5-14.5. At 3months, male progeny were left sedentary or were swim trained for 4weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males.
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Metilación de ADN/fisiología , Dietilestilbestrol/toxicidad , Estrógenos no Esteroides/toxicidad , Corazón/crecimiento & desarrollo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Biosíntesis de Proteínas/fisiología , Factores de Edad , Animales , Metilación de ADN/efectos de los fármacos , ADN Metiltransferasa 3A , Femenino , Corazón/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Biosíntesis de Proteínas/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
The detrimental effects of in utero exposure to the non-steroidal estrogen diethylstilbestrol (DES) are particularly marked in women. Fetal hearts express estrogen receptors, making them potentially responsive to DES. To examine whether gestational exposure to DES would impact the heart, we exposed pregnant C57bl/6n dams to DES (0.1, 1.0, and 10.0 µg·(kg body mass)(-1)·day(-1)) on gestation days 11.5-14.5, and examined the measured cardiac structure/function and calcium homeostasis protein expression in adult females. At baseline, echocardiography revealed eccentric hypertrophy in mice treated with 10.0 µg·(kg body mass)(-1)·day(-1) DES, and immunoblots showed increased SERCA2a in all DES-treated mice. Mice were swim-trained to assess cardiac remodeling. Swim-trained vehicle-treated mice developed eccentric hypertrophy without changing SERCA2 or calsequestrin 2 expression. In contrast, no DES-treated mice hypertrophied, and all increased in SERCA2a and calsequestrin 2 expression after training. To determine whether DES-induced changes in DNA methylation is part of the mechanism for its long-term effects, we measured DNA methyltransferase expression and DNA methylation. Global DNA methylation and DNA methyltransferase 3a expression were unchanged. However, DES-treated mice had increased DNA methylation in the calsequestrin 2 promoter. Thus, gestational exposure to DES altered female ventricular DNA, cardiac structure/function, and calcium homeostasis protein expression. We conclude that gestational exposure to estrogenizing compounds may impact cardiac structure/function in adult females.
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Metilación de ADN/efectos de los fármacos , Dietilestilbestrol/toxicidad , Corazón Fetal/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Hipertrofia Ventricular Izquierda/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Función Ventricular Izquierda/efectos de los fármacos , Factores de Edad , Animales , Secuencia de Bases , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Calsecuestrina/genética , Calsecuestrina/metabolismo , ADN (Citosina-5-)-Metiltransferasas/metabolismo , ADN Metiltransferasa 3A , Femenino , Corazón Fetal/crecimiento & desarrollo , Corazón Fetal/metabolismo , Regulación de la Expresión Génica , Edad Gestacional , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Hemodinámica/efectos de los fármacos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/genética , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/fisiopatología , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Embarazo , Regiones Promotoras Genéticas , ARN Mensajero/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Conducta Sedentaria , Factores Sexuales , Intercambiador de Sodio-Calcio/genética , Intercambiador de Sodio-Calcio/metabolismo , Natación , Ultrasonografía , Remodelación Ventricular/efectos de los fármacosRESUMEN
The impact of cancer therapies on adult cardiac function is becoming a concern as more children survive their initial cancer. Cardiovascular disease is now a significant problem to adult survivors of childhood cancer. Specifically, doxorubicin (DOX) may be particularly harmful in young girls. The objective of this study was to characterize DOX damage and determine the ability of dexrazoxane (DEX) to reduce DOX-mediated cardiac damage in sedentary and swim-trained female rats. Female Sprague-Dawley rats were left intact or ovariectomized (OVX) at weaning then injected with DEX (60 mg/kg) before DOX (3 mg/kg), DOX alone, or PBS. Rats were separated into sedentary and swim cohorts. Body weight was reduced in DOX:DEX- but not PBS- or DOX-treated rats. Echocardiographic parameters were similar in sedentary rats. Swim training revealed greater concentric remodeling in DOX-treated rats and reduced fractional shortening in DOX:DEX-treated rats. Calsequestrin 2 was reduced with DOX and increased with DOX:DEX postswim. Sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a was reduced and calsequestrin 2 reduced further by swim training only in intact rats. OVX rats were heavier and developed eccentric remodeling post-swim with DOX and eccentric hypertrophy with DOX:DEX. Changes in SERCA2a and calsequestrin 2 expression were not observed. Ovariectomized DOX- and DOX:DEX-treated rats stopped growing during swim training. DEX coinjection did not relieve DOX-mediated cardiotoxicity in intact or hormone-deficient rats. DOX-mediated reductions in growth, cardiac function, and expression of calcium homeostasis proteins were exacerbated by swim. DEX coadministration did not substantially relieve DOX-mediated cardiotoxicity in young female rats. Ovarian hormones reduce DOX-induced cardiotoxicity.
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Antineoplásicos/farmacología , Doxorrubicina/farmacología , Corazón/efectos de los fármacos , Ovariectomía , Razoxano/farmacología , Descanso/fisiología , Natación/fisiología , Animales , Calcio/metabolismo , Calsecuestrina/metabolismo , Ecocardiografía , Femenino , Corazón/fisiología , Modelos Animales , Miocardio/metabolismo , Ratas , Ratas Sprague-Dawley , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismoRESUMEN
Childhood cancer survivors can develop significant cardiac dysfunction in adulthood as a consequence of their cancer treatment. Studies have linked heart failure during pregnancy to childhood doxorubicin (DOX) exposure. We hypothesized that DOX injection would reduce cardiac function peripartum and that DOX-treated dams would show greater cardiac remodeling postweaning. Weanling female Sprague-Dawley rats were injected with phospate-buffered saline, DOX (3 mg/kg), or DOX plus the cardioprotectant dexrazoxane (DEX; 60 mg/kg) and followed for 2 pregnancies. DOX and DOX:DEX dams were fertile, but had fewer pups and more pup losses. Echocardiography, 1-day postpartum after each pregnancy, revealed greater increases in cardiac mass and eccentric hypertrophy in DOX-treated dams and early dilation in DOX:DEX dams. The expression of calcium homeostasis proteins can change after DOX treatment and cardiac remodeling. SERCA2a expression did not change. Reductions in phospholamban and phospho-serine 16-specific phospholamban expression in DOX dams were not relieved by DEX coinjection. DOX binds and inactivates calsequestrin 2 expression so increased calsequestrin 2 expression in DOX:DEX-treated dams suggests some DEX compensation. The eccentric hypertrophy and dilation development, despite compensatory changes in proteins controlling calcium cycling, suggest DOX damage with repeat pregnancy that was not alleviated fully by DEX.
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Antineoplásicos/antagonistas & inhibidores , Cardiotónicos/uso terapéutico , Doxorrubicina/antagonistas & inhibidores , Ventrículos Cardíacos/efectos de los fármacos , Complicaciones Cardiovasculares del Embarazo/prevención & control , Razoxano/uso terapéutico , Disfunción Ventricular Izquierda/prevención & control , Animales , Antineoplásicos/efectos adversos , Proteínas de Unión al Calcio/antagonistas & inhibidores , Proteínas de Unión al Calcio/biosíntesis , Proteínas de Unión al Calcio/metabolismo , Calsecuestrina/antagonistas & inhibidores , Calsecuestrina/biosíntesis , Calsecuestrina/metabolismo , Cardiotoxinas/efectos adversos , Cardiotoxinas/antagonistas & inhibidores , Doxorrubicina/efectos adversos , Femenino , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Infertilidad Femenina/inducido químicamente , Infertilidad Femenina/prevención & control , Periodo Posparto , Embarazo , Complicaciones Cardiovasculares del Embarazo/inducido químicamente , Complicaciones Cardiovasculares del Embarazo/metabolismo , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Resultado del Embarazo , Sustancias Protectoras/uso terapéutico , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacos , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/metabolismo , Disfunción Ventricular Izquierda/fisiopatología , Remodelación Ventricular/efectos de los fármacos , DesteteRESUMEN
AIMS: Infective endocarditis (IE) is a life-threatening disease associated with high mortality and morbidity worldwide. We sought to determine how socioeconomic factors might influence its epidemiology, clinical presentation, investigation and management, and outcome, in a large international multicentre registry. METHODS AND RESULTS: The EurObservational Programme (EORP) of the European Society of Cardiology EURO-ENDO (European Infective Endocarditis) registry comprises a prospective cohort of 3113 adult patients admitted for IE in 156 hospitals in 40 countries between January 2016 and March 2018. Patients were separated in three groups, according to World Bank economic stratification [group 1: high income (75.6%); group 2: upper-middle income (15.4%); group 3: lower-middle income (9.1%)]. Group 3 patients were younger [median age (interquartile range, IQR): group 1, 66 (53-75) years; group 2, 57 (41-68) years; group 3, 33 (26-43) years; P < 0.001] with a higher frequency of smokers, intravenous drug use, and human immunodeficiency virus infection (all P < 0.001) and presented later [median (IQR) days since symptom onset: group 1, 12 (3-35); group 2, 19 (6-54); group 3, 31 (12-62); P < 0.001] with a higher likelihood of developing congestive heart failure (13.6%, 11.1%, and 22.6%, respectively; P < 0.001) and persistent fever (9.8%, 14.2%, and 27.9%, respectively; P < 0.001). Among 2157 (69.3%) patients with theoretical indication for cardiac surgery, surgery was performed less frequently in group 3 patients (75.5%, 76.8%, and 51.3%, respectively; P < 0.001), who also demonstrated the highest mortality (15.0%, 23.0%, and 23.7%, respectively; P < 0.001). CONCLUSION: Socioeconomic factors influence the clinical profile of patients presenting with IE across the world. Despite younger age, patients from the poorest countries presented with more frequent complications and higher mortality associated with delayed diagnosis and lower use of surgery.
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Endocarditis Bacteriana , Endocarditis , Insuficiencia Cardíaca , Adulto , Humanos , Estudios Prospectivos , Endocarditis/diagnóstico , Endocarditis/epidemiología , Endocarditis/etiología , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/epidemiología , Sistema de RegistrosRESUMEN
Calcium flux into and out of the sarco(endo)plasmic reticulum is vitally important to cardiac function because the cycle of calcium entry and exit controls contraction and relaxation. Putative estrogen and androgen consensus binding sites near to a CpG island are present in the cardiac calsequestrin 2 (CSQ2) promoter. Cardiomyocytes express sex hormone receptors and respond to sex hormones. We hypothesized that sex hormones control CSQ2 expression in cardiomyocytes and so affect cardiac structure/function. Echocardiographic analysis of male and female C57bl6n mice identified thinner walled and lighter hearts in females and significant concentric remodeling after long-term gonadectomy. CSQ2 and sodium-calcium exchanger-1 (NCX1) expression was significantly increased in female compared with male hearts and decreased postovariectomy. NCX1, but not CSQ2, expression was increased postcastration. CSQ2 expression was reduced when H9c2 cells were cultured in hormone-deficient media; increased when estrogen receptor-α (ERα), estrogen receptor-ß (ERß), or androgen agonists were added; and increased in hearts from ERß-deficient mice. CSQ2 expression was reduced in mice fed a diet low in the methyl donor folic acid and in cells treated with 5-azadeoxycytidine suggesting an involvement of DNA methylation. DNA methylation in CpG in the CSQ2 CpG island was significantly different in males and females and was additionally changed postgonadectomy. Expression of DNA methyltransferases 1, 3a, and 3b was unchanged. These studies strongly link sex hormone-directed changes in CSQ2 expression to DNA methylation with changed expression correlated with altered left ventricular structure and function.
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Hormonas Esteroides Gonadales/fisiología , Función Ventricular Izquierda/fisiología , Animales , Secuencia de Bases , Calcio/fisiología , Calsecuestrina/genética , Calsecuestrina/fisiología , Línea Celular , Metilación de ADN , Ecocardiografía , Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/fisiología , Femenino , Regulación de la Expresión Génica , Hormonas Esteroides Gonadales/biosíntesis , Hormonas Esteroides Gonadales/genética , Homeostasis/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Datos de Secuencia Molecular , Miocardio/citología , Orquiectomía , Ovariectomía , Intercambiador de Sodio-Calcio/genéticaRESUMEN
AIM: Noninvasive markers of right ventricular (RV) diastolic dysfunction are limited by their lack of reproducibility and accuracy. We tested the hypothesis that right atrial (RA) size measured by echocardiography was correlated to invasive parameters of RV diastolic filling. METHODS AND RESULTS: We studied 31 consecutive adult patients with congenital heart disease. From 2D echocardiography images, we measured maximal RA long-axis and short-axis lengths, area and volume. We compared each of these measures to right ventricular end-diastolic pressure (RVEDP) and mean right atrial pressure (mRAP) measured by right heart catheterization. RA long-axis, short-axis, area, and volume correlated significantly with RVEDP (r = 0.78, P < 0.001; r = 0.61, P < 0.001; r = 0.79, P < 0.001; and r = 0.75, P < 0.001, respectively) and mRAP (r = 0.66, P < 0.001; r = 0.56, P = 0.002; r = 0.70, P < 0.001; r = 0.68, P < 0.001, respectively). Single cut points for each echocardiographic parameter demonstrated reasonable accuracy to rule-in and rule-out RVEDP ≥ 7 mm Hg (sensitivity = 74%, specificity = 82%, positive LR = 4.1, negative LR = 0.32 for RA long-axis of 49 mm; sensitivity = 89%, specificity = 82%, positive LR = 4.9, negative LR = 0.12 for RA area of 14 cm²; sensitivity = 89%, specificity = 82%, positive LR = 4.9, negative LR = 0.13 for RA volume of 37 mL). CONCLUSION: RA size measured by echocardiography is strongly correlated to invasive parameters of RV diastolic filling and predicts high RV end-diastolic pressure.
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Atrios Cardíacos/anatomía & histología , Atrios Cardíacos/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Adulto , Presión Sanguínea , Ecocardiografía , Femenino , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Estudios Retrospectivos , Función VentricularRESUMEN
Anthracyclines and HER2-targeted antibodies are very effective for the treatment of breast cancer, but their use is limited by cardiotoxicity. In this nested case-control study, we assessed the role of intermediary metabolism in 38 women with breast cancer treated with anthracyclines and trastuzumab. Using targeted mass spectrometry to measure 71 metabolites in the plasma, we identified changes in citric acid and aconitic acid that differentiated patients who developed cardiotoxicity from those who did not. In patients with cardiotoxicity, the magnitude of change in citric acid at three months correlated with the change in left ventricular ejection fraction (LVEF) and absolute LVEF at nine months. Patients with cardiotoxicity also demonstrated more pronounced changes in purine and pyrimidine metabolism. Early metabolic changes may therefore provide insight into the mechanisms associated with the development of chemotherapy-associated cardiotoxicity.
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Antibióticos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Ciclo del Ácido Cítrico/efectos de los fármacos , Doxorrubicina/efectos adversos , Cardiopatías/inducido químicamente , Miocitos Cardíacos/efectos de los fármacos , Nucleósidos/sangre , Adulto , Biomarcadores/sangre , Cardiotoxicidad , Cromatografía Líquida de Alta Presión , Femenino , Cardiopatías/metabolismo , Cardiopatías/fisiopatología , Humanos , Metabolómica , Persona de Mediana Edad , Miocitos Cardíacos/metabolismo , Prueba de Estudio Conceptual , Estudios Prospectivos , Espectrometría de Masa por Ionización de Electrospray , Volumen Sistólico/efectos de los fármacos , Factores de Tiempo , Trastuzumab/efectos adversos , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
BACKGROUND: During the development of heart failure (HF), the changes of contraction timing pattern and temporal heterogeneity of segmental contraction happen early and may precede both symptomatic HF and the decrease in left ventricular ejection fraction (LVEF). In patients treated with anthracyclines, both symptomatic HF and the decrease of LVEF are detected once significant myocardial injury has occurred. The aim of the current study was to investigate whether changes in the timing of contraction can be detected early after anthracyclines therapy. METHODS: Forty-one women (50 ± 11 years old) with newly diagnosed breast cancer were prospectively enrolled in two centers and underwent an echocardiogram before and after anthracyclines. Peak longitudinal myocardial systolic strain was measured on the apical four- and two-chamber views. The time to peak systolic longitudinal strain (TP), ejection time (ET), isovolumic contraction time (IVCT), systolic time, and diastolic time were measured using strain curves and Doppler tracings and compared before and after anthracyclines. The heterogeneity of contraction (dyssynchrony) was measured by the SD of the TP of all segments. RESULTS: Anthracyclines treatment was associated with an increase in heart rate (HR) and a decrease in TP. TP was correlated with HR. TP/ET was independent of HR and inversely correlated to peak strain both at baseline and after anthracyclines. TP/ET increased after anthracyclines (1.26 ± 0.19 to 1.31 ± 0.22; P < .001), and this increase was correlated with the decrease in strain. The increase in TP/ET was due to an increase in IVCT/ET. A similar degree of dyssynchrony was found at baseline and after anthracyclines. CONCLUSIONS: Anthracyclines treatment induces an increase in the duration of contraction, mainly by increasing the IVCT. This increase is correlated to the decrease in strain and may therefore have additional prognostic value.
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Antraciclinas/administración & dosificación , Antraciclinas/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Contracción Miocárdica/efectos de los fármacos , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/fisiopatología , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Boston , Neoplasias de la Mama/fisiopatología , Estudios Controlados Antes y Después , Acoplamiento Excitación-Contracción/efectos de los fármacos , Femenino , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Humanos , Persona de Mediana Edad , Quebec , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Volumen Sistólico , Resultado del Tratamiento , Ultrasonografía/métodos , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
BACKGROUND: Tissue Doppler imaging (TDI) is a novel echocardiographic method to quantify regional myocardial function. The objective of this study was to assess whether myocardial velocities and strain rate (SR) could be obtained by TDI in mice and whether these indices accurately quantified alterations in left ventricular (LV) systolic function. METHODS AND RESULTS: TDI was performed in 10 healthy mice to measure endocardial (v(endo)) and epicardial systolic velocities and SR. In further experiments, TDI indices were compared with dP/dt(max) and with sonomicrometer-derived regional velocities, at rest and after administration of dobutamine or esmolol. TDI indices were also studied serially in 8 mice before and 4 and 7 hours after endotoxin challenge. Myocardial velocities and SR were obtained in all mice with low measurement variability. TDI indices increased with administration of dobutamine (v(endo) from 2.2+/-0.3 to 3.8+/-0.2 cm/s [P<0.01]; SR from 12+/-2 to 20+/-2 s(-1) [P<0.05]) and decreased with administration of esmolol (v(endo) 1.4+/-0.2 cm/s [P<0.05]; SR 6+/-1 s(-1) [P<0.01]). Both indices correlated strongly with dP/dt(max) (r2=0.79 for SR and r2= 0.69 for v(endo); both P<0.0001). SR and shortening fraction were predictors of dP/dt(max) even after adjustment for the confounding effect of the other variables. V(endo) correlated closely with sonomicrometer-measured velocity (r2=0.71, P<0.0005). After endotoxin challenge, decreases in both v(endo) and SR were detected before decreases in shortening fraction became manifest. CONCLUSIONS: Myocardial velocities and SR can be measured noninvasively in mice with the use of TDI. Both indices are sensitive markers for quantifying LV global and regional function in mice.
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Ecocardiografía Doppler , Disfunción Ventricular Izquierda/diagnóstico , Animales , Cardiotónicos/farmacología , Dobutamina/farmacología , Ecocardiografía Doppler/métodos , Ecocardiografía Doppler/normas , Endotoxinas/farmacología , Pruebas de Función Cardíaca , Frecuencia Cardíaca , Cinética , Ratones , Movimiento , Propanolaminas/farmacología , Reproducibilidad de los ResultadosRESUMEN
Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.
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Antineoplásicos/efectos adversos , Cardiotoxicidad/diagnóstico , Cardiotoxicidad/prevención & control , Radioterapia/efectos adversos , Arritmias Cardíacas/etiología , Arritmias Cardíacas/terapia , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Cardiotónicos/uso terapéutico , Cardiotoxicidad/etiología , Cardiotoxinas/efectos adversos , Trombosis Coronaria/etiología , Trombosis Coronaria/terapia , Diagnóstico Precoz , Ecocardiografía Tridimensional , Humanos , Hipertensión/etiología , Hipertensión/terapia , Imagen por Resonancia Cinemagnética , Isquemia Miocárdica/etiología , Isquemia Miocárdica/terapia , Péptido Natriurético Encefálico/sangre , Neoplasias/terapia , Prevención Primaria , Factores de Riesgo , Troponina T/sangre , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/terapiaRESUMEN
Two-dimensional (2-D) planimetry is limited by the technical demands, time, and observer variability required to locate the minimal orifice area, limiting the confident clinical reporting of mitral valve area (MVA). In 27 consecutive patients, MVA was determined independently by 2 observers using the conventional 2-D method and a new 3-D-guided method. Using a matrix-array probe, the valve was visualized in a long-axis view and a cursor steered to intersect the leaflet tips and provide a perpendicular short-axis plane viewed side-by-side. Two-dimensional and 3-D-guided methods allowed planimetry in 24 patients. Consistent with better orifice localization, 3-D guidance eliminated the overestimation of internal orifice diameters in the planimetered short-axis view relative to the limiting diameter defined by the long-axis view (for 3-D guidance, 0.73 +/- 0.20 vs 0.73 +/- 0.21 cm, p = 0.98, vs 0.90 +/- 0.27 cm in the 2-D short-axis view, p <0.01). Accordingly, mean values for the smallest orifice area by 3-D guidance were less than by 2-D imaging (1.4 +/- 0.5 vs 1.5 +/- 0.5 cm(2), p <0.01), changing the clinical severity classification in 11 of 24 patients (46%). The 2-D method also overestimated MVA relative to 3-D guidance compared with Doppler pressure halftime and (n = 6) Gorlin areas. Phantom studies verified no differences in resolution for the 2 acquisition modes. Three-dimensional guidance reduced intraobserver variability from 9.8% to 3.8% (SEE 0.14 to 0.06 cm(2), p <0.01) and interobserver variability from 10.6% to 6.1% (SEE 0.15 to 0.09 cm(2), p <0.02). In conclusion, matrix-array technology provides a feasible and highly reproducible direct 3-D-guided method for measuring the limiting mitral orifice area.
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Ecocardiografía Tridimensional/métodos , Estenosis de la Válvula Mitral/diagnóstico por imagen , Adulto , Anciano , Cateterismo Cardíaco , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estenosis de la Válvula Mitral/clasificación , Estenosis de la Válvula Mitral/patología , Índice de Severidad de la EnfermedadRESUMEN
The increased pericardial fat which often accompanies overall obesity is thought to alter cardiac structure/function and increase the risk for atrial fibrillation. We hypothesized that chronic exposure to bisphenol A (BPA) would induce pericardial fat, cardiac hypertrophy or arrhythmia. C57bl/6n dams were exposed to BPA (25 ng/ml drinking water) beginning on gestation day 11 and progeny continued on 2.5 ng BPA/ml drinking water. The progeny of control dams (VEH) and dams treated with diethylstilbestrol (DES, 1 µg/kg/day, gestation days 11â¿¿14) had tap water. After weaning progeny were fed either a control (CD) or high fat diet (HFD) for 3 months. Pericardial fat was present in CD-BPA and CD-DES and not CD-VEH mice, and was increased in all HFD mice. Catecholamine challenge revealed no differences in males, but BPA-exposed females had longer P-wave and QRS complex duration. Only CD-BPA and CD-DES females developed cardiac hypertrophy which was independent of increased blood pressure. Calcium homeostasis protein expression changes in HFD-BPA and HFD-DES mice predict reduced SERCA2 activity in males and increased SERCA2 activity in females. Thus, chronic BPA exposure induced pericardial fat in the absence of HFD, and female-specific changes in cardiac hypertrophy development and cardiac electrical conduction after a catecholamine challenge.
RESUMEN
BACKGROUND: Trastuzumab, a HER2 monoclonal antibody, has transformed the prognosis of patients with the aggressive HER2-positive breast cancer type. Trastuzumab augments the cardiotoxic effects of anthracyclines, but its effect is thought to be at least partially reversible. The objective of this study was to examine the time trends of left ventricular (LV) size and function in a cohort of women treated with anthracyclines and trastuzumab. METHODS: Twenty-nine patients >18 years of age with first-time breast cancer treated with anthracyclines and trastuzumab were monitored using echocardiography before, at the completion of, and at a median follow-up of 24.7 months (interquartile range, 15.9-34 months) after the end of their cancer treatment. LV volume, LV ejection fraction, and global peak systolic longitudinal strain and strain rate were measured in the apical four- and two-chamber views. Left ventricular ejection fraction was measured using a modified Simpson's biplane method. RESULTS: LV end-diastolic and end-systolic volumes increased at the end of treatment compared with baseline and did not recover during follow-up. Left ventricular ejection fraction, strain, and strain rate decreased at the end of treatment compared with baseline (from 64 ± 6% to 59 ± 8%, from -20.0 ± 2.5% to -17.6 ± 2.6%, and from -1.26 ± 0.23 to -1.13 ± 0.16 sec(-1), respectively; P < .05 for all parameters) and remained decreased at follow-up. CONCLUSIONS: LV dilation and subclinical impairment in cardiac function persists >2 years after the end of anthracycline and trastuzumab treatment, without significant recovery after trastuzumab cessation, suggestive of long-term underlying cardiac damage and remodeling.
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Antraciclinas/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Volumen Cardíaco/efectos de los fármacos , Volumen Sistólico/efectos de los fármacos , Taxoides/administración & dosificación , Trastuzumab/administración & dosificación , Función Ventricular Izquierda/efectos de los fármacos , Antineoplásicos/administración & dosificación , Neoplasias de la Mama/fisiopatología , Relación Dosis-Respuesta a Droga , Ecocardiografía , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Factores de TiempoRESUMEN
OBJECTIVES: The aim of this study was to determine if individual or multiple biomarkers are associated with cardiotoxicity in patients with breast cancer undergoing cancer therapy. BACKGROUND: Current methods to identify patients at risk for cardiotoxicity from cancer therapy are inadequate. METHODS: We measured 8 biomarkers in a multicenter cohort of 78 patients with breast cancer undergoing doxorubicin and trastuzumab therapy: ultrasensitive troponin I (TnI), high-sensitivity C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor (sFlt)-1, and galectin (gal)-3. Cardiotoxicity, defined by the Cardiac Review and Evaluation Committee criteria, was assessed every 3 months for up to 15 months. Hazard ratios (HRs) of cardiotoxicity risk were assessed for each biomarker at baseline, at visit 2 (3 months), and as a function of the difference between visit 2 and baseline. Joint models were assessed for the most promising biomarkers. RESULTS: TnI, CRP, GDF-15, MPO, PlGF, and sFlt-1 levels increased from baseline to visit 2 (p < 0.05). A greater risk of cardiotoxicity was associated with interval changes in TnI (HR: 1.38 per SD; 95% confidence interval: 1.05 to 1.81; p = 0.02) and MPO (HR: 1.34 per SD; 95% confidence interval: 1.00 to 1.80; p = 0.048) and in models combining both markers (p = 0.007 and p = 0.03, respectively). The risk of cardiotoxicity was 46.5% in patients with the largest changes in both markers (ΔTnI >121.8 µg/l; ΔMPO >422.6 pmol/l). CONCLUSIONS: Early increases in TnI and MPO levels offer additive information about the risk of cardiotoxicity in patients undergoing doxorubicin and trastuzumab therapy. Independent validation of these findings is necessary before application to clinical practice.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Enfermedades Cardiovasculares/sangre , Peroxidasa/sangre , Troponina I/sangre , Adulto , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores/sangre , Neoplasias de la Mama/diagnóstico , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/diagnóstico , Estudios de Cohortes , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Taxoides/administración & dosificación , Taxoides/efectos adversos , Factores de Tiempo , Trastuzumab , Resultado del TratamientoRESUMEN
In the context of modern cancer chemotherapeutics, cancer survivors are living longer and being exposed to potential comorbidities related to non-cancer side effects of such treatments. With close monitoring of cancer patients receiving potentially cardiotoxic medical therapies, oncologists, and cardiologists alike are identifying patients in both clinical and subclinical phases of cardiovascular disease related to such chemotherapies. Specifically, cardiotoxicity at the level of the myocardium and potential for the development of heart failure are becoming a growing concern with increasing survival of cancer patients. Traditional chemotherapeutic agents used commonly in the treatment of breast cancer and hematologic malignancies, such as anthracyclines and HER-2 antagonists, are well known to be associated with cardiovascular sequelae. Patients often present without symptoms and an abnormal cardiac imaging study performed as part of routine evaluation of patients receiving cardiotoxic therapies. Additionally, patients can present with signs and symptoms of cardiovascular disease months to years after receiving the chemotherapies. As the understanding of the physiology underlying the various cancers has grown, therapies have been developed that target specific molecules that represent key aspects of physiologic pathways responsible for cancer growth. Inhibition of these pathways, such as those involving tyrosine kinases, has lead to the potential for cardiotoxicity as well. In view of the potential cardiotoxicity of specific chemotherapies, there is a growing interest in identifying patients who are at risk of cardiotoxicity prior to becoming symptomatic or developing cardiotoxicity that may limit the use of potentially life-saving chemotherapy agents. Serological markers and novel cardiac imaging techniques have become the source of many investigations with the goal of screening patients for pre-clinical cardiotoxicity. Additionally, studies have been performed.