RESUMO
Several clinical reports indicate that the use of amphetaminic anorectic drugs or ergot derivatives could cause valvular heart disease (VHD). We sought to investigate whether valvular lesions develop in response to long-term oral administration of these drugs and to identify drug-targeted biological processes that may lead to VHD. Treatment of New Zealand White rabbits with pergolide, dexfenfluramine, or high-dose serotonin for 16 weeks induced valvular alterations characterized by extracellular matrix remodeling. Transcriptome profiling of tricuspid valves using RNA sequencing revealed distinct patterns of differentially expressed genes (DEGs) that clustered according to the different treatments. Genes that were affected by the three treatments were functionally enriched for reduced cell metabolism processes. The two drugs yielded more changes in gene expression than serotonin and shared most of the DEGs. These DEGs were mostly enriched for decreased biosynthetic processes, increased cell-matrix interaction, and cell response to growth factors, including TGF-ß, which was associated with p38 MAPK activation. Treatment with pergolide specifically affected genes involved in homeostasis, which was corroborated by the activation of the master regulator of cell energy homeostasis, AMPK-α, as well as decreased levels of metabolism-related miR-107. Thus, both pergolide and dexfenfluramine may cause VHD through valve metabolic reprogramming and matrix remodeling.
Assuntos
Dexfenfluramina/efeitos adversos , Matriz Extracelular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Doenças das Valvas Cardíacas/induzido quimicamente , Pergolida/efeitos adversos , Valva Tricúspide/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Administração Oral , Animais , Proliferação de Células , Análise por Conglomerados , Ativação Enzimática , Feminino , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Homeostase , MicroRNAs/genética , Coelhos , Análise de Sequência de RNA , Serotonina/efeitos adversos , Transcriptoma , Fator de Crescimento Transformador beta/metabolismo , Valva Tricúspide/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
We present a case of endocarditis wherein organisms cultured from different valve leaflets yielded different daptomycin susceptibilities from each other and from organisms obtained from peripheral blood culture. Genomic analyses showed mutations in mprF, purR, and agrA Pharmacokinetic simulations showed consistent activity of daptomycin plus beta-lactam against all subpopulations. This represents an opportunity to understand S. aureus evolution and fitness in vivo on daptomycin therapy and the role of beta-lactams to prevent the selection of daptomycin-resistant subpopulations.
Assuntos
Daptomicina/farmacologia , Endocardite Bacteriana/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Valva Tricúspide/microbiologia , Valva Tricúspide/patologia , Aminoaciltransferases/genética , Proteínas de Bactérias/genética , Daptomicina/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação/genética , Proteínas Repressoras/genética , Valva Tricúspide/efeitos dos fármacos , Sequenciamento Completo do GenomaRESUMO
Ebstein's anomaly is a malformation of the tricuspid valve with myopathy of the right ventricle (RV) that presents with variable anatomic and pathophysiologic characteristics, leading to equally variable clinical scenarios. Medical management and observation is often recommended for asymptomatic patients and may be successful for many years. Tricuspid valve repair is the goal of operative intervention; repair also typically includes RV plication, right atrial reduction, and atrial septal closure or subtotal closure. Postoperative functional assessments generally demonstrate an improvement or relative stability related to degree of RV enlargement, RV dysfunction, RV fractional area change, and tricuspid valve regurgitation.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Fármacos Cardiovasculares/uso terapêutico , Anomalia de Ebstein/terapia , Insuficiência da Valva Tricúspide/terapia , Valva Tricúspide/efeitos dos fármacos , Valva Tricúspide/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Anomalia de Ebstein/complicações , Anomalia de Ebstein/diagnóstico por imagem , Anomalia de Ebstein/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Recuperação de Função Fisiológica , Resultado do Tratamento , Valva Tricúspide/anormalidades , Valva Tricúspide/fisiopatologia , Insuficiência da Valva Tricúspide/tratamento farmacológico , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/fisiopatologia , Função Ventricular Direita/efeitos dos fármacosRESUMO
OBJECTIVES: This study sought to define the relationship between functional tricuspid regurgitation (TR) and mortality in patients with heart failure with reduced ejection fraction (HFrEF); and to establish the prognostic value of quantitative measures of TR severity (i.e., effective regurgitant orifice area [EROA] and regurgitant volume). BACKGROUND: The significance of TR in chronic heart failure is controversial. Earlier studies have shown an independent impact of TR on mortality, whereas more recent evidence suggests myocardial impairment to be the driving force of mortality rather than TR itself. Earlier studies have used qualitative measures of TR severity, hence the prognostic value of more quantitative measures of TR severity (i.e., EROA and regurgitant volumes) remains unclear. METHODS: We enrolled 382 patients with HFrEF on guideline-directed medical therapy and assessed TR EROA and regurgitant volume by Doppler/2-dimensional echocardiography. All-cause mortality was defined as the primary study endpoint. RESULTS: TR severity was associated with the HFrEF phenotype with more symptoms (p = 0.004), higher neurohumoral activation (p < 0.001), progressive right-ventricular dilatation (p < 0.001), and impaired function (p < 0.001). Cox regression showed a strong association between quantitative measures of TR with mortality (all p < 0.001). Quantitative metrics of TR severity were consistently associated with mortality with a hazard ratio of 1.009 (95% confidence interval: 1.004 to 1.013; p < 0.001) per 0.01 cm2 increase of the EROA and of 1.013 (95% confidence interval: 1.007 to 1.020; p < 0.001) per 1-ml increase in regurgitant volume. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. A spline curve pattern illustrates the association with mortality with thresholds for the EROA ≥0.2 cm2, and the regurgitant volume ≥20 ml with sustained excess mortality thereafter. CONCLUSIONS: This large-scale outcome study demonstrates the prognostic value of quantitative Doppler-echocardiographic measures of TR severity in HFrEF. The thresholds for EROA and TR regurgitant volume associated with mortality in our study fall within current ranges defining nonsevere TR. This may potentially impact therapeutic decision making, particularly timing of intervention.
Assuntos
Ecocardiografia Doppler , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/diagnóstico por imagem , Idoso , Fármacos Cardiovasculares/uso terapêutico , Causas de Morte , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Volume Sistólico , Fatores de Tempo , Valva Tricúspide/efeitos dos fármacos , Valva Tricúspide/fisiopatologia , Insuficiência da Valva Tricúspide/tratamento farmacológico , Insuficiência da Valva Tricúspide/mortalidade , Insuficiência da Valva Tricúspide/fisiopatologia , Função Ventricular EsquerdaRESUMO
OBJECTIVE: To assess the agreement between 2-dimensional tricuspid annular plane systolic excursion (2D-TAPSE), 2D-TAPSE-apex, and 2D speckle tracking echocardiography (STE-TAPSE) in a cross-section of routine cardiac surgery patients. DESIGN: Retrospective, observational study. SETTING: Tertiary, academic referral hospital. PARTICIPANTS: Patients undergoing elective cardiac surgery with intraoperative transesophageal echocardiography (TEE) imaging. INTERVENTIONS: TEE imaging was reviewed and evaluated for the following three different measurements of transthoracic echocardiography-TAPSE surrogates: 2D-TAPSE, 2D-TAPSE-apex, and STE-TAPSE. Statistical analyses, including 2-sample t tests, linear regression, and agreement using the Bland-Altman methods, were performed. MEASUREMENTS AND MAIN RESULTS: Modest correlation was demonstrated between STE-TAPSE and 2D-TAPSE (R2â¯=â¯0.37; p < 0.001) and between STE-TAPSE and 2D-TAPSE-apex (R2â¯=â¯0.34; p < 0.001). There was good correlation between 2D-TAPSE and 2D-TAPSE-apex (R2â¯=â¯0.77, p < 0.001). The Bland-Altman analysis between these methods showed minimal bias: STE-TAPSE and 2D-TAPSE 0.84 mm, STE-TAPSE and 2D-TAPSE-apex 0.14 mm, and 2D-TAPSE and 2D-TAPSE-apex 0.98 mm. However, the agreement was poor, with 95% limits of agreement of -10.67 to 8.99 mm, -10.67 to 10.96 mm, and -4.91 to 6.88 mm, respectively. CONCLUSIONS: Correlation and minimal bias were found between the several proposed TEE surrogates of transthoracic echocardiography-TAPSE; however, there was poor agreement. Therefore, these surrogates are not interchangeable, and each method needs to be separately validated for clinical use to relevant perioperative outcomes.
Assuntos
Pressão Sanguínea/fisiologia , Procedimentos Cirúrgicos Cardíacos/normas , Ecocardiografia Transesofagiana/normas , Monitorização Intraoperatória/normas , Valva Tricúspide/efeitos dos fármacos , Valva Tricúspide/fisiologia , Idoso , Procedimentos Cirúrgicos Cardíacos/métodos , Estudos de Coortes , Ecocardiografia/métodos , Ecocardiografia/normas , Ecocardiografia Transesofagiana/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Estudos RetrospectivosRESUMO
OBJECTIVES: Our objective was to explore the effects of tolvaptan as a new therapeutic approach in patients with right heart failure with tricuspid insufficiency (TI). METHODS: This prospective, multicenter, non-randomized controlled pilot study enrolled patients (N = 40) with TI from the Shanghai Chest Hospital and Shanghai Tongren Hospital who fulfilled inclusion criteria between March 2015 and June 2016. Participants were assigned to receive either tolvaptan combined with torasemide (n = 20) or torasemide monotherapy (n = 20; control group). The primary endpoints were changes in patient weight and in tricuspid annular plane systolic excursion (TAPSE) after 10 days of treatment. The secondary endpoints included net fluid balance and cardiac functions before and after medication from the first to the tenth day of treatment. Safety was evaluated by monitoring adverse and serious adverse events. RESULTS: TAPSE significantly increased in the tolvaptan group compared with the control group after 10 days of medication (P = 0.029). Daily weight losses in the tolvaptan group significantly increased as the time of treatment increased (time × group, P = 0.022). Recovery to New York Heart Association (NYHA) grade I occurred 4 days earlier in the tolvaptan group. In addition, the net fluid balance and median net fluid balance were significantly higher in the tolvaptan group. Eight adverse events and one serious adverse event were recorded in the tolvaptan group and 15 adverse events were recorded in the control group. CONCLUSIONS: Our results indicate that tolvaptan might be a useful and safe drug to improve heart function in patients with right heart failure with TI after left heart valve replacement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier no. NCT02644616.
Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Implante de Prótese de Valva Cardíaca/efeitos adversos , Tolvaptan/uso terapêutico , Insuficiência da Valva Tricúspide/tratamento farmacológico , Idoso , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Feminino , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Tolvaptan/efeitos adversos , Torasemida/efeitos adversos , Torasemida/uso terapêutico , Resultado do Tratamento , Valva Tricúspide/efeitos dos fármacos , Valva Tricúspide/fisiopatologia , Insuficiência da Valva Tricúspide/complicações , Insuficiência da Valva Tricúspide/fisiopatologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
BACKGROUND: Dormant conduction unmasked by adenosine predicts clinical recurrences of cavotricuspid isthmus (CTI) dependent atrial flutter following catheter ablation. Conventional practice involves a waiting period of 20 to 30 minutes after achievement of a bidirectional line of block (BDB) to monitor for recovery of conduction. OBJECTIVE: Assess whether abolition of dormant conduction with adenosine immediately after CTI ablation and BDB can predict the lack of CTI conduction recovery during the following 30 minutes. METHODS: Consecutive patients undergoing catheter ablation for CTI-dependent atrial flutter were studied. Following the completion of CTI ablation and documentation of BDB, adenosine (≥12 mg IV) was administered immediately. In cases of dormant conduction, the CTI was ablated again until its abolition. After the achievement of BDB without dormant conduction, spontaneous CTI reconnection during the following 30 minutes and dormant conduction with adenosine at 30 minutes were evaluated. RESULTS: A CTI block was achieved in 171 patients. Nine patients (5.3%) had dormant conduction across the CTI immediately after ablation and BDB, and required further ablation. Two patients (1.2%) had subsequent spontaneous time-dependent reconnection within 30 minutes. Two other patients (1.2%) developed late dormant conduction with adenosine at 30 minutes. All 4 patients underwent further ablation. CONCLUSION: A negative adenosine challenge immediately after CTI ablation with bidirectional block, or after abolition of dormant conduction with further ablation, strongly predicted the absence of subsequent spontaneous reconnection within 30 minutes. Based on these results, the conventional waiting period is unnecessary in 97.6% patients without dormant conduction after CTI-dependent flutter ablation.
Assuntos
Adenosina/administração & dosagem , Flutter Atrial/diagnóstico por imagem , Flutter Atrial/terapia , Ablação por Cateter/métodos , Valva Tricúspide/diagnóstico por imagem , Idoso , Flutter Atrial/fisiopatologia , Feminino , Seguimentos , Bloqueio Cardíaco/induzido quimicamente , Bloqueio Cardíaco/diagnóstico por imagem , Bloqueio Cardíaco/fisiopatologia , Sistema de Condução Cardíaco/diagnóstico por imagem , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Valva Tricúspide/efeitos dos fármacos , Valva Tricúspide/fisiopatologiaRESUMO
OBJECTIVE: To quantify drug-induced changes in right ventricular (RV) systolic function after administration of pimobendan and atenolol. ANIMALS: 80 healthy privately-owned dogs. METHODS: Using a prospective, blinded, fully-crossed study design with randomized drug administration, RV systolic function was determined twice at two time periods; before and 3 h after administration of pimobendan (0.25 mg/kg PO) or atenolol (1 mg/kg PO). Indices of RV systolic function included tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulsed-wave tissue Doppler-derived systolic myocardial velocity of the lateral tricuspid annulus (S'), and speckle-tracking-derived global longitudinal RV free wall strain and strain rate. The effect of treatment on percent change from baseline RV function was analyzed with a linear mixed model including the covariates heart rate, body weight, age, gender, drug sequence, and time period. RESULTS: All indices showed a significant (p < 0.0001) increase and decrease from baseline following pimobendan and atenolol, respectively. Significant differences from baseline were attributed to drug treatment (p < 0.0001); whereas, effects of other covariates were not significant. The greatest percent changes, but also highest variability, were observed for S' and strain rate (p < 0.0001). Post-atenolol, a significantly greater proportion of dogs exceeded the repeatability coefficient of variation for FAC and S' compared to TAPSE (p ≤ 0.007). CONCLUSIONS: Echocardiographic indices in healthy dogs tracked expected changes in RV systolic function following pimobendan and atenolol and warrant study in dogs with cardiovascular disease.
Assuntos
Atenolol/farmacologia , Cães/fisiologia , Piridazinas/farmacologia , Valva Tricúspide/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Cardiotônicos/farmacologia , Estudos Cross-Over , Valva Tricúspide/diagnóstico por imagem , Ultrassonografia , Função Ventricular Direita/fisiologiaRESUMO
Companion animals are routinely anesthetized or heavily sedated for cardiac MRI studies, however effects of varying anesthetic protocols on cardiac function measurements are incompletely understood. The purpose of this prospective study was to compare effects of two anesthetic protocols (Protocol A: Midazolam, fentanyl; Protocol B: Dexmedetomidine) on quantitative and qualitative blood flow values measured through the aortic, pulmonic, mitral, and tricuspid valves using two-dimensional phase contrast magnetic resonance imaging (2D PC MRI) in healthy dogs. Mean flow per heartbeat values through the pulmonary artery (Qp) and aorta (Qs) were compared to right and left ventricular stroke volumes (RVSV, LVSV) measured using a reference standard of 2D Cine balanced steady-state free precession MRI. Pulmonary to systemic flow ratio (Qp/Qs) was also calculated. Differences in flow and Qp/Qs values generated using 2D PC MRI did not differ between the two anesthetic protocols (P = 1). Mean differences between Qp and RVSV were 3.82 ml/beat (95% limits of agreement: 3.62, -11.26) and 1.9 ml/beat (-7.86, 11.66) for anesthesia protocols A and B, respectively. Mean differences between Qs and LVSV were 1.65 ml/beat (-5.04, 8.34) and 0.03 ml/beat (-4.65, 4.72) for anesthesia protocols A and B, respectively. Mild tricuspid or mitral reflux was seen in 2/10 dogs using 2D PC MRI. No aortic or pulmonic insufficiency was observed. Findings from the current study indicated that these two anesthetic protocols yield similar functional measures of cardiac blood flow using 2D PC MRI in healthy dogs. Future studies in clinically affected patients are needed.
Assuntos
Anestésicos Intravenosos/administração & dosagem , Débito Cardíaco/efeitos dos fármacos , Meios de Contraste , Cães/fisiologia , Hipnóticos e Sedativos/administração & dosagem , Animais , Aorta/efeitos dos fármacos , Valva Aórtica/efeitos dos fármacos , Dexmedetomidina/administração & dosagem , Fentanila/administração & dosagem , Imagem Cinética por Ressonância Magnética/veterinária , Valva Mitral/efeitos dos fármacos , Estudos Prospectivos , Artéria Pulmonar/efeitos dos fármacos , Valva Pulmonar/efeitos dos fármacos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Reprodutibilidade dos Testes , Volume Sistólico/efeitos dos fármacos , Valva Tricúspide/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacosRESUMO
BACKGROUND: Amiodarone is commonly used in the acute care setting. However the acute hemodynamic and echocardiographic effect of intravenous amiodarone administered intraoperatively on right ventricular (RV) systolic and diastolic function using transesophageal echocardiography (TEE) has not been described. METHODS: The study design was a randomized controlled trial in elective cardiac surgical patients undergoing valvular surgery. Patients received an intravenous loading dose of 300 mg of either amiodarone or placebo in the operating room, followed by an infusion of 15 mg/kg for two days. Hemodynamic profiles, echocardiographic measurement of RV and left ventricular (LV) dimensions, Doppler interrogation of tricuspid and mitral valve, hepatic and pulmonary venous flow combined with tissue Doppler imaging of the tricuspid and mitral valve annulus were obtained before and after bolus. RESULTS: Although more patients in the placebo group had chronic obstructive lung disease (14 vs 6, p=0.05) and diabetes (14 vs 5; p=0.0244), there was no difference in terms of baseline hemodynamic, 2D and Doppler variables. After bolus, a significant increase in pulmonary artery pressure, central venous pressure and pulmonary vascular resistance index (p<0.05) was observed in the amiodarone group with reduction in systolic to diastolic (S/D) ratio of the hepatic (p=0.0247) and pulmonary venous (p=0.0052) velocity. CONCLUSION: Acute administration of amiodarone is associated with alteration in RV diastolic properties and has minimal negative inotropic effect on RV systolic function in cardiac surgical patients with valvular disease.
Assuntos
Amiodarona/administração & dosagem , Doenças das Valvas Cardíacas/cirurgia , Veias Hepáticas/diagnóstico por imagem , Valva Mitral/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Valva Tricúspide/diagnóstico por imagem , Função Ventricular Direita/efeitos dos fármacos , Administração Intravenosa , Amiodarona/farmacologia , Método Duplo-Cego , Ecocardiografia Doppler , Ecocardiografia Transesofagiana , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Hemodinâmica/efeitos dos fármacos , Veias Hepáticas/efeitos dos fármacos , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Valva Mitral/efeitos dos fármacos , Veias Pulmonares/efeitos dos fármacos , Valva Tricúspide/efeitos dos fármacosRESUMO
BACKGROUND: Based on the current understanding of cardiac conduction system development and the observation that arrhythmogenic foci can originate in areas near the atrioventricular annuli, we hypothesized that focal annular tachycardias, whether atrial or ventricular, share a common mechanism. We, therefore, prospectively evaluated this hypothesis in patients with sustained atrial and ventricular tachycardia originating from the peri-tricuspid and mitral annuli. METHODS AND RESULTS: Forty-nine consecutive patients with sustained, focal annular tachycardia comprised the study group. All underwent electrophysiological evaluation and the mode of tachycardia initiation, termination, sensitivity to catecholamine infusion, and response to adenosine/verapamil were evaluated. Electroanatomical activation maps identified the sites of arrhythmia origin. Tachycardias could be initiated or terminated or both with programmed stimulation in 46 of 46 patients and most (70%) were catecholamine facilitated. Of the 9 patients with sustained annular ventricular tachycardia, 3 were localized to the tricuspid annulus, and 6 to the mitral annulus. All the 9 ventricular tachycardias (100%) terminated with adenosine, 2 of 2 terminated with verapamil, and 2 of 2 terminated with Valsalva. Of the 40 patients with annular atrial tachycardia, 4 tachycardias were localized to the mitral annulus and 37 to the tricuspid annulus (including 9 para-Hisian), and all were adenosine sensitive. CONCLUSIONS: Peri-annular atrial and ventricular tissue correspond to a region enriched with arrhythmogenic foci, which may reflect a common developmental origin. Furthermore, the sensitivity of these tachycardias to adenosine provides evidence for a shared arrhythmia mechanism, consistent with intracellular calcium overload and triggered activity.
Assuntos
Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Valva Mitral/fisiopatologia , Taquicardia Atrial Ectópica/diagnóstico , Taquicardia Ventricular/diagnóstico , Valva Tricúspide/fisiopatologia , Adenosina/administração & dosagem , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/efeitos dos fármacos , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Taquicardia Atrial Ectópica/tratamento farmacológico , Taquicardia Ventricular/tratamento farmacológico , Valva Tricúspide/efeitos dos fármacos , Verapamil/administração & dosagemRESUMO
BACKGROUND: Given the association between valvular heart disease and drugs that alter serotonin metabolism, concerns have been raised about the possibility of an association between selective serotonin reuptake inhibitor (SSRI) use and drug-induced valvular disease. In France, SSRI use has been suggested to be an important confounding factor in the development of heart valve lesions in patients exposed to benfluorex in the context of the 'Médiator scandal'. AIMS: To address the relationship between SSRI use and valve regurgitation and morphology in a large cohort of patients exposed to benfluorex. METHODS: Overall, 832 consecutive patients exposed to benfluorex prospectively referred to 10 centres underwent complete echocardiography examinations according to a standardized protocol. Echocardiograms were independently and blindly read off-line by two experts. RESULTS: Ninety patients had been exposed to SSRIs for 3 months or more. The proportions of patients with no or trivial, mild, moderate or severe mitral regurgitation (MR) or aortic regurgitation (AR) were not different between SSRI patients and non-SSRI patients (P=0.63 and 0.58, respectively). The frequencies of AR ≥ mild (20 [22.2%] vs 145 [19.5%]; P=0.55) and MR ≥ mild (14 [15.6%] vs 118 [15.9%]; P=0.93) were similar in SSRI patients and non-SSRI patients. The frequencies of aortic and mitral valve abnormalities suggestive of drug-induced toxicity were also similar in the two patient groups. Multivariable logistic regression analysis confirmed the absence of any identifiable relationship between AR or MR and morphological abnormalities and SSRI use in the present cohort. CONCLUSION: Exposure to SSRIs was not associated with an increased risk of heart valve regurgitation or morphological abnormalities suggestive of drug-induced toxicity in this large cohort of patients exposed to benfluorex.
Assuntos
Depressores do Apetite/efeitos adversos , Fenfluramina/análogos & derivados , Doenças das Valvas Cardíacas/induzido quimicamente , Valvas Cardíacas/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Adulto , Idoso , Valva Aórtica/efeitos dos fármacos , Insuficiência da Valva Aórtica/induzido quimicamente , Distribuição de Qui-Quadrado , Ecocardiografia Doppler em Cores , Feminino , Fenfluramina/efeitos adversos , França , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Valvas Cardíacas/diagnóstico por imagem , Valvas Cardíacas/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valva Mitral/efeitos dos fármacos , Insuficiência da Valva Mitral/induzido quimicamente , Análise Multivariada , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Encaminhamento e Consulta , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Valva Tricúspide/efeitos dos fármacos , Insuficiência da Valva Tricúspide/induzido quimicamenteRESUMO
OBJECTIVES: To compare myocardial systolic and diastolic functions and pulmonary circulation by two-dimensional, M-mode, Doppler, and pulsed tissue Doppler imaging in patients with ß-thalassemia intermedia who received hydroxyurea at least for 1 yr, patients who did not receive hydroxyurea, and a healthy control group. METHODS: We assigned 84 patients with thalassemia intermedia into two groups: one of two was treated with hydroxyurea for at least 1 yr and no hydroxyurea. M-mode echocardiographic, Doppler, and pulsed Doppler tissue images were compared in these two groups and in 20 control participants who did not have thalassemia. For the estimation of pulmonary hypertension, pulmonary acceleration time below 100 ms was considered as an index of pulmonary hypertension. RESULTS: There were no significant differences in M-mode echocardiographic findings between three groups. Doppler echocardiography detected no significant differences between the treated and untreated groups. In treated hydroxyurea group, 11.7% patients had pulmonary acceleration time below 100 ms and in untreated group 21% (LR = 1.45, P = 0.22). Pulsed Doppler tissue imaging parameters did not differ significantly between treated and untreated patients (P > 0.05). Pulsed Doppler tissue images showed significant changes between patients and controls in peak systolic velocity of the septum, peak atrial velocity of the septum (Aas), the peak systolic velocity of the tricuspid valve (St), the peak early diastolic velocity of the tricuspid valve (Eat), and the peak late diastolic velocity of the tricuspid valve (Aat). CONCLUSION: This study revealed that in spite of decrease in estimated pulmonary hypertension in treated group, HU has no statistically significant effect on pulmonary acceleration time and M-mode, Doppler, and tissue Doppler changes of patients with TI.
Assuntos
Coração/efeitos dos fármacos , Coração/fisiopatologia , Hidroxiureia/uso terapêutico , Circulação Pulmonar/efeitos dos fármacos , Talassemia beta/tratamento farmacológico , Talassemia beta/fisiopatologia , Adolescente , Adulto , Antimetabólitos/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Ecocardiografia Doppler , Ecocardiografia Doppler de Pulso , Feminino , Hemoglobinas/metabolismo , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/efeitos dos fármacos , Valva Tricúspide/fisiopatologia , Adulto Jovem , Talassemia beta/diagnóstico por imagemRESUMO
OBJECTIVE: Pulmonary arterial (PA) vasoconstriction in cardiac surgery can originate from the action of combined humoral, endothelial, and sympathetic tone changes. The consequence of PA vasoconstriction is pulmonary hypertension (PHT) and, when present after cardiopulmonary bypass (CPB), can predispose to right ventricular dysfunction. Right ventricular dysfunction after CPB is a serious complication with high mortality rates. The extent to which sympathetic blockade could reduce PA vasoconstriction and reduce PHT is unknown. Pharmacologic stellate ganglion block (SGB) has been associated with a reduction in PHT, but its role and mechanism in cardiac surgery have not been described. Thus, the goal of the study was to test the hypothesis that echo-guided left SGB, performed before the induction of general anesthesia, could prevent PA pressure increases during CPB weaning. DESIGN: A prospective cohort study in cardiac surgical patients. SETTING: A tertiary care university hospital. PARTICIPANTS: Forty cardiac surgical patients. INTERVENTIONS: A left SGB was performed immediately before the induction of general anesthesia under ultrasound guidance and was compared with matched control patients. Standard hemodynamic and electrocardiographic monitoring was performed, and blood gas samples were drawn at specific predetermined time points for analysis. Rhythm disorders, echocardiographic parameters that included wall motion abnormalities, and biochemical parameters of myocardial ischemia were measured by an observer blinded to the allocated group. MEASUREMENTS AND MAIN RESULTS: Marked improvement in the PaO(2)/F(I)O(2) ratio in the SGB group was observed (mean difference = 77 mmHg, p = 0.0001). There were no differences between the groups in PA pressure over time during the procedure; central venous pressure was higher in the SGB group (p =0.0184). Reductions of right ventricular fractional area change (p = 0.0331) and tricuspid annulus displacement (p = 0.0048) were observed in the SGB group. The CK-MB was 1.5 times higher in the SGB group (p = 0.0211), but no patients developed myocardial infarction. CONCLUSIONS: Left SBG was associated with improved oxygenation that could partially explain its mechanism in acute PHT. Further studies are necessary to evaluate the usefulness of this technique in patients with a high risk of PHT during separation from CPB.
Assuntos
Bloqueio Nervoso Autônomo/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Gânglio Estrelado/diagnóstico por imagem , Idoso , Anestesia Geral , Anestésicos Locais , Arritmias Cardíacas/epidemiologia , Pressão Sanguínea/efeitos dos fármacos , Bupivacaína , Estudos de Coortes , Ponte de Artéria Coronária , Ecocardiografia Transesofagiana , Feminino , Humanos , Hipertensão Pulmonar/prevenção & controle , Complicações Intraoperatórias/epidemiologia , Lidocaína , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Oxigênio/sangue , Estudos Prospectivos , Artéria Pulmonar/fisiologia , Valva Tricúspide/efeitos dos fármacos , Valva Tricúspide/fisiologia , Função Ventricular Direita/fisiologiaRESUMO
RATIONALE: Calcification of heart valve structures is the most common form of valvular disease and is characterized by the appearance of bone-like phenotypes within affected structures. Despite the clinical significance, the underlying etiology of disease onset and progression is largely unknown and valve replacement remains the most effective treatment. The SRY-related transcription factor Sox9 is expressed in developing and mature heart valves, and its function is required for expression of cartilage-associated proteins, similar to its role in chondrogenesis. In addition to cartilage-associated defects, mice with reduced sox9 function develop skeletal bone prematurely; however, the ability of sox9 deficiency to promote ectopic osteogenic phenotypes in heart valves has not been examined. OBJECTIVE: This study aims to determine the role of Sox9 in maintaining connective tissue homeostasis in mature heart valves using in vivo and in vitro approaches. METHODS AND RESULTS: Using histological and molecular analyses, we report that, from 3 months of age, Sox9(fl/+);Col2a1-cre mice develop calcific lesions in heart valve leaflets associated with increased expression of bone-related genes and activation of inflammation and matrix remodeling processes. Consistently, ectopic calcification is also observed following direct knockdown of Sox9 in heart valves in vitro. Furthermore, we show that retinoic acid treatment in mature heart valves is sufficient to promote calcific processes in vitro, which can be attenuated by Sox9 overexpression. CONCLUSIONS: This study provides insight into the molecular mechanisms of heart valve calcification and identifies reduced Sox9 function as a potential genetic basis for calcific valvular disease.
Assuntos
Calcinose/metabolismo , Doenças das Valvas Cardíacas/metabolismo , Valva Mitral/metabolismo , Fatores de Transcrição SOX9/metabolismo , Valva Tricúspide/metabolismo , Fatores Etários , Envelhecimento , Animais , Animais Recém-Nascidos , Calcinose/genética , Calcinose/patologia , Cálcio/metabolismo , Embrião de Galinha , Colágeno Tipo II/genética , Modelos Animais de Doenças , Regulação para Baixo , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Técnicas de Silenciamento de Genes , Genótipo , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Inflamação/metabolismo , Inflamação/patologia , Integrases/genética , Masculino , Camundongos , Camundongos Transgênicos , Valva Mitral/efeitos dos fármacos , Valva Mitral/embriologia , Valva Mitral/patologia , Osteogênese/genética , Fenótipo , Fatores de Transcrição SOX9/genética , Técnicas de Cultura de Tecidos , Transfecção , Tretinoína/farmacologia , Valva Tricúspide/efeitos dos fármacos , Valva Tricúspide/embriologia , Valva Tricúspide/patologiaRESUMO
PURPOSE: In this prospective observational cohort study, we investigated whether tricuspid annular velocities (TAV) are altered after induction of anesthesia in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: Twenty-four elective CABG patients were assessed before and after induction of anesthesia, and a convenience sample of nine healthy volunteers was used for comparison of TAV only. Measurements included mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), and cardiac index (CI) as assessed post-induction. Tricuspid annular plane systolic excursion (TAPSE) was measured in anatomical M-mode. The S (systolic) wave velocity and isovolemic acceleration (IVA) were measured from colour tissue Doppler (TD). Paired and unpaired Student's t tests were used to compare all variables pre-and post-induction. RESULTS: In response to anesthetic induction, MAP decreased from 105 +/- 14 to 79 +/- 9 mmHg, but HR was unchanged (67 +/- 13 beats x min(-1) pre-induction compared with 67 +/- 9 beats x min(-1) post-induction). The mean PAP and CI post-induction were 20 +/- 6 mmHg and 2.3 +/- 0.4 L x min(-1) x m(-2), respectively. While there was no change post-induction in either S velocity (8.80 +/- 1.23 vs 9.0 +/- 1.92 cm x sec(-1)) or IVA (1.63 +/- 0.61 vs 1.84 +/- 0.83 m x sec(-2)), TAPSE decreased from 23 +/- 4 to 21 +/- 4 mm (P = 0.039). All pre-induction echocardiographic variables were lower in the CABG group compared with the normal group (IVA: 2.34 +/- 0.34 m x sec(-2), S wave: 11.14 +/- 2.78 cm x sec(-1), TAPSE 2D: 26 +/- 4 mm), respectively. CONCLUSIONS: Induction of anesthesia for CABG surgery does not alter velocity-based parameters of RV function. There was a small decrease in TAPSE. The TD parameters were lower in CABG patients compared with the normal group.
Assuntos
Anestesia , Valva Tricúspide/efeitos dos fármacos , Adulto , Estudos de Coortes , Ponte de Artéria Coronária , Ecocardiografia , Ecocardiografia Doppler em Cores , Feminino , Hemodinâmica/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valva Tricúspide/diagnóstico por imagem , Função Ventricular Direita/fisiologiaRESUMO
Right heart infective endocarditis in an elderly patient with no previous known risk factors is a very rare situation (even if subacute infective endocarditis has the same chance of occurrence at either a young person, or an elderly patient). We present the case of a 75-years old patient, with no previous cardiac history, addressed to our clinic with nonspecific septic symptoms associated with an edematous syndrome. The patient was treated for right heart valve infective endocarditis; a particularity may be the fact not all Duke criteria were respected. Iatrogeny was involved, our patient having administered a 7-day antibiotic treatment before hospital addressing. The therapeutic probe was positive: excellent evolution under treatment. Few cases of infective endocarditis of the tricuspid valve were reported worldwide, in which the source of infection was unknown in about 80% of cases. In two pediatric cases reported, tricuspid endocarditis was caused by Staphylococcus aureus septicemia following upper respiratory infection. This may also occur in adult cases. Further investigations should be carried out in the future to elucidate the source of infection. Isolated right-sided endocarditis should be included in the differential diagnosis of patients with febrile syndrome, respiratory symptoms and predisposing disease, even when they do not have a pacemaker and are not intravenous-drug users (IVDU).
Assuntos
Antibacterianos/uso terapêutico , Endocardite Bacteriana Subaguda/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Doenças das Valvas Cardíacas/tratamento farmacológico , Valva Tricúspide/efeitos dos fármacos , Idoso , Alcoolismo/complicações , Diagnóstico Diferencial , Edema Cardíaco/tratamento farmacológico , Endocardite Bacteriana Subaguda/complicações , Endocardite Bacteriana Subaguda/diagnóstico , Febre/microbiologia , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/microbiologia , Humanos , Masculino , Fatores de Risco , Fumar/efeitos adversos , Resultado do Tratamento , Valva Tricúspide/microbiologiaRESUMO
The aim of the experiments was to assess the toxicity of minoxidil, a potent vasodilator, in marmosets. The animals were treated either at escalating doses from 2 to 40 mg/kg, escalating doses from 40 to 200 mg/kg or single doses of 150 mg/kg or 200 mg/kg. ECG recording and echocardiographic examination were conducted before and 1h after treatment. Necropsy and histopathology were performed 24h after the last dose. The treatment with minoxidil induced myocardial necrosis, coronary arteriopathy and degeneration of renal tubules in animals treated with 150 mg/kg or 200 mg/kg. Myocardial necrosis associated with fibrosis in some animals was located mainly in the left and right ventricles (including papillary muscles), but also in the right atrium, left atrium and/or interventricular septum. Arteriopathy was observed in small coronary arteries of the right or left atrium. ECG and echocardiographic examinations showed that in animals treated with 150 mg/kg or 200 mg/kg, there were positive chronotropic and inotropic effects that compensated for the hypotensive effect of the drug and were considered to have played a key role in the pathogenesis of the cardiovascular lesions. The cardiotoxicity of minoxidil in marmosets was similar to that described in dogs, but occurred at much higher doses. In conclusion minoxidil produced cardiovascular toxicity in the marmoset, which was probably due to the marked changes in the cardiac function associated with exaggerated pharmacological effects of the compound. The marmosets were found to be less sensitive than dogs to the cardiotoxicity of minoxidil.
Assuntos
Callithrix/fisiologia , Doenças Cardiovasculares/induzido quimicamente , Minoxidil/toxicidade , Vasodilatadores/toxicidade , Animais , Análise Química do Sangue , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/fisiopatologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/metabolismo , Ecocardiografia , Eletrocardiografia/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Minoxidil/sangue , Valva Mitral/fisiologia , Contração Miocárdica/efeitos dos fármacos , Miocárdio/patologia , Necrose , Inibidores de Fosfodiesterase/farmacologia , Valva Tricúspide/efeitos dos fármacos , Troponina/sangue , Vasodilatadores/sangue , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacosRESUMO
OBJECTIVE: Possible acute effects of smoking mentholated cigarette on left and right ventricular function is not known. The aim of the study was to compare acute effects of normal and mentholated cigarettes smoking on both ventricular diastolic functions in chronic smokers. METHODS: In a single-blinded, cross-over, open label and controlled study acute effect of smoking of the mentholated and the regular cigarettes was evaluated. Eighteen other than healthy regular cigarette smokers and 20 nonsmoker control subjects were included into the study. To compare the acute effects of mentholated and regular cigarette in each subject echocardiographic examination including tissue Doppler imaging (TDI) were performed at baseline, than in the smokers group TDI was measure 20-30 minutes after smoking two either cigarettes. RESULTS: In response to smoking two cigarettes, mitral E/A values declined from 1.78+/-0.44 to 1.58+/-0.41 after the regular cigarette (p=0.0043) and from 1.78+/-0.44 to 1.53+/-0.40 after the mentholated cigarette (p=0.0035). Tricuspid E deceleration time values declined from 185.28+/-20.05 ms to 222.72+/-26.47 ms after the regular cigarette (p<0.001) and 185.28+/-20.05 ms to 241.53+/-47.63 ms after the mentholated cigarette (p<0.001). Smoking of mentholated cigarette, but not regular cigarette smoking, increased tricuspid E deceleration time and right ventricular isovolumic contraction time (p=0.044; p=0.024 respectively) and decreased the right ventricular Em values (p=0.027). CONCLUSION: Mentholated and regular cigarette smoking have acute detrimental effects on right and left ventricular systolic and diastolic function. Mentholated cigarettes cause additional unfavorable acute effects on especially right ventricular tissue Doppler velocities, relaxation and contraction indices compared to regular cigarettes.