RESUMEN
Valvular heart disease is a common cause of morbidity and mortality worldwide and has no effective medical therapy. Severe disease is managed with valve replacement procedures, which entail high health care-related costs and postprocedural morbidity and mortality. Robust ongoing research programs have elucidated many important molecular pathways contributing to primary valvular heart disease. However, there remain several key challenges inherent in translating research on valvular heart disease to viable molecular targets that can progress through the clinical trials pathway and effectively prevent or modify the course of these common conditions. In this scientific statement, we review the basic cellular structures of the human heart valves and discuss how these structures change in primary valvular heart disease. We focus on the most common primary valvular heart diseases, including calcific aortic stenosis, bicuspid aortic valves, mitral valve prolapse, and rheumatic heart disease, and outline the fundamental molecular discoveries contributing to each. We further outline potential therapeutic molecular targets for primary valvular heart disease and discuss key knowledge gaps that might serve as future research priorities.
Asunto(s)
American Heart Association , Enfermedades de las Válvulas Cardíacas , Humanos , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/metabolismo , Estados Unidos , AnimalesRESUMEN
AIMS: The aim of this study is to evaluate the effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve (BAV)-related aortopathy and ascending phenotype. METHODS: Consecutive paediatric patients (≤16 years) with BAV and ascending aorta (AsAo) dilation (z-score > 3) were enrolled in this observational retrospective cohort study. Patients receiving prophylactic treatment with either atenolol (0.5 to 1.0 mg/kg/daily) or losartan (0.7 to 1.4 mg/kg/daily) were compared with those who did not receive medical prophylaxis (control group). The primary outcome of interest was the annual rate of change in maximal AsAo diameter z-score in the treatment and control groups. RESULTS: From a cohort of 1005 patients, 120 (mean age 11.3 ± 4.5 years, 82% males) fulfilled the inclusion criteria and were included in the study. Patients in the treatment and control group had similar age, sex, family history of BAV, BAV morphology, and baseline AsAo diameter. During a median follow-up of 7.1 years (interquartile range 3.8-10.2), no differences were observed in the annual growth rate of aortic diameter z-score between patients on treatment and controls. The prevalence of aortic diameter progression was similar in the treatment and control groups, and treatment with atenolol or losartan was not associated with a lower rate of aortic disease progression. CONCLUSIONS: The findings revealed no significant difference in the annual aortic growth rate between treated and untreated patients. Larger cohort studies or, ideally, randomized clinical controlled trials are needed to validate these findings.
Asunto(s)
Antagonistas Adrenérgicos beta , Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Humanos , Masculino , Femenino , Niño , Estudios Retrospectivos , Adolescente , Antagonistas Adrenérgicos beta/uso terapéutico , Válvula Aórtica/anomalías , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/patología , Válvula Aórtica/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Losartán/uso terapéutico , Estudios de Seguimiento , Estudios de Cohortes , Atenolol/uso terapéutico , Resultado del Tratamiento , Aorta/efectos de los fármacos , Aorta/diagnóstico por imagen , Enfermedad de la Válvula Aórtica/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/complicaciones , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéuticoRESUMEN
BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.
Asunto(s)
Válvula Aórtica , Atorvastatina , Enfermedad de la Válvula Aórtica Bicúspide , Calcinosis , Progresión de la Enfermedad , Enfermedades de las Válvulas Cardíacas , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Atorvastatina/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/patología , Válvula Aórtica/anomalías , Válvula Aórtica/efectos de los fármacos , Calcinosis/tratamiento farmacológico , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Enfermedad de la Válvula Aórtica Bicúspide/diagnóstico por imagen , Enfermedad de la Válvula Aórtica Bicúspide/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/patología , Adulto , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Dilatación Patológica/tratamiento farmacológico , Estudios de Seguimiento , Método Doble Ciego , Resultado del Tratamiento , Aorta/diagnóstico por imagen , Aorta/patología , Aorta/efectos de los fármacos , Enfermedad de la Válvula Aórtica/tratamiento farmacológico , Estenosis de la Válvula AórticaRESUMEN
Currently, there is no specific medication approved for the treatment of valvular heart disease per se. Except for secondary mitral valve insufficiency and tricuspid valve insufficiency in pulmonary hypertension, drug therapy for higher-grade valvular heart disease is limited to diuretic therapy for symptom control. Conservative therapy for comorbidities and potential heart failure can be beneficial regardless of the specific valve lesion. In cases of aortic valve stenosis or insufficiency, controlling arterial hypertension is important. Patients with mitral valve stenosis benefit from rhythm and rate control. Diuretics can help reduce regurgitant volume in patients with primary mitral valve insufficiency and tricuspid valve insufficiency. In addition to drug therapy, maintaining functional capacity is crucial for the outcome of patients. Therefore, it is recommended to engage in active physical activity whenever possible, despite the presence of valvular heart disease.
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Enfermedades de las Válvulas Cardíacas , Humanos , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Adulto , Tratamiento Conservador/métodos , Diuréticos/uso terapéuticoRESUMEN
BACKGROUND: High circulating levels of Lp(a) (lipoprotein[a]) increase the risk of atherosclerosis and calcific aortic valve disease, affecting millions of patients worldwide. Although atherosclerosis is commonly treated with low-density lipoprotein-targeting therapies, these do not reduce Lp(a) or risk of calcific aortic valve disease, which has no available drug therapies. Targeting Lp(a) production and catabolism may provide therapeutic benefit, but little is known about Lp(a) cellular uptake. METHODS: Here, unbiased ligand-receptor capture mass spectrometry was used to identify MFSD5 (major facilitator superfamily domain containing 5) as a novel receptor/cofactor involved in Lp(a) uptake. RESULTS: Reducing MFSD5 expression by a computationally identified small molecule or small interfering RNA suppressed Lp(a) uptake and calcification in primary human valvular endothelial and interstitial cells. MFSD5 variants were associated with aortic stenosis (P=0.027 after multiple hypothesis testing) with evidence suggestive of an interaction with plasma Lp(a) levels. CONCLUSIONS: MFSD5 knockdown suppressing human valvular cell Lp(a) uptake and calcification, along with meta-analysis of MFSD5 variants associating with aortic stenosis, supports further preclinical assessment of MFSD5 in cardiovascular diseases, the leading cause of death worldwide.
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Enfermedad de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Aterosclerosis , Calcinosis , Enfermedades de las Válvulas Cardíacas , Humanos , Válvula Aórtica/metabolismo , Enfermedad de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/tratamiento farmacológico , Estenosis de la Válvula Aórtica/genética , Aterosclerosis/metabolismo , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/genética , Enfermedades de las Válvulas Cardíacas/complicaciones , Lipoproteína(a) , Factores de RiesgoRESUMEN
BACKGROUND: Pimobendan is an important therapy for dogs with myxomatous mitral valve disease (MMVD). The pharmacokinetics are reported in healthy dogs but not in dogs with heart disease. HYPOTHESIS/OBJECTIVES: To determine if dog characteristics such as age, breed, body condition score, ACVIM stage of heart disease or biochemical laboratory value alter the pharmacokinetics of orally administered pimobendan and its metabolite in a cohort of dogs with naturally occurring MMVD. ANIMALS: Fifty-seven client-owned dogs with MMVD ACVIM Stage B2, C, or D and administered pimobendan to steady state blood concentrations. METHODS: Prospective, observational study. Samples were collected using a sparse-sampling protocol at specific intervals after administration of pimobendan. Plasma pimobendan and the active metabolite (O-desmethyl-pimobendan, ODMP) concentrations were determined via high-pressure liquid chromatography and fluorescence detection. Data was analyzed via a population pharmacokinetic approach and nonlinear mixed effects modeling (NLME). Numerous covariates were examined in the NLME model. RESULTS: The absorption and elimination half-lives (t1/2 ) were approximately 1.4 and 1 hour for pimobendan and 1.4 and 1.3 hours for ODMP, respectively. Pharmacokinetic parameters were highly variable, especially the values for pimobendan absorption and elimination rate, and absorption rate of ODMP with coefficients of variation of 147.84%, 64.51% and 64.49%, respectively. No covariate evaluated was a significant source of variability. CONCLUSIONS AND CLINICAL IMPORTANCE: The pharmacokinetic parameters were highly variable among this group of dogs with MMVD. The variability was not associated with the dog's age, body weight or condition score, stage of heart disease, dose, serum creatinine, or alkaline phosphatase.
Asunto(s)
Enfermedades de los Perros , Cardiopatías , Enfermedades de las Válvulas Cardíacas , Humanos , Perros , Animales , Válvula Mitral , Estudios Prospectivos , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/veterinaria , Cardiopatías/veterinaria , Administración Oral , Enfermedades de los Perros/tratamiento farmacológicoRESUMEN
This review discusses the evolving topic of atrial cardiomyopathy concerning valvular heart disease. The pathogenesis of atrial cardiomyopathy involves multiple factors, such as valvular disease leading to atrial structural and functional remodeling due to pressure and volume overload. Atrial enlargement and dysfunction can trigger atrial tachyarrhythmia. The complex interaction between valvular disease and atrial cardiomyopathy creates a vicious cycle of aggravating atrial enlargement, dysfunction, and valvular disease severity. Furthermore, atrial remodeling and arrhythmia can predispose to atrial thrombus formation and stroke. The underlying pathomechanism of atrial myopathy involves molecular, cellular, and subcellular alterations resulting in chronic inflammation, atrial fibrosis, and electrophysiological changes. Atrial dysfunction has emerged as an essential determinant of outcomes in valvular disease and heart failure. Despite its predictive value, the detection of atrial fibrosis and dysfunction is challenging and is not included in the clinical routine. Transthoracic echocardiography and cardiac magnetic resonance imaging are the main diagnostic tools for atrial cardiomyopathy. Recently published data have revealed that both left atrial volumes and functional parameters are independent predictors of cardiovascular events in valvular disease. The integration of atrial function assessment in clinical practice might help in early cardiovascular risk estimation, promoting early therapeutic intervention in valvular disease.
Asunto(s)
Fibrilación Atrial , Cardiomiopatías , Insuficiencia Cardíaca , Enfermedades de las Válvulas Cardíacas , Humanos , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Cardiomiopatías/complicaciones , Insuficiencia Cardíaca/complicaciones , Fibrosis , Biología MolecularRESUMEN
BACKGROUND: Prosthetic Valve Thrombosis (PVT) is rare but life threatening condition which requires urgent intervention. Patient treatment outcome is not well studied in resource limited settings and the current study aims to explore the treatment outcome of patients with PVT at the Cardiac Center of Ethiopia. METHODS: The study was conducted at the Cardiac Center of Ethiopia which provides heart valve surgery. All patients who were diagnosed and managed for PVT in the center during the period July 2017 to March 2022 were included in the study. Data were collected through chart abstraction by using a structured questionnaire. Data analysis was done using SPSS version 20.0 for windows software. RESULT: Eleven patients (13 episodes of stuck valve) with PVT were included in the study and nine of them were female. The median age was 28 years old (IQR 22.5-34.0) with the youngest and oldest patients being 18 and 46 years old respectively. All the patients had bi-leaflet prosthetic mechanical valves (10 at mitral valve, two at aortic and mitral and one at aortic positions). The median duration of valve replacement before having PVT was 36 months (IQR 5-72). All patients reported good adherence to anticoagulant therapy; yet only five had optimal INR value. Nine patients presented with failure symptoms. Eleven patients received thrombolytic therapy and nine of them responded to it. One patient operated for failed thrombolytic therapy. Two patients responded to heparinization and optimization of anticoagulant therapy. Of the ten patients who received streptokinase, two of them developed fever and one patient developed bleeding as a complication of the treatment. All the patients survived hospital discharge. CONCLUSION: Prosthetic valve thrombosis was accompanied by sub-optimal anticoagulant therapy. Most patients responded to medical therapy alone.
Asunto(s)
Enfermedades de las Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Trombosis , Humanos , Femenino , Adulto , Adolescente , Adulto Joven , Persona de Mediana Edad , Masculino , Etiopía , Prótesis Valvulares Cardíacas/efectos adversos , Estudios Retrospectivos , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Resultado del Tratamiento , Trombosis/tratamiento farmacológico , Trombosis/etiología , Trombosis/diagnóstico , Anticoagulantes/uso terapéutico , Fibrinolíticos/uso terapéuticoRESUMEN
Aim: The risks of thromboembolism and major bleeding in atrial fibrillation (AF) patients were assessed according to the "Evaluated Heartvalves, Rheumatic or Artificial" (EHRA) classification. Additionally, the safety and efficacy of vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) were compared in AF patients with EHRA type 2 valvular heart disease (VHD) versus those with no VHD. Methods: AF patients enrolled in the "Jordan Atrial Fibrillation (JoFib)" study were followed up for thromboembolic events and major bleeding at 30, 180, and 365 days. Patients in the EHRA type 2 VHD and non-VHD groups were sub-grouped to compare different OACs. Results: 2020 AF patients were recruited. The thromboembolic risk was higher in EHRA type 2 VHD patients compared to non-VHD controls. Major bleeding also occurred at higher rates in EHRA type 2 patients. In addition, NOACs were more effective in preventing thromboembolic events than VKAs and non-anticoagulation in EHRA type 2 VHD patients. Furthermore, EHRA type 2 VHD patients taking rivaroxaban had significantly less thromboembolic risk than their non-anticoagulated counterparts. At the same time, apixaban and warfarin did not significantly lower the risk of thromboembolism compared to non-anticoagulation. Conclusion: AF patients with EHRA type 2 VHD are at significant risk of thromboembolism and major bleeding. Furthermore, NOACs were more effective than VKAs in preventing thromboembolic events in this group of patients without conferring an added risk of major bleeding. Moreover, rivaroxaban appears to be particularly efficacious.
Asunto(s)
Fibrilación Atrial , Enfermedades de las Válvulas Cardíacas , Accidente Cerebrovascular , Tromboembolia , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Rivaroxabán/efectos adversos , Anticoagulantes/efectos adversos , Administración Oral , Jordania , Accidente Cerebrovascular/prevención & control , Hemorragia/inducido químicamente , Tromboembolia/diagnóstico , Tromboembolia/epidemiología , Tromboembolia/etiología , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/diagnóstico , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológicoRESUMEN
PURPOSE OF REVIEW: There have been several advances in the diagnosis and management of valvular heart disease (VHD) over the last decade. These have been reflected in the latest European and North American guidelines, although both contain significant similarities and differences. In this review, we highlight the important overlaps and variations between the updated guidelines and their previous versions to help guide the general cardiologist. RECENT FINDINGS: There has been extensive revision on the use of percutaneous treatments, the indications for intervention in asymptomatic VHD, and perioperative bridging therapies. The updated guidelines provide new recommendations in many aspects of VHD; however, there remain significant gaps in the role of biomarkers in VHD and the long-term outcomes of novel oral anticoagulants (NOACs) and transcatheter therapies.
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Cardiólogos , Enfermedades de las Válvulas Cardíacas , Humanos , Administración Oral , Anticoagulantes/uso terapéutico , Enfermedades de las Válvulas Cardíacas/diagnóstico , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológicoRESUMEN
A 60-year-old patient, professor of physics, presented in 1999 with sudden-onset vitiligo associated with hyperprolactinemia and a prolactinoma. Fearful of potential surgical complications at the peak of his career, the patient declined surgery and opted for medical management with bromocriptine. The decreasing effectiveness of bromocriptine after 5 years required a switch to cabergoline. After a 15-year-course of cabergoline therapy with a cumulative dose of 572 mg, echocardiographic monitoring demonstrated aortic and mitral valve thickening and regurgitation. An additional 3 years of cabergoline treatment (cumulative dose: 649 mg) resulted in worsening valve thickening and regurgitation. It is well-recognized that such valvular changes may occur with high-dose cabergoline treatment. We report a case of mitral and aortic vavulopathy in a patient who was treated with long-term (18 years) low-dosage (.5-1 mg weekly) cabergoline. cabergoline, echocardiography, valvulopathy.
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Enfermedades de las Válvulas Cardíacas , Neoplasias Hipofisarias , Humanos , Persona de Mediana Edad , Cabergolina , Bromocriptina , Ergolinas/uso terapéutico , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/complicaciones , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/tratamiento farmacológicoAsunto(s)
Fibrilación Atrial , Enfermedades de las Válvulas Cardíacas , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Administración OralRESUMEN
BACKGROUND: Although apixaban and rivaroxaban are commonly used in patients with atrial fibrillation (AF) and valvular heart disease (VHD), there is limited evidence comparing the 2 drugs in these patients. OBJECTIVE: To emulate a target trial of effectiveness and safety of apixaban and rivaroxaban in patients with AF and VHD. DESIGN: New-user, active comparator, cohort study design. SETTING: Commercial health insurance database from 1 January 2013 to 31 December 2020. PATIENTS: New users of apixaban or rivaroxaban who had a diagnosis of AF and VHD before initiation of anticoagulant therapy. MEASUREMENTS: The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of gastrointestinal or intracranial bleeding. Cox proportional hazards regression with a robust variance estimator was used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: When compared with rivaroxaban in a propensity score-matched cohort of 19 894 patients (9947 receiving each drug), apixaban was associated with a lower rate of ischemic stroke or systemic embolism (HR, 0.57 [95% CI, 0.40 to 0.80]) and bleeding (HR, 0.51 [CI, 0.41 to 0.62]). The absolute reduction in the probability of stroke or systemic embolism with apixaban compared with rivaroxaban was 0.0026 within 6 months and 0.011 within 1 year of treatment initiation. The absolute reduction in the probability of bleeding events with apixaban compared with rivaroxaban was 0.012 within 6 months and 0.019 within 1 year of treatment initiation. LIMITATION: Short follow-up time and inability to ascertain some types of VHD. CONCLUSION: In this study of patients with AF and VHD, patients receiving apixaban had a lower risk for ischemic stroke or systemic embolism and for bleeding when compared with those receiving rivaroxaban. PRIMARY FUNDING SOURCE: National Institutes of Health.
Asunto(s)
Fibrilación Atrial , Enfermedades de las Válvulas Cardíacas , Rivaroxabán , Humanos , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Estudios de Cohortes , Embolia/epidemiología , Embolia/etiología , Embolia/prevención & control , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Hemorragia/inducido químicamente , Accidente Cerebrovascular Isquémico , Rivaroxabán/efectos adversos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/inducido químicamenteRESUMEN
BACKGROUND: Pimobendan might have favorable effects on renal function but this has not been well-studied in dogs with myxomatous mitral valve disease (MMVD). OBJECTIVES: Determine the effects of standard-dose (SD_pimo) and high-dose pimobendan (HD_pimo) on glomerular filtration rate (GFR) and cardiac size and function in dogs with preclinical MMVD. ANIMALS: Thirty nonazotemic dogs with stage B2 MMVD. METHODS: Prospective, randomized, double-blinded, placebo-controlled clinical study. Dogs had an echocardiographic examination, assessment of GFR (iohexol clearance), N-terminal probrain natriuretic peptide (NT-proBNP), and quality of life (QOL) score at baseline and 7 to 10 days after placebo (n = 6), SD_pimo 0.2 to 0.3 mg/kg q12 (n = 12), or HD_pimo 0.5 to 0.6 mg/kg q12h (n = 12). RESULTS: No significant differences in GFR or QOL scores were detected between groups (P ≥ .07). After HD_pimo, the mean [SD] percent change of NT_proBNP (-46.1 [20.2]%), left atrial volume (LAV; -27.1 [16.9]%), left ventricular end-diastolic volume (EDV; -21.8 [15.0]%), and end-systolic volume (ESV; -55.0 [20.7]%) were significantly different (P ≤ .004) from placebo (0.5 [19.9]%, 1.3 [15.6]%, -0.2 [8.2]%, -7.3 [35.6]%, respectively) but not the percent change after SD_pimo (-36.6 [16.1]%, -22.7 [14.9]%, -16.7 [12.5]%, -41.6 [14.8]%, respectively; P > .05). After SD_pimo, percent change of NT_proBNP, LAV, EDV, and ESV were significantly different from placebo (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that pimobendan (SD_pimo or HD_pimo) might not affect renal function in nonazotemic dogs with stage B2 MMVD. High-dose pimobendan did not demonstrate advantages over SD_pimo within the constraints of our study.
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Enfermedades de los Perros , Enfermedades de las Válvulas Cardíacas , Perros , Animales , Válvula Mitral/diagnóstico por imagen , Calidad de Vida , Estudios Prospectivos , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/veterinaria , Riñón/diagnóstico por imagen , Riñón/fisiologíaRESUMEN
Infective endocarditis in pregnancy is extremely rare in clinical practice. Guidelines addressing prophylaxis and management of infective endocarditis do not extensively deal with concomitant pregnancy, and case reports on infective endocarditis are scarce. Due to increased blood volume and hemodynamic changes in late pregnancy, endocardial neoplasms are easy to fall off and cause systemic or pulmonary embolism, respiratory, cardiac arrest and sudden death may occur in pregnant women, the fetus can suffer from intrauterine distress and stillbirth at any time, leading to adverse outcomes for pregnant women and fetuses. The disease is dangerous and difficult to treat, which seriously threatens the lives of mothers and babies. Early diagnosis and reasonable treatment can effectively improve the prognosis of patients. The most important method for the treatment of infective endocarditis requires early, adequate, long-term and combined antibiotic therapy. Moreover, surgical controversies regarding indication and timing of treatment exist, especially in pregnancy. In terms of the timing of termination of pregnancy, the timing of cardiac surgery, and the method of surgery, individualized programs must be adopted. A pregnant woman with 30+5 weeks of gestation is reported. She was admitted to hospital due to intermittent chest tightness, suffocation and fever, with grade â ¢ cardiac insufficiency. Imaging revealed large mitral valve vegetation, 22.0 mm×4.1 mm and 22.0 mm×5.1 mm, respectively, and severe valve regurgitation. Mitral valve perforation was more likely, blood culture suggested Staphylococcus epidermidis infection, after antibiotic conservative treatment, the effect was poor. After the joint consultation including cardiology, neonatology, interventional vascular surgery, anesthesiology, and obstetrics, the combined operation of obstetrics and cardiac surgery was performed in time. The heart was blocked for 60 minutes, the bleeding was 1 200 mL, the newborn was mildly asphyxiated after birth, and the birth weight was 1 890 g. Nine days after the operation, the patient was discharged from the hospital, and the newborn was discharged with the weight of 2 020 g. Critical cases like this require a thorough weighing of risks and benefits followed by swift action to protect the mother and her unborn child. An optimal outcome in a challenging case like this greatly depends on effective interdisciplinary communication, informed consent of the patient, and concerted action among the specialists involved.
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Procedimientos Quirúrgicos Cardíacos , Endocarditis Bacteriana , Endocarditis , Enfermedades de las Válvulas Cardíacas , Infecciones Estafilocócicas , Antibacterianos/uso terapéutico , Endocarditis/complicaciones , Endocarditis/diagnóstico , Endocarditis/tratamiento farmacológico , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/terapia , Femenino , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/diagnóstico , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Humanos , Recién Nacido , Válvula Mitral/cirugía , EmbarazoAsunto(s)
Enfermedades de las Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Trombosis , Fibrinolíticos/uso terapéutico , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Prótesis Valvulares Cardíacas/efectos adversos , Humanos , Terapia Trombolítica , Trombosis/tratamiento farmacológico , Trombosis/etiologíaRESUMEN
OBJECTIVE: To assess the cardiovascular safety of fenfluramine when used to treat children and young adults with Dravet syndrome. METHODS: Patients with Dravet syndrome who completed one of three phase 3 clinical trials of fenfluramine could enroll in the open-label extension (OLE) study (NCT02823145). All patients started fenfluramine treatment at an oral dose of 0.2 mg/kg/day. The dose was titrated based on efficacy and tolerability to a maximum of 0.7 mg/kg/day (absolute maximum 26 mg/day) or 0.4 mg/kg/day (absolute maximum 17 mg/day) in patients concomitantly receiving stiripentol. Serial transthoracic echocardiography was performed using standardized methods and blinded readings at OLE entry, after 4-6 weeks, and every 3 months thereafter. Valvular heart disease (VHD) was defined as ≥ moderate mitral regurgitation or ≥ mild aortic regurgitation combined with physical signs or symptoms attributable to valve dysfunction. Pulmonary artery hypertension (PAH) was defined as systolic pulmonary artery pressure >35 mmHg. RESULTS: A total of 327 patients (median age, 9.0 years; range, 2-19 years) have enrolled in the OLE and received ≥1 dose of fenfluramine. The median duration of treatment was 23.9 months (range, 0.2-42.6 months) and the median dose of fenfluramine was 0.44 mg/kg/day. No patient demonstrated VHD or PAH at any time during the OLE. SIGNIFICANCE/INTERPRETATION: This study, which represents the largest, longest, and most rigorous examination of cardiovascular safety of fenfluramine yet reported, found no cases of VHD or PAH. These results, combined with fenfluramine's substantial antiseizure efficacy, support a strong positive benefit-risk profile for fenfluramine in the treatment of Dravet syndrome.
Asunto(s)
Epilepsias Mioclónicas , Fenfluramina , Enfermedades de las Válvulas Cardíacas , Adolescente , Niño , Preescolar , Ecocardiografía , Epilepsias Mioclónicas/diagnóstico por imagen , Epilepsias Mioclónicas/tratamiento farmacológico , Síndromes Epilépticos , Fenfluramina/administración & dosificación , Fenfluramina/efectos adversos , Enfermedades de las Válvulas Cardíacas/inducido químicamente , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Humanos , Adulto JovenRESUMEN
Warfarin is the standard anticoagulation therapy for valvular atrial fibrillation (AF); however, new oral anticoagulants have emerged as an alternative. We compared the efficacy and safety of dabigatran with conventional treatment in AF associated with left-sided valvular heart disease (VHD), including mitral stenosis (MS). Patients with AF and left-sided VHD were randomly assigned to receive dabigatran or conventional treatment. The primary end point was the occurrence of clinical stroke or a new brain lesion (silent brain infarct and microbleed) on 1-year follow-up brain magnetic resonance imaging. Patients in the dabigatran group were switched from warfarin (n = 52), antiplatelets alone (n = 5), or no therapy (n = 2) to dabigatran. In the conventional group, 53 used warfarin (including 42 MS patients), and 7 used antiplatelets. No death or clinical stroke event occurred in either group during follow-up. Silent brain infarct and microbleed occurred in 20 and 2 patients in the dabigatran group and 20 and 4 patients in the conventional treatment group. The incidence rate of the primary end point did not significantly differ between groups (34% vs 40%, relative risk 0.87, 95% confidence interval 0.59 to 1.29, p = 0.491). The primary end point rate was similar between groups in 82 patients (40 in the dabigatran group and 42 in the conventional group) with MS (32% vs 34%, relative risk 0.93, 95% confidence interval: 0.57 to 1.50, p = 0.759). In conclusion, primary end point rates after treatment with dabigatran were similar to conventional treatment in patients with significant VHD and AF. New oral anticoagulants could be a reasonable alternative to warfarin in patients with AF and VHD, which should be confirmed in future large-scale studies.