RESUMO
In the present case report, we describe the management of severe coronary artery disease in a patient with Glanzmann thrombasthenia. To the best of our knowledge, there are no established guidelines for revascularization in this setting, and we pose novel discussion points regarding the nuanced care of this patient. (Level of Difficulty: Intermediate.).
RESUMO
Incretin based therapies such as dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1Ra) are increasingly used for the treatment of Type 2 diabetes mellitus. In clinical practice and in previously performed clinical trials, these agents are often used in combination with other oral anti-diabetic agents (OADs) and Insulin. Prior meta-analytic reviews however do not adequately address the impact of background therapy and active comparator arms. Accordingly, we aimed to further investigate the efficacy of incretin based therapies by updating existing reviews by including clinical trial evidence after 2008; estimating the pooled effect of incretin therapies on glycemic efficacy and weight-loss, stratified by comparator therapy (placebo, mono-therapy, etc.), estimating the impact of background OADs and within class (GLP-1Ra or DPP-4i) comparative efficacy, on glycemia control. 82 randomized controlled trials after 2008 with glycemic control and weight loss as primary end-points were included. Both DPP-4i and GLP-1Ra reduced HbA1c, but only GLP-1Ra caused weight loss when compared to either active comparator drugs or placebo. GLP-1Ra were more effective than DPP-4i in glycemia lowering. Long acting GLP-1Ra were more effective in HbA1c lowering than short-acting agents but with similar weight loss effect. The effect of DPP-4i incretin glycemic efficacy was not modified by background therapy used in the study.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Incretinas/administração & dosagem , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Ensaios Clínicos como Assunto/estatística & dados numéricos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Quimioterapia Combinada/métodos , Humanos , Hipoglicemiantes/efeitos adversos , Incretinas/efeitos adversosRESUMO
BACKGROUND: Pulmonary arterial hypertension (PAH) is a potentially serious cause of dyspnea and exercise limitation in patients with HIV infection. In this trial, we propose using exercise MRI in conjunction with cardiopulmonary testing to delineate PAH from other causes of cardiovascular dysfunction, identify individuals with exercise-induced PAH who are at high risk of developing resting PAH, and provide longitudinal estimates of progression of PAH and right ventricular function. METHODS: In this prospective observational study, HIV patients with dyspnea and exercise limitation in the absence of identifiable causes and those who meet the inclusion criteria will be enrolled based on resting pulmonary artery pressure (≤ or >40âmmHg) on a screening echocardiogram and exercise limitation on the Modified Medical Research Council dyspnea scale. Patients without evidence of resting PAH will be enrolled into both rest and exercise MRI and cardiopulmonary testing protocol, whereas patients with evidence of PAH on resting echocardiograms will undergo only resting cardiac MRI studies to evaluate right ventricular function and fibrosis. Both patient subgroups will be followed for 24 months to obtain longitudinal progression of the disease. In a sub-study, we will further analyze inflammatory variables that may predict these changes, thus allowing early identification of these patients. IMPLICATIONS AND CONCLUSIONS: This trial will be the first study to provide an understanding of the mechanisms underpinning the functional deterioration of the right ventricle in patients with HIV and will impart insight into the immune mediators of PAH progression and right ventricular functional deterioration in patients with HIV-PAH.
Assuntos
Exercício Físico , Infecções por HIV/complicações , Ventrículos do Coração/fisiopatologia , Hipertensão Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Ecocardiografia , Humanos , Hipertensão Pulmonar/etiologia , Imageamento por Ressonância Magnética , Estudos Prospectivos , Projetos de Pesquisa , Descanso , Função Ventricular DireitaRESUMO
Mineralocorticoid receptor (MR) activation plays an essential role in promoting inflammation, fibrosis, and target organ damage. Currently, no studies are investigating MR antagonism in patients with type 2 diabetes mellitus (T2DM) with chronic kidney disease, at high risk for cardiovascular complications, who are otherwise not candidates for MR antagonism by virtue of heart failure. Further, there is limited information on candidate therapies that may demonstrate differential benefit from this therapy. We hypothesized that MR antagonism may provide additional protection from atherosclerosis progression in higher-risk patients who otherwise may not be candidates for such a therapeutic approach. In this double-blind, randomized, placebo-controlled trial, subjects with T2DM with chronic kidney disease (≥ stage 3) will be randomized in a 1:1 manner to placebo or spironolactone (12.5 mg with eventual escalation to 25 mg daily over a 4-week period). The co-primary efficacy endpoint will be percentage change in total atheroma volume in thoracic aorta and left ventricular mass at 52 weeks in patients treated with spironolactone vs placebo. Secondary outcomes include 24-hour mean systolic blood pressure, central aortic blood pressure, and insulin resistance (HOMA-IR) at 6 weeks. A novel measure in the study will be changes in candidate miRNAs that regulate expression of NR3C2 (MR gene) as well as measuring monocyte/macrophage polarization in response to therapy with spironolactone. We envision that our strategy of simultaneously probing the effects of a drug combined with analysis of mechanisms of action and predictive response will likely provide key information with which to design event-based trials.
Assuntos
Aorta Torácica/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Imageamento por Ressonância Magnética , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/etiologia , Doenças da Aorta/patologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/etiologia , Aterosclerose/patologia , Protocolos Clínicos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Placa Aterosclerótica , Valor Preditivo dos Testes , Estudo de Prova de Conceito , Estudos Prospectivos , Projetos de Pesquisa , Transdução de Sinais/efeitos dos fármacos , Espironolactona/efeitos adversos , Resultado do Tratamento , Estados Unidos , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
The vast majority of sudden cardiac arrests occur in patients with structural heart disease and in approximately 10% of the cases, it can occur in those with structurally normal hearts. Brugada syndrome is an autosomal dominant sodium channelopathy that has been implicated in sudden deaths. Given their low prevalence, our knowledge about Brugada syndrome is still evolving. Apart from schizophrenia, there have been no reports of associated medical conditions. We recently encountered a patient with vascular Ehlers-Danlos syndrome who was also found to have Brugada syndrome. Both these conditions share some common clinical presentations including a propensity for sudden death.
RESUMO
Diabetes is an important risk factor for cardiovascular disease. However, clinical data suggests intensive glycemic control significantly increase rather than decrease cardiovascular mortality, which is largely due to the fact that a majority of oral anti-diabetic drugs have adverse cardiovascular effect. There are several large-scale clinical trials evaluating the cardiovascular safety of DPP4 inhibitors, a novel class of oral anti-diabetic medications, which have been recently completed. They were proven to be safe with regard to cardiovascular outcomes. However, concerns on the safety of heart failure have been raised as the SAVOR-TIMI 53 trial reported a 27% increase in the risk for heart failure hospitalization in diabetic patients treated with DPP4 inhibitor saxagliptin. In this review, we will discuss recent advances in the heart failure effects of DPP4 inhibition and GLP-1 agonism.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Saúde Global , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Humanos , Incidência , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Cardiac lipomas are rare benign tumors of the heart. They are usually asymptomatic and are thus most often diagnosed on autopsies. Symptoms, when present, depend upon the location within the heart. Typical locations are the endocardium of the right atrium and the left ventricle. Diagnostic modality of choice is cardiac MRI. Treatment guidelines have not yet been established due to the very low prevalence of these tumors and are thus guided by the patient's symptomatology. CASE PRESENTATION: We describe a case of an invasive cardiac lipoma, wherein the initial symptom of the patient was shortness of breath. Although the echocardiogram visualized the tumor in the right atrium, a cardiac MRI was performed for better tissue characterization. The MRI revealed a large, fat containing, septated mass in the right atrium with invasion into the inter-atrial septum and inferior cavoatrial junction. There was also invasion of the coronary sinus along the inferior and left lateral aspect of the posterior atrioventricular groove. Although the mass appeared to represent a lipoma by imaging characteristics, the unusual extension into the coronary sinus led to consideration of a low-grade liposarcoma in the differential. Thus a pre-operative biopsy was performed along with MDM2 gene amplification to rule out a liposarcoma preceding surgical excision. CONCLUSION: Cardiac lipomas are well-characterized on cardiac MRI, which is the diagnostic modality of choice. Typical locations are the right atrium and the left ventricle. However, in those with atypical features such as invasion of the coronary sinus, pre-operative biopsy for histopathologic confirmation is imperative to exclude well-differentiated liposarcoma. Our patient with a simple lipoma underwent partial resection to relieve symptoms. We discuss prognosis and treatment of symptomatic cardiac lipomas.
Assuntos
Átrios do Coração/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Lipoma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adulto , Biópsia , Diagnóstico Diferencial , Dispneia/etiologia , Ecocardiografia , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Lipoma/complicações , Lipoma/patologia , Lipoma/cirurgia , Masculino , Invasividade Neoplásica , Valor Preditivo dos Testes , Resultado do Tratamento , Carga TumoralRESUMO
The incidence of pulmonary nodules and lung cancer is rising. Some of this increase in incidence is due to improved pick up by newer imaging modalities. However, the goal is to diagnose these lesion, many of which are located in the periphery, by safe and relatively non-invasive methods. This has led to the emergence of numerous techniques such as electromagnetic navigational bronchoscopy (ENB). Current evidence supports a role for these techniques in the diagnostic pathway. However, numerous factor influence the diagnostic accuracy. Thus despite significant advances, more research needs to be undertaken to further improve the currently available diagnostic technologies.
RESUMO
We present the first reported case of the treatment and management of a giant bulla using percutaneous bullectomy and endobronchial valve placement. A 74-year-old woman with chronic obstructive pulmonary disease and a known large bulla in the left chest presented to the emergency department with acute-onset confusion after a traumatic fall. She was subsequently diagnosed with an intracranial hemorrhage in the distribution of the right basal ganglia. Chest imaging revealed a giant apical bulla occupying 80% of the left hemithorax. In addition, there was midline shift away from the affected side associated with volume loss in the right hemithorax and no radiographic evidence of aeration in the remainder of the left lung. Arterial blood gas analysis revealed significant hypercapnia. Surgical bullectomy was not an option, and thus, a novel approach was utilized to treat this patient.
Assuntos
Vesícula/cirurgia , Broncoscopia/métodos , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Vesícula/induzido quimicamente , Broncoscopia/instrumentação , Drenagem/métodos , Feminino , Humanos , Tomografia Computadorizada por Raios XAssuntos
Actinomicose/diagnóstico , Doenças do Esôfago/diagnóstico , Ceratose/diagnóstico , Actinomicose/complicações , Actinomicose/tratamento farmacológico , Actinomicose/patologia , Idoso , Antibacterianos/uso terapêutico , Transtornos de Deglutição/etiologia , Endoscopia do Sistema Digestório , Doenças do Esôfago/complicações , Doenças do Esôfago/patologia , Humanos , Ceratose/etiologia , Ceratose/patologia , Masculino , Índice de Gravidade de Doença , Redução de PesoRESUMO
A 36-year-old woman with no medical or surgical history was evaluated for weight loss. Abdominal computed tomography (CT) showed signs of Crohn's disease, which was later confirmed endoscopically. She was started on tumor necrosis factor-α (TNF-α) inhibitor therapy. Nine months after treatment, she experienced additional weight loss and a 7 x 8 x 8-cm mass on repeat CT. Biopsy revealed retroperitoneal fibromatosis, so TNF-α was continued. Repeat CT showed an enlarged mass. TNF-α therapy had a suspected role in mass growth, therapy was discontinued, and the mass surgically resected. One year after resection, she has regained weight with no recurrence of the mesenteric fibromatosis.
RESUMO
Acute megakaryocytic leukemia is a rare form of acute myeloid leukemia that carries a poor prognosis. As most cases of osteolytic lesions are due to plasma cell and myeloid malignancies, maintaining a broad differential directly influences clinical course. We document a 45-year-old patient with progressive constitutional symptoms, osteolytic bone lesions in the setting of hypercalcemia, who developed acutely worsening pancytopenia. The diagnosis of myeloid sarcoma with megakaryocytic differentiation was made after obtaining tissue from osteolytic bone that stained strong for CD34. Immunohistochemical testing underscores the importance of how serologic and urine testing remains limited and can delay early diagnosis in this disease.
RESUMO
In this review, we examine alirocumab (Praluent(®)), a monoclonal antibody to PCSK9 and its role in reducing LDL-C levels. By comparing the results of various studies and trials we discuss the efficacy and safety of alirocumab. We aim to guide clinicians of the role of alirocumab in clinical practice. Overall, PCSK9 inhibitors are promising new agents in further reducing LDL-C levels in addition to diet and maximally tolerated statin therapy. Long-term outcome studies are currently ongoing and will further delineate the role of PCSK9 inhibitors.
Assuntos
Anticorpos Monoclonais/uso terapêutico , LDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Inibidores de PCSK9 , Anticorpos Monoclonais Humanizados , HumanosRESUMO
Left ventricular non-compaction is a recently recognized, rare form of cardiomyopathy. It is based on the arrest of endomyocardial morphogenesis during embryogenesis. It was first described in 1984 by Engberding who described it as isolated 'sinusoids' within the LV. Right now its prevalence is estimated at 0.014 to 1.3 and 3-4% in heart failure patients. Its clinical manifestations are highly variable, ranging from no symptoms to disabling congestive heart failure, arrhythmias, and systemic thromboemboli. Doppler Echocardiogram is considered the diagnostic procedure of choice and treatment is symptomatic management of its symptoms and complications.
RESUMO
Blue rubber bleb nevus syndrome (BRBNS) is a congenital disorder with characteristic venous anomalies that can present with varying degree of blood loss. The most clinically significant symptoms in adults include gastrointestinal (GI) bleeding and iron deficiency anemia. Severe complications can include intestinal torsion, intussusception, and even perforation, with each leading to significant morbidity and mortality. This report serves to give a brief understanding of this rare disease along with current diagnostic and therapeutic options.
RESUMO
Patients with familial hypercholesterolemia or statin intolerance are especially challenging to manage since LDL cholesterol levels often remain considerably elevated despite clinicians' best efforts. With statins regarded as first-line pharmacologic therapy by the current American College of Cardiology/American Heart Association guidelines to reduce LDL cholesterol and cardiovascular risk, there is now a critical need to determine when other agents will play a role beyond maximally tolerated statin therapy and lifestyle changes. In this review, we take a closer look at evolocumab (Repatha(®)), one of the new injectable human monoclonal antibodies to PCSK9 and its efficacy and safety properties from the results of various trials.
Assuntos
Anticorpos Monoclonais/uso terapêutico , LDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Inibidores de PCSK9 , Anticorpos Monoclonais Humanizados , HumanosRESUMO
Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease. The presence of concomitant hypertension in diabetics is a major driver of excess cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1a) act on numerous pathways that intersect glycemic, weight, and blood pressure (BP) control. BP-lowering effects have been observed in mouse models of hypertension with a variety of GLP-1a. Acute administration of GLP-1a in humans has been shown to no effects and sometimes increased BP in humans. Chronic administration of GLP-1a, however, reduces clinic systolic BP (≈2 mmHg) at least when evaluated as a secondary end point in glycemia-lowering studies while simultaneously increasing heart rate. BP lowering has not been consistently observed in two recent double-blind controlled clinical trials evaluating ambulatory BP as the primary end point. While a number of mechanisms including vascular, myocardial, renal, and central nervous system pathways have been suggested in animal studies, these mechanistic pathways have not been sufficiently detailed in humans and it is unclear if the same pathways are operational. Further studies need to be conducted to unravel the full spectrum of effects of this drug class. An understanding of their effects on BP may help provide an explanation for the ability of GLP-1a to influence cardiovascular (CV) events in ongoing event-driven CV trials.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/agonistas , Animais , Doenças Cardiovasculares/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Fatores de RiscoRESUMO
We discuss a unique case of a 52-year-old man with no history of intravenous drug use or dental procedures who presented with neck pain, 2 weeks of fevers, chills, night sweats, cough, and dyspnea found to have isolated pulmonic valve (PV) endocarditis. The patient did not have an associated murmur, which is commonly seen in right-sided infectious endocarditis. A transthoracic echocardiogram showed a thickened PV leaflet, with subsequent transesophageal echocardiogram showing a PV mass. Speciation of blood cultures revealed Streptococcus oralis. In right-sided infective endocarditis, usually the tricuspid valve is involved; however, in our case the tricuspid valve was free of any mass or vegetation. The patient did meet Duke criteria and was thus started on long-term intravenous antibiotics for infectious endocarditis. The patient's symptoms quickly improved with antibiotics. A careful history and evaluating the patient's risk factors are key in earlier detection of infective endocarditis (IE). Because of early detection and a high index of suspicion, the patient had no further complications and did not require any surgery. In conclusion, clinical suspicion of right-sided IE should be high in patients who present with persistent fevers and pulmonary symptoms in order to reduce the risk of complications, and to improve outcomes.
RESUMO
Type 2 diabetes mellitus (T2DM) is a major risk factor for the development of cardiovascular disease (CVD). Due to the ever increasing incidence of both T2DM and CVD and coexistence of these disorders, numerous agents have been developed over the years to target complications. We focus on the efficacy and safety perspective of a long-acting formulation of the glucagon-like peptide-1 analog exenatide. Our review focuses on the various landmark trials, efficacy, safety profile, and patient perspectives of weekly exenatide that delineates its current and future role in the treatment of patients with T2DM and CVD.