RESUMO
Ischemic heart disease (IHD) affects about 16 million adults in the USA. Many more individuals likely harbor subclinical coronary disease. Hypertension (HTN) continues to be a potent and widespread risk factor for IHD. Among other Framingham risk factors of tobacco use, diabetes mellitus, dyslipidemia, and left ventricular hypertrophy, HTN plays an independent role in augmenting IHD risk, as well as a multiplicative role with respect to adverse outcomes when HTN is present concurrently with the other major IHD risk factors listed above. Over the past two decades, numerous studies and guideline reports have been presented with the aims of (a) elucidating the pathophysiology of IHD, (b) delineating an ideal blood pressure (BP) threshold at which to institute pharmacotherapy, and (c) defining the optimal pharmacologic elements of a therapeutic regimen. While there are active debates surrounding the existence and relevance of the J curve in IHD patients who have HTN, as well as the numerical level of the BP cutoff justifying drug therapy in the general population, there is a general consensus that the BP target in IHD patients should be lower than 140/90 mmHg. The most appropriate class (or classes) of medication recommended will depend on the comorbid conditions associated with each individual patient. Overall, however, there is no major evidence underscoring a significant difference between drug classes, provided the target BP is achieved, although it should be pointed out that the most recent (2015) American Heart Association (AHA)/American College of Cardiology (ACC)/American Society of Hypertension (ASH) guideline statement now elevates beta-blockers (BB) to the same level of recommendation as other classes of hypertension drugs in the treatment of patients who have hypertension and ischemic heart disease. Although most agents that reduce blood pressure will correspondingly lower myocardial workload, BB may exhibit a special advantage in IHD patients because BB (as well as verapamil and diltiazem subclasses of calcium channel blockers or CCB) act to lower HR as well as cardiac inotropy. Moreover, BB will remain an integral if not indispensable part of the management of IHD, especially in those with history of angina pectoris or MI, based on decades of favorable clinical as well as trial experience. This extensive salutary historical background has served as a foundation for the 2015 committee's decision to bring BB into the front rank of BP agents for those hypertensive individuals suffering simultaneously from IHD.
Assuntos
Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Determinação da Pressão Arterial , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Isquemia Miocárdica/complicações , Isquemia Miocárdica/fisiopatologia , Guias de Prática Clínica como Assunto , Prognóstico , Fatores de Risco , Estados UnidosRESUMO
Adenocarcinoma of the distal esophagus and esophagogastric junction continues to rise in incidence. An intestinal metaplasia (Barrett esophagus)-dysplasia-carcinoma sequence induced by gastroesophageal reflux disease is well established. However, a significant number of adenocarcinomas in the vicinity of the esophagogastric junction are seen in the background of gastric/cardiac-type mucosa without intestinal metaplasia. Thus, the aim of this study was to investigate the role of Barrett esophagus (intestinal-type mucosa) in the classification and prognosis of tumors of the distal esophagus and esophagogastric junction. Clinicopathological and molecular characteristics were examined in 157 consecutively resected adenocarcinomas of the distal esophagus and esophagogastric junction and were compared between tumors arising in association with intestinal-type and cardiac-type mucosa. Intestinal-type mucosa-associated adenocarcinomas were more likely to be associated with younger age (P=0.0057), reflux symptoms (P<0.0001), proximal location (P=0.0009), lower T stage (P<0.0001), fewer nodal metastases (P=0.0001), absence of lymphatic (P<0.0001), venous (P=0.0060) or perineural (P<0.0001) invasion. Histologically, intestinal-type mucosa-associated tumors were more likely to be low-grade glandular tumors (P=0.0095) of intestinal or mixed immunophenotype (P=0.015) and express nuclear ß-catenin (P=0.0080), whereas tumors arising in a background of cardiac-type mucosa were more frequently associated with EGFR amplification (P=0.0051). Five-year overall survival rate was significantly higher in patients with intestinal-type mucosa-associated tumors (28 vs 9%, P=0.0015), although no survival benefit was seen after adjusting for potential confounders. Our findings support the theory that multiple distinct pathways of tumorigenesis exist in the vicinity of the esophagogastric junction, including one in which tumors arise from dysplastic intestinal metaplasia (intestinal pathway), and one potentially involving dysplasia of the cardiac-type mucosa (non-intestinal pathway). Additional studies are warranted to further clarify their pathogenesis and the molecular mechanisms involved.
Assuntos
Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/complicações , Esôfago de Barrett/mortalidade , Cárdia/patologia , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Mucosa Intestinal/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/mortalidade , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/mortalidade , Análise Serial de TecidosRESUMO
BACKGROUND: Transthyretin (TTR) gene mutations are the most common cause of hereditary amyloidosis. Valine replaced by isoleucine in position 122 (V122I) variant is common, particularly in the black population. Carriers of V122I have increased risk for developing cardiac amyloidosis. Despite a relatively high prevalence, the penetrance of V122I is not firmly established. This study sought to determine the prevalence of clinically apparent cardiac amyloidosis among carriers of the TTR V122I variant. METHODS: BioVU, a Vanderbilt University resource linking DNA samples and pre-existing genetic data to de-identified electronic medical records was used to identify TTR V122I mutation carriers. Automated billing code queries (International Classification of Diseases, 9th revision codes), problem list searches, and manual chart reviews were used to identify subjects with clinically diagnosed cardiac amyloidosis. RESULTS: Among 28,429 subjects with available genotype data, 129 were V122I carriers. Carriers had a median age of 42 years (interquartile range 16-64). Noncarriers had a median age of 62 years, (interquartile range 41-77). The carrier rate was 3.7% in blacks and 0.02% in whites. Overall, the prevalence of clinically apparent cardiac amyloidosis was 0.8% in carriers and 0.04% in noncarriers (P = .05). Above age 60, the prevalence of cardiac amyloidosis was 2.6% in carriers and 0.06% in noncarriers (P = .03). CONCLUSION: Carriers of the TTR V122I variant are at a higher risk for development of cardiac amyloidosis, particularly at age>60 years. However, clinically apparent cardiac amyloidosis in this population was uncommon. These results support that the penetrance of TTR V122I is age dependent and suggest it may be significantly lower than previously reported.
Assuntos
Neuropatias Amiloides Familiares/genética , Cardiopatias/patologia , Pré-Albumina/genética , Adolescente , Adulto , Idoso , Neuropatias Amiloides Familiares/patologia , Bases de Dados Genéticas , Feminino , Predisposição Genética para Doença , Cardiopatias/genética , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Paravalvular aortic regurgitation affects some patients after surgically implanted prosthesis. The number of patients affected is likely to increase with increased utilization of nonsurgical valve replacement techniques. These patients are at increased risk of persistent clinical symptoms often requiring repair. Clinical and procedural outcomes are of importance when performing these procedures and managing these patients. We describe a case where two different leaks around an aortic prosthesis improved with closure of one defect.
RESUMO
Some cardiac valve masses may have embolic potential with worrisome consequences. We describe the dilemmas of and solutions for a highly mobile papillary fibroelastoma on the aortic valve in a nonsurgical patient undergoing transcatheter aortic valve replacement. It was performed safely. The potential strategies to minimize the risk of embolization are discussed.