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BACKGROUND: After previous earthquakes, a high prevalence of deep vein thrombosis (DVT) has been reported. We examined DVT prevalence and risk factors in evacuees of the Kumamoto earthquakes by performing mobile DVT screening at various evacuation centers around the epicenter. MethodsâandâResults: For 1 month after the Kumamoto earthquake on 14 April 2016, mobile DVT screening using portable ultrasonography (US) was performed at 80 evacuation centers. Questionnaires, physical examination, and US of the lower limb were carried out, and simple D-dimer measurements were undertaken for DVT-positive examinees. The total number of examinees was 1,673, of whom 178 (10.6%) had DVT. The prevalence of DVT seemed to be gradually decreasing in the screening period, but age, use of sleep medication, prevalence of hypertension, dyslipidemia, leg edema, and lower leg varix were significantly higher in the DVT positive group than in the negative group. On multivariable logistic regression analysis, high age (≥70 years old), use of sleep medication, lower leg edema, and lower leg varix were significant predictors of DVT. In examinees with these 4 predictors, the DVT positive rate was 71.4%. CONCLUSIONS: In the first month after the Kumamoto earthquakes, DVT prevalence and severity, evaluated on D-dimer level, decreased with the passage of time. Mobile DVT screening indicated significant factors stratifying DVT risk in the evacuees.
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Terremotos , Trombose Venosa/etiologia , Adulto , Fatores Etários , Idoso , Edema , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Japão , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Ultrassonografia , Varizes , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologiaRESUMO
We detected symptomatic atrial fibrillation in a 64-year-old man who had undergone mitral valvuloplasty. While performing transesophageal echocardiography (TEE) in the left lateral decubitus position, we detected an isoechoic mass lesion at the bottom of the left atrial appendage (LAA). After changing the patient's position from left to right, the mass lesion dropped down from the bottom of the LAA, spread out into the left atrium, and appeared as a spontaneous echocardiographic contrast with mobility. We therefore diagnosed the mass lesion as not a thrombus but sludge. Changing the patient's position during TEE is useful for distinguishing sludge from thrombi.
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Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/fisiopatologia , Ecocardiografia Transesofagiana/métodos , Posicionamento do Paciente/métodos , Trombose , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , PosturaRESUMO
Ultrasonography is useful not only for screening, but also for evaluating pathological conditions and followup because it can be performed repeatedly and noninvasively at bedside. This paper discusses the importance of the functional assessment of vascular access, as well as the examination method and points for diagnosis of venous thrombosis.
Assuntos
Trombose Venosa/diagnóstico por imagem , Humanos , UltrassonografiaRESUMO
A 60-year-old man was referred to our hospital because of dyspnea on exertion. He was diagnosed with heart failure due to an old myocardial infarction. Myocardial stress perfusion scintigraphy revealed inducible myocardial ischemia. Coronary angiography revealed hazy slit lesions in both the left anterior descending (LAD) and right coronary arteries (RCA). We first performed percutaneous coronary intervention (PCI) on the LAD lesion. Subsequently, we performed PCI for the RCA lesion using multiple imaging modalities. We observed a lotus root-like appearance in both the LAD and RCA, and PCI was successful for both vessels. We describe this rare case in detail.
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Vasos Coronários/patologia , Vasos Coronários/cirurgia , Insuficiência Cardíaca/diagnóstico , Infarto do Miocárdio/complicações , Angiografia Coronária , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Tomografia de Coerência Óptica , Ultrassonografia de IntervençãoRESUMO
A 63-year-old man with chest pain at rest was referred to our hospital. Transthoracic echocardiography showed a mobile ball-like mass at the top of the right coronary cusp. Subsequently, transesophageal echocardiography also showed a mobile mass at the right coronary cusp. Aortic valve replacement with a mechanical valve was performed under general anesthesia. We diagnosed this condition as papillary fibroelastoma based upon the pathological findings with hematoxylin and eosin staining, and Elastica van Gieson staining. Coronary angiography revealed no organic lesions. The operation was successful, and the patient remains asymptomatic. We speculate that the resting chest pain was induced by transient occlusion of the right coronary orifice by the tumor. We describe this rare case in detail including a review of the literature.
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Angina Instável/patologia , Valva Aórtica/cirurgia , Cardiomiopatias/patologia , Neoplasias Cardíacas/patologia , Doenças das Valvas Cardíacas/patologia , Dor no Peito/etiologia , Ecocardiografia Transesofagiana , Neoplasias Cardíacas/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Próteses Valvulares Cardíacas , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: We sought to identify the feasibility of speckle tracking echocardiography (STE) to predict cardiac resynchronization therapy (CRT) responders in a prospective multicenter study. METHODSâANDâRESULTS: Patients who were newly implanted with a CRT device were enrolled. Time (T) from QRS to maximum peak radial and circumferential strain (CS) in 6 segments on the left ventricular (LV) short-axis plane, and to the maximum peak of longitudinal strain in 18 segments on 3 apical LV planes was measured (Tmax). In segments with multiple peaks on the time-strain curves, time to the first peak (Tfirst) was also assessed. Difference in T between the earliest and latest segment and standard deviation (SD) of T in each strain component were assessed. CRT responders were defined as having LV end-systolic volume reduction >15% at 6 months after CRT. Clinical outcomes were assessed with a composite endpoint of death from cardiac causes or unplanned hospitalization for heart failure. Among 180 patients, 109 patients were identified as responders. Tfirst-SD of CS >116 ms was selected as the best independent predictor of CRT responders (P<0.001, hazard ratio=9.83, 95% confidence interval 3.78-25.6). In addition, Tfirst-SD of CS was associated with the clinical endpoints. CONCLUSIONS: This prospective multicenter study revealed the high feasibility of dyssynchrony assessment by STE, which may improve the ability to predict CRT responders.
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Terapia de Ressincronização Cardíaca , Ecocardiografia , Monitorização Fisiológica , Idoso , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Weak aortic media layers can lead to intimal tear (IT) in patients with overt aortic dissection (AD), and aortic plaque rupture is thought to progress to penetrating atherosclerotic ulcer (PAU) with intramural hematoma (IMH). However, the influences of shear stress and atherosclerosis on IT and PAU have not been fully examined. Ninety-eight patients with overt AD and 30 patients with IMH and PAU admitted to our hospital from 2002 to 2007 were enrolled. The greater curvatures of the aorta, including the anterior and right portions of the ascending aorta and anterior portion of the aortic arch, were defined as sites of high shear stress. The other portions of the aorta were defined as sites of low shear stress based on anatomic and hydrodynamic theories. Aortic calcified points (ACPs) were manually counted on computed tomography slices of the whole aorta every 10 mm from the top of the arch to the abdominal bifurcation point. IT was more often observed at sites of high shear stress in overt AD than in PAU (73.5 vs 20.0 %, P < 0.0001). Significantly more ACPs were present in PAU than in overt AD (18.6 ± 8 vs 13.3 ± 10, P = 0.007). The present study suggests that high shear stress and less severe atherosclerosis could induce the occurrence of an IT, thereafter progressing to overt AD, and that low shear stress and more severe atherosclerosis could proceed to PAU with IMH. These findings may help to identify the entrance-tear site.
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Aorta/fisiopatologia , Aneurisma Aórtico/etiologia , Dissecção Aórtica/etiologia , Ruptura Aórtica/etiologia , Aterosclerose/complicações , Calcificação Vascular/complicações , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/fisiopatologia , Aorta/patologia , Aneurisma Aórtico/diagnóstico , Aneurisma Aórtico/fisiopatologia , Ruptura Aórtica/diagnóstico , Ruptura Aórtica/fisiopatologia , Aortografia/métodos , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Estresse Mecânico , Tomografia Computadorizada por Raios X , Calcificação Vascular/diagnóstico , Calcificação Vascular/fisiopatologiaRESUMO
BACKGROUND: There are few reports on transthoracic echocardiography (TTE) for the evaluation of valvular heart disease in a specific area or region. METHODS AND RESULTS: This cross-sectional questionnaire-based survey was conducted in 2023 in Kumamoto Prefecture, where 106 hospitals provide cardiology services. Ninety-three (88%) of the hospitals completed questionnaires regarding TTE. The severity of low flow/low gradient AS was evaluated by dobutamine stress echocardiography in only 7% of hospitals and exercise stress echocardiography for asymptomatic mitral regurgitation in only 5%. Multivariate logistic regression analysis revealed that participation in remote multi-institutional echocardiographic meetings and use of the Kumamoto Prefecture echocardiographic manual were significantly associated with the use of a multi-window approach (P < 0.05). CONCLUSIONS: In Kumamoto Prefecture, echocardiographic measurements are performed according to the recommendations at a relatively low rate. Dissemination of recommendations through remote meetings and the use of the echocardiographic manual may increase the likelihood of TTE being performed according to the recommendations.
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Síndrome de Budd-Chiari/diagnóstico , Trombose/tratamento farmacológico , Anticoagulantes/uso terapêutico , Síndrome de Budd-Chiari/complicações , Síndrome de Budd-Chiari/tratamento farmacológico , Embolia , Humanos , Masculino , Pessoa de Meia-Idade , Trombose/diagnóstico por imagem , Veia Cava Inferior/patologiaRESUMO
Objective: On April 16, 2016, earthquakes struck Kumamoto. In this report, the incidence and treatment of venous thromboembolism (VTE) in patients presenting to our hospital are summarized. Materials and Methods: We reviewed the details of 22 consecutive patients who were diagnosed with VTE at our hospital during the 2 weeks after the earthquakes. Results: Nineteen of the 22 patients stayed in their cars overnight after the earthquakes. Particularly, during the first 4 days, seven consecutive patients were hospitalized for pulmonary thromboembolism. All seven patients had sheltered in their cars after the earthquakes. The two patients transported on days 2.42 and 3.54 were the most severe cases. One patient was admitted after emergency initiation of venoarterial extracorporeal membrane oxygenation for treatment of hemodynamic collapse, whereas the other patient was admitted after resuscitation. By contrast, deep vein thrombosis (DVT) alone occurred within 5-9 days of the earthquakes. Bilateral DVT was the most common, which was followed by DVT on the right side only. Conclusion: The incidence of VTE might be higher after an earthquake, and an overnight stay in a car might be a risk factor for VTE. Stable patients based on the D-dimer concentration can be managed with nonwarfarin oral anticoagulants.
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Background: Whether drug therapy slows the growth of abdominal aortic aneurysms (AAAs) in the Japanese population remains unknown. MethodsâandâResults: In a multicenter prospective open-label study, patients with AAA at the presurgical stage (mean [±SD] AAA diameter 3.27±0.58 cm) were randomly assigned to treatment with candesartan (CAN; n=67) or amlodipine (AML; n=64) considering confounding factors (statin use, smoking, age, sex, renal function), with effects of blood pressure control minimized setting a target control level. The primary endpoint was percentage change in AAA diameter over 24 months. Secondary endpoints were changes in circulating biomarkers (high-sensitivity C-reactive protein [hs-CRP], malondialdehyde-low-density lipoprotein, tissue-specific inhibitor of metalloproteinase-1, matrix metalloproteinase [MMP] 2, MMP9, transforming growth factor-ß1, plasma renin activity [PRA], angiotensin II, aldosterone). At 24 months, percentage changes in AAA diameter were comparable between the CAN and AML groups (8.4% [95% CI 6.23-10.59%] and 6.5% [95% CI 3.65-9.43%], respectively; P=0.23]. In subanalyses, AML attenuated AAA growth in patients with comorbid chronic kidney disease (CKD; P=0.04) or systolic blood pressure (SBP) <130 mmHg (P=0.003). AML exhibited a definite trend for slowing AAA growth exclusively in never-smokers (P=0.06). Among circulating surrogate candidates for AAA growth, PRA (P=0.02) and hs-CRP (P=0.001) were lower in the AML group. Conclusions: AML may prevent AAA growth in patients with CKD or lower SBP, associated with a decline in PRA and circulating hs-CRP.
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BACKGROUND: The recently developed real-time 3-dimensional echocardiography (RT3DE) is a promising imaging method to quantify cardiac chamber volumes and their functions in clinical practice. However, normal reference values of RT3DE parameters have not been fully investigated in a large, healthy Japanese population. METHODS AND RESULTS: This study consisted of 410 healthy subjects aged from 20 to 69 years who had a RT3DE at one of the 23 collaborating institutions. All subjects had no history of cardiac disease and no risk factors. The mean values in men and women were as follows: 50 ± 12 ml/m(2) and 46 ± 9 ml/m(2) for left ventricular (LV) end-diastolic volume index, 19 ± 5 ml/m(2) and 17 ± 4 ml/m(2) for end-systolic volume index, 61 ± 4% and 63 ± 4% for ejection fraction, 64 ± 1 2 g/m(2) and 56 ± 11 g/m(2) for mass index, 23 ± 6 ml/m(2) and 24 ± 6 ml/m(2) for left atrial (LA) maximum volume index, 10 ± 3 ml/m(2) and 10 ± 3 ml/m(2) for minimum volume index, and 58 ± 6% and 58 ± 6% for percent volume change. LV sizes decreased with age, whereas LV mass index did not change. LA sizes slightly increased with age. CONCLUSIONS: This multicenter investigation determined normal reference values for LV and LA sizes, and their functional parameters on RT3DE in a large, healthy Japanese population. The results of the present study support the use of RT3DE for the diagnosis and management of cardiovascular disease.
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Ecocardiografia Tridimensional , Ventrículos do Coração/diagnóstico por imagem , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Adulto , Idoso , Povo Asiático , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/fisiologiaRESUMO
Aortic aneurysms expand asymptomatically and rupture lethally. Acute aortic dissection is also a highly lethal cardiovascular emergency and requires prompt recognition. Although cardiovascular ultrasonography has a suboptimal accuracy rate for detecting aortic dissection, it is noninvasive, readily available, and easy to use. Recently, the concept of point-of-care ultrasound (POCUS) refers to the use of portable and/or implemented ultrasound at the patient's bedside for diagnostic and therapeutic purposes. Aortic POCUS could become an important tool for aortic aneurysm screening and primary diagnosis of acute aortic dissection.
Assuntos
Aneurisma Aórtico , Dissecção Aórtica , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Dissecção Aórtica/diagnóstico por imagem , Aneurisma Aórtico/diagnóstico por imagem , Ultrassonografia , EcocardiografiaRESUMO
Background: There are few reports on the current awareness and status of venous ultrasonography, including the number of specialists who perform this procedure, in a specific regional area in Japan. MethodsâandâResults: This cross-sectional survey study was conducted in Kumamoto Prefecture from October 2018 to March 2019. Of the 366 medical institutions providing cardiology services in Kumamoto Prefecture, 259 (101 general hospitals, 158 small clinics) responded to our questionnaire. In 2017, 21,773 venous ultrasound tests were performed, 21,101 (97%) of which were performed in hospitals and only 672 (3%) were performed in clinics. Both the number of institutions performing venous ultrasounds and the number of tests performed increased over time. Although 317 medical staff in Kumamoto Prefecture were performing transthoracic echocardiography (TTE) when the questionnaires were collected, only 210 performed venous ultrasounds. Although 91% (61/67) of medical institutions could perform TTE within 30 min, only 77% (53/69) performed venous ultrasounds within 30 min. The number of venous ultrasounds per population×100 was largest in the Kumamoto and Kamimashiki areas (1.67) and smallest in the Kamoto area (0.05). Conclusions: This is the first report to reveal the current awareness and status of venous ultrasonography in a specific region in Japan. There are several problems to be overcome, such as a lack of venous ultrasound specialists and the regional disparity in venous ultrasounds in Kumamoto Prefecture.
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Background: There are few reports on current awareness and status of transthoracic echocardiography (TTE), including the actual performance rate according to echocardiographic guidelines, in a specific area or region. MethodsâandâResults: This cross-sectional survey study was conducted in Kumamoto Prefecture from October 2018 to March 2019. There are 366 medical institutions advocating cardiology in Kumamoto Prefecture. Of these, 259 (101 hospitals and 158 clinics) returned questionnaires regarding TTE. In all, 150,570 TTEs were performed in 2017. Of these, 132,771 (88%) were performed in hospitals and 17,799 (12%) were performed in clinics. Physicians performed only 5% of TTEs, whereas sonographers performed 86%. Although the modified Simpson method was performed in 90% of hospitals, 3-dimensional echocardiography was performed in only 2% of hospitals. In addition, the left atrial volume index was not examined in approximately 60% of hospitals, and the mean E/E' ratio was not examined in 80% of hospitals. Multivariable logistic regression analysis revealed that having a Fellow of the Japan Society of Ultrasonic in Medicine was significantly and independently associated with guideline-oriented TTE (odds ratio 9.43; 95% confidence interval 1.22-72.71, P<0.05). Conclusions: The rate of echocardiographic measurements performed according to echocardiographic guidelines is exceptionally low in Kumamoto Prefecture. Sufficient dissemination of echocardiographic guidelines may be important in improving this rate.
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BACKGROUND: Although type B aortic dissection has been treated with beta blockers to lower the arterial blood pressure (BP), there has been little evidences about reduction in heart rate (HR). We assessed whether tight HR control improved the outcome of medical treatment in patients with aortic dissection. METHODS AND RESULTS: From 1997 to 2005, 171 patients with acute aortic dissection medically treated and controlled to lower BP under 120 mm Hg were enrolled. Based on the average HR at 3, 5, and 7 days after the onset, patients were divided into tight HR (<60 beat per minute) control group (32 patients; mean HR of 56.6+/-3.1 beat per minute) and conventional HR (>/=60 beat per minute) control group (139 patients; mean HR of 71.7+/-8.2 beat per minute). We compared the frequency of aortic events including late organ or limb ischemia, aortic rupture, recurrent dissection, and aortic expansion of >5 mm, and surgical requirement between two groups. During a median follow-up of 27.0 months, late organ or limb ischemia, aortic rupture, recurrent dissection, pathological aortic expansion, and aortic surgery occurred in 0, 8, 14, 39, and 26 patients, respectively. Reduction in aortic events was observed in tight HR control group (12.5%) compared to conventional HR control group (36.0%), (Odds ratio: 0.25, C.I.: 0.08 to 0.77, P<0.01). CONCLUSIONS: The present study demonstrated that tight heart rate control improved the outcome of medical treatment in patients with aortic dissection.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Aneurisma Aórtico/tratamento farmacológico , Dissecção Aórtica/tratamento farmacológico , Dissecção Aórtica/fisiopatologia , Frequência Cardíaca , Doença Aguda , Dissecção Aórtica/complicações , Aorta/cirurgia , Aneurisma Aórtico/complicações , Aneurisma Aórtico/fisiopatologia , Ruptura Aórtica/epidemiologia , Ruptura Aórtica/etiologia , Pressão Sanguínea/efeitos dos fármacos , Extremidades/irrigação sanguínea , Seguimentos , Humanos , Incidência , Isquemia/etiologia , Recidiva , Resultado do Tratamento , Procedimentos Cirúrgicos VascularesRESUMO
We here present a 59-year-old man who had undergone peritoneal dialysis (PD) for 7 years and hemodialysis for the following 6 years in the Japanese Red Cross Kumamoto Hospital. Six years after commencing PD, transthoracic echocardiography showed a highly echoic mass with a transverse diameter of almost 15 mm in the posterior mitral leaflet. Because the mass increased from 2 years after initiation of hemodialysis, reaching over 25 mm by 6 years after commencing hemodialysis, tumor resection and mitral valve replacement were performed. When the surface of the mass was incised, white opalescent liquid drained out of the mass and histological examination showed multiple calcified nodules and granulation tissue, resulting in diagnosis of a caseous calcification of mitral annulus.
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BACKGROUND: In patients undergoing dialysis therapy, mitral annular calcification (MAC) is a powerful predictor of cardiovascular events and all-cause mortality. However, there is little data on predictors for MAC progression in patients undergoing dialysis therapy. METHODS AND RESULTS: We retrospectively analyzed 98 hemodialysis-dependent patients in Japanese Red Cross Kumamoto Hospital who underwent routine transthoracic echocardiography (TTE) in 2017. Three patients with history of surgical valve replacement or severe valvular heart diseases were excluded. In the 95 enrolled patients, MAC was detected by TTE in 28 patients (29%). A multivariate logistic regression analysis revealed that duration of hemodialysis therapy was independently associated with presence of MAC (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.02-1.16; pâ¯<â¯0.01). Among the 95 patients, 72 patients also underwent routine TTE 5â¯years previously in 2012. In these patients, progression of MAC from 2012 to 2017 was observed in 11 patients (15%). A multivariate logistic regression analysis revealed that number of coronary risk factors (OR: 2.67; 95% CI: 1.24-5.76; pâ¯=â¯0.01), baseline MAC diameter (OR: 1.23; 95% CI: 1.05-1.45; pâ¯=â¯0.01), and left atrial diameter (OR: 0.81; 95% CI: 0.68-0.95; pâ¯=â¯0.01) were significantly associated with progression of MAC. CONCLUSIONS: Accumulation of coronary risk factors was associated with progression of MAC in patients undergoing dialysis. Management of coronary risk factors may be important for inhibition of MAC progression.
Assuntos
Doenças das Valvas Cardíacas , Efeitos Adversos de Longa Duração , Valva Mitral , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica , Idoso , Calcinose/diagnóstico , Calcinose/etiologia , Progressão da Doença , Ecocardiografia/métodos , Feminino , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/prevenção & controle , Humanos , Japão/epidemiologia , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/etiologia , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Diálise Renal/métodos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Medição de Risco , Fatores de Risco , Prevenção SecundáriaRESUMO
The majority of aortic aneurysms comorbid with atherosclerosis can be asymptomatic and are discovered incidentally on routine physical examination or on imaging studies for other indications. Transthoracic echocardiography is a basic modality to assess patients with coronary artery disease and can be used for the screening of aortic aneurysm. Acute aortic dissection is a highly lethal cardiovascular emergency and requires prompt recognition. Although cardiovascular echo has a suboptimal accuracy rate for detecting aortic dissection, it is noninvasive, readily available, and easy to use. Recently, the concept of point-of-care ultrasound (POCUS) refers to the use of portable ultrasound at the patient's bedside for diagnostic and therapeutic purposes. POCUS could become an important tool in the screening and primary diagnosis for acute aortic dissection. Transesophageal echocardiography (TEE) was established to detect aortic dissection and determine the therapy. However, the use of TEE has decreased with the progress of contrast-enhanced computed tomography. Currently, attention is paid to TEE in the monitoring for the operation of aortic dissection, the use on bedside, and in emergency room, and the precise evaluation of aortic dissection for the patient with a history of allergy of contrast media and/or renal disturbance.