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Fabry disease is a rare X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme, galactosidase A, that can result in a progressive increase in the left ventricle (LV) wall thickness from glycosphingolipid deposition leading to myocardial fibrosis, conduction abnormalities, arrhythmias, and heart failure. We present a case of a patient with advanced Fabry cardiomyopathy, in whom a small LV apical aneurysm was incidentally discovered on abdominal imaging, which could have easily evaded detection on standard transthoracic echocardiography. The LV apex should be thoroughly interrogated in patients with Fabry cardiomyopathy, as the finding of LV aneurysm could have important management implications with respect to the prevention of stroke and sudden cardiac death.
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Cardiomiopatias , Doença de Fabry , Aneurisma Cardíaco , Arritmias Cardíacas , Ecocardiografia , Humanos , MiocárdioRESUMO
BACKGROUND: Combined post- and precapillary pulmonary hypertension (CpcPH) portends poor outcomes in pulmonary hypertension related to left heart disease (PH-LHD). While recent evidence does not support the use of targeted pulmonary arterial hypertension (PAH) therapy in PH-LHD, there is a lack of clinical data on their use in CpcPH. We evaluated the outcomes in patients with CpcPH treated with PAH therapies. METHODS: Retrospectively, 50 patients meeting hemodynamic criteria of CpcPH and started on PAH-targeted drugs were identified. Fifty age- and gender-matched PAH patients were chosen as controls. We evaluated the change in 6-minute walk distance, World Health Organization functional class (FC), tricuspid annular plane systolic excursion, BNP or NT-proBNP, and pulmonary artery systolic pressure at 3, 6, 12, and 24 months of follow-up. RESULTS: After adjusting for age and gender, there was no improvement in World Health Organization FC in CpcPH over 2 years (odds ratio of change to FC I/II 1.01, 95% CI: 0.98-1.04). There was no significant improvement in 6-minute walk distance (ß coefficient 0.21, 95% CI: -0.98 to 1.4), reduction in BNP/NT-proBNP (ß coefficient -12.16, 95% CI: -30.68 to 6.37), increase in tricuspid annular plane systolic excursion (ß coefficient 0.074, 95% CI: 0.010-0.139), or decrease in pulmonary artery systolic pressure (0.996, 95% CI: 0.991-1.011) in CpcPH with therapy. There was higher mortality in CpcPH compared to PAH on treatment (24% vs 4%, Pâ¯=â¯.003). CONCLUSIONS: There were no improvements in symptoms, exercise capacity, or echocardiographic parameters with PAH-targeted therapy in CpcPH. Further studies into potential treatments benefiting this population are needed.
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Anti-Hipertensivos/uso terapêutico , Hemodinâmica/fisiologia , Hipertensão Pulmonar/tratamento farmacológico , Ecocardiografia , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Despite maturing experience and growing procedural familiarity, there remain challenges in percutaneous left atrial appendage (LAA) closure due to anatomical complexities. METHODS: We report a complex and extremely large LAA that was successfully closed percutaneously using a LAmbre Closure System (Lifetech Scientific Corp.). Cardiac computed tomography angiography demonstrated a gigantic multilobed LAA measuring 48 × 45.3 mm at the level of the ostium that cannot be occluded by the currently approved LAA closure devices in Canada. RESULTS: The manufacturer custom-made a LAmbre 30/50 mm (lobe/disc) device to fit this patient's LAA according to his CTA, which was successfully deployed under fluoroscopy and transesophageal echocardiogram guidance without procedure-related complications. CONCLUSION: The LAmbre device may be considered to close very large LAAs.
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Apêndice Atrial , Fibrilação Atrial , Dispositivo para Oclusão Septal , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Canadá , Cateterismo Cardíaco/efeitos adversos , Ecocardiografia Transesofagiana , Humanos , América do Norte , Resultado do TratamentoRESUMO
Pulmonary artery sarcoma is a rare malignant neoplasm. Here, we describe a patient with a pulmonary artery sarcoma, which was only subtly visible and therefore not fully appreciated on initial transthoracic echocardiogram. Characterization of the tumor was aided by the use of multimodality imaging that included computed tomography, magnetic resonance imaging, and positron emission tomography. Familiarity with its appearance on multiple imaging modalities including echocardiography is important to ensure timely diagnosis, although the optimal treatment strategy is still unknown, and the prognosis remains poor.
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Imagem Multimodal/métodos , Artéria Pulmonar/diagnóstico por imagem , Sarcoma/diagnóstico por imagem , Neoplasias Vasculares/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Ecocardiografia , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons , Artéria Pulmonar/cirurgia , Sarcoma/cirurgia , Tomografia Computadorizada por Raios X , Neoplasias Vasculares/cirurgia , Adulto JovemRESUMO
BACKGROUND: Quadricuspid aortic valve (QAV) is a rare congenital cardiac defect. This study sought to determine QAV frequency in a large echocardiography database, to characterize associated cardiovascular abnormalities, and to describe long-term outcomes. METHODS AND RESULTS: Fifty patients (mean ± SD age, 43.5 ± 21.8 years at the time of the index diagnosis; female sex, 52%) received a diagnosis of QAV between January 1, 1975, and March 14, 2014 (frequency, 0.006%). The QAV was type A in 32% and type B in 32% (Hurwitz and Roberts classification). Aortic dilatation was present in 29% of the patients, and 26% had moderate or severe aortic valve regurgitation at the index diagnosis. Stenosis affected only 8% of the valves and was mild. Other findings, including abnormalities of other cardiac valves, septal defects, persistent left superior vena cava, and patent ductus arteriosus, were present in 32% of patients. During a mean ± SD follow-up of 4.8 ± 5.6 years, 8 patients underwent aortic valve surgery, with severe aortic valve regurgitation being the surgical indication in 7 patients. One patient with mild to moderate aortic valve regurgitation underwent aortic valve repair for obstruction of the left coronary ostium by the accessory cusp of QAV. No infective endocarditis or aortic dissection was found. Overall survival was 91.5% and 87.7% at 5 and 10 years. CONCLUSIONS: Aortic dilatation and other structural cardiac abnormalities were relatively common among patients with QAV. Aortic valve regurgitation was the predominant hemodynamic abnormality and the indication for aortic valve surgery in most patients who received surgery. Long-term survival was excellent.
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Valva Aórtica/anormalidades , Valva Aórtica/diagnóstico por imagem , Anormalidades Cardiovasculares/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Ultrassonografia , Adulto JovemRESUMO
Left ventricular (LV) geometric patterns aid clinicians in the diagnosis and prognostication of various cardiomyopathies. The aim of this study is to assess the accuracy and reproducibility of LV dimensions and wall thickness using deep learning (DL) models. A total of 30,080 unique studies were included; 24,013 studies were used to train a convolutional neural network model to automatically assess, at end-diastole, LV internal diameter (LVID), interventricular septal wall thickness (IVS), posterior wall thickness (PWT), and LV mass. The model was trained to select end-diastolic frames with the largest LVID and to identify four landmarks, marking the dimensions of LVID, IVS, and PWT using manually labeled landmarks as reference. The model was validated with 3,014 echocardiographic cines and the accuracy of the model was evaluated with a test set of 3,053 echocardiographic cines. The model accurately measured LVID, IVS, PWT, and LV mass compared to study report values with a mean relative error of 5.40%, 11.73%, 12.76%, and 13.93%, respectively. The ð 2 of the model for the LVID, IVS, PWT, and the LV mass was 0.88, 0.63, 0.50, and 0.87, respectively. The novel DL model developed in this study was accurate for LV dimension assessment without the need to select end-diastolic frames manually. DL automated measurements of IVS and PWT were less accurate with greater wall thickness. Validation studies in larger and more diverse populations are ongoing.
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PURPOSE: There is lack of validated methods for quantifying the size of pleural effusion from standard transthoracic (TTE) windows. The purpose of this study is to determine whether pleural effusion (Peff) measured from routine two-dimensional (2D) TTE views correlate with chest radiograph (CXR). MATERIALS AND METHODS: We retrospectively identified all inpatients who underwent a TTE and CXR within 2 days in a large tertiary care center. Peff was measured on TTE from parasternal long axis (PLAX), apical four-chamber (A4C), and subcostal views and on CXR. Logistic regression models were used determine optimal cut points to predict moderate or greater Peff. RESULTS: In 200 patients (mean age 69.3 ± 14.3 years, 49.5% female), we found statistically significant associations between Peff size assessed by all TTE views and CXR, with weak to moderate correlation (PLAX length: 0.21 (95% CI [0.05, 0.35]); PLAX depth: 0.21 (95% CI [0.05, 0.35]); A4C left: 0.31 (95% CI [0.13, 0.46]); A4C right: 0.39 (95% CI [0.17, 0.57]); subcostal: 0.38 (95% CI [0.07, 0.61]). The best TTE thresholds for predicting moderate or greater left-sided Peff on CXR was PLAX length left > = 8.6 cm (sensitivity 78%, specificity 54%, PPV 26%, and NPV 92%). The best TTE thresholds for predicting moderate or greater right-sided Peff on CXR was A4C right > = 2.6 cm (sensitivity 87%, specificity 60%, PPV 37%, and NPV 94%). CONCLUSIONS: We identified statistically significant associations with Peff size measured on TTE and CXR. The predictive ability of TTE to identify moderate or large pleural effusion is limited.
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Ecocardiografia , Derrame Pleural , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Ecocardiografia/métodos , Reprodutibilidade dos TestesRESUMO
We sought to determine the cardiac ultrasound view of greatest quality using a machine learning (ML) approach on a cohort of transthoracic echocardiograms (TTE) with abnormal left ventricular (LV) systolic function. We utilize an ML model to determine the TTE view of highest quality when scanned by sonographers. A random sample of TTEs with reported LV dysfunction from 09/25/2017-01/15/2019 were downloaded from the regional database. Component video files were analyzed using ML models that jointly classified view and image quality. The model consisted of convolutional layers for extracting spatial features and Long Short-term Memory units to temporally aggregate the frame-wise spatial embeddings. We report the view-specific quality scores for each TTE. Pair-wise comparisons amongst views were performed with Wilcoxon signed-rank test. Of 1,145 TTEs analyzed by the ML model, 74.5% were from males and mean LV ejection fraction was 43.1 ± 9.9%. Maximum quality score was best for the apical 4 chamber (AP4) view (70.6 ± 13.9%, p<0.001 compared to all other views) and worst for the apical 2 chamber (AP2) view (60.4 ± 15.4%, p<0.001 for all views except parasternal short-axis view at mitral/papillary muscle level, PSAX M/PM). In TTEs scanned by professional sonographers, the view with greatest ML-derived quality was the AP4 view.
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Ecocardiografia , Disfunção Ventricular Esquerda , Masculino , Humanos , Valor Preditivo dos Testes , Ecocardiografia/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda/fisiologia , Volume Sistólico , Aprendizado de MáquinaRESUMO
BACKGROUND: There is limited data on the residual echocardiographic findings including strain analysis among post-coronavirus disease (COVID) patients. The aim of our study is to prospectively phenotype post-COVID patients. METHODS: All patients discharged following acute COVID infection were systematically followed in the post-COVID-19 Recovery Clinic at Vancouver General Hospital and St. Paul's Hospital. At 4-18 weeks post diagnosis, patients underwent comprehensive echocardiographic assessment. Left ventricular ejection fraction (LVEF) was assessed by 3D, 2D Biplane Simpson's, or visual estimate. LV global longitudinal strain (GLS) was measured using a vendor-independent 2D speckle-tracking software (TomTec). RESULTS: A total of 127 patients (53% female, mean age 58 years) were included in our analyses. At baseline, cardiac conditions were present in 58% of the patients (15% coronary artery disease, 4% heart failure, 44% hypertension, 10% atrial fibrillation) while the remainder were free of cardiac conditions. COVID-19 serious complications were present in 79% of the patients (76% pneumonia, 37% intensive care unit admission, 21% intubation, 1% myocarditis). Normal LVEF was seen in 96% of the cohort and 97% had normal right ventricular systolic function. A high proportion (53%) had abnormal LV GLS defined as < 18%. Average LV GLS of septal and inferior segments were lower compared to that of other segments. Among patients without pre-existing cardiac conditions, LVEF was abnormal in only 1.9%, but LV GLS was abnormal in 46% of the patients. CONCLUSIONS: Most post-COVID patients had normal LVEF at 4-18 weeks post diagnosis, but over half had abnormal LV GLS.
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Left atrial (LA) volume and function are robust markers of cardiovascular risks and adverse cardiac outcomes. With advances in imaging technology, including tissue Doppler, strain, and strain rate imaging, we can now determine LA volume and function more precisely and this is anticipated to augment our ability to risk stratify, incremental to clinical risk profiling. There is increasing evidence that LA remodeling is treatable and is reversible. Serial LA volume and function assessment may provide a simple and quantifiable way of determining severity of risk and treatment impact. While reverse LA remodeling is expected to improve cardiac outcomes, data to confirm this remain forthcoming.
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Função do Átrio Esquerdo/fisiologia , Fibrilação Atrial/fisiopatologia , Volume Cardíaco/fisiologia , Átrios do Coração/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Prognóstico , Medição de Risco/métodos , UltrassonografiaRESUMO
BACKGROUND: Unlike left ventricular (LV) ejection fraction, which provides a precise, reliable, and prognostically valuable measure of systolic function, there is no single analogous measure of LV diastolic function. OBJECTIVES: We aimed to develop a continuous score to grade LV diastolic function using machine learning modeling of echocardiographic data. METHODS: Consecutive echo studies performed at a tertiary-care center between February 1, 2010, and March 31, 2016, were assessed, excluding studies containing features that would interfere with diastolic function assessment as well as studies in which 1 or more parameters within the contemporary diastolic function assessment algorithm were not reported. Diastolic function was graded based on 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guidelines, excluding indeterminate studies. Machine learning models were trained (support vector machine [SVM], decision tree [DT], XGBoost [XGB], and dense neural network [DNN]) to classify studies within the training set by diastolic dysfunction severity, blinded to the ASE/EACVI classification. The DNN model was retrained to generate a regression model (R-DNN) to predict a continuous LV diastolic function score. RESULTS: A total of 28,986 studies were included; 23,188 studies were used to train the models, and 5,798 studies were used for validation. The models were able to reclassify studies with high agreement to the ASE/EACVI algorithm (SVM, 83%; DT, 100%; XGB, 100%; DNN, 98%). The continuous diastolic function score corresponded well with ASE/EACVI guidelines, with scores of 1.00 ± 0.01 for studies with normal function and 0.74 ± 0.05, 0.51 ± 0.06, and 0.27 ± 0.11 for mild, moderate, and severe diastolic dysfunction, respectively (mean ± 1 SD). A score of <0.91 predicted abnormal diastolic function (area under the receiver operator curve = 0.99), while a score of <0.65 predicted elevated filling pressure (area under the receiver operator curve = 0.99). CONCLUSIONS: Machine learning can assimilate echocardiographic data and generate an automated continuous diastolic function score that corresponds well with current diastolic function grading recommendations.
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Disfunção Ventricular Esquerda , Humanos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Valor Preditivo dos Testes , Função Ventricular Esquerda , Diástole , Aprendizado de MáquinaRESUMO
Limited views are often obtained in the setting of cardiac ultrasound, however, the likelihood of missing left ventricular (LV) dysfunction based on a single view is not known. We sought to determine the echo views that were least likely to miss LV systolic dysfunction in consecutive transthoracic echocardiograms (TTEs). Structured data from TTEs performed at 2 hospitals from September 25, 2017, to January 15, 2019, were screened. Studies of interest were those with reported LV dysfunction. Views evaluated were the parasternal long-axis (PLAX), parasternal-short axis at mitral (PSAX M), papillary muscle (PSAX PM), and apical (PSAX A) levels, apical 2 (AP2), apical 3 (AP3), and apical 4 (AP4) chamber views. The probability that a view contained at least 1 abnormal segment was determined and analyzed with McNemar's test for 21 adjusted pair-wise comparisons. There were 4102 TTE studies included for analysis. TTEs on males comprised 72.7% of studies with a mean LV ejection fraction of 42.8 ± 9.7%. The echo view with the greatest likelihood of encompassing an abnormal segment was the AP2 view with a prevalence of 93.4% (p < 0.001, compared to all other views). The PLAX view performed the worst with a prevalence of 82.5% (p < 0.015, compared to all other views). The best parasternal view for the detection of abnormality was the PSAX PM view at 90.4%. In conclusions, a single echo view will contain abnormal segments > 82% of the time in the setting of LV systolic dysfunction, with a prevalence of up to 93.4% in the apical windows.
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The diagnostic accuracy of the cardiothoracic ratio on chest X-ray to detect left ventricular (LV) enlargement has not been well defined despite its traditional association with cardiomegaly. We aimed to determine whether the cardiothoracic ratio can accurately predict LV enlargement based on indexed linear measurements of the LV on transthoracic echocardiography (TTE). We included consecutive patients who had a TTE and a posteroanterior chest X-ray performed within 90 days of each other at a tertiary care center. LV size was determined by measuring the LV end-diastolic dimension (LVEDD) and LV end-diastolic dimension indexed (LVEDDI) to body surface area. The cardiothoracic ratio was calculated by dividing the maximum transverse diameter of the cardiac silhouette by the maximum transverse diameter of the right and left lung boundaries. 173 patients were included in the study (mean age 68 ± 15 years, 49.1% female). Mean cardiothoracic ratio was 0.56 ± 0.09, and the mean LVEDD and indexed LVEDDI were of 47 ± 8.6 mm and dimension of 27 ± 4.5 mm/m2 respectively. There was no significant correlation between the cardiothoracic ratio measured on chest X-ray and either the LVEDD or LVEDDI measured on TTE (r = 0.011, p = 0.879; r = 0.122, p = 0.111). The ability of the cardiothoracic ratio to predict LV enlargement (defined as LVEDDI > 30 mm/m2) was not statistically significant. The cardiothoracic ratio on chest X-ray is not a predictor of LV enlargement based on indexed linear measurements of the LV by TTE.
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BACKGROUND: Echocardiographic assessment of diastolic function is complex but can aid in the diagnosis of heart failure, particularly in patients with preserved ejection fraction. In 2016, the American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) published an updated algorithm for the evaluation of diastolic function. The objective of our study was to assess its impact on diastolic function assessment in a real-world cohort of echo studies. METHODS: We retrospectively identified 71,727 consecutive transthoracic echo studies performed at a tertiary care center between February 2010 and March 2016 in which diastolic function was reported based on the 2009 ASE Guidelines. We then programmed a software algorithm to assess diastolic function in these echo studies according to the 2016 ASE/EACVI Guidelines. RESULTS: When diastolic function assessment based on the 2009 guidelines was compared to that using the 2016 guidelines, there were significant differences in proportion of studies classified as normal (23% vs. 32%) or indeterminate (43% vs. 36%) function, and mild (23% vs. 23%), moderate (10% vs. 8%), or severe (1% vs. 2%) diastolic dysfunction, with poor agreement between the two methods (Kappa 0.323, 95% CI 0.318-0.328). Furthermore, within the subgroup of studies with preserved ejection fraction and no evidence of myocardial disease, there was significant reclassification from mild diastolic dysfunction to normal diastolic function. CONCLUSION: The updated guidelines result in significant differences in diastolic function interpretation in the real world. Our findings have important implications for the identification of patients with or at risk for heart failure.
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Cardiomiopatias , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Diástole , Ecocardiografia , Humanos , Estudos RetrospectivosRESUMO
Animal studies suggest that decreased vascular mitochondrial DNA copy number can promote hypertension. We conducted a chart review of blood pressure and hemodynamics in patients with either mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS, n = 36) or individuals with variants in the mitochondrial DNA polymerase gamma (POLG, n = 26). The latter included both pathogenic variants and variants of unknown significance (VUS). Hypertension rates (MELAS 50%, POLG 50%) were elevated relative to Canadian norms in 20-39 (MELAS) and 40-59 (MELAS and POLG) years of age groups. Peripheral resistance was high in the hypertensive versus normotensive patients, potentially indicative of microvascular disease. Despite antihypertensive treatment, systolic blood pressure remained elevated in the POLG versus MELAS group. The risk of hypertension was not associated with MELAS heteroplasmy. Hypertension rates were not different between individuals with known pathogenic POLG variants and those with VUS, including common variants. Hypertension (HT) also did not differ between patients with POLG variants with (n = 17) and without chronic progressive external opthalmoplegia (n = 9) (CPEO). HT was associated with variants in all three functional domains of POLG. These findings suggest that both pathogenic variants and several VUS in the POLG gene may promote human hypertension and extend our past reports that increased risk of HT is associated with MELAS.
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DNA Polimerase gama/genética , Hipertensão/epidemiologia , Síndrome MELAS/epidemiologia , Mutação Puntual , Adulto , Distribuição por Idade , Idoso , Anti-Hipertensivos/uso terapêutico , Canadá/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Síndrome MELAS/genética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: This study examined the impact of mitral valve repair (MVRe) on survival of patients with moderate or severe (≥2+) MR and ischemic cardiomyopathy randomized to coronary artery bypass grafting (CABG) versus CABG+surgical ventricular reconstruction (SVR) in the STICH trial. METHODS: Among patients with moderate or severe MR and ischemic cardiomyopathy undergoing CABG or CABG+SVR, the impact of MVRe on mortality between the two treatment arms was compared. RESULTS: Among 867 patients with assessment of baseline MR severity, 211 had moderate or severe MR. After excluding 7 patients who underwent mitral valve replacement, 50, 44, 62, and 48 patients underwent CABG, CABG+MVRe, CABG+SVR, and CABG+SVR+MVRe, respectively. Four-year mortality rates were lower following CABG+MVRe than CABG alone (16% vs. 55%; adjusted hazard ratio [HR] 0.30; 95% CI 0.13-0.71). In contrast, the CABG+SVR+MVRe and CABG+SVR groups had similar 4-year mortality of 39% vs. 39% (adjusted HR 0.88; 95% CI 0.46-1.70). MVRe had a more favorable effect on survival in patients undergoing CABG alone compared to CABG+SVR (p=0.013). Baseline MR severity was similar between patients that received CABG+MVRe and those that underwent CABG+SVR+MVRe. A larger proportion of patients demonstrated a reduction in MR between 4 and 24 months after CABG+MVRe compared to CABG+SVR+MVRe (50.0% versus 25.0%, p=0.023). CONCLUSION: In patients with moderate or severe MR and ischemic cardiomyopathy undergoing CABG, MVRe appears to have a favorable effect on survival. The addition of SVR to CABG may attenuate the anticipated benefits of MVRe by limiting the long-term reduction of MR with MVRe.
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AIM: The objective of this study was to examine the interaction ofa 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) with a nitric oxide (NO) donor from the perspective of the impact on cardiomyocyte cell viability. METHODS: Embryonic chick cardiomyocytes in culture were treated with a wide range of concentrations of sodium nitroprusside (SNP), which releases NO and also generates toxic reactive nitrogen species. SNP was combined with the HMG-CoA reductase inhibitor lovastatin and cell viability was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. RESULTS: SNP and lovastatin each produced a significant (p < 0.01) concentration-dependent increase in cell death. Using SNP concentrations at or below the ED50, SNP (0.01, 0.1 or 0.5 mmol/l) increased the amount of cell death when combined with lovastatin (1, 10, 50 and 100 micromol/l). At lovastatin concentrations of 50 micromol/l and less, the amount of cell death was consistently similar to the arithmetic sum of SNP and lovastatin, suggesting that there was an additive and not synergistic relationship between SNP and lovastatin. In combination with lovastatin (100 micromol/l), however, the amount of cell death was consistently lower than the calculated expected value and suggested saturation of a common mechanism. The combination of SNP and lovastatin produced the characteristic microscopic changes of apoptosis. Considering that both SNP and lovastatin can activate caspase-3, cells were treated with the caspase-3 inhibitor Ac-DEVD-CHO. This inhibitor produced a significant (p < 0.05) and consistent 30% reduction in the amount of cell death induced by SNP and lovastatin. CONCLUSION: These data suggest that the cardiomyocyte toxicity from NO continues to be evident uninterrupted by and not accentuated by the presence of an HMG-CoA inhibitor. The cardiac adverse effect of each of these agents utilizes a common pathway involving caspase-3 so that their cardiotoxicity can be blunted by a caspase-3 inhibitor.
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Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lovastatina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Animais , Inibidores de Caspase , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Relação Dose-Resposta a Droga , Interações Medicamentosas , Microscopia de Fluorescência , Miócitos Cardíacos/citologia , Oligopeptídeos/farmacologiaAssuntos
Tumor Carcinoide , Neoplasias Ovarianas , Insuficiência da Valva Tricúspide , Feminino , Humanos , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , Tumor Carcinoide/diagnóstico por imagem , Tumor Carcinoide/cirurgia , Tumor Carcinoide/patologia , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/cirurgia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologiaRESUMO
Fabry disease is an X-linked lysosomal storage disorder that results from a deficiency of α-galactosidase A. Increased left ventricular wall thickness has been the most commonly described cardiovascular manifestation of the disease. However, a variety of other structural and functional abnormalities have also been reported. Echocardiography is an effective noninvasive method of assessing the cardiac involvement of Fabry disease. A more precise and comprehensive characterization of Fabry cardiomyopathy using conventional and novel echocardiographic techniques may lead to earlier diagnosis, more accurate prognostication, and timely treatment. The aim of this review is to provide a comprehensive overview of the structural and functional abnormalities on echocardiography that have thus far been described in patients with Fabry disease and to highlight potential areas that would benefit from further research.