Clerio F. Azevedo

Prognostic Significance of Myocardial Fibrosis Quantification by Histopathology and Magnetic Resonance Imaging in Patients With Severe Aortic Valve Disease

OBJECTIVES We sought to determine whether the quantitative assessment of myocardial fibrosis (MF), either by histopathology or by contrast-enhanced magnetic resonance imaging (ce-MRI), could help predict long-term survival after aortic valve replacement. BACKGROUND Severe aortic valve disease is characterized by progressive accumulation of interstitial MF. METHODS Fifty-four patients scheduled to undergo aortic valve replacement were examined by ce-MRI. Delayed-enhanced images were used for the quantitative assessment of MF. In addition, interstitial MF was quantified by histological analysis of myocardial samples obtained during open-heart surgery and stained with picrosirius red. The ce-MRI study was repeated 27+/-22 months after surgery to assess left ventricular functional improvement, and all patients were followed for 52+/-17 months to evaluate long-term survival. RESULTS There was a good correlation between the amount of MF measured by histopathology and by ce-MRI (r=0.69, p<0.001). In addition, the amount of MF demonstrated a significant inverse correlation with the degree of left ventricular functional improvement after surgery (r=-0.42, p=0.04 for histopathology; r=-0.47, p=0.02 for ce-MRI). Kaplan-Meier analyses revealed that higher degrees of MF accumulation were associated with worse long-term survival (chi-square=6.32, p=0.01 for histopathology; chi-square=5.85, p=0.02 for ce-MRI). On multivariate Cox regression analyses, patient age and the amount of MF were found to be independent predictors of all-cause mortality. CONCLUSIONS The amount of MF, either by histopathology or by ce-MRI, is associated with the degree of left ventricular functional improvement and all-cause mortality late after aortic valve replacement in patients with severe aortic valve disease.

Prognostic Value of CT Angiography in Patients With Inconclusive Functional Stress Tests

OBJECTIVES We attempted to determine the prognostic value of coronary computed tomographic angiography (CTA) in patients with inconclusive functional stress tests. BACKGROUND Patients with suspected coronary artery disease (CAD) and inconclusive noninvasive cardiac stress tests represent a frequent management challenge. METHODS We examined 529 consecutive patients with suspected CAD and prior inconclusive functional stress tests. All patients underwent a coronary CTA scan using a 64-slice multidetector row scanner. CAD severity by coronary CTA was categorized as: 1) no evidence of CAD; 2) nonobstructive coronary plaques (< 30%); 3) mild stenosis (30% to 49%); 4) moderate stenosis (50% to 69%); and 5) severe stenosis (≥ 70%). Patients were also categorized according to a modified Duke prognostic CAD index. Survival analyses were performed using Cox proportional hazards models adjusted for baseline risk factors and coronary artery calcium score. The primary outcome of the study was the combined endpoint of all-cause mortality and nonfatal myocardial infarction. RESULTS Among patients with inconclusive stress tests, the large majority (69%) did not demonstrate significant CAD by coronary CTA. During a mean follow-up of 30.1 ± 11.1 months, there were 20 (3.8%) deaths and 17 (3.2%) nonfatal myocardial infarctions. Multivariable Cox regression analysis revealed that the presence of increasing degrees of obstructive CAD by CTA was an independent predictor of adverse events (hazard ratio [HR]: 1.66 [95% confidence interval (CI): 1.23 to 2.23], p = 0.001). Indeed, the presence of ≥ 50% coronary stenosis was associated with an increased risk of events (HR: 3.15 [95% CI: 1.26 to 7.89], p = 0.01). Likewise, the Duke prognostic CAD index was also found to be an independent predictor of events (HR: 1.54 [95% CI: 1.20 to 1.97], p = 0.001). CONCLUSIONS Among patients with inconclusive functional stress tests, the noninvasive assessment of CAD severity by coronary CTA has been shown to provide incremental prognostic information beyond the evaluation of traditional risk factors and coronary artery calcium score.

Contrast-enhanced magnetic resonance imaging identifies focal regions of intramyocardial fibrosis in patients with severe aortic valve disease: Correlation with quantitative histopathology.

BACKGROUND Chronic aortic valve disease (AVD) is characterized by progressive accumulation of interstitial myocardial fibrosis (MF). However, assessment of MF accumulation has only been possible through histologic analyses of endomyocardial biopsies. We sought to evaluate contrast-enhanced magnetic resonance imaging (ce-MRI) as a noninvasive method to identify the presence of increased MF in patients with severe AVD. METHODS Seventy patients scheduled to undergo aortic valve replacement surgery were examined by cine and ce-MRI in a 1.5-T scanner. Cine images were used for the assessment of left ventricular (LV) volumes, mass, and function. Delayed-enhancement images were used to characterize the regions of MF. In addition, histologic analyses of myocardial samples obtained during aortic valve replacement surgery were used for direct quantification of interstitial MF. Ten additional subjects who died of noncardiac causes served as controls for the quantitative histologic analyses. RESULTS Interstitial MF determined by histopathologic analysis was higher in patients with AVD than in controls (2.7% +/- 2.0% vs 0.6% +/- 0.2%, P = .001). When compared with histopathologic results, ce-MRI demonstrated a sensitivity of 74%, a specificity of 81%, and an accuracy of 76% to identify AVD patients with increased interstitial MF. There was a significant inverse correlation between interstitial MF and LV ejection fraction (r = -0.67, P < .0001). Accordingly, patients with identifiable focal regions of MF by ce-MRI exhibited worse LV systolic function than those without MF (45% +/- 14% vs 65% +/- 14%, P < .0001). CONCLUSIONS Contrast-enhanced MRI allows for the noninvasive detection of focal regions of MF in patients with severe AVD. Moreover, patients with identifiable MF by ce-MRI exhibited worse LV functional parameters.

Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy: A Randomized Clinical Trial

Importance In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), interventions reducing the progression of myocardial disease could affect survival. Objective To assess the effect of early angiotensin-converting enzyme (ACE) inhibitor therapy in patients with normal left ventricular function on the progression of myocardial fibrosis (MF) identified on cardiovascular magnetic resonance (CMR). Design, Setting, and Participants A randomized clinical trial conducted in 2 centers included 76 male patients with DMD or BMD undergoing 2 CMR studies with a 2-year interval for ventricular function and MF assessment. In a non–intent-to-treat trial, 42 patients with MF and normal left ventricular ejection fraction (LVEF) were randomized (1:1) to receive or not receive ACE inhibitor therapy. The study was conducted from June 26, 2009, to June 30, 2012. Data analysis was performed from June 30, 2013, to October 3, 2016. Interventions Randomization (1:1) to receive or not receive ACE inhibitor therapy. Main Outcomes and Measures Primary outcome was MF progression from baseline to the 2-year CMR study. Results Of the 76 male patients included in the study, 70 had DMD (92%) and 6 had BMD (8%); mean (SD) age at baseline was 13.1 (4.4) years. Myocardial fibrosis was present in 55 patients (72%) and LV systolic dysfunction was identified in 13 patients (24%). Myocardial fibrosis at baseline was an independent indicator of lower LVEF at follow-up (coefficient [SE], −0.16 [0.07]; P = .03). Among patients with MF and preserved LVEF (42 [55%]), those randomized (21 patients in each arm) to receive ACE inhibitors demonstrated slower MF progression compared with the untreated group (mean [SD] increase of 3.1% [7.4%] vs 10.0% [6.2%] as a percentage of LV mass; P = .001). In multivariate analysis, ACE inhibitor therapy was an independent indicator of decreased MF progression (coefficient [SE], −4.51 [2.11]; P = .04). Patients with MF noted on CMR had a higher probability of cardiovascular events (event rate, 10 of 55 [18.2%] vs 0 of 21 [0%]; log-rank P = .04). Conclusions and Relevance In this 2-year, follow-up, randomized clinical trial of patients with Duchenne or Becker muscular dystrophy whose LVEF was preserved and MF was present as determined on CMR, ACE inhibitor therapy was associated with significantly slower progression of MF. The presence of MF was associated with worse patient prognosis. Trial Registration clinicaltrials.org Identifier: NCT02432885

Accuracy of multidetector computed tomography for detection of coronary artery stenosis in acute coronary syndrome compared with stable coronary disease: A CORE64 multicenter trial substudy☆ , ☆☆

BACKGROUND Multi-detector computed tomography angiography (MDCTA) is a promising method for risk assessment of patients with acute chest pain. However, its diagnostic performance in higher-risk patients has not been investigated in a large international multicenter trial. Therefore, in the present study we sought to estimate the diagnostic accuracy of MDCTA to detect significant coronary stenosis in patients with acute coronary syndrome (ACS). METHODS Patients included in the CORE64 study were categorized as suspected-ACS or non-ACS based on clinical data. A 64-row coronary MDCTA was performed before invasive coronary angiography (ICA) and both exams were evaluated by blinded, independent core laboratories. RESULTS From 371 patients included, 94 were categorized as suspected ACS and 277 as non-ACS. Patient-based analysis showed an area under the receiver-operating-characteristic curve (AUC) for detecting ≥ 50% coronary stenosis of 0.95 (95% CI: 0.88-0.98) in ACS and 0.92 (95% CI: 0.88-0.95) in non-ACS group (P=0.29). The sensitivity, specificity, positive and negative predictive values of MDCTA were 0.90(0.80-0.96), 0.88(0.70-0.98), 0.95(0.87-0.99) and 0.77(0.58-0.90) in suspected ACS patients and 0.87(0.81-0.92), 0.86(0.79-0.92), 0.91(0.85-0.95) and 0.82(0.74-0.89) in non-ACS patients (P NS for all comparisons). The mean calcium scores (CS) were 282 ± 449 in suspected ACS and 435 ± 668 in non-ACS group. The accuracy of CS to detect significant coronary stenosis was only moderate and the absence or minimal coronary artery calcification could not exclude the presence of significant coronary stenosis, particularly in ACS patients. CONCLUSIONS The diagnostic accuracy of MDCTA to detect significant coronary stenosis is high and comparable for both ACS and non-ACS patients.

On Fibrosis, Prognosis, and the Unique Role of CMR : A Paradigm Shift From “Bright Is Dead” to “Bright Is Bad”∗

“Learning never exhausts the mind.” —Leonardo da Vinci [(1)][1] With an increasingly aging population, aortic stenosis (AS) has become the most frequent valvular heart disease in North America and Europe. It is a progressive condition characterized by a long latent asymptomatic period,

The myocardial area at risk

Sudden occlusion of a coronary artery initiates an expanding array of functional, metabolic and structural abnormalities, ultimately leading to myocyte necrosis, which extends from the subendocardial to the subepicardial layers of the perfusion bed—what Reimer called the ‘wavefront phenomenon’.1 In this setting, the myocardial area at risk (AAR) is defined as the myocardial tissue within the vascular territory that is distal to the culprit lesion of the infarct-related artery. If not timely reperfused, this area is at definite risk of ischaemic death. In humans, the portion of the AAR, that is irreversibly injured (ie, infarcted) ranges from 0% (aborted infarction) to as much as 88%.2 The proportion of the AAR that ultimately survives—that is, the salvaged myocardium—is dependent on multiple factors, including time to reperfusion, ischaemic preconditioning, collateral flow, distal embolisation, reperfusion injury and microvascular dysfunction. Since the extent of myocardial salvage is an important determinant of final infarct size, the quantitative assessment of myocardial salvage offers tremendous potential to aid in the development of novel therapeutic strategies targeted at reducing ischaemic/reperfusion injury in the setting of acute myocardial infarction (MI). The extent of myocardial salvage is defined as the difference between the total AAR and final infarct size. Therefore, in recent years there has been a renewed interest in techniques used for the assessment of the myocardial AAR in patients with acute MI. However, in contrast to myocardial delayed enhancement MRI (MDE-MRI), which represents a robust and validated technique that allows for an accurate assessment and detailed characterisation of the infarcted regions,3 quantification of the AAR still remains challenging. In animal studies, fluorescein staining and fluorescent microspheres are the reference standard for measuring the AAR.4–6 In humans, a commonly used technique is single-photon emission tomography, which requires …

Software livre e de código aberto para avaliação de imagens de angiotomografia de coronárias

BACKGROUND The standardization of images used in Medicine in 1993 was performed using the DICOM (Digital Imaging and Communications in Medicine) standard. Several tests use this standard and it is increasingly necessary to design software applications capable of handling this type of image; however, these software applications are not usually free and open-source, and this fact hinders their adjustment to most diverse interests. OBJECTIVE To develop and validate a free and open-source software application capable of handling DICOM coronary computed tomography angiography images. METHODS We developed and tested the ImageLab software in the evaluation of 100 tests randomly selected from a database. We carried out 600 tests divided between two observers using ImageLab and another software sold with Philips Brilliance computed tomography appliances in the evaluation of coronary lesions and plaques around the left main coronary artery (LMCA) and the anterior descending artery (ADA). To evaluate intraobserver, interobserver and intersoftware agreements, we used simple and kappa statistics agreements. RESULTS The agreements observed between software applications were generally classified as substantial or almost perfect in most comparisons. CONCLUSION The ImageLab software agreed with the Philips software in the evaluation of coronary computed tomography angiography tests, especially in patients without lesions, with lesions < 50% in the LMCA and < 70% in the ADA. The agreement for lesions > 70% in the ADA was lower, but this is also observed when the anatomical reference standard is used.

Bioimpedância transtorácica comparada à ressonância magnética na avaliação do débito cardíaco

BACKGROUND Cardiac magnetic resonance imaging is considered the gold-standard method for the calculation of cardiac volumes. Transthoracic impedance cardiography assesses the cardiac output. No studies validating this measurement, in comparison to that obtained by magnetic resonance imaging, are available. OBJECTIVE To evaluate the performance of transthoracic impedance cardiography in the calculation of the cardiac output, cardiac index and stroke volume using magnetic resonance imaging as the gold-standard. METHODS 31 patients with a mean age of 56.7 ± 18 years were assessed; of these, 18 (58%) were males. Patients whose indication for magnetic resonance imaging required pharmacologic stress test were excluded. Correlation between methods was assessed using the Pearsons coefficient, and dispersion of absolute differences in relation to the mean was demonstrated using the Bland-Altmans method. Agreement between methods was analyzed using the intraclass correlation coefficient. RESULTS The mean cardiac output by transthoracic impedance cardiography and by magnetic resonance imaging was 5.16 ± 0.9 and 5.13 ± 0.9 L/min, respectively. Good agreement between methods was observed for cardiac output (r = 0.79; p = 0.0001), cardiac index (r = 0.74; p = 0.0001) and stroke volume (r = 0.88; p = 0.0001). The analysis by the Bland-Altman plot showed low dispersion of differences in relation to the mean, with a low amplitude of agreement intervals. Good agreement between the two methods was observed when analyzed by the intraclass correlation coefficient, with coefficients for cardiac output, cardiac index and stroke volume of 0.78, 0.73 and 0.88, respectively (p < 0.0001 for all comparisons). CONCLUSION Transthoracic impedance cardiography proved accurate in the calculation of the cardiac output in comparison to cardiac magnetic resonance imaging.

Single-Breathhold Four-Dimensional Assessment of Left Ventricular Morphological and Functional Parameters by Magnetic Resonance Imaging Using the VAST Technique.

Introduction: The accurate and reproducible assessment of cardiac volumes, function, and mass is of paramount importance in cardiology. In the present study we sought to determine whether the 3D cine-magnetic resonance (MR) technique, using the variable asymmetric sampling in time (VAST) approach, provided an accurate assessment of LV functional parameters when compared with the conventional 2D cine-MR technique. Methods: A total of 43 consecutive patients referred for a CMR examination for clinical reasons and 14 healthy volunteers were included in the study. Cine images were acquired using a steady-state free precession pulse sequence. Two different multiphase acquisitions were performed: conventional 2D cine-MR and 3D cine-MR. The short-axis cine images acquired by both cine-MR techniques were used for the quantitative assessment of LV end-diastolic, end-systolic and stroke volumes, LV mass and ejection fraction. Results: All CMR examinations were completed successfully, with both cine-MR imaging techniques yielding interpretable diagnostic results in all patients. Regarding the quantitative assessment, Bland-Altman analyses demonstrated a good agreement between the measurements of both cine-MR techniques for all LV parameters. In addition, the agreement between 2D and 3D cine-MR techniques for the qualitative assessment of LV global function was perfect (kappa = 1.0, P<0.001) for the two observers in consensus. The assessment performed by the third independent observer also demonstrated very good agreement (kappa = 0.88, P<0.001). Conclusion: The single breathhold 3D cine-MR technique provides an accurate and reproducible quantitative assessment of LV volumes, mass and function when compared with the conventional 2D cine-MR method.