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Background: Preclinical studies have demonstrated that high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion (sonothrombolysis) can restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI)., Objectives: This study tested the clinical effectiveness of sonothrombolysis in patients with STEMI., Methods: Patients with their first STEMI were prospectively randomized to either diagnostic ultrasound-guided high MI impulses during an intravenous Definity (Lantheus Medical Imaging, North Billerica, Massachusetts) infusion before, and following, emergent percutaneous coronary intervention (PCI), or to a control group that received PCI only (n = 50 in each group). A reference first STEMI group (n = 203) who arrived outside the randomization window was also analyzed. Angiographic recanalization before PCI, ST-segment resolution, infarct size by magnetic resonance imaging, and systolic function (LVEF) at 6 months were compared., Results: ST-segment resolution occurred in 16 (32%) high MI PCI versus 2 (4%) PCI-only patients before PCI, and angiographic recanalization was 48% in high MI/PCI versus 20% in PCI only and 21% in the reference group (p < 0.001). Infarct size was reduced (29 ± 22 g high MI/PCI vs. 40 ± 20 g PCI only; p = 0.026). LVEF was not different between groups before treatment (44 ± 11% vs. 43 ± 10%), but increased immediately after PCI in the high MI/PCI group (p = 0.03), and remained higher at 6 months (p = 0.015). Need for implantable defibrillator (LVEF ≤30%) was reduced in the high MI/PCI group (5% vs. 18% PCI only; p = 0.045)., Conclusions: Sonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in systolic function after STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial fibrosis (MF) according to cardiac magnetic resonance (CMR) is a frequent finding in Chagas cardiomyopathy and has been associated with risk factors of poor outcome., Objectives: The goal of this study was to determine the prognostic value of MF in predicting combined hard events or all-cause mortality., Methods: Patients with Chagas cardiomyopathy who had a previous CMR evaluation were included, and clinical follow-up was retrospectively obtained. The primary outcome was a combination of all-cause mortality, heart transplantation, antitachycardia pacing or appropriate shock from an implantable cardioverter-defibrillator, and aborted sudden cardiac death; the secondary outcome was all-cause mortality., Results: A total of 130 patients were included; mean age was 53.6 ± 11.5 years, and 53.9% were female. The majority of patients reported no symptoms of heart failure or arrhythmia, but electrocardiographic and echocardiographic abnormalities were common. On CMR, left ventricular dilatation and dysfunction were frequent, and MF was found in 76.1%, with a mean mass of 15.2 ± 16.5 g. Over a median follow-up of 5.05 years, 58 (44.6%) patients reached the combined endpoint, and 45 (34.6%) patients died. MF was associated with the primary outcome as a continuous variable (adjusted hazard ratio: 1.031; 95% CI: 1.013 to 1.049; p = 0.001) and as a categorical variable (MF ≥12.3 g) (adjusted hazard ratio: 2.107; 95% CI: 1.111 to 3.994; p = 0.022), independently from the Rassi risk score. MF expressed as a continuous variable was also associated with all-cause mortality (adjusted hazard ratio: 1.028; 95% CI: 1.005 to 1.051; p = 0.017) independently from the Rassi risk score., Conclusions: MF is an independent predictor of adverse outcome in Chagas cardiomyopathy. Our data may support the use of CMR in better risk-stratifying this population and possibly guiding therapy., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Pre-clinical trials have demonstrated that, during intravenous microbubble infusion, high mechanical index (HMI) impulses from a diagnostic ultrasound (DUS) transducer might restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI)., Objectives: The purpose of this study was to test the safety and efficacy of this adjunctive approach in humans., Methods: From May 2014 through September 2015, patients arriving with their first STEMI were randomized to either DUS intermittent HMI impulses (n = 20) just prior to emergent percutaneous coronary intervention (PCI) and for an additional 30 min post-PCI (HMI + PCI), or low mechanical index (LMI) imaging only (n = 10) for perfusion assessments before and after PCI (LMI + PCI). All studies were conducted during an intravenous perflutren lipid microsphere infusion. A control reference group (n = 70) arrived outside of the time window of ultrasound availability and received emergent PCI alone (PCI only). Initial epicardial recanalization rates prior to emergent PCI and improvements in microvascular flow were compared between ultrasound-treated groups., Results: Median door-to-dilation times were 82 ± 26 min in the LMI + PCI group, 72 ± 15 min in the HMI + PCI group, and 103 ± 42 min in the PCI-only group (p = NS). Angiographic recanalization prior to PCI was seen in 12 of 20 HMI + PCI patients (60%) compared with 10% of LMI + PCI and 23% of PCI-only patients (p = 0.002). There were no differences in microvascular obstructed segments prior to treatment, but there were significantly smaller proportions of obstructed segments in the HMI + PCI group at 1 month (p = 0.001) and significant improvements in left ventricular ejection fraction (p < 0.005)., Conclusions: HMI impulses from a diagnostic transducer, combined with a commercial microbubble infusion, can prevent microvascular obstruction and improve functional outcome when added to the contemporary PCI management of acute STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to assess the impact of patient population characteristics on accuracy by computed tomography angiography (CTA) to detect obstructive coronary artery disease (CAD)., Background: The ability of CTA to exclude obstructive CAD in patients of different pre-test probabilities and in presence of coronary calcification remains uncertain., Methods: For the CORE-64 (Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography) study, 371 patients underwent CTA and cardiac catheterization for the detection of obstructive CAD, defined as ≥50% luminal stenosis by quantitative coronary angiography (QCA). This analysis includes 80 initially excluded patients with a calcium score ≥600. Area under the receiver-operating characteristic curve (AUC) was used to evaluate CTA diagnostic accuracy compared to QCA in patients according to calcium score and pre-test probability of CAD., Results: Analysis of patient-based quantitative CTA accuracy revealed an AUC of 0.93 (95% confidence interval [CI]: 0.90 to 0.95). The AUC remained 0.93 (95% CI: 0.90 to 0.96) after excluding patients with known CAD but decreased to 0.81 (95% CI: 0.71 to 0.89) in patients with calcium score ≥600 (p = 0.077). While AUCs were similar (0.93, 0.92, and 0.93, respectively) for patients with intermediate, high pre-test probability for CAD, and known CAD, negative predictive values were different: 0.90, 0.83, and 0.50, respectively. Negative predictive values decreased from 0.93 to 0.75 for patients with calcium score <100 or ≥100, respectively (p = 0.053)., Conclusions: Both pre-test probability for CAD and coronary calcium scoring should be considered before using CTA for excluding obstructive CAD. For that purpose, CTA is less effective in patients with calcium score ≥600 and in patients with a high pre-test probability for obstructive CAD., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study was designed to evaluate whether the absence of coronary calcium could rule out >or=50% coronary stenosis or the need for revascularization., Background: The latest American Heart Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients., Methods: A substudy was made of the CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors) multicenter trial comparing the diagnostic performance of 64-detector computed tomography to conventional angiography. Patients clinically referred for conventional angiography were asked to undergo a CS scan up to 30 days before., Results: In all, 291 patients were included, of whom 214 (73%) were male, and the mean age was 59.3 +/- 10.0 years. A total of 14 (5%) patients had low, 218 (75%) had intermediate, and 59 (20%) had high pre-test probability of obstructive coronary artery disease. The overall prevalence of >or=50% stenosis was 56%. A total of 72 patients had CS = 0, among whom 14 (19%) had at least 1 >or=50% stenosis. The overall sensitivity for CS = 0 to predict the absence of >or=50% stenosis was 45%, specificity was 91%, negative predictive value was 68%, and positive predictive value was 81%. Additionally, revascularization was performed in 9 (12.5%) CS = 0 patients within 30 days of the CS. From a total of 383 vessels without any coronary calcification, 47 (12%) presented with >or=50% stenosis; and from a total of 64 totally occluded vessels, 13 (20%) had no calcium., Conclusions: The absence of coronary calcification does not exclude obstructive stenosis or the need for revascularization among patients with high enough suspicion of coronary artery disease to be referred for coronary angiography, in contrast with the published recommendations. Total coronary occlusion frequently occurs in the absence of any detectable calcification. (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors [CORE-64]; NCT00738218).

Objectives: This study sought to analyze whether cardiovascular magnetic resonance (CMR) can detect and quantify myocardial damage in the early stages of cardiomyopathy in muscular dystrophies (MD)., Background: Muscular dystrophy is a genetic disease that involves skeletal and cardiac tissues of humans. Cardiomyopathy is common, and death secondary to cardiac or respiratory diseases occurs early in life. Cardiovascular magnetic resonance is a reliable method for assessing global and regional cardiac function, allowing also for the detection of myocardial fibrosis (MF)., Methods: Ten patients with Duchenne or Becker dystrophies were studied by CMR. Physical examination, Chagas disease serological tests, electrocardiogram, chest radiograph, total creatine kinase, and Doppler echocardiogram were also obtained in all patients., Results: Patients with MF had a lower ejection fraction than those without. Myocardial fibrosis (midwall and/or subepicardial) was observed in 7 of the 10 patients, and the lateral wall was the most commonly involved segment. There was moderate correlation between segmental MF and dysfunction., Conclusions: Cardiovascular magnetic resonance can identify MF and may be useful for detecting the early stages of cardiomyopathy in MD. Future work will be needed to evaluate whether CMR can influence cardiomyopathy and outcomes.

Objectives: We sought to investigate whether myocardial delayed enhancement (MDE) by magnetic resonance imaging (MRI) could quantify myocardial fibrosis (MF) in patients with Chagas' heart disease (CHD), thus defining the severity of the disease., Background: Myocardial fibrosis secondary to ischemic disease can be imaged using MDE. Advanced CHD is characterized by progressive MF., Methods: Fifty-one patients with CHD were enrolled: 15 seropositive asymptomatic participants in the indeterminate phase (IND); 26 patients with known clinical CHD; and 10 patients with known CHD and ventricular tachycardia (VT). Using a 1.5-T MRI system, we acquired left ventricular (LV) short-axis slices using cine-MRI (LV function) and inversion-recovery gradient-echo (MDE)., Results: Myocardial fibrosis by MRI was present in 68.6% of all patients, in 20% of IND, 84.6% of CHD, and 100% of VT (p < 0.001). Quantified MF increased progressively across disease severity subgroups (0.9 +/- 2.3% in IND; 16.0 +/- 12.3% in CHD; and 25.4 +/- 9.8% in VT, p < 0.001) and New York Heart Association functional classes (I: 7.5 +/- 9.5%; II: 21.9 +/- 13.8%; and III: 25.3 +/- 9.9% of LV mass, p < 0.001). Left ventricular ejection fraction and MF had significant negative correlation (r = -0.78, p < 0.001), similar to the segmental MF and function: 4.9 +/- 15.1% of MF in normal function, 32.5 +/- 32.5% in mildly hypokinetic, 57.8 +/- 31.4% in severely hypokinetic, and 72.3 +/- 36.2% in akinetic and dyskinetic segments, respectively (p < 0.001)., Conclusions: In CHD, MDE by MRI quantifies MF that not only can be detected in the early asymptomatic stages but parallels well-established prognostic factors and provides unique information for clinical disease staging.

Objectives: The goal of this study was to develop and validate a method to estimate left ventricular end-systolic elastance (E(es)) in humans from noninvasive single-beat parameters., Background: Left ventricular end-systolic elastance is a major determinant of cardiac systolic function and ventricular-arterial interaction. However, its use in heart failure assessment and management is limited by lack of a simple means to measure it noninvasively. This study presents a new noninvasive method and validates it against invasively measured E(es)., Methods: Left ventricular end-systolic elastance was calculated by a modified single-beat method employing systolic (P(s)) and diastolic (P(d)) arm-cuff pressures, echo-Doppler stroke volume (SV), echo-derived ejection fraction (EF) and an estimated normalized ventricular elastance at arterial end-diastole (E(Nd)): E(es(sb)) = [P(d) - (E(Nd(est)) x P(s) x 0.9)[/(E(Nd(est)) x SV). The E(Nd) was estimated from a group-averaged value adjusted for individual contractile/loading effects; E(es(sb)) estimates were compared with invasively measured values in 43 patients with varying cardiovascular disorders, with additional data recorded after inotropic stimulation (n = 18, dobutamine 5 to 10 microg/kg per min). Investigators performing noninvasive analysis were blinded to the invasive results., Results: Combined baseline and dobutamine-stimulated E(es) ranged 0.4 to 8.4 mm Hg/ml and was well predicted by E(es(sb)) over the full range: E(es) = 0.86 x E(es(sb)) + 0.40 (r = 0.91, SEE = 0.64, p < 0.00001, n = 72). Absolute change in E(es(sb)) before and after dobutamine also correlated well with invasive measures: E(es(sb)): DeltaE(es) = 0.86 x DeltaE(es(sb)) + 0.67 (r = 0.88, p < 0.00001). Repeated measures of E(es(sb)) over two months in a separate group of patients (n = 7) yielded a coefficient of variation of 20.3 +/- 6%., Conclusions: The E(es) can be reliably estimated from simple noninvasive measurements. This approach should broaden the clinical applicability of this useful parameter for assessing systolic function, therapeutic response and ventricular-arterial interaction.

Objectives: The goal of this study was to characterize detailed transmural left ventricular (LV) function at rest and during dobutamine stimulation in subendocardial and transmural experimental infarcts., Background: The relation between segmental LV function and the transmural extent of myocardial necrosis is complex. However, its detailed understanding is crucial for the diagnosis of myocardial viability as assessed by inotropic stimulation., Methods: Short-axis tagged magnetic resonance images were acquired at five to seven levels encompassing the LV from base to apex in seven dogs 2 days after a 90-min closed-chest left anterior descending coronary occlusion, followed by reflow. Myocardial strains were measured transmurally in the entire LV by harmonic phase imaging at rest and 5 ig x kg(-1) x min(-1) dobutamine. Risk regions were assessed by radioactive microspheres, and the transmural extent of the infarct was assessed by 2,3,5 triphenyltetrazolium chloride staining., Results: Circumferential shortening (Ecc), radial thickening (Err) and maximal shortening at rest were greater in segments with subendocardial versus transmural infarcts, both in subepicardium (-1.1+/-1.0 vs. 2.5+/-0.6% for Ecc, -0.5+/-1.9 vs. -1.8+/-1.0% for Err, p < 0.05) and subendocardium (-2.0+/-1.4 vs. 2.8+/-0.8%, 2.4+/-1.7 vs. 0.0+/-0.9%, respectively, p < 0.05). Under inotropic stimulation, risk regions retained maximal contractile reserve. Recruitable deformation was found in outer layers of subendocardial infarcts (p < 0.01 for Ecc and Err) but also in inner layers (p < 0.01). Conversely, no contractile reserve was observed in segments with transmural infarcts., Conclusions: Under dobutamine challenge, recruitment of myofiber shortening and thickening was observed in inner layers of segments with subendocardial infarcts. These results may have important clinical implications for the detection of myocardial viability.

Objectives: We aimed to validate contrast-enhanced echocardiography (CE) in the quantification of microvascular obstruction (MO) against magnetic resonance imaging (MRI) and the histopathologic standards of radioactive microspheres and thioflavin-S staining. We also determined the time course of MO at days 2 and 9 after infarction and reperfusion., Background: Postinfarction MO occurs because prolonged ischemia produces microvessel occlusion at the infarct core, preventing adequate reperfusion. Microvascular obstruction expands up to 48 h after reperfusion; the time course beyond 2 days is unknown. Though used to study MO, CE has not been compared with MRI and thioflavin-S, which yield precise visual maps of MO., Methods: Ten closed-chest dogs underwent 90-min coronary artery occlusion and reperfusion. Both CE and MRI were performed at 2 and 9 days after reperfusion. The MO regions by both methods were quantified as percent left ventricular (% LV) mass. Radioactive microspheres were injected for blood flow determination. Postmortem, the myocardium was stained with thioflavin-S and 2,3,5-triphenyltetrazolium chloride., Results: Expressed as % total LV, MO by MRI matched in size MO by microspheres using a flow threshold of <40% remote (4.96+/-3.52% vs. 5.32+/-3.98%, p=NS). For matched LV cross sections, MO by CE matched in size MO by microspheres using a flow threshold of <60% remote (13.27+/-4.31% vs. 13.5+/-4.94%, p=NS). Both noninvasive techniques correlated well with microspheres (MRI vs. CE, r=0.87 vs. 0.74; p=NS). Microvascular obstruction by CE corresponded spatially to MRI-hypoenhanced regions and thioflavin-negative regions. For matched LV slices at 9 days after reperfusion, MO measured 12.94+/-4.51% by CE, 7.11+/-3.68% by MRI and 9.18+/-4.32% by thioflavin-S. Compared to thioflavin-S, both noninvasive techniques correlated well (CE vs. MRI, r=0.79 vs. 0.91; p=NS). Microvascular obstruction size was unchanged at 2 and 9 days (CE: 13.23+/-4.11% vs. 12.69+/-4.97%; MRI: 5.53+/-4.94% vs. 4.68+/-3.44%; p=NS for both)., Conclusions: Both CE and MRI can quantify MO. Both correlate well with the histopathologic standards. While MRI can detect regions of MO with blood flow <40% of remote, the threshold for MO by CE is <60% remote. The extent of MO is unchanged at 2 and 9 days after reperfusion.