The Impact of Sonothrombolysis on Left Ventricular Diastolic Function and Left Atrial Mechanics Preventing Left Atrial Remodeling in Patients With ST Elevation Acute Myocardial Infarction.

BACKGROUND: The diagnostic ultrasound-guided high mechanical index impulses during an intravenous microbubble infusion (sonothrombolysis) improve myocardial perfusion in acute ST segment elevation myocardial infarction, but its effect on left ventricular diastolic dysfunction (DD), left atrial (LA) mechanics and remodeling is unknown. We assessed the effect of sonothrombolysis on DD grade and LA mechanics. METHODS: One hundred patients (59 ± 10 years; 34% women) were randomized to receive either high mechanical index impulses plus percutaneous coronary intervention (PCI) (therapy group) or PCI only (control group) (n = 50 in each group). Diastolic dysfunction grade and LA mechanics were assessed immediately before and after PCI and at 48 to 72 hours, 1 month, and 6 months of follow-up. Diastolic dysfunction grades were classified as grades I, II, and III. The LA mechanics was obtained by two-dimensional speckle-tracking echocardiography-derived global longitudinal strain (GLS). RESULTS: As follow-up time progressed, increased DD grade was observed more frequently in the control group than in the therapy group at 1 month and 6 months of follow-up (all P < .05). The LA-GLS values were incrementally higher in the therapy group when compared with the control group at 48 to 72 hours, 24.0% ± 7.3% in the therapy group versus 19.6% ± 7.2% in the control group, P = .005; at 1 month, 25.3% ± 6.3% in the therapy group versus 21.5% ± 8.3% in the control group, P = .020; and at 6 months, 26.2% ± 8.7% in the therapy group versus 21.6% ± 8.5% in the control group, P = .015. The therapy group was less likely to experience LA remodeling (odds ratio, 2.91 [1.10-7.73]; P = .03). LA-GLS was the sole predictor of LA remodeling (odds ratio, 0.79 [0.67-0.94]; P = .006). CONCLUSION: Sonothrombolysis is associated with better DD grade and LA mechanics, reducing LA remodeling.

Effects of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients with Acute Myocardial Infarction.

INTRODUCTION: Clopidogrel has been demonstrated to be effective in improving coronary microcirculation (CM) among patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytics. Ticagrelor is a more potent adenosine diphosphate (ADP) receptor blocker proven to be superior to clopidogrel among patients with acute coronary syndromes. The present study aimed to compare the effects of ticagrelor and clopidogrel on CM in patients with STEMI treated with fibrinolytics. METHODS: The present study prospectively included 48 patients participating in the TREAT trial, which randomly assigned patients with STEMI undergoing fibrinolysis to ticagrelor versus clopidogrel. The primary endpoint of this study was the evaluation of the CM using the global myocardial perfusion score index (global MPSI) obtained by myocardial contrast echocardiography (MCE). Platelet aggregation to ADP was evaluated by Multiplate® and expressed as area under the curve (AUC). RESULTS: The global MPSI demonstrated no differences between the groups [mean 1.4 (1.2-1.5) in the ticagrelor group and 1.2 (1.2-1.5) in the clopidogrel group (p = 0.41)]. Platelet aggregability was lower in the ticagrelor group (18.1 ± 9.7 AUC), compared to the clopidogrel group (26.1 ± 12.5 AUC, p = 0.01). CONCLUSION: We found no improvement in coronary microcirculation with ticagrelor compared to clopidogrel among patients with STEMI treated with fibrinolytics, despite the fact that platelet aggregation to ADP was lower with ticagrelor. CLINICAL TRIALS REGISTRATION: NCT03104062.

In-hospital COVID-19 infection echocardiographic analysis: a Brazilian, tertiary single-centre experience.

BACKGROUND: Information is lacking concerning in-hospital echocardiography analysis of COVID-19 infection in Brazil. We evaluated echocardiographic parameters to predict a composite endpoint of mortality, pulmonary thromboembolism or acute renal failure. METHODS: A prospective full echocardiographic study of consecutive patients hospitalized with COVID-19, single tertiary centre in Brazil. We correlated echocardiographic findings to biomarkers, clinical information, thoracic tomography, and in-hospital composite endpoint of mortality, pulmonary thromboembolism or renal failure. RESULTS: One hundred eleven patients from March to October 2020, 67 ± 17 years, 65 (58.5%) men, death was observed in 21/111 (18.9%) patients, 48 (43%) required mechanical ventilation, myocardial infarction occurred in 10 (9%), pulmonary thromboembolism in 7 (6.3%) patients, haemodialysis was required for 9 (9.8%). Echocardiography was normal in 51 (46%) patients, 20 (18%) presented with decreased left ventricle ejection, 18 (16.2%) had abnormal left ventricle global longitudinal strain, 35 (31%) had diastolic dysfunction, 6 (5.4%) had an E/e'ratio > 14, 19 (17.1%) presented with right ventricle dilated/dysfunction, 31 (28%) had pericardial effusion. The echocardiographic parameters did not correlate with mortality, biomarkers, clinical events. Tricuspid velocity was related to the composite endpoint of mortality, pulmonary thromboembolism or acute renal failure (p: 00.3; value: 2.65 m/s; AUC ROC curve: 0.739; sensitivity: 73.3; specificity: 66.7; CI: 0.95, inferior: 0.613; superior: 0,866). CONCLUSIONS: Among hospitalized patients with COVID-19, echocardiography was normal in 51(46%) patients, and 20 (18%) patients presented with a decreased left ventricle ejection fraction. Tricuspid velocity was related to the composite endpoint of mortality, pulmonary thromboembolism or acute renal failure.

Sonothrombolysis Improves Myocardial Dynamics and Microvascular Obstruction Preventing Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction.

BACKGROUND: It has recently been demonstrated that high-energy diagnostic transthoracic ultrasound and intravenous microbubbles dissolve thrombi (sonothrombolysis) and increase angiographic recanalization rates in patients with ST-segment-elevation myocardial infarction. We aimed to study the effect of sonothrombolysis on the myocardial dynamics and infarct size obtained by real-time myocardial perfusion echocardiography and their value in preventing left ventricular remodeling. METHODS: One hundred patients with ST-segment-elevation myocardial infarction were randomized to therapy (50 patients treated with sonothrombolysis and percutaneous coronary intervention) or control (50 patients treated with percutaneous coronary intervention only). Left ventricular volumes, ejection fraction, risk area (before treatment), myocardial perfusion defect over time (infarct size), and global longitudinal strain were determined by quantitative real-time myocardial perfusion echocardiography and speckle tracking echocardiography imaging. RESULTS: Risk area was similar in the control and therapy groups (19.2±10.1% versus 20.7±8.9%; P=0.56) before treatment. The therapy group presented a behavior significantly different than control group over time (P<0.001). The perfusion defect was smaller in the therapy at 48 to 72 hours even in the subgroup of patients with no recanalization at first angiography (12.9±6.5% therapy versus 18.8±9.9% control; P=0.015). The left ventricular global longitudinal strain was higher in the therapy than control immediately after percutaneous coronary intervention (14.1±4.1% versus 12.0±3.3%; P=0.012), and this difference was maintained until 6 months (17.1±3.5% versus 13.6±3.6%; P<0.001). The only predictor of left ventricular remodeling was treatment with sonothrombolysis: the control group was more likely to exhibit left ventricular remodeling with an odds ratio of 2.79 ([95% CI, 0.13-6.86]; P=0.026). CONCLUSIONS: Sonothrombolysis reduces microvascular obstruction and improves myocardial dynamics in patients with ST-segment-elevation myocardial infarction and is an independent predictor of left ventricular remodeling over time.

Sonothrombolysis in ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention.

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).

Diagnostic Ultrasound Impulses Improve Microvascular Flow in Patients With STEMI Receiving Intravenous Microbubbles.

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).