With growing evidence in clinical practice, the understanding of coronary syndromes has gradually evolved out of focusing on the well-established link between stenosis of epicardial coronary artery and myocardial ischemia to the structural and functional abnormalities at the level of coronary microcirculation, known as coronary microvascular dysfunction (CMD). CMD encompasses several pathophysiological mechanisms of coronary microcirculation and is considered as an important cause of myocardial ischemia in patients with angina symptoms without obstructive coronary artery disease (CAD). As a result of growing knowledge of the understanding of CMD assessed by multiple non-invasive modalities, CMD has also been found to be involved in other cardiovascular diseases, including primary cardiomyopathies as well as heart failure with preserved ejection fraction (HFpEF). In the past 2 decades, almost all the imaging modalities have been used to non-invasively quantify myocardial blood flow (MBF) and promote a better understanding of CMD. Myocardial contrast echocardiography (MCE) is a breakthrough as a non-invasive technique, which enables assessment of myocardial perfusion and quantification of MBF, exhibiting promising diagnostic performances that were comparable to other non-invasive techniques. With unique advantages over other non-invasive techniques, MCE has gradually developed into a novel modality for assessment of the coronary microvasculature, which may provide novel insights into the pathophysiological role of CMD in different clinical conditions. Moreover, the sonothrombolysis and the application of artificial intelligence (AI) will offer the opportunity to extend the use of contrast ultrasound theragnostics.
Background: This study aimed to evaluate the multiple interactions between therapeutic ultrasound (TUS), microbubbles (MB), and recombinant tissue plasminogen activator (r-tPA) by using three-dimensional (3D) ultrasound to examine the impact of thrombolysis with r-tPA on epicardial recanalization and microcirculation in patients with acute ST-segment-elevation myocardial infarction (STEMI).Methods: Acute thrombotic occlusion of the left anterior descending (LAD) artery was induced in 32 Bama pigs, who were fed a high-cholesterol diet and randomized into four groups: (I) a 3D-sono-assisted-thrombolysis (3D/TUS + MB + r-tPA) group; (II) a 3D/TUS + MB group; (III) a full-dose r-tPA group; and (IV) a 3D/TUS alone group. Epicardial angiographic recanalization rate, microcirculation in the at-risk myocardium, STsegment elevation on electrocardiogram, and changes in the at-risk myocardium and the myocardial infarct area were compared between the groups.Results: After treatment, distal LAD recanalization was observed in 87.5% (7/8) of pigs in the 3D/TUS + MB + r-tPA group, which was significantly higher than the rates observed in the 3D/TUS + MB (37.5%) and the full-dose r-tPA (50.0%) groups (all P<0.05). The average acoustic intensity in the 3D/TUS + MB + r-tPA group (193.78±10.15 dB) was also significantly higher than that in the 3D/TUS + MB (154.29±31.94 dB) and the r-tPA (141.42±28.31 dB) groups (all P<0.05). The decrease in ST-segment elevation in the 3D/TUS + MB + r-tPA group (1.31±1.22 mm) was significantly higher than that in the 3D/TUS + MB (5.38±1.77 mm) and the r-tPA (4.30±2.08 mm) groups (all P<0.05). Furthermore, the ratio of the infarcted myocardial area divided by the at-risk myocardial area was markedly lower in the 3D/TUS + MB + r-tPA group (0.51±0.14) than in the 3D/TUS + MB (0.69±0.28) and r-tPA (0.75±0.23) groups (all P<0.05).Conclusions: Three-dimensional sono-assisted-thrombolysis directly improves infarct-related recanalization rates, enhances microcirculation, reduces r-tPA dosage, and ameliorates the thrombolytic effect of r-tPA in acute STEMI.
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