Combined use of external therapeutic ultrasound and tirofiban has synergistic therapeutic effects on no-reflow after myocardial reperfusion.

OBJECTIVE: This study aimed to evaluate the effects of the combined use of external therapeutic ultrasound (ETUS) and the specific glycoprotein IIb/IIIa inhibitor tirofiban on myocardial no-reflow in a canine model of acute myocardial infarction after reperfusion. METHODS: The canine myocardial no-reflow model was established by a 3-hour occlusion of the left anterior desecending coronary artery followed by a 2-hour reperfusion. Twenty-four canines were divided into four groups (6/group): (1) control, (2) tirofiban alone, (3) ETUS combined with tirofiban (ETUS + tirofiban), and (4) ETUS alone. RESULTS: The area of no-reflow in each of the three treatment groups was significantly decreased, compared with the control group, with the ETUS + tirofiban group having the smallest area. Also, the ETUS + tirofiban group had the highest recanalized rate of microvessels in the no-reflow area and fewer impaired cellular organelles. The recovery rates of the endocardial and middle circumferential strain as well as longitudinal strain in the ETUS + tirofiban group were significantly greater than those of the tirofiban group. Moreover, the expression of hypoxia-inducible factor-1α (HIF-1α) was significantly increased in the ETUS + tirofiban group, compared with the other groups. CONCLUSIONS: The combined use of ETUS and tirofiban offers synergistic benefits for the treatment of myocardial no-reflow.

Early resolution of ST-segment elevation after reperfusion therapy for acute myocardial infarction: Its relation to echocardiography-determined left ventricular global and regional function and deformation.

AIMS: To evaluate the relationships between ST-segment resolution (STR) and echocardiography-determined left ventricular (LV) global and regional function and deformation in the sub-acute phase of STEMI. METHODS AND RESULTS: STR, defined as either complete (≥70%) or incomplete (<70%), was evaluated 60minutes after primary percutaneous coronary intervention (PCI) of 84 STEMI patients. Conventional two-dimensional (2D) echocardiography and 2D speckle-tracking echocardiography (STE) were performed at 3-7days after reperfusion. LV deformation [including the infarction-related regional longitudinal (RLS), circumferential (RCS), and radial (RRS) strains, and global longitudinal (GLS), circumferential (GCS), and radial (GRS) strains] was measured by 2D STE. LV segmental function was assessed by wall motion score index (WMSI). Patients in incomplete vs. complete STR groups had higher WMSI (p<0.001); decreased peak amplitude of RLS (p<0.001), RCS (p=0.008), RRS (p=0.002); and decreased peak amplitude of GLS (p<0.001), GCS (p<0.001), GRS (p=0.003). RLS (r=0.27, p=0.015) and GLS (r=0.33, p=0.003) were best correlates of STR at the regional and global level, respectively. CONCLUSIONS: STR correlated with global and regional LV function and deformation in patients with sub-acute phase of STEMI after PCI. RLS and GLS were the strongest correlates of STR at the regional and global levels, respectively.

Pharmacoinvasive therapy for ST elevation myocardial infarction in China: a pilot study.

Most patients with acute ST-elevation myocardial infarction (STEMI) cannot receive timely primary percutaneous coronary intervention (PCI) because of lack of facilities or delays in patient transfer or catheterization team mobilization. In these patients, early routine post-thrombolysis PCI might be a reasonable, useful strategy. This study investigated feasibility and safety of early PCI after successful half-dose alteplase reperfusion in a Chinese population. Patients with STEMI received half-dose alteplase if expected time delay to PCI was ≥90 min. Patients who reached clinical criteria of successful thrombolysis reperfusion were recommended to undergo diagnostic angiography within 3-24 h after thrombolysis. Patients with residual stenosis ≥70% in the infarct-related artery underwent PCI, regardless of flow or patency status. Epicardial arterial flow was assessed using thrombolysis in myocardial infarction (TIMI) flow grade and TIMI frame count (CTFC). Myocardial perfusion was assessed using myocardial blush grade (MBG) and TIMI myocardial perfusion frame count (TMPFC). Forty-nine patients were enrolled and underwent diagnostic angiography 3-11.3 h (median 6.5 h) after thrombolysis. Forty-six patients underwent PCI. No procedure-related complications occurred, except two patients who had no reflow after PCI. Twenty-two (47.8%) patients had TIMI grade 3 flow before PCI and 33 (71.7%) after PCI. CTFC was significantly improved after PCI (48.5 ± 32.1 vs. 37.9 ± 25.6, P = 0.01). MBG and TMPFC exhibited a similar improving trend after PCI, and the best myocardial perfusion tended to be achieved 3-12 h after lysis. During the 30-day follow-up, there were two deaths. The composite end point of death, cardiogenic shock, heart failure, reinfarction, and recurrent ischemia occurred in four patients. TIMI minor bleeding occurred in four patients. No TIMI major bleeding and stroke occurred. Early routine PCI after half-dose alteplase thrombolysis in Chinese population appears feasible. A larger clinical trial should be designed to further elucidate its efficacy and safety. Early PCI after thrombolysis in STEMI: The EARLY-PCI pilot feasibility study, ChiCTR-TNC-11001363.

Risk of device-related thrombosis following short-term oral anticoagulation with low-dose dabigatran versus warfarin after Watchman left atrial appendage occlusion.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) provides an alternative for poor candidates for long-term oral anticoagulation (OAC). To prevent device-related thrombosis (DRT), OAC should be continued for the first 45 days to allow complete endothelialization post-LAAO implantation. Whereas, evidence is limited on the feasibility and safety of direct oral anticoagulants (DOACs) used after LAAO. METHODS: This was a retrospective observational single-center study of AF patients undergoing LAAO with a Watchman device and receiving either low-dose dabigatran (110mg twice daily) or warfarin in the peri- and post-procedural period for 45 days. Transesophageal echocardiography was scheduled to perform at 6 weeks, 6 months, and 12 months after the procedure to assess the stability of the device and to detect DRT. Incidence of thromboembolic and bleeding events were also evaluated during the follow-up period. RESULTS: There were a total of 84 patients who successfully underwent Watchman implantation, with 38 patients (45.2%) receiving low-dose dabigatran and 46 patients (54.8%) using warfarin post-LAAO. Peri-procedural complications occurred in 10 patients, with 3 patients in the dabigatran group and 7 patients in the warfarin group (7.9% vs. 15.2%, p = 0.30). During the 12-month follow-up, 1 patient experienced major bleeding and 16 patients suffered minor bleeding in the warfarin group, while 5 patients treated with dabigatran had minor bleeding (34.8% vs. 13.2%, p = 0.02). Besides, 6 DRT (15.8%) were detected in dabigatran groups, and the incidence was higher than in the warfarin group (15.8% vs. 2.2%, p = 0.03). No DRT-related ischemic events were found. CONCLUSIONS: This study suggested that short-term low-dose dabigatran (110 mg twice daily) could significantly decrease the risk of bleeding compared with warfarin at the expense of increased risk of DRT post-LAAO. Therefore, low-dose dabigatran should be used with caution for post-implant anticoagulation of LAAO. Further studies are urgently needed on the feasibility and safety of DOACs post-LAAO.

TIMI myocardial perfusion frame count: a new method to assess myocardial perfusion and its predictive value for short-term prognosis.

OBJECTIVES: We sought to develop a new quantitative method to evaluate the degree of myocardial perfusion. BACKGROUND: Currently available methods for assessing myocardial perfusion, both TIMI myocardial perfusion grading (TMPG) and myocardial blush grading (MBG), are subjective. METHODS: TIMI Myocardial Perfusion Frame Count (TMPFC), an objective method that measures the filling and clearance of contrast in the myocardium using cine-angiographic frame-counting, was developed to quantify myocardial perfusion. Myocardial perfusion of 45 normal coronary arteries in 15 patients, and 137 culprit arteries in 137 patients immediately after primary angioplasty, was successfully assessed with TMPFC. RESULTS: The mean TMPFC in the normal arteries was 83.47 +/- 17.96 frames (95% CI: 78.07 frames

Initial anticoagulation experience with standard-dose rivaroxaban after Watchman left atrial appendage occlusion.

BACKGROUND: Warfarin is now recommended as the standard anti-thrombotic regimen to allow complete endothelialization over the Watchman device post percutaneous left atrial appendage occlusion (LAAO). However, the need for frequent monitoring, narrow therapeutic range, dietary restrictions and multiple drug interactions associated with warfarin have contributed to increasing uptake of non-vitamin K oral anticoagulants (NOACs) worldwide. At present, the feasibility and safety of NOACs instead of warfarin post-LAAO is lacking. METHODS: Patients who underwent successful Watchman device implantation between October 1, 2016 and September 30, 2017 were enrolled in a retrospective database. And only patients who received rivaroxaban in the periprocedural period were included in this study. Transesophageal echocardiography (TEE) follow-up was scheduled at 6 weeks, at 6 months, and at 12 months post-implantation to detect device-related thrombosis (DRT) or peri-device leak. Meanwhile, thromboembolic and bleeding events were also evaluated at the time of follow-up. RESULTS: Totally, 57 Watchman devices were successfully implanted and 10 patients who were allocated to rivaroxaban at the dosage of 20 mg once daily were included. During the follow-up, none of the patients using rivaroxaban experienced DRT, peri-device leak, thromboembolic complications and major bleeding events, except for 2 patients who suffered minor bleeding during the 6 weeks follow-up. CONCLUSIONS: This study suggests that a short course of standard-dose rivaroxaban following Watchman LAAO is associated with low incidence of thrombotic complications and bleeding events, and might be a feasible alternative regimen in Chinese. Further randomized trials and large sample of real-world studies are needed to validate our finding.

Rationale and design of a prospective multi-center randomized trial of EARLY treatment by rivaroxaban versus warfarin in ST-segment elevation MYOcardial infarction with Left Ventricular Thrombus (EARLY-MYO-LVT trial).

BACKGROUND: Left ventricular thrombus (LVT), a common complication of acute ST-segment elevation myocardial infarction (STEMI), is associated with increased risk of systemic embolism and high mortality. Current STEMI guidelines recommend adding anticoagulant therapy to dual antiplatelet therapy (DAPT) if early-formulated LVT were detected, for which vitamin K antagonist (VKA) is the standard anticoagulant agent. The role of non-VKA oral anticoagulants (NOACs) in this scenario is uncertain. METHODS: The EARLY-MYO-LVT study will be a prospective, multi-center and randomized trial designed to investigate the efficacy and safety of rivaroxaban versus warfarin in the treatment of post-STEMI LVT. It will enroll 280 patients with STEMI who have developed LVT within the first month of symptom onset. They will be randomized at 1:1 ratio into the group of rivaroxaban 15 mg daily or VKA treatment (with targeted INR 2-2.5) on the basis of standard DAPT (100 mg daily aspirin plus 75 mg daily clopidogrel) for 3-6 months. The primary efficacy endpoint will be the probability of LVT resolution after 3-month triple therapy, and the principal safety outcome will be the incidence of major bleeding events during the treatment. DISCUSSION: The described study will systemically assess the efficacy and safety of NOACs-based anticoagulant therapy in the treatment of LVT subsequent to STEMI. TRIAL REGISTRATION: The EARLY-MYO-LVT trial (Clinical trial number: NCT03764241).

Optimal nonvitamin K antagonist oral anticoagulant therapy in a warfarin-sensitive patient after left atrial appendage closure: A case report.

RATIONALE: Developing an optimal medication strategy poses a challenging task in fragile patients after left atrial appendage closure (LAAC). We report an optimal nonvitamin K antagonist oral anticoagulant (NOAC) therapy in a warfarin-sensitive patient after LAAC. PATIENT CONCERNS: A 77-year-old nonvalvular atrial fibrillation (NVAF) male carrying 2 warfarin-sensitive alleles experienced 2 gum-bleeding with the international normalized ratio (INR) around 3. DIAGNOSES: Persistent NVAF with a history of subtotal gastrectomy and moderate renal insufficiency. INTERVENTIONS: Warfarin was discontinued and vitamin K1 was immediately administrated via intravenous infusion. LAAC was regarded as a preferable option, and rivaroxaban 15 mg daily was managed after LACC. OUTCOMES: Complete endothelialization on the surface of device was detected via transoesophageal echocardiography (TEE), and no peridevice spillage and adverse event occurred. LESSONS: A post-LAAC treatment with NOAC may be a viable regimen in patients intolerant to warfarin.

Impact of Early ST-Segment Changes on Cardiac Magnetic Resonance-Verified Intramyocardial Haemorrhage and Microvascular Obstruction in ST-Elevation Myocardial Infarction Patients.

The aim of this study was to explore the significance of different ST-segment changes before and after percutaneous coronary intervention (PCI), in relation to cardiac magnetic resonance (CMR)-verified microvascular obstruction (MVO) along with intramyocardial hemorrhage (IMH) in ST-elevation myocardial infarction (STEMI) patients.This study enrolled 108 STEMI patients who received primary PCI and had no contraindication of CMR investigation. Sum ST-segment elevation (STE), maximal STE on admission and sum ST-segment resolution (STR), and single-lead STR and residual STE at 60 minutes after primary PCI were assessed. MVO and IMH were determined by contrast-enhanced CMR.Patients were classified into 3 groups: 30 patients with MVO(-)/IMH(-), 25 with MVO(+)/IMH(-), and 53 with MVO(+)/IMH(+). Sum STE (P = 0.001), maximal STE (P < 0.001), and residual STE (P = 0.025) were highest and single-lead STR was lowest (P = 0.044) in the MVO(+)/IMH(+) group. Receiver operator characteristics curve analysis revealed that maximal STE was the most powerful factor for distinguishing between MVO(+) and MVO(-) patients (optimal threshold = 0.5 mV, area under the curve, AUC = 0.718, P < 0.001), or IMH(+) and IMH(-) patients (optimal threshold = 0.5 mV, AUC = 0.697, P < 0.001). In multivariate analysis, maximal STE was identified as the most powerful independent predictor of MVO (odds ratio [OR] = 4.30, P < 0.001) and IMH (OR = 2.44, P = 0.001), whereas sum STE was the strongest correlate of both the number of MVO segments (r = 0.42, P < 0.001) and IMH segments (r = 0.43, P < 0.001).The presence of MVO and IMH in infarcted tissue was relevant to ST-segment changes in STEMI patients. Maximal STE was a powerful independent predictor of the presence of MVO and IMH, whereas sum STE was a strong correlate of the number of MVO and IMH segments.